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.

Today, individuals have greater access to information about their healththaneverbefore(Randeree,2009;Eysenbach,2008).Muchofthis changeisdue, inlargepart, toadvancesinbiotechnologyandtheseque- ing of the human genome (Manolio & Collins, 2009). It is now possible, forexample, forindividualstologontotheInternetand, forafeeofs- eral hundred dollars, order an at-home DNA collection kit and have the resultsofamyriadofgenetictestsdelivereddirectlytotheire-mailinbox (Gurwitz&Bregman-Eschet,2009).Insomecases, thesetestresultsmay indicatepersonalriskforcommonchronicdiseases, suchascertainforms ofcancer, diabetes, cardiovasculardisease, andseveralothers.Companies marketing these test kits often claim that promoting greater access to and awareness of the association between genes and health, and one's genetic susceptibilities to disease, leads to more proactive and insig- fulmethodsofindividualhealthmanagement(Hogarth, Javitt,&Melzer, 2008). Moreover, it is consistent with an emerging trend in medicine - that of consumer-oriented medicine - which places health information toolsdirectlyinthehandsofpatientsunderthepremiseoffosteringbetter patient-providercollaboration(Silvestre, Sue,&Allen,2009). Though the principles behind this direct-to-consumer approach to genetics seem laudable and perhaps even exciting, there is consid- ablecontroversyastowhat, ifany, utilitytheinformationactuallyholds (Geransar&Einsiedel,2008;Wasson, Cook,&Helzlsouer,2006).Unlike geneticteststhatarediagnostic(e.g., chromosomeanalysisforDowns- drome)orhighlypredictive(e.g., BRCA1andBRCA2testingforhereditary breast-ovarian cancer risk), this new wave of presymptomatic predictive genetictestsforcommondiseaseyieldsresultsthataremuchmoreunc- tainbecausethestatisticalmodelsonwhichtheyarepresentlybasedare imperfectandwithlimiteddata(Ng, Murray, Levy,&Venter,2009). Theabovescenarioraisesmanyquestionsfortoday'shealth-carec- sumers. For example, for whom is this information applicable, and for whatpopulationsorsubpopulationsisitnot?Underwhatcircumstances might this information be useful, and when should it be disregarded as irrelevant?Andperhapsmostimportantly, what, ifanything, canbedone inlightofinformationaboutpersonalgeneticrisktoeffectivelylowerthe oddsofbecomingsickandraisetheoddsofstayinghealthy? vii viii PREFACE Becausetheprevalenceofmostdiseasesvariesasafunctionofage, gender, race/ethnicity, and other personal characteristics, answers to these questions are complex and many are just beginning to be und- stood(Khouryetal.,2009).Someexpertshaveconcludedthattheanswers tosuchquestionsremainoutofreachatthepresenttimeandmayc- tinue to be elusive for another 5-10 years (Frazer, Murray, Schork, & Topol,2009).Yet, twenty-?rstcenturyhealth-careconsumers, providers, and policy makers face these choices now about incorporating personal genetic information into health management and often do so without a complete and accurate understanding of the potential impact of their decisionsonmultiplelevels(Carlson,2009).

Androgens and androgen receptors (AR) play critical roles in the development and progression of prostate cancer, the most frequently diagnosed cancer and second leading cause of cancer death in US males. AR is an androgen-dependent DNA-binding transcription factor that regulates the expression of androgen-responsive genes. Identification and characterization of androgen-responsive genes provide insights into the cellular mechanisms of androgen action and may lead to new approaches in diagnosis, prognosis, prevention and/or treatment of prostate cancer. This volume provides critical information from well respected experts in the field. Some of the exciting topics include the new understanding of mechanisms underlining the regulation of androgen-responsive gene expression, and functions of various androgen-responsive genes in biological processes essential in carcinogenesis including cell growth, angiogenesis, and epithelial-to-mesenchyme transition (EMT). Other important aspects addressed are the current and potential clinic applications of knowledge on androgen-responsive gene regulation and function. This book is intended for researchers, scientists, faculty, and advanced graduate students with an interest in androgen action and prostate cancer.

