This guide provides an easy-to-use desk reference for diagnostic information on commonly used hematology, clinical chemistry and urinalysis parameters. Additional reference materials are provided as an aid in evaluating clinical pathology data. For many toxicologists, the evaluation of hematology, clinical chemistry and urinalysis data can be the most challenging aspect of animal toxicity studies. In a typical toxicity study, dozens of parameters are measured several times over the course of the study. There may be hundreds of data points, each of which needs to be considered. A Toxicologist's Guide to Clinical Pathology in Animals will serve as an essential primer for toxicologists in training and in industry as well as for researchers and professionals in a veterinary practice or a laboratory.

The unexpected and premature passing away of Professor Ebrahim H. "Abe" Mamdani on January, 22, 2010, was a big shock to the scientific community, to all his friends and colleagues around the world, and to his close relatives. Professor Mamdani was a remarkable figure in the academic world, as he contributed to so many areas of science and technology. Of great relevance are his latest thoughts and ideas on the study of language and its handling by computers. The fuzzy logic community is particularly indebted to Abe Mamdani (1941-2010) who, in 1975, in his famous paper An Experiment in Linguistic Synthesis with a Fuzzy Logic Controller, jointly written with his student Sedrak Assilian, introduced the novel idea of fuzzy control. This was an elegant engineering approach to the modeling and control of complex processes for which mathematical models were unknown or too difficult to build, yet they could effectively and efficiently be controlled by human operators. This ground-breaking idea has found innumerable applications and can be considered as one of the main factors for the proliferation and adoption of fuzzy logic technology. Professor Mamdani's own life and vital experience are illustrative of his "never surrendering" attitude while facing adversaries, which is normal for a person proposing any novel solution, and represent a great example for everybody. His subtle sense of humor, his joy for life, and his will to critically help people, especially young people, were characteristics deeply appreciated by all the people who enjoyed and benefited from his friendship and advice. This book constitutes a posthumous homage to Abe Mamdani. It is a collection of original papers related in some way to his works, ideas and vision, and especially written by researchers directly acquainted with him or with his work. The underlying goal of this book will be fulfilled if, in the very spirit of Mamdani's legacy, the papers will trigger a scientific or philosophical debate on the issues covered, or contribute to a cross-fertilization of ideas in the various fields.

The book highlights work from many different labs that taught us abnormal HDACs potentially contribute to the development or progression of many human diseases including immune dysfunctions, heart disease, cancer, memory impairment, aging, and metabolic disorders.

Known for flexibility and robustness, PCR techniques continue to improve through numerous developments, including the identification of thermostable DNA polymerases which exhibit a range of properties to suit given applications. PCR Protocols, Third Edition selects recently developed tools and tricks, contributed by field-leading authors, for the significant value that they add to more generally established methods. Along with the cutting-edge methodologies, this volume describes many core applications, such as PCR cloning and sequencing, expression, copy number or methylation profile analysis, 'DNA fingerprinting', diagnostics, protein engineering, interaction screening as well as a chapter highlighting workflow considerations and contamination control, crucial for all PCR methods. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary reagents and materials, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, PCR Protocols, Third Edition seeks to further elucidate this essential technique while also providing core principles with broad applications for scientists of all backgrounds.

A comprehensive reference work: This looseleaf work is an authoritative compilation of methods for the detection of autoantibodies (Section A: Methods of Autoantibody Detection); the structure, function, and molecular and biochemical concepts of autoantigens (Section B: Autoantigens); and the clinical significance of measuring autoantibodies in patients with rheumatic, connective tissue and autoimmune diseases (Section C: Clinical Significance of Autoantibodies). This unique work brings together all the molecular and medical information - very difficult to retrieve otherwise - in ONE publication. The Editors and contributors are leading experts in the immunological, molecular biological, and clinical fields. The format of this looseleaf publication allows regular updating of data as well as inclusion of new advances in research on autoimmunity. Until now, the work (Basic work including Supplement 1) included Section A, and the larger part of Section B, both in an attractive and robust ringbinder. Audience: By nature and design of this exciting reference work, it is especially aimed at scientists, including immunologists, pathologists and molecular biologists, and clinical chemists, as well as clinicians specializing in rheumatic diseases and autoimmune disorders, inflammation or clinical immunology. Supplement 2: This supplement primarily contains Section C (Clinical Significance of Autoantibodies). As in the other sections, the contents are presented in a consistently structured manner, beautifully illustrated with photos and schematic figures. Extensive literature references are provided. Also, this supplement includes an addition to Section B (Autoantigens), being chapter B.1.5: The Antigens Defined by Antikeratin Antibodies (AKA).

