Clinical and internal medicine Books

Book SynopsisThe Biology and Therapeutic Application of Mesenchymal Cells comprehensively describes the cellular and molecular biology of mesenchymal stem cells and mesenchymal stromal cells, describing their therapeutic potential in a wide variety of preclinical models of human diseases and their mechanism of action in these preclinical models. Chapters also discuss the current status of the use of mesenchymal stem and stromal cells in clinical trials in a wide range of human diseases and disorders, for many of which there are limited, or no other, therapeutic avenues. Provides coverage on both the biology of mesenchymal stem cells and stromal cells, and their therapeutic applications Describes the therapeutic potential of mesenchymal stem and stromal cells in a wide variety of preclinical models of human diseases and their mechanism of action in these preclinical models Discusses the current status of mesenchymal stem and stromal cells in clinical trials iTable of ContentsContributors, xxvii Editor’s Preface, xxxv Section I: An overview of mesenchymal stem cells and mesenchymal stromal cells 1 The mesenchymal stem cell, the mesenchymal stromal cell, and the mesenchymal stromal cell exosome, 3Kerry Atkinson 2 The nomenclature of mesenchymal stem cells and mesenchymal stromal cells, 8Armand Keating Section II: The isolation and ex vivo expansion of mesenchymal stromal cells 3 The isolation and expansion of mesenchymal stromal cells from bone marrow, 13Celena F. Heazlewood 4 The biology and clinical applications of mesenchymal stromal cells derived from human gestational tissues, 24Celena F. Heazlewood 5 Human placenta-derived mesenchymal stem/stromal cells: fetal and maternal origins and critical parameters forex vivo expansion, 32Rebecca A. Pelekanos and Varda S. Sardesai Section III: The cellular and molecular biology of mesenchymal stromal cells 6 Epigenetic regulation of mesenchymal stem/stromal cell growth and multipotentiality, 41Sarah Elizabeth Hemming, Dimitrios Cakouros, and Stan Gronthos 7 Biological changes in human mesenchymal stromal cells during monolayer culture, 58Marietta Herrmann and Jennifer J. Bara 8 The effect of three-dimensional aggregates on the biology of mesenchymal stromal cells, 75Yijun Liu, Ang-Chen Tsai, Xuegang Yuan, and Teng Ma 9 Cell–cell signaling pathways that regulate mesenchymal stromal cell differentiation, 91Leah Etheridge, Rebecca A. Mason, Fatima Saleh, and Paul Genever 10 Regulation of mitochondrial transport in mesenchymal stromal cells, 104Shravani Mukherjee, Naveen K. Bhatraju, Tanveer Ahmad, and Anurag Agrawal 11 The regulation of adipogenesis from adipose-derived stem/stromal cells, 114Lin Chen and Lei Liu 12 Modulation of osteogenic differentiation in mesenchymal stromal cells, 131Sean Gaynard, Jessica Hayes, and Mary Murphy 13 The role of glycogen synthase kinase-3 inhibitors on bone remodeling, 148K. Jane Escott and Patrick J. O’Shea 14 Early molecular events during in vitro chondrogenesis, 167Tommy A. Karlsen, Rune B. Jakobsen, and Jan E. Brinchmann 15 The role of the extracellular matrix in the differentiation of mesenchymal stromal cells, 191Peishun Shou, Qing Chen, and Yufang Shi 16 Effects of hypoxic culture on bone marrow multipotent mesenchymal stromal cells: from bench to bedside, 196Shih-Chieh Hung 17 The role of cyclic tensile strain on osteogenesis and angiogenesis in human mesenchymal stem/stromal cells, 208Adisri Charoenpanich, Josephine Bodle, and Elizabeth Loboa 18 The evolving concept of mesenchymal stromal cells in regenerative medicine: from cell differentiation tosecretome, 222F.G. Teixeira, A. Pires, S.C. Serra, N. Sousa, and A.J. Salgado 19 The secretome of mesenchymal stem/stromal cells undergoing chondrogenic differentiation and those undergoing osteogenic or adipogenic differentiation, 236Beatriz Rocha, Francisco J. Blanco, and Cristina Ruiz-Romero 20 Mesenchymal stromal cell extracellular vesicles/exosomes, 250Ronne Wee Yeh Yeo, Ruenn Chai Lai, and Sai Kiang Lim 21 Role of tunneling nanotube crosstalk with distressed cardiomyocytes in controlling the heart repair potential of mesenchymal stromal cells, 264Anne-Marie Rodriguez and Meriem Mahrouf-Yorgov 22 The preferential homing of mesenchymal stromal cells to sites of inflammation, 286Catherine Sullivan 23 The role of chemokines in mesenchymal stromal cell homing to sites of inflammation, including infarctedmyocardium, 314Shan Wang and Yaojiong Wu 24 Live cell imaging and single cell tracking of’mesenchymal stromal cells in vitro, 323James A. Cornwell, Maria Z. Gutierrez, Richard P. Harvey and Robert E. Nordon 25 The role of mesenchymal stem/stromal cells in angiogenesis, 347Annelies Bronckaers and Ivo Lambrichts 26 The relationship between mesenchymal stromal cells and endothelial cells, 366Seyed Mahdi Nassiri and Reza Rahbarghazi 27 The radioresistance of mesenchymal stromal cells and their potential role in the management of radiation injury, 391Tara Sugrue, Irene Calvo-Asensio, and Rhodri Ceredig 28 The implications of multipotent mesenchymal stromal cells in tumor biology and therapy, 415Pratika Y. Hernanda, Maikel P. Peppelenbosch, and Qiuwei Pan 29 Mesenchymal stem/stromal cell therapy: mechanism of action and host response, 426Aideen Ryan, Mary Murphy, and Frank Barry 30 The differences between mesenchymal stromal cells and fibroblasts, 441Luigi Balducci, Sharon Natasha Cox, and Giulio Alessandri 31 Derivation of mesenchymal stem/stromal cells from induced pluripotent stem cells, 456Rebecca A. Pelekanos 32 The role of mesenchymal stem cells in hematopoiesis, 467Jean-Pierre Levesque, Rebecca N. Jacobsen, and Ingrid G. Winkler 33 The modulatory effects of mesenchymal stromal cells onthe innate immune system, 481Ko-Jiunn Liu, Men-Luh Yen, Li-Tzu Wang, and B. Linju Yen 34 The modulatory effects of mesenchymal stromal cells on the adaptive immune system, 490B. Linju Yen, Ko-Jiunn Liu, Men-Luh Yen, and Huey-Kang Sytwu 35 The role of mesenchymal stromal cells in the repair of acute organ injury, 496A.A. Temnov, A.V. Vagabov, A.N. Sklifas, V.I. Novoselov, and Y.A. Belyi 36 The use of mesenchymal stromal cells in the treatment of diseases of the cornea, 524Damien G. Harkin, Allison J. Sutherland, Laura J. Bray, Leanne Foyn, Fiona J. Li, and Brendan G. Cronin 37 The role of paracrine factors secreted by mesenchymal stromal cells in acute tissue injury, 544Ying Wang, Tania Velletri, Chunxing Zheng, and Yufang Shi 38 Treatment of lung disease by mesenchymal stromal cell extracellular vesicles, 553Antoine Monsel, Ying-gang Zhu, Varun Gudapati, and Jae-Woo Lee 39 Evaluating mesenchymal stem/stromal cells for treatment of asthma and allergic rhinitis, 573Tatyana Gavrilova, Saritha Kartan, Lauren S. Sherman, Oleta A. Sandiford, and Pranela Rameshwar 40 Stem cell therapies for Huntington’s disease, 581A.T. Crane, J. Rossignol, and G. L. Dunbar Section IV: The role of bioengineering in the therapeutic applications of mesenchymal stromal cells 41 Endometrial mesenchymal stromal cell and tissue engineering for pelvic organ prolapse repair, 601Shanti Gurung, Jerome A. Werkmeister, and Caroline E. Gargett 42 Closed automated large-scale bioreactors for manufacturing mesenchymal stromal cells for clinical use, 616Kerry Atkinson, Nicholas Timmins, G. Kiel, Celena Heazlewood, Michael Doran, and Gary Brooke Section V: GMP manufacturing of mesenchymal stromal cells for clinical use 43 Current good manufacturing practice for the isolation and ex vivo expansion of mesenchymal stromal cells derived from term human placenta for use in clinical trials, 621Kerry Atkinson, Dahlia Khalil, Celena Heazlewood, and Nina Ilic 44 A comparison of high-tier regulatory documents pertaining to biologic drugs including mesenchymal stromal cells in Australia, Europe, and the USA using a manual documentary analysis, 628Nina Ilic Section VI: The therapeutic application of mesenchymal stromal cells 45 The use of mesenchymal stromal cells in acute and chronic heart disease, 647Ariel Wolf, Wayne Balkan, and Joshua Hare 46 The role of mesenchymal stem/stromal cells in the management of critical limb ischemia, 661P.K. Gupta, Chullikana Anoop, Balasubramanian Sudha, R Mathiazhagan, Raj Swathi Sundar, and Majumdar Anish Sen 47 The role of mesenchymal stromal cells in the management of musculoskeletal disorders, 677Stefan Zwingenberger, Ishaq Ojodu, Maik Stiehler, and Stuart B. Goodman 48 The potential role of bone marrow mesenchymal stromal cells in the treatment of ischemic stroke, 690Yujun Pan and Ruohan Sun 49 The role of mesenchymal stromal cells in spinal cord injury, 714P. Jendelova, L. Machova-Urdzikova, and E. Sykova 50 The role of mesenchymal stromal cells in the treatment of ulcerative colitis and Crohn’s disease, 730Céline Gregoire, Chantal Lechanteur, Alexandra Briquet, Etienne Baudoux, Olivier Giet, Olivier Delloye, Frédéric Baron, Edouard Louis, and Yves Beguin 51 Mesenchymal stromal cells targeting kidney disease: benefits of a combined therapeutic approach, 754Brooke M. Huuskes and Sharon D. Ricardo 52 The biology and potential clinical applications of mesenchymal stromal cells in diseases of the lung, 770Yuben P. Moodley, Jesse D. Armitage, and Dino B.A. Tan 53 The role of mesenchymal stromal cells in diseases of the lung, 787Kerry Atkinson 54 Mesenchymal stromal cells for the treatment of’autoimmune diseases, 794Christopher N. Lewis and Jacques Galipeau 55 The role of mesenchymal stromal cells in bacterial infection, 814Sailaja Ghanta, Konstantin Tsoyi, and Mark A. Perrella 56 The use of mesenchymal stromal cells in solid organ transplantation, 825Céline Gregoire, Alexandra Briquet, François Jouret, Chantal Lechanteur, Etienne Baudoux, Olivier Giet, Olivier Delloye, Frédéric Baron, Olivier Detry, and Yves Beguin 57 The role of mesenchymal stromal cells in allogeneic hematopoietic stem cell transplantation, 836Kerry Atkinson 58 The role of mesenchymal stromal cells in the management of skin wounds, 841Sung-Whan Kim 59 The role of mesenchymal stromal cells in skin wound healing, 845Miao Teng and Hengshu Zhang Section VII: Mesenchymal stromal cells as delivery vehicles for therapeutic agents 60 The role of mesenchymal stromal cells in human brain tumors, 859Brittany C. Parker Kerrigan, Tal Shahar, Shinji Yamashita, and Frederick F. Lang 61 Mesenchymal stromal cells as gene delivery vehicles to treat nonmalignant diseases, 873Julie R. Beegle, Jan A. Nolta, and Fernando A. Fierro 62 Gene therapy for cancer using mesenchymal stromal cells, 892Ryosuke Uchibori and Keiya Ozawa Section VIII: The present and the future 63 Breaking news, 901Kerry Atkinson 64 Reconciling the stem cell and paracrine paradigms of mesenchymal stem cell function, 912Siddaraju V. Boregowda and Donald G. Phinney Glossary, 927 Index, 949

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Book SynopsisAll three An Aid to the MRCP PACES volumes, covering Stations 1, 2, 3, 4 and 5, together at a specially discouted price.