This book presents a comprehensive collection of detailed state-of-the-art exon skipping and splices modulation protocols. Chapters detail 14 genetic diseases, AON-mediated therapies, and CRISPR/Cas9-mediated gene editing therapies. 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. Authoritative and cutting-edge, Exon Skipping and Inclusion Therapies: Methods and Protocols aims to help researchers initiate the development of next-generation therapies.

This book sheds new light on the physiology, molecular biology and pathophysiology of epithelial ion channels and transporters. It combines the basic cellular models and functions by means of a compelling clinical perspective, addressing aspects from the laboratory bench to the bedside. The individual chapters, written by leading scientists and clinicians, explore specific ion channels and transporters located in the epithelial tissues of the kidney, intestine, pancreas and respiratory tract, all of which play a crucial part in maintaining homeostasis. Further topics include the fundamentals of epithelial transport; mathematical modeling of ion transport; cell volume regulation; membrane protein folding and trafficking; transepithelial transport functions; and lastly, a discussion of transport proteins as potential pharmacological targets with a focus on the pharmacology of potassium channels.

Significant advances in our knowledge of genetics were made during the twentieth century but in the most recent decades, genetic research has dramatically increased its impact throughout society. Genetic issues are now playing a large role in health and public policy, and new knowledge in this field will continue to have significant implications for individuals and society. Written for the non-majors human genetics course, Human Genetics, 3E will increase the genetics knowledge of students who are learning about human genetics for the first time. This thorough revision of the best-selling Human Genome,2E includes entirely new chapters on forensics, stem cell biology, bioinformatics, and societal/ethical issues associated with the field. New special features boxes make connections between human genetics and human health and disease. Carefully crafted pedagogy includes chapter-opening case studies that set the stage for each chapter; concept statements interspersed throughout the chapter that keep first-time students focused on key concepts; and end-of-chapter questions and critical thinking activities. This new edition will contribute to creating a genetically literate student population that understands basic biological research, understands elements of the personal and health implications of genetics, and participates effectively in public policy issues involving genetic information .
Includes topical material on forensics, disease studies, and the human genome project to engage non-specialist students

Full, 4-color illustration program enhances and reinforces key concepts and themes

Uniform organization of chapters includes interest boxes that focus on human health and disease, chapter-opening case studies, and concept statements to engage non-specialist readers

This volume seeks to understand how organisms and gene functions are influenced by environmental cues while accounting for variation that takes place within and among environmental populations and communities. Microbial Environmental Genomics (MEG) guides readers through methods to analyse the diversity of different organism types (archaea, bacteria, fungi, protists and microfauna), interactions between fungi and trees, and methods to identify and characterize functions and functional diversity of both pro- and eukaryotes. Written for the Methods in Molecular Biology series, 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. Authoritative and practical, Microbial Environmental Genomics (MEG) will serve as a primary research reference for researchers and research managers in environmental microbiology working in the expanding field of molecular ecology and environmental genomics.

This volume aims to connect current ideas and concepts about GI disorders with the search for novel therapeutics. Towards this goal, authors provide a timely state-of-the-art overview of the GI tract in health and disease, current treatment approaches and ongoing developments in drug discovery, and their potential for the better treatment of patients with GI disorders.

Over the last two decades advances in genotyping technology, and the development of quantitative genetic analytical techniques have made it possible to dissect complex traits and link quantitative variation in traits to allelic variation on chromosomes or quantitative trait loci (QTLs). In Quantitative Trait Loci (QTLs):Methods and Protocols, expert researchers in the field detail methods and techniques that focus on specific components of the entire process of quantitative train loci experiments. These include methods and techniques for the mapping populations, identifying quantitative trait loci, extending the power of quantitative trait locus analysis, and case studies. Written in the highly successful Methods in Molecular Biology (TM) series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Thorough and intuitive, Quantitative Trait Loci (QTLs):Methods and Protocols aids scientists in the further study of the links between phenotypic and genotypic variation in fields from medicine to agriculture, from molecular biology to evolution to ecology.