Matthias Kaeding discusses Bayesian methods for analyzing discrete and continuous failure times where the effect of time and/or covariates is modeled via P-splines and additional basic function expansions, allowing the replacement of linear effects by more general functions. The MCMC methodology for these models is presented in a unified framework and applied on data sets. Among others, existing algorithms for the grouped Cox and the piecewise exponential model under interval censoring are combined with a data augmentation step for the applications. The author shows that the resulting Gibbs sampler works well for the grouped Cox and is merely adequate for the piecewise exponential model.

In this book, Dr. Li and his author team plan to emphasize why mouse models are useful in vivo systems for understanding disease mechanisms and developing therapeutic strategies in blood cancers. The authors do not intend to cover all types of blood cancers; instead, they will focus on some major ones such as leukemias and lymphomas. However, the authors will try to cover as much as they can the cancer types and point out that many blood cancers need to be studied in mouse disease models although they are still not available at present. A major focus in the book will be to show what we can or cannot learn from mouse disease models and to also show the critical contributions of mouse models in therapeutic drug development.

Healthcare and Biotechnology in the 21st Century: Concepts and Case Studies introduces students not pursuing degrees in science or engineering to the remarkable new applications of technology now available to physicians and their patients and discusses how these technologies are evolving to permit new treatments and procedures. The book also elucidates the societal and ethical impacts of advances in medical technology, such as extending life and end of life decisions, the role of genetic testing, confidentiality, costs of health care delivery, scrutiny of scientific claims, and provides background on the engineering approach in healthcare and the scientific method as a guiding principle. This concise, highly relevant text enables faculty to offer a substantive course for students from non-scientific backgrounds that will empower them to make more informed decisions about their healthcare by significantly enhancing their understanding of these technological advancements.

This proposed text appears to be a good introduction to evolutionary computation for use in applied statistics research. The authors draw from a vast base of knowledge about the current literature in both the design of evolutionary algorithms and statistical techniques. Modern statistical research is on the threshold of solving increasingly complex problems in high dimensions, and the generalization of its methodology to parameters whose estimators do not follow mathematically simple distributions is underway. Many of these challenges involve optimizing functions for which analytic solutions are infeasible. Evolutionary algorithms represent a powerful and easily understood means of approximating the optimum value in a variety of settings. The proposed text seeks to guide readers through the crucial issues of optimization problems in statistical settings and the implementation of tailored methods (including both stand-alone evolutionary algorithms and hybrid crosses of these procedures with standard statistical algorithms like Metropolis-Hastings) in a variety of applications. This book would serve as an excellent reference work for statistical researchers at an advanced graduate level or beyond, particularly those with a strong background in computer science.

In this accessible overview of current knowledge, an expert team of editors and authors describe experimental approaches to consciousness. These approaches are shedding light on some of the hitherto unknown aspects of the distinct states of human consciousness, including the waking state, different states of sleep and dreaming, meditation and more. The book presents the latest research studies by the contributing authors, whose specialities span neuroscience, neurology, biomedical engineering, clinical psychology and psychophysiology, psychosocial medicine and anthropology. Overall this anthology provides the reader with a clear picture of how different states of consciousness can be defined, experimentally measured and analysed. A future byproduct of this knowledge may be anticipated in the development of systematic corrective treatments for many disorders and pathological problems of consciousness.

Immunofluorescence, a suitable laboratory method for the microscopic demonstration of antigens and antibodies in biological materials, useable, for example, to provide evidence for the pathogenesis of disease in histological or cytological preparations and for tumour cell differentiation. For this reason immunofluorescence has a decisive role as the method of choice for the diagnosis of auto-immune diseases. This primer on immunofluorescence techniques, which first appeared in 1979, is a richly illustrated handbook suitable for everyday practical work in the laboratory, useable as both an introduction to the subject as well as an atlas. In hardly any other area of medicine are there so many new findings to report. The second edition of this book is concerned not only with the detection methods which now form an essential and established part of diagnostic techniques, but also with the most recent research results such as the discovery of antibodies against Auerbach's plexus and against podocytes...