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Book SynopsisNtoumanis and Myers have done sport and exercise science researchers and students a tremendous service in producing An Introduction to Intermediate and Advanced Statistical Analyses for Sport and Exercise Scientists.Table of ContentsAbout the editors xiii List of contributors xv Foreword xix Preface xxi 1 Factorial ANOVA and MANOVA 1 General Introduction 1 Hypothesis Testing 2 Alpha Level 2 Assumptions 3 Further Considerations 4 Utility in Sport and Exercise Sciences 6 Treatment Conditions 6 Existing Conditions 6 Individual Characteristics 7 Recent Usage 7 The Substantive Example 7 Univariate: Factorial ANOVA 8 Univariate Assumptions 8 The Synergy 10 Factorial ANOVA Analysis Plan 10 Example of a Write]Up Compatible with the APA Publication Manual 11 Factorial MANOVA Analysis Plan 13 Example of a Write]Up Compatible with the APA Publication Manual 13 Summary 16 Acknowledgment 18 References 18 2 Repeated measures ANOVA and MANOVA 19 General Introduction 19 Between] versus Within]Subjects Variables 19 Hypothesis Testing 20 Assumptions 20 Further Considerations 21 Utility in Sport and Exercise Sciences 22 Multiple Treatment Conditions 23 Multiple Assessments 23 Longitudinal Studies 23 Recent Usage 24 The Substantive Example 24 Univariate: Repeated Measures ANOVA 24 Univariate Assumptions 25 Multivariate: Repeated Measures MANOVA 26 Multivariate Assumptions 26 The Synergy 27 Repeated Measures ANOVA Analysis Plan 27 Example of a Write]Up Compatible with the APA Publication Manual 29 Repeated Measures MANOVA Analysis Plan 29 Example of a Write]Up Compatible with the APA Publication Manual 31 Summary 32 Acknowledgment 34 References 34 3 Mediation and moderation via regression analysis 35 General Introduction 35 Utility of the Methods in Sport and Exercise Science 36 The Substantive Example 38 Mediation 38 The Synergy 38 Mediation 38 The Substantive Example 44 Moderation 44 The Synergy 45 Moderation 45 Summary 53 References 55 4 Item response theory and its applications in Kinesiology 57 General Introduction 57 What Is IRT? 59 Other Commonly Used IRT Models 60 Assumptions Related to IRT 62 Unidimensionality 62 Local Independence 62 Addressing Model]Data Fit 62 Inspecting Model Assumptions 63 Inspecting Expected Model Features 63 Inspecting Overall Model]Data Fit 64 Computer Simulation for Model]Data Fit Testing 64 Unique Features and Advantages of IRT 65 Estimation Invariance 65 Common Metric Scale 65 Item and Test Information 66 Test Relative Efficiency 68 Global “Reliability” Is no Longer a Concern 69 Item Bank and IRT]Based Test Construction 69 Parameter Estimation and Software 71 Utility of the Methodology in Kinesiology 71 IRT Limitations and Future Direction 72 Conclusion 73 References 74 5 Introduction to factor analysis and structural equation modeling 79 General Introduction 79 Utility of the Method in Sport and Exercise Science 80 Terminology and Methodology 83 Evaluating Model Fit 86 Interpreting Parameter Estimates 88 The Substantive Example 89 The Synergy 91 EFA: Establishing the Factor Structure 91 CFA: Testing the Measurement Models 93 Structural Equation Modeling: Adding the Regression Paths 96 Summary 98 References 99 6 Invariance testing across samples and time: Cohort]sequence analysis of perceived body composition 101 General Introduction to the Importance of Measurement Invariance 102 Cohort]Sequential Designs: Longitudinal Invariance across Samples and Time 106 Substantive Application: Physical Self]Concept 107 Methodology 111 The PSDQ Instrument 111 Statistical Analyses 111 Goodness of Fit 112 Results 113 Basic Cohort]Sequence Model: Four Cohort Groups and Four Waves 113 Cohort]Sequence Design of Multiple Indicators, Multiple Causes Models 115 Use of Model Constraint with Orthogonal Polynomial Contrasts to Evaluate Cohort Sequence and MIMIC Latent Means 116 Use of Latent Growth Curve Models to Evaluate Stability/Change over Time 119 LGC Results 123 Summary, Implications, and Further Directions 123 Methodological Implications, Limitations, and Further Directions 123 References 125 7 Cross]lagged structural equation modeling and latent growth modeling 131 General Introduction 131 A Theoretical Framework for the Study of Change 132 Utility of the Method in Sport and Exercise Science 132 Analysis of Change 132 The Substantive Example 134 Theoretical Background 134 The Data: Participants and Measurement 134 The Synergy 135 CLPM 135 CLPM Example 137 Latent Growth Modeling 140 LGM Example 141 Model 2a: Unconditional LGM 143 Model 2b: Conditional LGM 145 Model 2c: Unconditional LGM with TVCs 145 Model 3: Parallel Process LGM 146 Model 4: Second]Order LGM 148 Summary 150 References 151 8 Exploratory structural equation modeling and Bayesian estimation 155 General Introduction 155 Utility of the Methods in Sport and Exercise Science 156 The Substantive Example(s) 159 The Motivational Correlates of Mentally Tough Behavior 159 Developing Synergies through Statistical Modeling 161 ESEM 161 Bayesian Estimation 168 Summary 179 References 180 9 A gentle introduction to mixture modeling using physical fitness performance data 183 General Introduction 183 Utility of the Method in Sport and Exercise Science 186 The Substantive Example(s) 187 Class Enumeration in Mixture Models 188 The Estimation of Mixture Models 190 The Synergy 190 LPA of Grade 5 Students and Tests of Invariance across Gender Groups 190 Inclusion of Covariates in LPA Solutions 195 LTA 196 Mixture Regression Analyses of Grade 5 Students 198 Latent Basis Growth Mixture Analyses: Cardiovascular Fitness 202 Piecewise Growth Mixture Analyses: Physical Strength 203 Summary 204 Acknowledgments 205 References 206 10 Multilevel (structural equation) modeling 211 General Introduction 211 Multilevel Structural Equation Modeling 212 Utility of the Methodology in Sport and Exercise Science 214 The Substantive Examples 215 Coaching Competency–Collective Efficacy–Team Performance: 1–1–2 216 Action Planning Intervention–Physical Activity Action Plans–Physical Activity: 2–1–1 217 The Synergy 218 Coaching Competency–Collective Efficacy–Team Performance: 1–1–2 219 Action Planning Intervention–Physical Activity Action Plans–Physical Activity: 2–1–1 222 Summary 229 References 230 11 Application of meta]analysis in sport and exercise science 233 General Introduction 233 Stages of Meta]Analysis 233 Key Elements of Meta]Analysis 234 Goals of Meta]Analysis 236 Utility of the Methodology in Sport and Exercise Science 238 The Substantive Example 238 The Synergy 241 Univariate Meta]Analysis 241 Multivariate Meta]Analysis 245 Summary 249 Acknowledgment 251 References 251 12 Reliability and stability of variables/instruments used in sport science and sport medicine 255 Introduction 255 A. Assessment of Test–Retest Agreement Using Interval/Ratio Data 256 A Worked Example Using the Test–Retest Differences of the Biceps Skinfold Measurements 257 B. Utility of the Assessment of Test–Retest Stability Using Categorical/Likert]Type Data 260 The Substantive Example 261 Utility of the Test–Retest Stability Using Nonparametric Data 261 The Synergy 262 Utility of the Item by Item Approach to Test–Retest Stability 263 The Synergy 263 Summary 265 References 266 13 Sample size determination and power estimation in structural equation modeling 267 General Introduction 267 Power 268 Power Analysis in SEM 268 Utility of the Methodology in Sport and Exercise Science 269 Power Analysis Regarding Model]Data Fit: An Introduction 269 Power Analysis Regarding Focal Parameters: An Introduction 270 The Substantive Example 272 Bifactor Model in Sport and Exercise Science 272 Bifactor Model and the PETES 273 The Synergy 275 Power Analysis Regarding Model]Data Fit: A Demonstration 276 Power Analysis Regarding Focal Parameters: A Demonstration 278 Summary 281 References 282 Index 285

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Book SynopsisThe comprehensive and authoritative guide to clinical reproductive science The field of clinical reproductive science continues to evolve; this important resource offers the basics of reproductive biology as well as the most recent advance in clinical embryology. The author - a noted expert in the field - focuses on the discipline and covers all aspects of this field. The text explores causes of male and female infertility and includes information on patient consultation and assessment, gamete retrieval and preparation, embryo culture, embryo transfer and cryopreservation. Comprehensive in scope, the text contains an introduction to the field of clinical reproductive science and a review of assisted reproductive technology. The author includes information on a wide range of topics such as gonadal development, the regulation of meiotic cell cycle, the biology of sperm and spermatogenesis, in vitro culture, embryo transfer techniques, fundamentals of fertilisation, oocyte activation aTable of ContentsList of Contributors xi About the Editor xv Preface xvii Acknowledgements xix About the Companion Website xxi Section One Reproductive Science: Fundamentals of Human Reproductive Biology 1 1 Sexual Differentiation, Gonadal Development, and Development of the External Genitalia: A Review of The Regulation of Sexual Differentiation 3Rebecca M. Perrett 2 Male and Female Reproductive Anatomy 35Sara Sulaiman and James Coey 3 Fundamentals of Reproductive Endocrinology 45Derrick Ebot, Haider Hilal, Michael Carroll, and James Coey 4 The Ovaries, Oocytes, and Folliculogenesis 57Jacques Gilloteaux and James Coey 5 The Human Spermatozoa 65Allan Pacey and Katrina Williams 6 The Biology of Fertilization 75Michael Carroll 7 Human Embryo Development: From Zygote Stage to Peri‐Implantation Blastocyst 93Stéphane Berneau and Michael Carroll 8 The Female Reproductive Tract and Early Embryo Development: A Question of Supply and Demand 99Henry J. Leese and Daniel R. Brison Section Two Clinical Reproductive Science: Causes of Male and Female Infertility 109 9 Disorders of Male Reproductive Endocrinology 111Michael Carroll 10 Disorders of Female Reproductive Endocrinology 125Mahshid Nickkho‐Amiry and Cheryl T. Fitzgerald 11 Oocyte Aneuploidy and the Maternal Age Effect 133Mary Herbert 12 Female Reproductive Pathology: Peritoneal, Uterine, and Fallopian Tube Pathologies 147Kenneth Ma Kin Yue, Rosa Trigas, and Edmond Edi‐Osagie 13 Pathologies of the Male Reproductive Tract 159Aarush Sajjad, Muhammad A. Akhtar, and Yasmin Sajjad 14 The Impact of Infections on Reproduction and Fertility 177Val Edwards Jones 15 Nutrition, Fetal Health, and Pregnancy 189Emma Derbyshire 16 The Embryonic Environment and Developmental Origins of Health 195Tom P. Fleming and Congshan Sun 17 Lifestyle and Environmental Impacts on Fertility 205Ana‐Maria Tomova and Michael Carroll Section Three Clinical Reproductive Science In Practice: IVF and Assisted Reproductive Technologies 215 18 Assessing the Infertile Couple 217Narmada Katakam, Ruth Arnesen, Caroline Watkins, Bert Stewart, and Luciano G. Nardo 19 Ovarian Stimulation Protocols 231Nikolaos Tsampras and Cheryl T. Fitzgerald 20 Oocyte Retrieval Techniques and Culture of Oocytes 241Dawn Yell 21 Sperm Preparation: Strategy and Methodology 251Stephen Harbottle 22 Diagnostic Semen Analysis: Uncertainty, Clinical Value, and Recent Advances 265Mathew Tomlinson 23 Surgical Sperm Retrieval 279Muhammad A. Akhtar, Elizabeth Hester, Solmaz Gul Sajjad, and Yasmin Sajjad 24 In Vitro Fertilization and Intracytoplasmic Sperm Injection 291Bryan Woodward 25 Morphological Assessment of Embryos in Culture 303J. Diane Critchlow 26 In Vitro Culture of Gametes and Embryos – The Culture Medium 317Robbie Kerr 27 Incubators in the Assisted Reproductive Technology Laboratory 333Louise Hyslop 28 Embryo Transfer Techniques and Improving Embryo Implantation Rates 341Rachel Cutting 29 Cryopreservation of Gametes and Embryos 351Tope Adeniyi 30 Preimplantation Genetic Diagnosis and Screening 371Colleen Lynch and Brendan Ball 31 Long‐Term Follow‐Up of Children Conceived Through In Vitro Fertilization 385Omar Abdel‐Mannan and Alastair G. Sutcliffe Index 393