In this volume of Methods in Molecular Biology (TM), expert investigators offer comprehensive, complementary, and cutting-edge technologies for studies of gene regulation. The chapters of Gene Regulation: Methods and Protocols are organized to provide an integrated and a coherent view of control systems and their associated components. The protocols are broad in their scope. They include molecular, biochemical, spectroscopic techniques as well as high throughput strategies. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Comprehensive and broad in their scope, the protocols are useful to researchers in many disciplines including molecular biology, genomics, biochemistry, biomedicine, nutrition, and agricultural sciences.

This collection of reviews will be of considerable interests to biologists and MDs working on any aspect of cardiovascular function. With state-of-the-art reviews written by competent experts in the field, the content is also of interest for MSc and PhD students in most fields of cardiovascular physiology.

How does the genome, interacting with the multi-faceted environment, translate into the development by which the human brain achieves its astonishing, adaptive array of cognitive and behavioral capacities? Why and how does this process sometimes lead to neurodevelopmental disorders with a major, lifelong personal and social impact?

This volume of "Progress in Brain Research" links findings on the structural development of the human brain, the expression of genes in behavioral and cognitive phenotypes, environmental effects on brain development, and developmental processes in perception, action, attention, cognitive control, social cognition, and language, in an attempt to answer these questions.
Leading authors review the state-of-the-art in their field of investigation and provide their views and perspectives for future researchChapters are extensively referenced to provide readers with a comprehensive list of resources on the topics coveredAll chapters include comprehensive background information and are written in a clear form that is also accessible to the non-specialist