Biotargets of Cancer in Current Clinical Practice presents an updated and reasoned review of the current status of knowledge concerning the major cancer types with a special focus on the current biomarkers, genes involved and the potential future targets of innovative therapies. The volume includes for each major cancer type, a comprehensive although concise discussion of epidemiology, affirmed and innovative biomarkers for diagnosis, and descriptions of the relevant genes for prognosis and (individualized) therapy through biotarget-specific new molecular treatments, with the latest information on the validation status of each novel biomarker. Individual chapters are dedicated to the major cancer types, plus a special chapter on metastasis. The present debate on patentability of genetic information applied to diagnostics and therapeutics of cancer is also discussed.

Molecular biology has rapidly advanced since the discovery of the basic flow of information in life, from DNA to RNA to proteins. While there are several important and interesting exceptions to this general flow of information, the importance of these biological macromolecules in dictating the phenotypic nature of living creatures in health and disease is paramount. In the last one and a half decades, and particularly after the completion of the Human Genome Project, there has been an explosion of technologies that allow the broad characterization of these macromolecules in physiology, and the perturbations to these macromolecules that occur in diseases such as cancer. In this volume, we will explore the modern approaches used to characterize these macromolecules in an unbiased, systematic way. Such technologies are rapidly advancing our knowledge of the coordinated and complicated changes that occur during carcinogenesis, and are providing vital information that, when correctly interpreted by biostatistical/bioinformatics analyses, can be exploited for the prevention, diagnosis, and treatment of human cancers. The purpose of this volume is to provide an overview of modern molecular biological approaches to unbiased discovery in cancer research. Advances in molecular biology allowing unbiased analysis of changes in cancer initiation and progression will be overviewed. These include the strategies employed in modern genomics, gene expression analysis, and proteomics.

The objective of this volume is togive an overview of the present state of the art of pediatric clinical pharmacology including developmental physiology, pediatric-specific pathology, special tools and methods for development of drugs for children (assessment of efficacy, toxicity, long-term safety etc.) as well as regulatory and ethical knowledge and skills. In the future, structural and educational changes have to lead back to a closer cooperation and interaction of pediatrics with (clinical) pharmacology and pharmacy."

380 years ago, in the year 1614, Ubbo Emmius transplanted the gene ofscience from Ostfriesland into the education genome ofthe city ofGroningen as devel- oped by Regnerus Praedinius. He thereby founded the University ofGroningen. It is with great pleasure that the Faculty of Medicine as one of the founding faculties ofour University, welcomes you to this 19th International Symposium ofBloodTransfusion, whichwill coverthe themeofHereditaryDiseasesandtheir relation to Transfusion Medicine, where cell expansion, gene transfer and gene therapy are the read thread. Since the earlydays there has beena specificand sincere interest in inborn errors ofmetabolism and hereditarydisorders. This interest has resulted in a structured research, diagnostic and counselling facilities, and therapeuticapproaches where various disciplines within our faculty work closely together with groups from related faculties of the University of Groningen, as well as other national and international scientific institutions. The field of inborn errors, genetic abnormalities and mutations, and hereditary diseases covers a broad gamma of extremely interesting and exciting scientific aspects,whichrangefrom clearphysicalaberrationstomolecularanalysisofgenes and genomes, coding areas and amino acid sequences. It is intriguing to realise that the balance of life seemingly depends on the position or presence of one single molecule as a part ofthe total complex ofgenetic information in the cell.

Since the establishment of the DNA structure researchers have been highly interested in the molecular basis of the inheritance of genes and of genetic disorders. Scientific investigations of the last two decades have shown that, in addition to oncogenic viruses and signalling pathways alterations, genomic instability is important in the development of cancer. This view is supported by the findings that aneuploidy, which results from chromosome instability, is one of the hallmarks of cancer cells. Chromosomal instability also underpins our fundamental principles of understanding tumourigenesis: It thought that cancer arises from the sequential acquisition of genetic alterations in specific genes. In this hypothesis, these rare genetic events represent rate-limiting 'bottlenecks' in the clonal evolution of a cancer, and pre-cancerous cells can evolve into neoplastic cells through the acquisition of somatic mutations. This book is written by international leading scientists in the field of genome stability. Chapters are devoted to genome stability and anti-cancer drug targets, histone modifications, chromatin factors, DNA repair, apoptosis and many other key areas of research. The chapters give insights into the newest development of the genome stability and human diseases and bring the current understanding of the mechanisms leading to chromosome instability and their potential for clinical impact to the reader.