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Book SynopsisHelps those that use cell preservation to develop new protocols or improve existing protocols This book provides readers with the tools needed to develop or debug a preservation protocol for cells. The core structure and content of the text grew from a professional short course that has been offered at the Biopreservation Core Resource for the last 10 years. This comprehensive text describes, step by step, the individual elements of a protocol, including the relevant scientific principles for each phase of the protocol. It can be used by anyone who is involved in cell preservationeven by those who are not experts in freezing of cellsbecause it provides the scientific basis for those that want to understand the basis for the protocol. Preservation of Cells: A Practical Manual begins by first introducing readers to the subject of preserving cells. It then goes on to cover Pre-freeze Processing and Characterization; Formulation and Introduction of CryopreserTable of ContentsPreface xiii Acknowledgments xvii Nomenclature xix 1 Introduction 1 Mammalian Cells: Modern Workhorses 1 Products from Cells 1 Cells as Therapeutic Agents 2 Biomarkers for Health or Disease 2 In Vitro Models 3 Bridging the Gap 3 The Preservation Toolkit 5 Hypothermic Storage 5 Cryopreservation 6 Vitrification 7 Dry State Storage 8 Fit]for]Purpose 8 One Size Does Not Fit All 9 The Process is the Product 9 Reproducibility 12 Safety 12 Dispelling the Myth of the Cold Black Box 12 References 13 2 Pre]freeze Processing and Characterization 15 Pre]freeze Processing 15 Digestion of Cells from Intact Tissue 15 Hypothermic Storage 16 Selection of Subpopulations 17 Activation or Stimulation 18 Genetic Modification 18 Culture 19 Pre]freeze Process Monitoring 19 Pre]freeze Characterization 20 Identity 20 Genetic Stability 21 Enumeration 21 Purity 22 Adventitious Agents 22 Microbial Testing of Cell Therapy Products 23 Special Considerations for the Characterization of Cell Therapies 24 Annotation of Pre]freeze Processing 24 Scientific Principles 25 Putting Principles into Action 25 References 26 3 Formulation and Introduction of Cryopreservation Solutions 29 Importance of Cryoprotective Agents 29 Mechanisms of Cryoprotection 31 Formulating a Cryopreservation Solution 31 Formulation of a Vitrification Solution 33 Characterization and Quality Control for Cryoprotective Solutions 34 Toxicity of CPAs 35 Osmotic Toxicity 35 Biochemical Toxicity 36 Developing a Protocol for Introducing CPA Solutions 37 The Basic Experiment 37 Introduction of Vitrification Solutions 38 Cell Concentration 39 Removal of CPA Solution 40 Safety Considerations for Cryopreservation Solutions 40 Cryopreservation Containers 41 Overwraps 42 Labeling 43 Sample Annotation 44 Scientific Principles 44 Putting Principles into Practice 44 References 44 4 Freezing Protocols 47 Importance of Cooling Rate 47 Controlled]rate Freezing 48 Controlled Cooling]rate Protocols 49 Segment 1: Initial Hold Period 49 Segment 2: Cooling 50 Uncontrolled Nucleation 53 Manual Nucleation 54 Automatic Nucleation 54 Verifying Segment 2 (Including S2a) 55 “Delayed” Latent Heat 55 Segment 3 56 Verifying Segment 3 56 Other Types of Controlled]rate Protocols 57 Passive Freezing 57 Transfer to Storage 59 Vitrification 60 Independent Temperature Measurement 60 Scientific Principles 61 Putting Principles into Practice 62 References 62 5 Storage and Shipping of Frozen Cells 65 Scientific Basis for Selection of a Storage Temperature 65 Additional Considerations for Vitrified Samples 67 Standards, Guidelines, and Best Practices 67 Facilities 68 Storage Equipment and Environment 69 Mapping Storage Devices and Setting Alarm Limits 70 Monitoring Systems 71 Safety 71 Inventory Management System 72 Stability in Storage 72 Temperature Fluctuations 73 Influence of Background Ionizing Radiation on Stability in Storage 74 Shelf]Life of Samples in Storage 75 Fit]for]Purpose Storage Practices 75 Risk Mitigation in Long]Term Storage 76 Shipping or Transport of Cells 76 General Shipping Considerations 77 Liquid Nitrogen Dry Shippers 78 Temperature Mapping of a Shipper 79 Packaging of Samples Being Shipped 79 Monitoring of Shipments 79 Responsibilities 79 Sample Annotation 80 Scientific Principles 80 Putting Principles into Practice 81 References 81 6 Thawing and Post]Thaw Processing 85 Thawing Equipment 86 Transporting Samples Prior to Thawing 87 Estimating Your Thawing Rate 87 Thawing and Infusion of Cell Therapy Products 89 Safety Considerations for Thawing 90 Post]Thaw Processing 90 Post]Thaw Washing 90 Dilution 91 Infusion of Cells Immediately Post]Thaw 91 Removal of Vitrification Solutions 92 Wash Solutions 92 Scientific Principles 94 Putting Principles into Practice 94 References 94 7 Post]Thaw Assessment 97 Common Measures Used in Post]Thaw Assessment 98 Physical Integrity 98 Metabolic Activity 99 Mechanical Activity 100 Mitotic Activity 101 Differentiation Potential 102 Transplantation Potential 103 Strategies to Improve the Accuracy and Reproducibility of Post]Thaw Assessment 103 Eliminate Measurement Bias 103 Compensating for Post]Thaw Apoptosis 105 Post]Thaw Assessment Using a Single Measure 106 Optical Methods of Post]Thaw Assessment 106 Release Criteria 107 Scientific Principles 107 Putting Principles into Practice 107 References 108 8 Algorithm]Driven Protocol Optimization 111 Small Cell Number/High Throughput Approach 113 Validating Operation of the Algorithm 114 Flexibility 115 Practical Notes 115 Modeling in Cryobiology 115 References 116 Protocols Introduction 117 Protocol Contributors 118 Cryopreservation of Endothelial Cells in Suspension 119 Principle 119 Equipment and Supplies 119 Equipment 119 Supplies 120 Safety 120 Procedure 121 Cell Preparation 121 Preparation of Cryoprotectant Solution 121 Using Powdered HES 122 Using Pentastarch Solution 122 Cryoprotectant Addition 122 Freezing 122 Controlled]rate Freezing with a Methanol Bath 122 Alternative Freezing Procedure 123 Thawing 123 Expected Results 123 References 123 Cryopreservation of Peripheral Blood Mononuclear Cells from Whole Blood 125 Principle 125 Protocol 1: Isolation of PBMCS Directly over Ficoll]Hypaque 125 Equipment 125 Materials 126 Reagents 126 Procedure 126 Protocol 2: Isolation of PBMCS Using SepMates 127 Equipment 127 Materials 128 Reagents 128 Procedure 128 Appendix A Human Serum AB Freezing Media 129 Materials 129 Equipment 130 Reagents 130 Procedure 130 Cryopreservation of Human Adipose Stem Cells 131 Principle 131 Equipment and Supplies 131 Reagents and Media 132 Procedure 133 Isolation of Human ASCs from Lipoaspirate 133 Magnetic Cell Sorting (Optional) 135 Cryopreservation 135 Controlled]rate Freezing of Human ASCs 135 Thawing Human ASCs 137 Notes 138 Reference 139 Cryopreservation of Red Blood Cells 141 Method I: High Glycerol/Slow Cooling Technique (Meryman and Hornblower 1972) 141 Preparation of the RBC Concentrate 141 Addition of the Cryoprotective Solution 141 Cooling 142 Rewarming 142 Removal of the Cryoprotectant and Debris 142 Method II: A Low Glycerol/Rapid Cooling Technique (Rowe, Eyster, and Kellner 1968) 143 Method III: Hydroxyethylstarch/Rapid Cooling Technique (Sputtek 2007) 144 References 146 Cryopreservation of Oocytes by Slow Freezing 147 Principle 147 Specimen Requirements 147 Equipment and Supplies Needed 147 Equipment 147 Supplies 148 Procedure 148 Safety 152 Calculations 152 Reporting Results 152 Procedure Notes 153 Limitations of Procedure 153 Oocyte Vitrification and Warming 155 Principle 155 Equipment and Supplies 155 Equipment 155 Supplies 155 Procedure 156 Quality Control 160 Safety 161 Transportation of Hematopoietic Progenitor Cells and Other Cellular Products 163 Principle/Rationale 163 Specimen 163 Equipment/Reagents 163 Quality Control 164 Procedure 164 Additional Information 165 Further Reading 165 Cryopreservation of Hematopoietic Progenitor Cells 167 Principle/Rationale 167 Protocol/Processing Schema 168 Specimen 168 Equipment/Reagents 168 QualityControl 169 Procedure169 Appendix A Alternate Cryopreservation Harness Set]2 or 4 Bags 173 Further Reading 173 Thawing of Hematopoietic Progenitor Cells 175 Principle/Rationale 175 Equipment/Reagents 175 QualityControl 176 Procedure176 Further Reading 177 Processing and Cryopreservation of T]Cells 179 Principle/Rationale 179 Protocol/Processing Schema: N/A 179 Specimens179 Equipment/Reagents 179 Quality Control 180 Procedure 180 Further Reading 182 Thawing and Reinfusion of Cryopreserved T]Cells 183 Principle/Rationale 183 Protocol/Processing Schema 183 Specimen 184 Equipment/Reagents 184 Quality Control 184 Procedure 184 Further Reading 187 Index 189

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Book SynopsisGeneral Practice Cases at a Glance is a workbook of clinical scenarios, ideal for those working in general practice, on their GP rotations, or looking to improve their history-taking, diagnostic and management planning skills.Trade Review"The more clinical cases one studies, the better the critical skills one develops in learning how to approach the numerous complaints one may encounter, along with developing the understanding that there can be many presentations of a common diagnosis. This books adds a number of cases to help this development." (Doody Enterprises 2016)Table of ContentsPreface vii Part 1 Introduction 1 1 The consultation 2 2 Clinical reasoning to reach a diagnosis 4 Part 2 Cases 7 1 My baby is burning up 8 2 I need something for hay fever 10 3 I can’t seem to shift this cough 12 4 My knee is very bad 14 5 I have migraine 16 6 I’ve come for my flu jab 18 7 He’s a little terror 20 8 I’ve got a problem with my shoulder 22 9 I can’t believe how much weight I’ve put on 24 10 It’s my back passage 26 11 I am pregnant again 28 12 My baby has an upset tummy 30 13 My ear really hurts 32 14 I’m worried about my drinking 33 15 She cries all the time 34 16 I need something to help me sleep 36 17 My eye hurts 38 18 I think I should get this prostate test, doctor 40 19 I can’t live with this pain much longer 41 20 I’ve got a red eye 44 21 I’m fed up with my spots 46 22 I’ve come for the results of my blood tests 48 23 I’d like to talk to you about HRT 50 24 I’ve got a bit of a discharge 52 25 I’m feeling tired and woozy 54 26 I think I need to get my blood pressure checked 56 27 Well, I’m pregnant 58 28 I’ve been feeling short of breath 60 29 She’s coughing non-stop 62 30 I’m worried about my memory 64 31 I’ve got this pain in my chest, doctor 66 32 I’ve been having terrible stomach cramps 68 33 I’m concerned this mole has been growing 70 34 I seem to have lost weight 72 35 I’m worried about my erection 74 36 I think the cancer has got me 76 37 I’m all over the place these days 78 38 She’s had tummy ache for two days 80 39 I don’t want to have my period when I am on holiday 82 40 It’s my leg 84 41 I’m having terrible diarrhoea 86 42 The nurse did my diabetes check last week. I’m here for the results 88 43 My skin is really itchy 90 44 Doctor, I’m just feeling really down 92 45 I’ve got a really bad burning in my stomach 93 46 I want to talk about my risk of breast cancer 94 47 I’ve got a terrible back ache 96 48 I’d like antibiotics please 98 49 I’m tired all the time 100 50 I’m worried about this lump, doctor 102 List of abbreviations 105 Index of cases by speciality 106 Index 107