ThediscoveryofmicroRNAshasrevealedanunexpectedandspectacularadditional levelof?netuningofthegenomeandhowgenesareusedagainandagainin differentcombinationstogeneratethecomplexitythatunderliesforinstancethe brain. SincetheinitialstudiesperformedinC. elegans,wegavegoneafarwayto begintounderstandhowmicroRNApathwayscanhaveanimpactonhealthand diseaseinhuman. AlthoughmicroRNAsareabundantlyexpressedinthebrain, relativelylittleisknownaboutthemultiplefunctionsoftheseRNAmoleculesinthe nervous system. Nevertheless,we knowalready that microRNA pathways play majorrolesintheproliferation,differentiation,functionandmaintenanceofneu- nalcells. SeveralintriguingstudieshavelinkedmicroRNAsasmajorregulatorsof theneuronalphenotype,andhaveimplicatedspeci?cmicroRNAsintheregulation ofsynapseformationandplasticity. DysfunctionofmicroRNApathwaysisalso slowlyemergingasapotentialimportantcontributortothepathogenesisofmajor neurodegenerativedisorderssuchasAlzheimer'sdiseaseandParkinson'sdisease. Thesenovelinsightsappeartobeparticularpromisingfortheunderstandingofthe veryfrequentandbadlyunderstoodsporadicformsofthesediseasesascomparedto thegeneticforms. Thus,thebetterunderstandingoftheimplicationsofthisnovel ?eldofmolecularbiologyiscrucialforthebroadareaofneurosciences,fromthe fundamentalaspectstotheclinic,andfromnoveldiagnostictopotentiallythe- peuticapplicationsforsevereneurologicalandmaybepsychiatricdiseases. The presentvolumegatherscontributionstotheColloqueMe'decineetRechercheonthe implicationsofmicroRNAsinneuroscienceorganizedbytheFondationIpsen,in Paris,onApril20,2009. Ithadasobjectivetobringtogetherneuroscientistsfrom differentareasofresearchtodiscusstheircurrentinsightsintothewonderfulworld ofmicroRNAs,andtohearanddiscusstheirresearchandviewsaboutmicroRNA biologyinneuronalprocessesandinbraindisorders. BartdeStrooper YvesChristen v Acknowledgments The editors wish to thank Jacqueline Mervaillie and Sonia Le Cornec for the organizationofthemeetingandMaryLynnGagefortheeditingofthebook. vii Contents Pro?lingthemicroRNAs ...1 KennethS. Kosik,ThalesPapagiannakopoulos,NaXu, KawtherAbu-Elneel,TsunglinLiu,andMinJeongKye TheWideVarietyofmiRNAExpressionPro?les intheDevelopingandMatureCNS ...9 MarikaKapsimali InteractionsbetweenmicroRNAsandTranscription FactorsintheDevelopmentandFunction oftheNervousSystem ...19 DavidJ. Simon AmicroRNAFeedbackCircuitinMidbrainDopamineNeurons ...27 AsaAbeliovich Fine-tuningmRNATranslationatSynapseswithmicroRNAs ...35 GerhardM. Schratt NeuronalP-bodiesandTransportofmicroRNA-Repressed mRNAs ...4 5 FlorenceRage CrosstalkbetweenmicroRNAandEpigeneticRegulation inStemCells ...57 KeithSzulwach,ShuangChang,andPengJin microRNAsinCNSDevelopmentandNeurodegeneration: InsightsfromDrosophilaGenetics ...69 StephenM. Cohen ix x Contents DrosophilaasaModelforNeurodegenerativeDisease: RolesofRNAPathwaysinPathogenesis ...79 NancyM. Bonini microRNAsinSporadicAlzheimer'ThediscoveryofmicroRNAshasrevealedanunexpectedandspectacularadditional levelof?netuningofthegenomeandhowgenesareusedagainandagainin differentcombinationstogeneratethecomplexitythatunderliesforinstancethe brain. SincetheinitialstudiesperformedinC. elegans,wegavegoneafarwayto begintounderstandhowmicroRNApathwayscanhaveanimpactonhealthand diseaseinhuman. AlthoughmicroRNAsareabundantlyexpressedinthebrain, relativelylittleisknownaboutthemultiplefunctionsoftheseRNAmoleculesinthe nervous system. Nevertheless,we knowalready that microRNA pathways play majorrolesintheproliferation,differentiation,functionandmaintenanceofneu- nalcells. SeveralintriguingstudieshavelinkedmicroRNAsasmajorregulatorsof theneuronalphenotype,andhaveimplicatedspeci?cmicroRNAsintheregulation ofsynapseformationandplasticity. DysfunctionofmicroRNApathwaysisalso slowlyemergingasapotentialimportantcontributortothepathogenesisofmajor neurodegenerativedisorderssuchasAlzheimer'sdiseaseandParkinson'sdisease. Thesenovelinsightsappeartobeparticularpromisingfortheunderstandingofthe veryfrequentandbadlyunderstoodsporadicformsofthesediseasesascomparedto thegeneticforms. Thus,thebetterunderstandingoftheimplicationsofthisnovel ?eldofmolecularbiologyiscrucialforthebroadareaofneurosciences,fromthe fundamentalaspectstotheclinic,andfromnoveldiagnostictopotentiallythe- peuticapplicationsforsevereneurologicalandmaybepsychiatricdiseases. The presentvolumegatherscontributionstotheColloqueMe'decineetRechercheonthe implicationsofmicroRNAsinneuroscienceorganizedbytheFondationIpsen,in Paris,onApril20,2009. Ithadasobjectivetobringtogetherneuroscientistsfrom differentareasofresearchtodiscusstheircurrentinsightsintothewonderfulworld ofmicroRNAs,andtohearanddiscusstheirresearchandviewsaboutmicroRNA biologyinneuronalprocessesandinbraindisorders. BartdeStrooper YvesChristen v Acknowledgments The editors wish to thank Jacqueline Mervaillie and Sonia Le Cornec for the organizationofthemeetingandMaryLynnGagefortheeditingofthebook. vii Contents Pro? lingthemicroRNAs ...1 KennethS. Kosik,ThalesPapagiannakopoulos,NaXu, KawtherAbu-Elneel,TsunglinLiu,andMinJeongKye TheWideVarietyofmiRNAExpressionPro?les intheDevelopingandMatureCNS ...9 MarikaKapsimali InteractionsbetweenmicroRNAsandTranscription FactorsintheDevelopmentandFunction oftheNervousSystem ...19 DavidJ. Simon AmicroRNAFeedbackCircuitinMidbrainDopamineNeurons ...27 AsaAbeliovich Fine-tuningmRNATranslationatSynapseswithmicroRNAs ...35 GerhardM. Schratt NeuronalP-bodiesandTransportofmicroRNA-Repressed mRNAs ...45 FlorenceRage CrosstalkbetweenmicroRNAandEpigeneticRegulation inStemCells ...57 KeithSzulwach,ShuangChang,andPengJin microRNAsinCNSDevelopmentandNeurodegeneration: InsightsfromDrosophilaGenetics ...69 StephenM. Cohen ix x Contents DrosophilaasaModelforNeurodegenerativeDisease: RolesofRNAPathwaysinPathogenesis ...79 NancyM. Bonini microRNAsinSporadicAlzheimer'sDiseaseandRelated Dementias ...91 Se'bastienS. He'bert,WimMandemakers,AikateriniS. Papadopoulou, andBartDeStrooper microRNADysregulationinPsychiatricDisorders ...99 BinXu,JosephA. Gogos,andMariaKarayiorgou Index ...1 19 Contributors Abeliovich Asa Columbia University Medical Center, 630 West 168th Street, Room15-405,NewYork,NY10032,USA,aa900@columbia. edu Abu-ElneelKawther NeuroscienceResearchInstitute,DepartmentofMolecular CellularandDevelopmentalBiology,UniversityofCaliforniaSantaBarbara,USA BoniniNancyM. UniversityofPennsylvania,306LeidyLaboratories,Depa- mentofBiology,Philadelphia,PA19104,USA,nbonini@sas. upenn. edu Chang Shuang Department of Human Genetics, Emory University School of Medicine,Atlanta,GA30322,USA CohenStephenM. TemasekLifeSciencesLaboratoryLimited,1ResearchLink National University of Singapore, 117604 Singapore, SINGAPORE, steve@ tll. org. sg DeStrooperBart Centerforhumangenetics,K. U. LeuvenandDepartmentof molecularanddevelopmentalgenetics,VIBLeuven,BELGIUM GogosJosephA. DepartmentofPhysiology&CellularBiophysicsandDepa- mentofNeuroscience,ColumbiaUniversity,NewYork,USA He'bert Se'bastien S. Centre de Recherche du CHUQ (CHUL), Axe Neur- ciences,Universite'Laval,De'partementdeBiologieme'dicale,2705Boul. Laurier, LocalRC-9800,Que'bec,Qc,Canada,sebastien. hebert@crchul. ulaval. ca JinPeng DepartmentofHumanGeneticsandGraduatePrograminGeneticsand MolecularBiology,EmoryUniversitySchoolofMedicine,Atlanta,GA30322, USA,pjin@genetics. emory. edu ' ' ' ' KapsimaliMarika INSERMU784,GenetiqueMoleculaireduDeveloppement, ' Ecole Normale Superieure, 46 rue d'Ulm, 75230 PARIS Cedex 05 FRANCE, kapsimal@biologie. ens. fr xi xii Contributors Karayiorgou Maria Columbia University, Department of Psychiatry, 1051 RiversideDrive,Unit#28,NewYorkNY10032,USA,mk2758@columbia. edu Kosik Kenneth S. Neuroscience Research Institute, Department of Molecular Cellular and Developmental Biology, University of California Santa Barbara, BiologyII,Room6139A,SantaBarbara,CA93106,USA,kosik@lifesci. ucsb.