While the historic roots of clinical chemistry originate from the chemical sciences the growth of the subject has been dependent upon the poli tical, social, economic and technologic national soil in which it has developed. Thus the present leaders in this field have backgrounds variously in chemistry, medicine, pharmacy or sometimes biology. Today, clinical chemistry has attained stature as a unified independent discipline. It is characterized by active and productive international and national societies; its function codified in the law of many countries; its scientific content the sole subject of international and national journals as well as textbooks and educational programs; and its inter national, regional and national meetings have become focal points for major exchange of scientific, clinical and technical information and exhibition. The positive impact of the discipline upon the delivery of health care has given it a significant position in the economics of public health. As a consequence it has become the most rapidly-growing segment of the industrial and commercial component of health main tenance. These changes have brought the need to define the educational and training processes to prepare future leaders of clinical chemistry. The diverse backgrounds of the present directors of clinical chemicallabora tories has required that the viewpoints of chemists, pharmacists, physicians and biologists be brought into harmony. This has been achieved by the years of discussion, debate and review by colleagues of varied professional backgrounds. This monograph reflects their consensus viewpoint for the practice of clinical chemistry at its most advanced level."

In transfusion medicine the scientific fundamentals of immunology have had a considerable clinical impact. Transfusion may suppress the immunity but some patients could suffer disadvantages including GvHD, alloimmunisation and possible cancer, where white cells (WBC) play pivotal roles in this phenomenon, presenting antigens and producing cytokines. A clinical application of this practice is LAK-cells targeted against cancer. MHC on the WBC may provide additional immunological modulations through series of secondary messengers. Thus reduction of WBC in the blood and bone marrow may be advantageous for patients. On the other hand, sharing a part of MHC or making the transplanted white cells anergic by storage may be even more advantageous for patients. CMV infection could mimic part of this MHC. UV radiation is effective in the inactivation of the WBC although filters are easy means for such removal. However, their accurate quantification requires flow cytometry that has considerable potential application in blood transfusions. Idiotypic antibody could play an important role in platelet theory. However, the potential infection risks in transfusion like HIV and HCV remain, but application of molecular biological methods like PCR or RT/PCR has great potentials in detection of infectious diseases, transplantation and genetic disorders. Immuno affinity purified concentrates, like factor IX and protein C, could reduce patients' immune functions, where in the future protein C could be derived from transgenic animals. Advances are sure to emerge through adoptive immunotherapy and gene therapies are exciting prospects when genes transferred into lymphocytes could be used to correct cell mediated immune deficiency, as in ADA.

Case Studies in Pediatric Critical Care presents a spectrum of real and interesting case studies relating to critically ill children. Each case study includes details of the presenting history and symptomatology, results of investigations and the subsequent critical care management of the patient. Cases have been chosen to illustrate the increasingly diverse range of problems that may be encountered by pediatric critical care physicians throughout the world. Alongside each case is a comprehensive discussion of the various treatment strategies available, and a short list of invaluable learning points summarize the key take-home messages of each case. Concise, practical and relevant, and written by expert pediatric intensivists, Case Studies in Pediatric Critical Care is an invaluable resource for anyone involved in the care of critically ill children.

Cell Surface Receptors: A Short Course on Theory and Methods, Second Edition is a primer for the study of cell surface receptors. The simplified discussion of methods and their underlying principles removes the usual intimidation caused by the specialized vocabulary or sophisticated mathematics that characterize many of the primary papers in this field. In this way, the basic concepts become emphasized. This volume is a starting point: a textbook as well as a manual to which the investigator can return for a refresher course, when needed.

When Volume 1 (Toxicolpgy) in this series of Standard Operating Procedures was pub lished in early 1979, the FDA's Good Laboratory Practice Regulations did not have the force of United States Law, but nevertheless had a substantial impact on the conduct of toxicology in laboratories throughout the world. These Regulations are now in force, and Volume 2 (Pathology) was published later the same year. Our critics have implied that we have attempted to reduce toxicology to the level of the cookery book, or alternatively that we seek to impose our standards on others, In some sinister way ensuring that the IRI code will become the international norm. We dismiss these criticisms as arrant nonsense. The many thousands of volumes already sold worldwide can provide at best a framework for adaptation to suit local laboratory condi tions, and thus speed to GLP compliance those organisations which might otherwise have remained foundering at the starting post. If Volumes 1 and 2 of this series have con tributed anything to the conduct of toxicology it must surely be in those non-English speaking nations which, because of the international nature of pharmaceutical and chemical trading, are required by commercial pressures to be in compliance with a foreign law formulated in unfamiliar terminology and introduced for reasons that are not immediately obvious. Much has happened in the short period of time since Volumes 1 and 2 were published."