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Book SynopsisIn the era of cost cutting and lack of adequate health insurance for many patients, clinical skills and time spent with patients are not adequately compensated.Table of ContentsTable of Normal Laboratory Values, ix About the Author, xi Dedication, xiii Acknowledgments, xv Preface, xvii Introduction, xix How the book should be used and understood, xxi 1 Skin and Soft Tissue Infections, 1 Case 1.1 Soft tissue infection following traumatic aquatic exposure, 1 Case 1.2 Soft tissue infection of the hand and wrist in an 81-year-old man, 6 Case 1.3 A 41-year-old Caucasian female with right arm swelling, 12 Case 1.4 A 24-year-old female with fever and arm swelling, 15 Case 1.5 A 72-year-old male with necrotic soft tissue elbow infection, 16 Case 1.6 A 37-year-old man with severe body aches and fever, 18 2 Fever of Unknown Origin and Drug-Induced Fever, 25 Case 2.1 Hypersensitivity masquerading as sepsis, 25 Case 2.2 A psychiatric patient with HIV infection and fever, 32 Case 2.3 A hypertensive patient with 2 months of fever and chills, 36 Brief review and discussion of drug-induced fever, 38 Lessons learned from these two cases, 40 3 Dermatologic Manifestations of Infectious and Non-infectious Diseases, 41 Case 3.1 A 45-year-old patient referred for "persistent shingles", 41 Case 3.2 A 39-year-old female with fever and acute rash illness, 46 Case 3.3 A 45-year-old female with subacute rash illness for 2 weeks, 50 Case 3.4 An 82-year-old man with a chronic non-healing elbow wound, 55 4 Diseases Acquired Through Close Contact with Animals, 61 Case 4.1 A 10-month-old child with "worms", 61 Case 4.2 Infectious complication of cat scratch, 67 Case 4.3 A young man with acute left arm lymphadenopathy, 72 5 Travel-associated Blood-borne Parasitic Infection, 77 Case 5.1 A 15-year-old adolescent male with fever and thrombocytopenia, 77 Case 5.2 A 23-year-old Caucasian male with fever and chills, 81 Case 5.3 A 57-year-old male with acute-onset fever and chills, 83 Comparison of the characteristics of five patients with malaria seen between 1998 and 2015, 86 6 Gulf Coast Tick Rash Illness, 93 Case 6.1 Woman with rash and prolonged eschar following a tick bite, 93 Case 6.2 A 58-year-old male with generalized body aches and fever, 97 7 Infectious Diseases Associated with Trauma and Outdoor Activities, 103 Introduction, 103 Case 7.1 A 30-year-old man with thumb infection and forearm nodules, 103 Case 7.2 Severe infection and sepsis following recreational fishing, 108 Classification and characteristics of infectious diseases associated with trauma and outdoor activities, 114 8 Acute and Chronic Subcutaneous Fungal Infections, 121 Case 8.1 Exophytic skin lesion masquerading as cancer, 121 Case 8.2 Chronic persistent subcutaneous fungal infection of the leg, 124 Case 8.3 A young man with a laceration injury contaminated with soil, 130 9 Endocarditis with Unusual Organisms or Characteristics, 137 Case 9.1 Man with dyspnea, cough, fever, and weight loss, 137 Case 9.2 Confusing staining characteristics and false identification of a pathogen by automated system in a seriously ill patient, 143 10 Severe Systemic Fungal and Other Infections in AIDS Patients, 153 Case 10.1 HIV patient with progressive shortness of breath, 153 Case 10.2 Recurrent multiorgan infection in an immunocompromised patient, 161 11 Toxic Manifestations of Infectious and Non-infectious Diseases, 171 Case 11.1 An odd presentation for toxic shock syndrome, 171 Case 11.2 A peculiar and dramatic presentation of septic shock, 176 Case 11.3 A 45-year-old woman with rash, hepatitis, and lymphadenopathy, 185 12 Skin and Soft Tissue Infections Seen Post Hurricane Katrina in 2005, 195 Introduction, 195 Case 12.1 A 76-year-old Caucasian female with leg laceration, 195 Case 12.2 A 76-year-old man with rapid-onset cellulitis, 198 Case 12.3 A 61-year-old man with diabetic neuropathy, 200 Case 12.4 A 45-year-old man from a refugee camp with calf laceration, 201 General comments on soft tissue infections in relation to Hurricane Katrina, 202 13 Other Miscellaneous Infections, 211 Case 13.1 A 17-month-old child with facial swelling and adenopathy, 211 Case 13.2 Persistent headache in a 50 year old with known migraine, 217 Case 13.3 A 54-year-old man with skin lesions with central numbness, 223 Case 13.4 Delayed diagnosis in a young woman with migratory joint pain, 231 Index, 241

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Book SynopsisHealthcare Professionalism: Improving Practice through Reflections on Workplace Dilemmas provides the tools and resources to help raise professional standards within the healthcare system. Taking an evidence and case-based approach to understanding professional dilemmas in healthcare, this book examines principles such as applying professional and ethical guidance in practice, as well as raising concerns and making decisions when faced with complex issues that often have no absolute right answer. Key features include: Real-life dilemmas as narrated by hundreds of healthcare students globally A wide range of professionalism and inter-professionalism related topics Information based on the latest international evidence Using personal incident narratives to illustrate these dilemmas, as well as regulatory body professionalism standards, Healthcare Professionalism is an invaluable resource for students, healthcare professTrade Review'...excellent layout and presentation, especially the way the text is broken up into boxes to highlight common themes throughout each chapter, such as learning outcomes for reflective sessions and case study narratives. Each chapter is also rounded off with a summary, discussion points, learning activities and recommended reading, which helps the reader to draw conclusions at each stage to consolidate learning...there is much learning to be gained from the insightful reflections of a wider, multidisciplinary body of students' – Nursing Standard 'This book explores important professionalism dilemmas, including patient safety errors, consent and confidentiality ... The chapters include thought-provoking narratives on personal incidents and case studies that clearly link theory with practice. Detailed referencing provides an evidence-based, robust approach to tackling professionalism dilemmas.' – Surgeons’ News, The Royal College of Surgeons of Edinburgh“This book presents a valuable and realistic structure for teaching and learning how to become and develop as professional in any healthcare discipline. The usefulness of this book lies in the approach to guiding and developing the student's professional identify and the educator's teaching strategies to promote corrective actions based on reflections shaped by professional dilemmas founded on failures of professionals in various healthcare disciplines” Linda S. Hansen, MSN, RN, Michigan State University College of Nursing on behalf of Doody’s Aug 17 'The key strength of this book is that it continually links the theory of professionalism to the reality of day-to-day practice ... the authors do an excellent job of exposing the commonalities and differences in the perspectives of the various health care professions.' Anesthesia and Analgesia Table of ContentsForeword xi About the Authors xiii Acknowledgements xv Author Contributions xvii 1 Introduction 1 References 4 2 What is Healthcare Professionalism? 7 Introduction 8 Who is Responsible for Setting Professionalism Codes of Conduct? 8 What is the Ethical Basis of Healthcare Professionalism? 10 How is Professionalism Understood Across Regulatory Bodies’ Codes of Conduct? 12 How is Professionalism Linguistically Framed Across Healthcare Professionalism Codes of Conduct? 15 What are Stakeholders’ Understandings of Professionalism Across Different Country Cultures? 16 What are Students’ Understandings of Professionalism Across Country Cultures? 19 Professionalism: Embodied Identities? 23 Chapter Summary 25 References 26 3 Teaching and Learning Healthcare Professionalism 31 Introduction 32 Why Teach and Learn Professionalism? 32 What is a Curriculum? 33 How is Professionalism Taught and Learnt? 35 What Curricula‐related Professionalism Dilemmas do Healthcare Students Experience? 42 Chapter Summary 45 References 46 4 Assessing Healthcare Professionalism 51 Introduction 52 Why Assess Professionalism? 52 How is Professionalism Assessed? 53 What are the Key Challenges Facing Professionalism Assessment? 56 What Assessment‐related Professionalism Dilemmas are Learners Experiencing? 58 Chapter Summary 65 References 67 5 Identity‐related Professionalism Dilemmas 71 Introduction 71 How do Professional Identities Relate to Learning? 72 Are Professional Identities Easily Developed? 73 What are the Consequences of Professional Identities? 74 What are Identity‐related Professionalism Dilemmas? 75 What Identity‐related Professionalism Dilemmas Occur Across the Pre‐university to Year 1 Transition? 76 Identity Dilemmas Across Undergraduate Healthcare Education 78 Identity Dilemmas Across Transitions into Practice 81 Emotional impact and resistance 82 Chapter Summary 83 References 85 6 Consent‐related Professionalism Dilemmas 89 Introduction 90 What is Consent and why does it Matter? 90 What are the Common Myths about Patient consent for student involvement in their care? 93 What are Common Consent‐related Professionalism Dilemmas? 97 What is the Impact of Consent‐related Professionalism Dilemmas? 100 How do Students Act in the Face of Consent‐related Professionalism Dilemmas? 102 Chapter summary 103 References 105 7 Patient Safety‐related Professionalism Dilemmas 109 Introduction 110 How Have Patient Safety and Associated Terms been Defined? 110 What are the Factors that can Influence Patient Safety in the Workplace? 111 What Types of Patient Safety‐related Dilemmas Occur Across Different Healthcare Professions? 113 How can Healthcare Learners’ Actions and Roles Develop a Positive Workplace Culture of Patient Safety? 119 Chapter Summary 122 References 123 8 Patient Dignity‐related Professionalism Dilemmas 127 Introduction 128 What is Patient Dignity? 128 Why Does Patient Dignity Matter? 129 What are Dignity Violations and How do they Arise? 130 What Patient Dignity‐related Professionalism Dilemmas do Healthcare Learners Witness or Participate in? 133 What is the Impact of Patient Dignity‐related Professionalism Dilemmas? 139 How do Learners Act in the Face of Patient Dignity‐related Professionalism Dilemmas? 140 Chapter Summary 142 References 143 9 Abuse‐related Professionalism Dilemmas 145 Introduction 146 What are Equality, Diversity and Dignity at Work and Why Do They Matter? 146 What is Workplace Abuse and its Relationship with Power? 149 What are the Causes of Workplace Abuse? 151 What are the Consequences of Workplace Abuse? 152 What Abuse‐related Professionalism Dilemmas do Healthcare Learners Experience? 152 How can Workplace Abuse be Prevented and Managed? 158 Chapter Summary 160 References 161 10 E‐professionalism‐related Dilemmas 167 Introduction 168 What are the Benefits of OSNs for Professionalism? 168 What are the Challenges of OSNs for Professionalism? 169 What is E‐professionalism and Why is it Important? 170 What E‐professionalism Lapses do Healthcare Learners Commit? 172 What are the Repercussions for E‐professionalism‐related Lapses? 176 What are the Psychological, Social and Technological Factors Associated with Social Media Use? 177 What are the Regulatory Recommendations for the Prevention and Management of E‐professionalism Lapses? 180 Chapter Summary 181 References 182 11 Professionalism Dilemmas Across National Cultures 187 Introduction 188 What is Culture? 188 What Different Cultural Dimensions are there? 189 What are Eastern and Western Cultural Spaces? 191 How can we Develop Cultural and Intercultural Capability? 195 What are the Professionalism Dilemmas Across Different Cultural Spaces? 198 How are Situations Culturally Interpreted? Intercultural Dilemmas on Medical Electives by Western Students 202 Chapter Summary 204 References 205 12 Professionalism Dilemmas Across Professional Cultures 207 Introduction 208 What are the Roles of Different Healthcare Professionals? 209 How do Professionalism Dilemmas Compare Across Healthcare Students? 211 Interprofessional Dilemmas: Hierarchies, Roles and Conflict 214 How do Dilemmas Around Role Boundaries Come About? 218 What are Students’ Reactions and Actions in the Face of Interprofessional Dilemmas? 219 How can Interprofessional Conflict be Managed? 220 Chapter Summary 222 References 224 13 Conclusions 227 Power, Hierarchy, Conformity and Resistance 227 Negative Emotions, Empathy and Moral Distress 228 Looking Forward: Education, Training and Practice 229 Looking Forward: Research 231 Looking Back: Researcher Reflexivity 232 Coda 233 References 234 Afterword: Healthcare Professionalism: Improving Practice through Reflections on Workplace Dilemmas 237 Index 241

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Book SynopsisApplied Anatomy for Clinical Procedures at a Glance is a concise resource combining high-quality images and step-by-step instructions to provide expert guidance on the major core training pathways in medicine, surgery and anaesthesia. Written by an experienced team of Foundation Training programme directors and clinical skills examiners, this unique revision and learning guide aligns with training pathways rather than anatomical area to support Foundation doctors and core trainees master these vital clinical procedures. Succinct yet thorough descriptions of each procedure include photographs of surface anatomy, line diagrams of the anatomy, instructions on the procedural techniques, and practical tips for performing the procedures safely whilst minimising risks of complications. All major aspects of Foundation procedures and Core training in applied anatomy are covered, including catheterisation, ECGs, central venous cannulation, basic suturing and anastomotic techniques, endotracheTable of ContentsContributors vii 1 Scrubbing up 1Sherif Kirollos and Ramez Kirollos 2 Setting up a sterile field and draping the patient 4Sherif Kirollos and Ramez Kirollos 3 Three-way tap 6Jane Sturgess 4 Common equipment for core clinical procedures 8Jane Sturgess 5 Local anaesthetic infiltration 12Sherif Kirollos and Ramez Kirollos 6 Obtaining consent 14Francesca Crawley 7 Manometer for central venous pressure and lumbar puncture 16Jane Sturgess 8 Bladder irrigation sets 18Jane Sturgess 9 Underwater seal for chest drains 20Jane Sturgess 10 Male catheterisation 22Francesca Crawley 11 Female catheterisation 24Francesca Crawley 12 Arterial blood gases 26Francesca Crawley 13 Performing an electrocardiogram 30Francesca Crawley 14 Oropharyngeal airway 32Jane Sturgess 15 Nasopharyngeal airway 34Jane Sturgess 16 Laryngeal mask airway 36Jane Sturgess 17 Central venous cannulation (high approach internal jugular) 38Jane Sturgess 18 Central venous cannulation (low approach internal jugular) 42Jane Sturgess 19 Central venous cannulation (subclavian) 46Jane Sturgess 20 Direct current cardioversion 50Francesca Crawley 21 Intercostal drains 52Francesca Crawley 22 Pleural tap 54Francesca Crawley 23 Inserting a nasogastric tube 56Francesca Crawley 24 Lumbar puncture 58Jane Sturgess 25 Bone marrow aspirate 62Francesca Crawley and Charles Crawley 26 Ascitic tap 64Francesca Crawley 27 Paracentesis 66Francesca Crawley 28 Knee aspiration 68Sherif Kirollos and Ramez Kirollos 29 Skin biopsy 70Sherif Kirollos and Ramez Kirollos 30 Basic suturing 72Sherif Kirollos and Ramez Kirollos 31 Basic anastomotic techniques 76Sherif Kirollos and Ramez Kirollos 32 Abscess drainage and debridement 78Sherif Kirollos and Ramez Kirollos 33 Bag mask ventilation (adults) 82Jane Sturgess 34 Endotracheal intubation (adults) 86Jane Sturgess 35 Needle cricothryoidotomy (adults) 90Jane Sturgess 36 Surgical cricothyroidotomy 94Sherif Kirollos and Ramez Kirollos 37 Defibrillation 96Francesca Crawley 38 Spinal injection 100Jane Sturgess 39 Epidural injection 104Jane Sturgess 40 Procedure-related safety 108Kirsty Cattle Index 110