This open access book is a step-by-step introduction on how shell scripting can help solve many of the data processing tasks that Health and Life specialists face everyday with minimal software dependencies. The examples presented in the book show how simple command line tools can be used and combined to retrieve data and text from web resources, to filter and mine literature, and to explore the semantics encoded in biomedical ontologies. To store data this book relies on open standard text file formats, such as TSV, CSV, XML, and OWL, that can be open by any text editor or spreadsheet application. The first two chapters, Introduction and Resources, provide a brief introduction to the shell scripting and describe popular data resources in Health and Life Sciences. The third chapter, Data Retrieval, starts by introducing a common data processing task that involves multiple data resources. Then, this chapter explains how to automate each step of that task by introducing the required commands line tools one by one. The fourth chapter, Text Processing, shows how to filter and analyze text by using simple string matching techniques and regular expressions. The last chapter, Semantic Processing, shows how XPath queries and shell scripting is able to process complex data, such as the graphs used to specify ontologies. Besides being almost immutable for more than four decades and being available in most of our personal computers, shell scripting is relatively easy to learn by Health and Life specialists as a sequence of independent commands. Comprehending them is like conducting a new laboratory protocol by testing and understanding its procedural steps and variables, and combining their intermediate results. Thus, this book is particularly relevant to Health and Life specialists or students that want to easily learn how to process data and text, and which in return may facilitate and inspire them to acquire deeper bioinformatics skills in the future.