This is the fourth volume of Standard Operating Procedures (SOPs) compiled from documents prepared in these laboratories in part fulfilment of the requirements of various Good Laboratory Practice (GLP) regulations and guidelines. SOPs have now become an everyday feature of work in most industrial and contract toxicology laboratories. They provide a written definition of the mechanics of unit operations which together comprise the framework for experiments in safety evaluation. Metabolic studies and analytical chemistry are closely linked to toxicology since they embody essential aspects of the overall assessment of product safety. Some authorities consider certain parts of these subjects to be outwith the scope of the GLP requirements but for the reasons stated this is contrary to our own view. We have tried where possible to define in SOP format for use in our own laboratories the unit operations involved in these disciplines and they form the basis of this volume. Some relevant material from previous volumes has been brought together in updated form and is also presented here for completeness. Dr I P Sword Managing Director Inveresk Research International Musselburgh EH21 7UB Scotland ix Introduction GENERAL 1. The Food and Drug Administration of the US Government published its Good Laboratory Practice Regulations for Non-Clinical Laboratory Studies in the Federal Register (22 December 1978). The Regulations are the culmin ation of a number of years of investigation into the standards to which safety evaluation studies were performed in laboratories in the USA."

John Sinclair and a panel of expert investigators present a comprehensive collection of cellular and molecular techniques for the analysis of cytomegalovirus (CMV) biology and its pathogenetic mechanisms. The methods-all described in step-by-step detail with ready reproducibility in mind-range from basic virus culture to complex molecular analysis of CMV structure and function. Included are methods for CMV detection using both immunological and biological techniques, methods for analyzing fundamental aspects of the CMV infection cycle, and methods for analyzing T cell response to cytomegalovirus infection in the human host. Comprehensive and state-of-the-art, Cytomegalovirus Protocols provides investigators with a collection of the key methods that are illuminating not only the basic biology of this complex and intriguing human herpesvirus, but also its significant role in human infectious diseases and their emergent therapies.

During the past two decades, many books, governmental reports and regu lations on safety measures against chemieals, fire, microbiological and radioactive hazards in laboratories have been published from various coun tries. These topics have also been briefly discussed in books on laboratory planning and management. The application ofvarious scientific instruments based on different ionizing and non-ionizing radiations have brought new safety problems to the laboratory workers of today, irrespective of their scientific disciplines, be they medicine, natural or life sciences. However, no comprehensive laboratory handbook dealing with aIl these hazards, some of which are recently introduced, had so far been available in a single volume. Therefore, it was thought worthwhile to publish this Handbook on safety and health measures for laboratories, with contributions from several experts on these subjects. As this second edition of the Handbook, like the first edition, is a multiauthor volume, some duplication in conte nt among chapters is unavoidable in order to maintain the context of a chapter as weIl as make each chapter complete. An attempt has also been made to maintain the central theme, which is how to work in a laboratory with maximum possible environmental safety."

Radiophannaceuticals labeled with short-lived radionuclides are utilized to unravel biochemical processes, and to diagnosis and treat diseases of the living body are-developed through extensive evaluation in ~iological models. 'fhC first attempt to compile information was a volume entitled ANIMAL MODELS IN RADIOTRACER DESIGN that was edited by William C. Eckelman and myself in 1983. The volume had a focus on the animal models that investigators were using in order to design radiotracers that displayed in vivo selectivity as measured by biodistribution and pharmacokinetic studies. A concern in the early days of nuclear medicine was species differences. Often a series of labeled compounds were evaluated in a several different animal models in order to gain confidence that the selected radiotracer would behave appropriately in humans. During the past 12 years there have been remarkable advances in molecular genetics, molecular biology, synthetic radiopharmaceutical chemistry, molecular modeling and visualization, and emission tomography. Biological models can now be selected that are better defined in terms of molecular aspects of the disease process. The development of high resolution PET and SPET for clinical applications facilitates the development of new radiopharmaceuticals by the use of models to quantitatively evaluate drug effects, and progression of disease, and hence to arrive at better diagnosis and treatments for animals and humans. With these advances there is an effective use of biological models, and the refinement of alternatives for the development of new radiophannaceuticals.