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Book SynopsisAlthough there are many texts that provide quality information for the identification of fungi, researchers and technologists rarely have time to read the text. Most are rushed for time and seek morphological information that helps guide them to the identification of fungi.Table of ContentsPreface xi Acknowledgments xiii Abbreviations xv Part I Divisions of the Fungi 1 1 Morphological Growth Index 3 1.1 Filamentous Bacteria 3 1.2 Yeasts and Yeast‐like Organisms 3 1.3 Yeast/Yeast‐like Organisms That Produce Hyphae 4 1.4 Thermally Dimorphic Fungi 4 1.5 Thermally Monomorphic Molds 4 1.6 Dematiaceous (Brown or Black Colored Fungi) 6 1.7 Other Fungi for Which No Photographs are Available 8 2 Division of Fungi by Type of Sporulation 9 2.1 Annelloconidia 9 2.2 Arthroconidia 9 2.3 Arthroconidia and Blastoconidia 9 2.4 Arthroconidia; Spherule in Tissue 9 2.5 Basidiospores 9 2.6 Phialoconidia 9 2.7 Produce Only Macroconidia 10 2.8 Macroconidia and Microconidia 10 2.9 Perithecium and Ascospores 10 2.10 Sporangia or Sporangiospores 10 2.11 Sporangia with Rhizoids 11 2.12 Produce Only Microconidia 11 2.13 Microconidia and Chlamydoconidia 11 2.14 Microconidia and Arthroconidia 11 2.15 Microconidia and Cleistothecium 11 2.16 Yeast Only 12 2.17 Yeast and Hyphae and Phialides 12 2.18 Yeast and Pseudohyphae 12 2.19 Yeast and Conidia 12 3 Division of Fungi, Yeast, and Bacteria by Morphological Group 13 3.1 Actinomycetes, Yeast, and Yeast‐like Organisms 13 3.2 Dimorphic Organisms 13 3.3 Dermatophytes 13 3.4 Zygomycetes (Aseptate) 14 3.5 Hyaline Molds (Septate) 14 3.6 Dematiaceous Fungi (Septate) 14 Part II Descriptions and Photographs of Microorganisms 17 4 Actinomycetes, Yeast (Thermally Monomorphic), and Yeast‐like Organisms 19 4.1 Microorganisms with Fungal‐like Morphology Occurring in Fungal Cultures 19 4.2 Yeast and Yeast‐like Fungi 19 4.3 Candida spp 34 4.4 Prototheca spp 36 4.5 Arthrographis kalrae 39 4.6 Cryptococcus neoformans 44 4.7 Geotrichum candidum 47 4.8 Malassezia spp 56 4.9 Trichosporon spp 58 5 Yeast (Thermally Dimorphic) 63 5.1 Blastomyces dermatitidis 63 5.2 Coccidioides immitis 69 5.3 Histoplasma capsulatum 73 5.4 Sporothrix schenckii 83 6 Zygomycetes (Aseptate) 89 6.1 Lictheimia (Absidia) corymbifera 89 6.2 Conidiobolus lamprauges, coronatus, incongruus 95 6.3 Cunninghamella bertholletiae 102 6.4 Mucor spp 106 6.5 Rhizomucor spp 116 6.6 Rhizopus spp 121 6.7 Syncephalastrum racemosum 130 7 Dermatophytes 135 7.1 Microsporum spp 135 7.2 Trichophyton spp 145 7.3 Epidermophyton floccosum 161 8 Hyaline Molds (Septate) 167 8.1 Aspergillus spp 167 8.2 Beauveria bassiana 182 8.3 Emmonsia spp 187 8.4 Fusarium spp 193 8.5 Gliocladium 215 8.6 Malbranchea spp 220 8.7 Paecilomyces spp 223 8.8 Penicillium spp 228 8.9 Ramichloridium spp 232 8.10 Schizophyllum commune 238 8.11 Scopulariopsis brevicaulis 244 8.12 Scopulariopsis brumptii 250 8.13 Sepedonium spp 254 8.14 Sporotrichum pruinosum 258 8.15 Trichoderma spp 264 8.16 Trichothecium roseum 271 8.17 Chrysosporium tropicum 274 9 Dematiaceous Fungi (Septate) 281 9.1 Acremonium spp 281 9.2 Alternaria spp 289 9.3 Aureobasidium pullulans 292 9.4 Bipolaris spicifera, Curvularia hawaiiensis (B. hawaiensis), and C. australiensis (B. australiensis) 297 9.5 Chaetomium spp 305 9.6 Cladophialophora (Xylohypha) bantiana 308 9.7 Cladophialophora boppi 311 9.8 Cladophialophora carrionii 314 9.9 Cladosporium sphaerospermum 317 9.10 Cladosporium spp 320 9.11 Curvularia spp 327 9.12 Epicoccum spp 332 9.13 Exserohilum spp 337 9.14 Fonsecaea 343 9.15 Hormonema dematioides 351 9.16 Hortaea (Phaeoannellomyces, Exophiala) werneckii 355 9.17 Madurella spp 361 9.18 Neoscytalidium spp 369 9.19 Nigrospora spp 376 9.20 Ochroconis (Dactylaria) spp 380 9.21 Phaeoacremonium parasiticum 385 9.22 Phialemonium spp 390 9.23 Phialophora spp 395 9.24 Pithomyces sp 401 9.25 Pseudallescheria boydii 407 9.26 Scedosporium 412 9.27 Stachybotrys chartarum 417 9.28 Stemphylium sp 422 9.29 Ulocladium sp 425 9.30 Phoma sp 429 9.31 Rhinocladiella basitona 435 9.32 Exophiala dermatitidis (Wangella dermatitidis) 441 9.33 Exophiala jeanselmei 447 Additional Reading 453 Index 000

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Book SynopsisProviding the practicing and trainee hematologist with a practical and immediately applicable compendium of answers the Clinical Manual of Blood and Bone Marrow Transplantation covers the spectrum of the hematopoietic cell transplant specialty, in particular practical issues in transplant patient care, and the set up and functioning of a transplant program. Supplies the practicing and trainee hematologist with a practical and immediately applicable compendium of answers to clinical questionsCovers the spectrum of the hematopoietic cell transplant specialty, in particular practical issues in transplant patient care, and the set up and functioning of a transplant programContains concise chapters written with a focus on tables, algorithms and figures to aid rapid referralBenefits from expert contributions from an international authorshipTrade Review"... the book provides a concise practical expert review in a well-organized format of 42 chapters, each annotated with numerous practical headings to enhance focused learning. The expert authors of each chapter in the Clinical Manual of Blood and Bone Marrow Transplantation are part of that success story, and their up-to-date contributions to the field are elucidated in the clearest of terms in this worthy addition to the literature. This book is recommended for The ASCO Post readers, especially residents and fellows who are interested in pursuing a career in blood cancers" (The ASCO Post, September 2017)Table of ContentsContributors, ix Preface, xiv 1 Donor and graft selection strategy, 1Ayman Saad, Marisa B. Marques, and Shin Mineishi 2 HLA typing and implications, 9Bronwen E. Shaw and Stephen R. Spellman 3 Risk]benefit assessment in allogeneic hematopoietic transplant: Factors, scores, and models, 19Mahmoud Elsawy and Mohamed L. Sorror 4 Donor and recipient pre]transplant evaluation, 36Shuang Fu and Navneet S. Majhail 5 Autologous and allogeneic progenitor cell mobilization, 45Racquel D. Innis]Shelton and Luciano J. Costa 6 Hematopoietic stem and progenitor cell collection by apheresis: Techniques and tricks, 53Anand Padmanabhan 7 Hematopoietic cell processing: From procurement to infusion, 59Jay S. Raval, Kathryn McKay, and Yara A. Park 8 Graft manipulation: T-cell depletion and beyond, 66Christina Cho and Miguel]Angel Perales 9 Graft]versus]host disease prophylaxis, 73Melhem Solh and Asad Bashey 10 Acute lymphoblastic leukemia, 80Ghada Zakout and Adele K. Fielding 11 Acute myeloid leukemia, 89Hillard M. Lazarus and Masumi Ueda 12 Myelodysplastic syndromes, 97Melinda Biernacki and H. Joachim Deeg 13 Chronic myelogenous leukemia, 108Daniel Egan and Jerald Radich 14 Philadelphia chromosome negative myeloproliferative neoplasms, 116Nicolaus Kröger 15 Chronic lymphocytic leukemia, 123Fabienne McClanahan Lucas and John Gribben 16 Hodgkin Lymphoma, 131Anna Sureda and Eva Domingo]Domenech 17 Indolent lymphomas, 140Narendranath Epperla, Hamza Hashmi, and Mehdi Hamadani 18 Diffuse large B-cell lymphoma, 151Syed Abbas Ali, Istvan Redei, and Syed A. Abutalib 19 Mantle cell lymphoma, 164Narendranath Epperla and Timothy S. Fenske 20 T-cell lymphoma, 179Adrienne A. Phillips and Koen van Besien 21 Primary CNS lymphoma, 188Henry C. Fung, Philip Pancari, and Patricia Kropf 22 Autologous hematopoietic transplant in multiple myeloma, 194Nisha S. Joseph, Ajay K. Nooka, and Sagar Lonial 23 Allogeneic hematopoietic transplant in multiple myeloma, 207Parameswaran Hari and Binod Dhakal 24 Light]chain amyloidosis, 214Amara S. Hussain and Anita D’Souza 25 Autoimmune disorders, 221Adam Bryant and Harold Atkins 26 Testicular cancer, 229Moshe C. Ornstein, Navneet S. Majhail, and Timothy Gilligan 27 Sickle cell disease, 236Sonali Chaudhury and Shalini Shenoy 28 Hematopoietic cell transplant in thalassemia, 246Emanuele Angelucci and Federica Pilo 29 Fanconi anemia, 255Flore Sicre de Fontbrune, Jean Soulier, and Regis Peffault de Latour 30 Immunodeficiency disorders, 264Jennifer A. Kanakry and Dennis D. Hickstein 31 Inherited metabolic disorders, 272Jaap Jan Boelens and Robert F. Wynn 32 Aplastic anemia and paroxysmal nocturnal hemoglobinuria, 281Andrew C. Dietz and Michael A. Pulsipher 33 HIV infection and transplantation, 290Nitya Nathwani, Stephen J. Forman, and Amrita Krishnan 34 Engraftment and graft failure: Assessment and practical considerations, 297Yogesh Jethava, Madan Jagasia, Mohamed Mohty, and Bipin N. Savani 35 Immune reconstitution and tolerance, 304udovic Belle and William R. Drobyski 36 Donor lymphocyte infusion, 315David C. Halverson and Daniel Fowler 37 Diagnosis and treatment of acute graft]versus]host disease, 324Natasha Kekre and Vincent T. Ho 38 Diagnosis and treatment of chronic graft]versus]host disease, 334Sabarinath Venniyil Radhakrishnan and Daniel R. Couriel 39 Prevention and treatment of infection, 348Corrado Girmenia, Gian Maria Rossolini, and Claudio Viscoli 40 Early non]infectious complications after hematopoietic cell transplantation, 359Piyanuch Kongtim and Stefan O. Ciurea 41 Post]transplant lymphoproliferative disorders, 369Michael D. Keller, Conrad R. Cruz, and Catherine M. Bollard 42 Survivorship issues after transplantation, 376Vanessa E. Kennedy, Madan Jagasia, and Bipin N. Savani Index, 384