The discovery of stress-induced mutagenesis has changed ideas about mutation and evolution, and revealed mutagenic programs that differ from standard spontaneous mutagenesis in rapidly proliferating cells. The stress-induced mutations occur during growth-limiting stress, and can include adaptive mutations that allow growth in the otherwise growth-limiting environment. The stress responses increase mutagenesis specifically when cells are maladapted to their environments, i.e. are stressed, potentially accelerating evolution then. The mutation mechanism also includes temporary suspension of post-synthesis mismatch repair, resembling mutagenesis characteristic of some cancers. Stress-induced mutation mechanisms may provide important models for genome instability underlying some cancers and genetic diseases, resistance to chemotherapeutic and antibiotic drugs, pathogenicity of microbes, and many other important evolutionary processes. This book covers pathways of stress-induced mutagenesis in all systems. The principle focus is mammalian systems, but much of what is known of these pathways comes from non-mammalian systems.

The earliest descriptions of human chromosomes initiated the genomics revolution that is now upon us. Array Comparative Genomic Hybridization: Protocols and Applications explores the scope of what is now possible as far as documenting abnormalities associated with several human cancers. While the technology for interrogating the human genome continues to evolve, refinement of comparative genomic hybridization (CGH) using array CGH and related technologies have provided enormous insight into human cancers at an affordable scale. Written in the successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Array Comparative Genomic Hybridization: Protocols and Applications provides researchers with well-honed methodologies to learn these techniques for their own use in research or clinical diagnostic laboratories.

This volume provides descriptions of the occurrence of the UPR, methods used to assess it, pharmacological tools and other methodological approaches to analyze its impact on cellular regulation. The authors explain how these methods are able to provide important biological insights.

This volume provides descriptions of the occurrence of the UPR, methods used to assess it, pharmacological tools and other methodological approaches to analyze its impact on cellular regulation. The authors explain how these methods are able to provide important biological insights.

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.

This book focuses on interdisciplinary research in the field of biomedical engineering and neuroscience. Biomedical engineering is a vast field, ranging from bioengineering to brain-computer interfaces. The book explores the system-level function and dysfunction of the nervous system from scientific and engineering perspectives. The initial sections introduce readers to the physiology of the brain, and to the biomedical tools needed for diagnostics and effective therapies for various neurodegenerative and regenerative disorders. In turn, the book summarizes the biomedical interventions that are used to understand the neural mechanisms underlying empathy disorders, and reviews recent advances in biomedical engineering for rehabilitation in connection with neurodevelopmental disorders and brain injuries. Lastly, the book discusses innovations in machine learning and artificial intelligence for computer-aided disease diagnosis and treatment, as well as applications of nanotechnology in therapeutic neurology.