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Book SynopsisA clinically oriented handbook providing up-to-date recommendations for mastering the practical aspects of patient management for venous thromboembolism Venous thromboembolism (VTE) is associated with high morbidity and mortality both in and out of the hospital setting, and is one of the commonest reasons for hospital attendances and admissions. Designed as a practical resource, the Handbook of Venous Thromboembolism covers the practical aspects of venous thromboembolism management in short and easily followed algorithms and tables. This important text helps physicians keep up-to-date with the latest recommendations for treating venous thromboembolism in clinic-oriented settings. Experts in fields such as the radiological diagnosis of pulmonary embolism and thrombophilia testing, give a succinct summary of the investigation, diagnosis and treatment of venous thromboembolism and include evidence-based guidelines. With contributions from a team on internationally recognized experts, HTable of ContentsList of Contributors viii Foreword xi Section I Clinical Overview 1 1 Risk Factors for Venous Thromboembolism 3Peter E. Rose 2 Management of Venous Thrombosis in the Lower Limbs 13Dan Horner 3 Clinical Presentation of Acute Pulmonary Embolism 21C.E.A. Dronkers, M.V. Huisman and F.A. Klok Section II Diagnosis 27 4 Clinical Prediction Scores 29Kerstin de Wit and Lana A. Castellucci 5 Laboratory Aspects in Diagnosis and Management of Venous Thromboembolism 35Giuseppe Lippi and Emmanuel J. Favaloro 6 Thrombophilia Testing 49Massimo Franchini 7 Radiological Diagnosis of Pulmonary Embolism 55Joachim E. Wildberger and Marco Das 8 The Antiphospholipid Syndrome 60Karen Breen Section III Treatment 67 9 Inpatient or Outpatient Anticoagulation 69Lauren Floyd and Jecko Thachil 10 An Anticoagulant Service in Practice 73Kathy Macintosh, Dawn Kyle and Linda Smith 11 Point of Care Testing 86Dianne Patricia Kitchen 12 Direct Oral Anticoagulants in the Prevention and Management of Venous Thromboembolism 94Yen]Lin Chee and Henry G. Watson 13 The Role of Thrombolysis in the Management of Venous Thromboembolism 102Carlos J. Guevara and Suresh Vedantham 14 Inferior Vena Cava Filters in the Management of Venous Thromboembolism 114Anita Rajasekhar and Molly W. Mandernach Section IV Special Situations 129 15 VTE in Pregnancy 131Catherine Nelson Piercy 16 Paediatric Venous Thromboembolism 145Paul Monagle and Rebecca Barton 17 Cancer]associated Thrombosis 153Simon Noble 18 Venous Thromboembolism Management in Obese Patients 161Kathryn Lang and Jignesh Patel 19 Venous Thromboembolism in Intensive Care 169Gill Parmilan and Jecko Thachil 20 Venous Thromboembolism; a Primary Care Perspective 174David Fitzmaurice Section V Unusual Site Thrombosis 181 21 Cerebral Venous Thrombosis 183Christian Weimar 22 Upper Extremity Thrombosis 192Scott M. Stevens and Scott C. Woller 23 Management of Intra]abdominal Thrombosis 205Serena M. Passamonti, Francesca Gianniello and Ida Martinelli 24 Thrombosis in the Retinal Circulation 216Wenlan Zhang and Paul Hahn Section VI Long]term Sequelae of VTE 229 25 Post]thrombotic Syndrome 231Andrew Busuttil and Alun H. Davies 26 Chronic Thromboembolic Pulmonary Hypertension 240Demosthenes G. Papamatheakis and William R. Auger 27 Predicting Recurrent VTE 255R. Campbell Tait Section VII Controversies 263 28 Cancer Screening in Unprovoked Venous Thromboembolism 265David Keeling 29 Sub]segmental and Incidental PE – to Treat or Not? 269Jecko Thachil 30 Management of Distal Vein Thrombosis 273Giuseppe Camporese and Enrico Bernardi Section VIII Prevention 281 31 A Summary of the Evidence for VTE Prevention, with a Focus on the Controversies 283Catherine Bagot 32 VTE Prevention: Real World Practice 293Emma Gee 33 VTE Root Cause Analysis – How To Do It 301Alison Moughton, Francesca Jones and Will Lester Index

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Book SynopsisAn important resource that reviews the various infectious diseases that affect bats and bat populations Bats and Human Health: Ebola, SARS, Rabies and Beyond covers existing literature on viral, bacterial, protozoan, and fungal infections of bats and how these infections affect bat populations. The book also offers an overview of the potential for zoonotic transmission of infectious diseases from bats to humans or domestic animals. While most prior publications on the subject have dealt only with bat viral infections, this text closely covers a wide range of bat infections, from viral and bacterial infections to protist and fungal infections. Chapters on viral infections cover rabies, filoviruses, henipaviruses, and other RNA viruses, as well as information on bat virome studies. The book then provides information on bacterial infectionsincluding arthropod-borne and other bacteria that affect batsbefore moving on to protist infections, including apicompleTable of ContentsForeword xv A Brief Introduction to Unique Features of Bats in Relation to Infectious Diseases xv About the companion website xix I Introduction 1 1 BAT IMMUNOLOGY 3 1.1 Introduction to the Immune System of Bats 3 1.1.1 White blood cell count and other serological parameters 3 1.1.2 Innate versus adaptive immunity 4 1.1.3 MicroRNA 5 1.2 Viral Pattern‐Recognition Receptors and the Bat Immune Response to Microbes 5 1.3 Introduction to the Interferons 7 1.3.1 Regulation of interferon production 7 1.3.2 The JAK‐STAT pathway and interferon‐stimulated genes 8 1.3.3 Type I interferons 10 1.3.4 Type II interferon 12 1.3.5 Type III interferons 12 1.3.6 Viral avoidance of the host IFN response 14 1.4 Antibodies and B Lymphocytes 15 1.5 Macrophages, Dendritic Cells, and Proinflammatory Cytokines 16 1.6 T Lymphocytes 17 1.7 Other Parameters of the Immune Response 18 1.8 Conclusions 19 References 21 II Viral Infections of Bats 25 2 RABIES VIRUS AND OTHER BAT RHABDOVIRUSES 27 2.1 Introduction to the Family Rhabdoviridae 27 2.2 Lyssaviruses 27 2.2.1 Rabies virus 32 2.2.2 Other lyssaviruses of bats 36 2.2.3 Lyssavirus transmission 40 2.2.4 Lyssavirus sites of infection 41 2.2.5 Lyssavirus entry into cells 42 2.2.6 Prevention of lyssavirus infection 43 2.2.7 Immune response to lyssaviruses 44 2.2.8 Lyssavirus surveillance 45 2.3 Other Rhabdoviruses 45 2.3.1 The Kern Canyon serogroup of genus Vesiculovirus 46 2.3.2 Kumasi rhabdovirus 47 2.3.3 Unclassified rhabdoviruses 47 2.4 Conclusions 48 References 49 3 HENIPAVIRUSES AND OTHER PARAMYXOVIRUSES OF BATS 53 3.1 Introduction to Paramyxoviridae 53 3.2 Diseases Associated with Paramyxoviridae 59 3.2.1 Henipaviruses and disease 59 3.2.2 Morbilliviruses and disease 59 3.2.3 Rubulaviruses and disease 60 3.3 Henipaviruses in Bats 60 3.3.1 Henipaviruses in bats from Oceania and Southeast Asia 60 3.3.2 Henipaviruses and bats from Africa 61 3.3.3 Henipaviruses in bats from Madagascar 62 3.3.4 Henipavirus proteins and infection of bats 62 3.4 Hendra Virus 64 3.4.1 Hendra virus in Australian bats, horses, and humans 64 3.4.2 Factors affecting levels of Hendra viruses in bats and the potential for zoonotic transmission 65 3.5 Nipah Virus 66 3.5.1 Nipah virus in humans and pigs 66 3.5.2 Nipah virus in bats from Malaysia and Indonesia 67 3.5.3 Nipah virus in bats from India and Bangladesh 68 3.5.4 Interspecies Nipah virus transmission via date palm sap and bat urine 68 3.6 Cedar Virus 70 3.7 Protective Bat Responses to Henipavirus Infection 70 3.7.1 The interferon/STAT pathway and henipaviruses 70 3.7.2 Antibodies and henipaviruses 72 3.7.3 Apoptosis 72 3.8 Methods of Preventing Henipavirus Infection 73 3.9 Rubulaviruses 74 3.9.1 Bat parainfluenza virus 74 3.9.2 Menangle virus in bats and domestic animals 74 3.9.3 Tioman virus in bats and humans 75 3.9.4 Tuhoko viruses in bats 75 3.9.5 Achimota viruses in bats 75 3.9.6 Sosuga virus in bats and humans 76 3.9.7 Jeilongvirus in bats 76 3.9.8 Mumps‐like bat virus 76 3.9.9 Mapuera virus in bats 76 3.10 Morbilliviruses in Bats 77 3.11 Belinga bat Virus 77 3.12 Large, Multiviral Studies of Paramyxoviruses in Bats 78 3.12.1 Multiviral paramyxoviruses studies in Asia 78 3.12.2 Multiviral paramyxoviruses studies in Africa 78 3.12.3 Multiviral paramyxoviruses studies in Madagascar and islands of the Southwest Indian Ocean 79 3.12.4 Multiviral paramyxoviruses studies in Oceania 79 3.13 Conclusions 80 References 82 4 FILOVIRUSES AND BATS 89 4.1 Filoviruses 89 4.1.1 History of filovirus infection 90 4.1.2 Filovirus disease 91 4.1.3 The roles of viral proteins 91 4.2 Marburg Virus 96 4.2.1 Marburg virus in humans and bats 96 4.2.2 Experimental infection of bats with Marburg virus 98 4.3 Ebola Virus 99 4.3.1 Ebola virus in humans and bats 99 4.3.2 Ebola virus and bats prior to the 2014 outbreak 99 4.3.3 EBOV incidence in bats during and after the 2014 outbreak 100 4.4 Lloviu and Related Filoviruses in Bats 101 4.5 Seasonality of Filovirus Infection in Bats 101 4.6 Factors Affecting Zoonotic Infection by Filoviruses 102 4.7 Filoviruses in Animals Other Than Bats 103 4.8 Conclusions 104 References 106 5 BATS AND CORONAVIRUSES 111 5.1 Introduction 111 5.2 SARS Coronavirus 114 5.2.1 The history of SARS 114 5.2.2 SARS pathology 115 5.2.3 Viral and cellular proteins and their role in entry into the host cells 116 5.2.4 SARS in civits and raccoon dogs 118 5.2.5 Relatedness of bat SARS‐like CoV to SARS‐CoV 119 5.3 MERS Coronavirus 122 5.3.1 MERS pathology 122 5.3.2 Viral and cellular proteins and their role in entry into the host cells 123 5.3.3 MERS‐CoV and spillover from domestic livestock 124 5.3.4 Relatedness of bat‐CoV to MERS‐CoV 126 5.3.5 Transmission of MERS‐CoV 130 5.4 Other Coronaviruses of Bats 131 5.5 Conclusions 133 References 134 6 OTHER RNA VIRUSES AND BATS 139 6.1 Introduction 139 6.2 Baltimore Class III Viruses and Bats 139 6.2.1 Orbiviruses 140 6.2.2 Rotaviruses 140 6.2.3 Pteropine orthomyxovirus group 140 6.2.4 Mammalian orthoreoviruses 154 6.3 Baltimore Class IV Viruses 156 6.3.1 Astroviruses 156 6.3.2 Flaviviruses 158 6.3.3 Hepeviruses 164 6.3.4 Picornaviruses 164 6.4 Baltimore Class V Viruses 165 6.4.1 Bunyaviridae 165 6.4.2 Orthomyxoviruses 168 6.4.3 Arenaviridae 170 6.5 Large, Multi‐Virus Studies 171 6.6 Conclusions 171 References 174 7 BALTIMORE CLASS I AND CLASS II DNA VIRUSES OF BATS 181 7.1 Introduction to Double‐ and Single‐ Stranded DNA Viruses 181 7.2 Baltimore Class I Viruses 181 7.2.1 Poxviruses 190 7.2.2 Adenoviruses 191 7.2.3 Herpesviruses 192 7.2.4 Papillomaviruses 194 7.2.5 Polyomaviruses 194 7.3 Baltimore Class II Viruses 196 7.3.1 Parvoviruses 196 7.3.2 Dependoviruses 197 7.3.3 Circular replication‐associated protein encoding single‐stranded DNA viruses 197 7.4 Conclusions 199 References 201 8 REVERSE‐TRANSCRIBING BAT VIRUSES AND LARGE‐SCALE BAT VIROME STUDIES 205 8.1 Baltimore Class VI Retroviruses 205 8.1.1 Exogenous and endogenous retroviruses and their life‐cycles 205 8.1.2 Viral polyproteins 208 8.1.3 Retroviral genera 209 8.1.4 Endogenous gammaretroviruses of bats and other mammals 209 8.1.5 Betaretroviruses of bats and other mammals 210 8.2 Evidence of Ancient Endogenous Virus Genomic Elements in Bat Chromosomes 211 8.2.1 Endogenous bornavirus genomic elements in bat chromosomes 212 8.2.2 Endogenous Ebola and Marburg virus genomic elements in bat chromosomes 212 8.3 Hepadnaviruses – Baltimore Class VII Reverse‐Transcribing DNA Viruses 213 8.3.1 Human hepatitis B virus 213 8.3.2 Orthohepadnaviruses and bats 214 8.4 Large‐Scale Bat Virome Studies 215 8.4.1 Bat virome studies in North America 215 8.4.2 Bat virome studies in Europe 215 8.4.3 Bat virome studies in Asia and Southeast Asia 216 8.4.4 Bat virome studies in Oceania 217 8.5 Conclusions 217 References 218 III Bacterial Infections of Bats 221 9 ARTHROPOD‐BORNE BACTERIAL INFECTIONS OF BATS 223 9.1 Introduction 223 9.2 Bartonella 226 9.2.1 Bartonella in bats from Asia 226 9.2.2 Bartonella in bats from Africa 226 9.2.3 Bartonella in bats from Europe 228 9.2.4 Bartonella in bats from the Americas 228 9.3 Borrelia 229 9.4 Rickettsia 230 9.4.1 Rickettsia and human disease 230 9.4.2 Rickesttsia and bats 231 9.5 Bat Ectoparasites As Bacterial Vectors 231 9.5.1 Bacteria from bat flies 231 9.5.2 Bacteria from bat ticks 232 9.6 Conclusions 234 References 235 10 OTHER BACTERIA AND BATS 239 10.1 Introduction 239 10.2 Leptospira 245 10.2.1 Leptospira in South America 245 10.2.2 Leptospira in Africa 246 10.2.3 Leptospira in islands of the Indian Ocean 246 10.2.4 Leptospira in Australia 247 10.3 Yersinia 248 10.4 Pasteurella 249 10.5 Mycoplasma 250 10.6 Waddlia 250 10.7 Rickettsia and Similar Bacteria 251 10.8 Bat Gastrointestinal Tract Bacteria 251 10.8.1 Gastrointestinal bacteria in bats of Southeast Asia and Oceania 251 10.8.2 Gastrointestinal bacteria in bats of Madagascar 252 10.8.3 Gastrointestinal bacteria in bats of the Americas 253 10.9 Large‐Scale Studies of Other Bat Bacteria 254 10.10 Bacterial Species Beneficial to Bats 255 10.11 Conclusions 256 References 257 IV Protist Infections of Bats 261 11 APICOMPLEXANS AND BATS 263 11.1 Introduction to Apicomplexa and Coccidea 263 11.2 Order Haemosporida 269 11.2.1 Invertebrate hosts of Haemosporida 269 11.2.2 Bat hosts of Haemosporida 270 11.3 Order Piroplasmida 272 11.3.1 Babesia species and bats 272 11.3.2 Other Piroplasmida in bats 272 11.4 Order Eimeriida 273 11.4.1 Toxoplasma gondii and bats 273 11.4.2 Eimeria species and bats 276 11.5 Order Adeleida, Crytoporidium Species, and Bats 277 11.6 Conclusions 278 References 280 12 KINETOPLASTIDS AND BATS 285 12.1 Kinetoplastids 285 12.2 Trypanosomes 289 12.2.1 Life cycles of trypanosomes 289 12.2.2 Trypanosomes and disease 290 12.2.3 Trypanosomes infecting bats throughout the world 290 12.2.4 Trypanosoma cruzi 293 12.3 Leishmania 295 12.3.1 Leishmania and disease 295 12.3.2 Leishmania and bats 296 12.4 Conclusions 297 References 298 V Fungal Infections of Bats 303 13 WHITE‐NOSE SYNDROME AND BATS 305 13.1 Introduction to Pseudogymnoascus destructans 305 13.2 White‐Nose Syndrome 306 13.2.1 Arousal, loss of fat reserves, and dehydration 308 13.2.2 The role of torpor in WNS disease dynamics 309 13.2.3 WNS and wing damage 310 13.3 The Geographical Distribution of White‐Nose Syndrome 311 13.3.1 WNS in North America 311 13.3.2 WNS in Europe 312 13.3.3 WNS in Eastern Asia 313 13.4 The Effects of White‐Nose Syndrome on Selected North American Bat Populations 313 13.4.1 WNS and Myotis lucifugus 313 13.4.2 WNS and Myotis sodalis 314 13.5 The Bat Immune Response to White‐Nose Syndrome 315 13.5.1 Leukocyte counts 315 13.5.2 Antifungal activity in the plasma 315 13.5.3 T helper cell activity in infected bats 315 13.5.4 Inflammatory activity in infected bats 315 13.5.5 Differences in the immune response to WNS in European and North American bats 316 13.5.6 Immune‐mediated pathology in WNS 317 13.6 Antifungal Agents 317 13.6.1 Antifungal compounds 317 13.6.2 Antifungal agents derived from bacteria 318 13.6.3 Antifungal agents derived from fungi 318 13.7 The Mycobiome of White‐Nose Syndrome‐Infected Hibernacula 319 13.8 Recovery and Recolonization 320 References 321 14 HISTOPLASMA CAPSULATUM AND OTHER FUNGI AND BATS 327 14.1 Fungal Species and Bats 327 14.1.1 Histoplasma capsulatum 327 14.1.2 Blastomyces dermatitidis 336 14.1.3 Pneumocystis 337 14.1.4 Coccidioides 337 14.1.5 Encephalitozoon 337 14.1.6 Other fungi of bats 338 14.2 Broad Surveys of Fungi in Bats 338 14.2.1 Asia 338 14.2.2 Europe 338 14.2.3 The Americas 339 14.2.4 Fungi inhabiting bat external surfaces 340 14.3 Experimental Infection of Bats with Fungi 341 14.4 Immune Response to Fungi 341 14.5 Yeast in Bats 342 14.5.1 Candida 342 14.5.2 Malassezia 342 14.5.3 Yeasts in Japan 342 14.6 Conclusions 343 VI Zoonotic Disease Transmission and Bats 349 15 ZOONOTIC TRANSMISSION OF DISEASE BY BATS AND OTHER ANIMALS 351 15.1 Introduction 351 15.2 Zoonotic Transmission of Infection by Bats 353 15.2.1 Direct or indirect zoonotic transmission by bats to humans 354 15.2.2 Transmission and persistence of viruses within and among bat species over large geographical ranges 354 15.2.3 Seasonal changes contributing to zoonotic transmission from bats 355 15.3 Zoonotic Transmission of Infection by other Animal Species 356 15.3.1 Zoonotic transmission by rodents 357 15.3.2 Zoonotic transmission by companion animals 359 15.3.3 Zoonotic transmission by selected agricultural animals 360 15.4 Factors that Increase the Risk of Zoonotic Infection by Bats 362 15.4.1 Increasing urbanization of bats 362 15.4.2 Human activities that increase contact with bats, including the bushmeat trade 362 15.5 Strategies to Prevent Zoonotic Transmission from Bats to Humans or other Animals 363 15.6 Conclusions 364 References 366 Index 371