Foreword by Walter J. Freeman.

The induction of unconsciousness using anesthetic agents demonstrates that the cerebral cortex can operate in two very different behavioral modes: alert and responsive vs. unaware and quiescent. But the states of wakefulness and sleep are not single-neuron properties---they emerge as bulk properties of cooperating populations of neurons, with the switchover between states being similar to the physical change of phase observed when water freezes or ice melts. Some brain-state transitions, such as sleep cycling, anesthetic induction, epileptic seizure, are obvious and detected readily with a few EEG electrodes; others, such as the emergence of gamma rhythms during cognition, or the ultra-slow BOLD rhythms of relaxed free-association, are much more subtle. The unifying theme of this book is the notion that all of these bulk changes in brain behavior can be treated as phase transitions between distinct brain states.

Modeling Phase Transitions in the Brain contains chapter contributions from leading researchers who apply state-space methods, network models, and biophysically-motivated continuum approaches to investigate a range of neuroscientifically relevant problems that include analysis of nonstationary EEG time-series; network topologies that limit epileptic spreading; saddle--node bifurcations for anesthesia, sleep-cycling, and the wake--sleep switch; prediction of dynamical and noise-induced spatiotemporal instabilities underlying BOLD, alpha-, and gamma-band Hopf oscillations, gap-junction-moderated Turing structures, and Hopf-Turing interactions leading to cortical waves.

Rheumatic (or systemic autoimmune) diseases disproportionately affect young women: the female-to-male ratio for patients with systemic lupus erythematosus during the reproductive years is approximately 9:1. In the mid- to late-twentieth century, women with rheumatic disease diagnoses were often advised to avoid pregnancy due to fear of disease exacerbation and adverse outcome. In more recent years, many women with rheumatic disease have deferred childbearing until a later age due to active disease or unsafe therapies. However, with advances in rheumatology therapies, obstetric monitoring, and reproductive medicine technologies, increasing numbers of women with rheumatic diseases are pursuing pregnancy. As a result, obstetricians and rheumatologists need to be aware of the current state of knowledge and the recommendations for management of pregnancy in these patients. Contraception and Pregnancy in Patients with Rheumatic Disease explains the basics of contraception, fertility treatment, and pregnancy in rheumatic disease patients and serves as a guide and reference tool for both rheumatologists and OB/GYNs. Most general rheumatologists and OB/GYNs have limited experience in caring for rheumatic disease patients during pregnancy, and many do not have ready access to expert colleagues in this area. This book summarizes the current state of knowledge and presents a general approach for assessment of the rheumatic disease patient considering pregnancy, hormonal contraception or infertility treatment.

Together with early theoretical work in population genetics, the debate on sources of genetic makeup initiated by proponents of the neutral theory made a solid contribution to the spectacular growth in statistical methodologies for molecular evolution. Evolutionary Genomics: Statistical and Computational Methods is intended to bring together the more recent developments in the statistical methodology and the challenges that followed as a result of rapidly improving sequencing technologies. Presented by top scientists from a variety of disciplines, the collection includes a wide spectrum of articles encompassing theoretical works and hands-on tutorials, as well as many reviews with key biological insight. Volume 2 begins with phylogenomics and continues with in-depth coverage of natural selection, recombination, and genomic innovation. The remaining chapters treat topics of more recent interest, including population genomics, -omics studies, and computational issues related to the handling of large-scale genomic data. Written in the highly successful Methods in Molecular Biology (TM) series format, this work provides the kind of advice on methodology and implementation that is crucial for getting ahead in genomic data analyses. Comprehensive and cutting-edge, Evolutionary Genomics: Statistical and Computational Methods is a treasure chest of state-of the-art methods to study genomic and omics data, certain to inspire both young and experienced readers to join the interdisciplinary field of evolutionary genomics.