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Book SynopsisThe first guide to identifying and assessing changes following urologic surgerywith follow-up protocols What is the normal appearance of a kidney after radio frequency ablation of a tumor and what does a local recurrence look like? How does the urine flow down the ureters after a trans-uretero-ureterostomy? What is the normal appearance of the urinary tract after a cystoplasty? Most clinicians would be hard-pressed to provide answers to such fundamental questions concerning post-surgical anatomy and physiology, and equally challenged to find evidence-based information on the subject. Most of the literature in radiology and urologic surgery is orientated towards diagnosis and disease management. Although this often includes complications and outcomes, the clinician is often in the dark as to the anatomical and physiological changes that follow successful treatmentespecially in cases involving conservative or reconstructive surgery. To rectify this, the editors inTable of ContentsList of Contributors xiiiAcknowledgements xv Introduction 1 Christopher Woodhouse and Alex Kirkham 1 Subtotal Nephrectomy and Tumour Ablation 5 David Nicol, Alison Elstob, Christopher Anderson, and Graham Munneke Introduction 5 Procedures 5 Partial Nephrectomy 5 Early Imaging 6 Late Imaging 7 Ablative Therapies 10 Complications 13 Successful Tumour Ablation 14 Treatment Failure 15 Surveillance 18 Follow-up Imaging 18 Partial Nephrectomy 18 Ablative Therapies 19 Surveillance 19 Conclusions 19 References 20 2 Renal Transplantation 23 Rhana H. Zakri, Giles Rottenberg, and Jonathon Olsburgh Introduction 23 The Role of Ultrasound Imaging 23 Vascular Complications 23 Transplant Renal Artery Stenosis 23 Transplant Renal Vein Thrombosis 25 Transplant Renal Artery Thrombosis 26 Arteriovenous Fistula 27 Follow-up 27 Urological Complications 27 Ureteric Complications 28 Anastomotic Urinary Leak or Urinoma 28 Missed Duplex Transplant Ureter 29 Ureteric Stenosis 30 Transplant Ureteric Reflux 30 Bladder Complications 30 Urinary Fistulae 30 General Complications 31 Lymphocoeles 31 Renal Transplant Stone Disease 31 Renal Transplant Trauma 32 Oncological Complications 32 Transplant Renal Cell Carcinoma 32 Transplant Ureteric Transitional Cell Carcinoma 33 Conclusions 33 References 34 3 Imaging After Endo-urological Stone Treatment 37 Daron Smith and Clare Allen Introduction 37 The Procedures 37 Conservative Management 37 Ureteric Stones: Results and Complications 41 Extracorporeal shock wave lithotripsy 41 Ureteroscopy 41 Renal Stones: Results and Complications 44 Flexible Ureterorenoscopy 44 Percutaneous Surgery 46 Complications and Follow-up 48 Residual Fragments After ESWL, URS, FURS and PCNL 48 Radiation Exposure for Patients with Stones 53 References 54 4 Pelvi-ureteric Junction Reconstruction 57 Mohamed Ismail and Hash Hashim Introduction 57 Antenatal Hydronephrosis 57 Pathophysiological Effect of True Pelvi-ureteric Obstruction 58 Physiological and Anatomical Changes in the Kidney Following Pyeloplasty 59 Incidental PUJO in adults 61 Long-term Follow-up 62 Conclusions 63 References 64 5 Retroperitoneal Fibrosis 67 Paul Scheel and Bruce Berlanstein Introduction 67 Available Treatments 67 Medical Therapy 67 Surgical Treatment 69 Follow-up 70 Imaging 70 Stent Removal 70 Complications 71 Stent-related Complications 71 Hydrocoeles 73 Long-term Follow-up 73 Recurrent Disease 74 References 75 6 Urinary Diversion 77 Christopher Woodhouse and Alex Kirkham Introduction 77 The Procedures 77 Clinical Follow-up of Ileal Conduits 78 Postoperative Imaging 78 The ‘Loopogram’ 78 Ultrasound 81 Nephrostomy and Antegrade Imaging 83 Monitoring of Asymptomatic Patients 83 Management of Bacteriuria and Sepsis 84 References 85 7 Ureteric Reconstruction and Replacement 87 Christopher Woodhouse and Aslam Sohaib Introduction 87 Procedures 87 Stents and Nephrostomies 87 Uretero-pyelostomy 87 Uretero-calycostomy 88 Trans-uretero-ureterostomy 88 Ureteric Re-implantation 88 Autotransplantation 90 Intestine 90 Complex Lower Urinary Tract Reconstruction 90 Other Materials and Experimental Techniques 90 Clinical Follow-up and Complications 91 Stents and Nephrostomies 91 Reconstruction with Urothelium 94 Autotransplantation 95 Intestine 96 References 98 8 Conservative and Reconstructive Bladder Surgery 101 Pardeep Kumar Introduction 101 Extravasation 101 Bladder Perforation 101 Reconstruction Following Ureteric Injury and Partial Cystectomy 103 The Irradiated Bladder 106 Complications After Posterior Exenteration 106 Conclusions 107 References 107 9 Bladder Augmentation in Children 109 Paddy Dewan and Padma Rao Introduction 109 The Procedures 109 Augmentation with Ileum or Colon 109 Gastrocystoplasty 109 Seromuscular Cystoplasty 109 Auto-augmentation 110 Uretero-cystoplasty 110 Clinical Follow-up 111 Postoperative Imaging 113 Complications of Enterocystoplasty 115 Metabolic and Electrolyte Disorders 115 Stones 115 Perforation 117 Neoplastic Progression 118 Unique Complications of Gastrocystoplasty 119 Hypochloraemic Metabolic Alkalosis 119 Hypergastrinaemia 119 Haematuria-Dysuria Syndrome 120 Changes Over Time 120 References 121 10 Radiology and Follow-up of the Neobladder 125 Richard Hautmann and Bjoern G. Volkmer Introduction 125 The Procedure 125 Radical Cystectomy in Females 125 Radical Cystectomy in Males 125 The Neobladder 125 Postoperative Imaging 126 Clinical Follow-up 127 Clinical Examination 127 Bladder and Urine Investigations 128 Renal Investigations 128 Oncologic Follow-up Specific to the Neobladder 132 Local Recurrence 132 Secondary Tumour Growth in Urinary Diversions for Benign Disease 134 Complications 135 Complications up to 90 Days 135 Long-term Complications 135 Changes Over Time 136 Reservoir Control 136 Incontinence 136 Voiding Failure (Hypercontinence) 136 Metabolic Changes (see also Chapter 11) 138 References 138 11 General Consequences of Lower Urinary Tract Replacement and Reconstruction 141 Christopher Woodhouse and Alex Kirkham Introduction 141 Reservoirs 141 The Stomach 141 Ileum 141 Gastrointestinal Consequences 141 Storage Consequences 143 Colon 143 Gastrointestinal Consequences 143 Storage Consequences 143 Rectum 145 Continence (Mainz II) 146 Anastomotic Cancer 147 Urodynamic Findings 149 Stones 149 Renal Function 151 Perforation 151 Histological Changes 153 Infection 155 Neoplasia 156 Urine Testing for Pregnancy 157 The Conduit and Continence 157 References 158 12 Surgery on the Benign Prostate 163 Doug Pendse and Mark R. Feneley Introduction 163 Procedures 163 Outcomes and Complications 165 Postoperative Failure to Void 166 Continued Failure to Void or Unsatisfactory Voiding 166 Sexual Function 168 Incontinence 170 Stricture 170 Unexpected Malignancy 171 Changes Over Time 171 References 172 13 Imaging After Treatment of Prostate Cancer 177 Alex Kirkham Introduction 177 Appearances After Radical Prostatectomy 177 Residual Tumour After Radical Prostatectomy 179 The Prostate After Ablative Therapies 179 Early Appearances 180 Early Complications 181 Appearances at 2–5 Months 182 Appearances at 6 Months: Assessing Residual and Recurrent Tumour 182 Nuclear Medicine Studies 184 A Schedule for Follow-up 184 References 184 14 Urethroplasty 189 Simon Bugeja, Clare Allen, and Daniella E. Andrich Introduction 189 Pericatheter Urethrogram 189 Ascending and Descending Urethrography 190 Radiological Appearance After Different Types of Urethroplasty 191 Traumatic Strictures 192 Idiopathic Bulbar Strictures 193 Penile Urethroplasty 193 Use of Ultrasound in Urethroplasty Follow-up 194 Follow-up After Urethroplasty 196 Radiological Appearance and Surgical Management of Recurrent Strictures After Urethroplasty 197 References 198 15 The Postoperative Appearance and Follow-up of Urinary Tract Prostheses 201 Alex Kirkham Introduction 201 Penile Prostheses 201 Normal Appearance and Imaging Techniques 201 Problems of Positioning and Length 203 Artificial Urinary Sphincters 204 Disorders of Function and Position 205 InfectioninImplantedDevices 206 Metallic Stents 208 References 208 Index 211

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Book SynopsisTRANSPORTERS AND DRUG-METABOLIZING ENZYMES IN DRUG TOXICITY Explore up-to-date coverage on the interaction between drug metabolism enzymes, transporters, and drug toxicity with this leading resources Transporters and Drug-Metabolizing Enzymes in Drug Toxicity delivers a comprehensive and updated review of the relationship between drug metabolism, transporters, and toxicity, providing insights into a major challenge in drug development accurate assessment of human drug toxicity. Combining two disciplines frequently considered independently of one another, the book combines drug metabolism and toxicology with a focus on the role of biotransformation on drug toxicity and as a major factor for species and individual differences. Mechanism and species differences in drug metabolizing enzymes and transporters are discussed, as are the methods used to investigate the role of drug metabolizing enzymes and transporters in drug toxicity. Finally, the distinguTable of ContentsPreface xix List of Contributors xxi Part I Overview 1 1 Overview: Drug Metabolism, Transporter-Mediated Uptake and Efflux, and Drug Toxicity 3Albert P. Li 1.1 Drug Toxicity as a Challenge in Drug Development 3 1.2 Fate of an Orally Administered Drug 4 1.3 The Multiple Determinant Hypothesis for Idiosyncratic Drug Toxicity 5 1.4 Concluding Remarks 7 1.4.1 A Comprehensive Approach to Safety Evaluation in Drug Development 7 1.4.2 The Dose Makes the Poison – Paracelsus Updated 8 References 8 2 Transporter, Drug Metabolism, and Drug-Induced Liver Injury in Marketed Drugs 11Minjun Chen, Kristin Ashby, and Yue Wu 2.1 Introduction 11 2.2 Hepatic Metabolism 12 2.2.1 Phase I Metabolism 12 2.2.2 Phase II Metabolism 14 2.3 Reactive Metabolite Formation and Assessment 14 2.3.1 Metabolism and Reactive Metabolites 15 2.3.2 Dose and Reactive Mtabolites 16 2.3.3 Structural Alerts for Avoiding Reactive Metabolites 16 2.3.4 Experimental Approaches for Assessing Reactive Metabolites 18 2.3.4.1 Covalent Binding Assay 18 2.3.4.2 Electrophile Trapping Experiments 18 2.3.4.3 Time Dependent Inactivation of CYP450 Enzymes 19 2.4 Hepatic Transporters 20 2.5 Genetic Variants and Their Impact for Pharmacokinetic Behavior and Safety 24 2.5.1 CYP3A424 2.5.2 CYP3A526 2.5.3 CYP2D626 2.5.4 CYP2C927 2.5.5 CYP2C1927 2.5.6 CYP2B628 2.5.7 UGT1A128 2.5.8 NAT2 28 2.5.9 Hepatic Transporters 29 2.6 Summary 29 Acknowledgment 30 Disclaimer 30 References 30 3 Drug-Metabolism Enzymes and Transporter Activities as Risk Factors of Selected Marketed Drugs Associated with Drug-Induced Fatalities 41Albert P. Li 3.1 Introduction 41 3.2 Acetaminophen 41 3.2.1 Drug Metabolism and Toxicity 42 3.2.2 Transporters and Toxicity 42 3.2.3 Risk Factors 43 3.3 Cerivastatin 43 3.3.1 Drug Metabolism and Toxicity 43 3.3.2 Transporter and Toxicity 44 3.3.3 Risk Factors 44 3.4 Felbamate 45 3.4.1 Drug Metabolism and Toxicity 45 3.4.2 Transporters and Toxicity 46 3.4.3 Risk Factors 46 3.5 Flucloxacillin 46 3.5.1 Drug Metabolism and Toxicity 46 3.5.2 Transporters and Toxicity 47 3.5.3 Risk Factors 47 3.6 Nefazodone 47 3.6.1 Drug Metabolism and Toxicity 48 3.6.2 Transporters and Toxicity 48 3.6.3 Risk Factors 48 3.7 Obeticholic Acid 49 3.7.1 Drug Metabolism and Toxicity 49 3.7.2 Transporters and Toxicity 50 3.7.3 Risk Factors 50 3.8 Sitaxentan 50 3.8.1 Drug Metabolism and Toxicity 51 3.8.2 Transporters and Toxicity 51 3.8.3 Risk Factors 51 3.9 Sorivudine 52 3.9.1 Drug Metabolism and Toxicity 52 3.9.2 Transporters and Toxicity 52 3.9.3 Risk Factors 52 3.10 Tacrine 52 3.10.1 Drug Metabolism and Toxicity 54 3.10.2 Transporters and Toxicity 54 3.10.3 Risk Factors 54 3.11 Terfenadine 55 3.11.1 Drug Metabolism and Toxicity 55 3.11.2 Transporter and Toxicity 56 3.11.3 Risk Factors 56 3.12 Troglitazone (Rezulin®) 56 3.12.1 Drug Metabolism and Toxicity 57 3.12.2 Transporter and Toxicity 57 3.12.3 Risk Factors 58 3.13 Trovafloxacin 58 3.13.1 Metabolism and Toxicity 59 3.13.2 Transporters and Toxicity 59 3.13.3 Risk Factors 59 3.14 Conclusions 60 References 61 Part II Drug Metabolizing Enzymes and Drug Toxicity 79 4 Drug-Metabolizing Enzymes and Drug Toxicity 81Albert P. Li 4.1 Introduction 81 4.2 Drug-Metabolism Enzymes Involved in Metabolic Activation and Detoxification 81 4.3 Cytochrome P450 Monooxygenase (CYP) 82 4.3.1 CYP1A 82 4.3.1.1 Metabolic Activation 82 4.3.1.2 Drug Substrates 83 4.3.1.3 Inducers 83 4.3.1.4 Inhibitors 83 4.3.1.5 Individual Variations 83 4.3.1.6 Involvement in Drug Toxicity 83 4.3.2 CYP2A6 84 4.3.2.1 Substrates 84 4.3.2.2 Inducers 84 4.3.2.3 Inhibitors 84 4.3.2.4 Individual Variations 85 4.3.2.5 Involvement in Drug Toxicity 85 4.3.3 CYP2B6 85 4.3.3.1 Substrates 85 4.3.3.2 Inducers 86 4.3.3.3 Inhibitors 86 4.3.3.4 Individual Variations 86 4.3.3.5 Involvement in Drug Toxicity 86 4.3.4 CYP2C8 87 4.3.4.1 Substrates 87 4.3.4.2 Inducers 87 4.3.4.3 Inhibitors 87 4.3.4.4 Individual Variations 88 4.3.4.5 Involvement in Drug Toxicity 88 4.3.5 CYP2C9 88 4.3.5.1 Substrates 88 4.3.5.2 Inducers 88 4.3.5.3 Inhibitors 88 4.3.5.4 Individual Variations 89 4.3.5.5 Involvement in Drug Toxicity 89 4.3.6 CYP2C19 89 4.3.6.1 Substrates 89 4.3.6.2 Inducers 89 4.3.6.3 Inhibitors 89 4.3.6.4 Individual Variations 90 4.3.6.5 Involvement in Drug Toxicity 90 4.3.7 CYP2D6 90 4.3.7.1 Substrates 90 4.3.7.2 Inducers 90 4.3.7.3 Inhibitors 90 4.3.7.4 Individual Variations 90 4.3.7.5 Involvement in Drug Toxicity 91 4.3.8 CYP2E1 91 4.3.8.1 Substrates 91 4.3.8.2 Inducers 91 4.3.8.3 Inhibitors 91 4.3.8.4 Involvement in Drug Toxicity 91 4.3.9 CYP2J2 92 4.3.9.1 Substrates 92 4.3.9.2 Inhibitors 92 4.3.9.3 Inducers 92 4.3.9.4 Individual Variations 92 4.3.9.5 Involvement in Drug Toxicity 92 4.3.10 CYP3A 93 4.3.10.1 Substrates 93 4.3.10.2 Inducers 93 4.3.10.3 Inhibitors 93 4.3.10.4 Individual Variations 93 4.3.10.5 Involvement in Drug Toxicity 94 4.4 Non-P450 Drug-Metabolizing Enzymes 94 4.4.1 Flavin-Containing Monooxygenases (FMOs) 94 4.4.1.1 Substrates 94 4.4.1.2 Inducers 95 4.4.1.3 Inhibitors 95 4.4.1.4 Individual Variations 95 4.4.1.5 Involvement in Drug Toxicity 95 4.4.2 Monoamine Oxidase (MAO) 95 4.4.2.1 Substrates 96 4.4.2.2 Inducers 96 4.4.2.3 Inhibitors 96 4.4.2.4 Individual Variations 96 4.4.2.5 Involvement in Drug Toxicity 96 4.4.3 Alcohol Dehydrogenase (ADH) and Aldehyde Dehydrogenase (ALDH) 97 4.4.3.1 Substrates 97 4.4.3.2 Inducers 97 4.4.3.3 Inhibitors 97 4.4.3.4 Individual Variations 97 4.4.3.5 Involvement in Drug Toxicity 98 4.4.4 Aldehyde Oxidase (AOX) 98 4.4.4.1 Substrates 98 4.4.4.2 Inducers 98 4.4.4.3 Inhibitors 98 4.4.4.4 Individual Variations 99 4.4.4.5 Involvement in drug toxicity 99 4.4.5 Carboxylesterases (CESs) 99 4.4.5.1 Substrates 99 4.4.5.2 Inducers 99 4.4.5.3 Inhibitors 100 4.4.5.4 Individual Variations 100 4.4.5.5 Involvement in Drug Toxicity 100 4.4.6 N-Acetyltransferase (NAT) 100 4.4.6.1 Substrates 100 4.4.6.2 Inducers 100 4.4.6.3 Inhibitors 101 4.4.6.4 Individual Variations 101 4.4.6.5 Involvement in Drug Toxicity 101 4.4.7 Glutathione Transferase (GST) 101 4.4.7.1 Substrates 101 4.4.7.2 Inducers 102 4.4.7.3 Inhibitors 102 4.4.7.4 Individual Variations 102 4.4.7.5 Involvement in Drug Toxicity 102 4.4.8 Methyltransferase (MT) 103 4.4.8.1 Substrates 103 4.4.8.2 Inhibitors 103 4.4.8.3 Individual Variations 103 4.4.8.4 Involvement in Drug Toxicity 103 4.4.9 Uridine Glucuronosyltransferase (UGT) 103 4.4.9.1 Substrates 104 4.4.9.2 Inducers 104 4.4.9.3 Inhibitors 104 4.4.9.4 Individual Variations 104 4.4.9.5 Involvement in Drug Toxicity 104 4.4.10 Sulfotransferase (SULT) 105 4.4.10.1 Substrates 105 4.4.10.2 Inducers 105 4.4.10.3 Inhibitors 106 4.4.10.4 Individual Variations 106 4.4.10.5 Involvement in Drug Toxicity 106 4.5 Conclusions 106 References 107 5 Genetic Polymorphism of Drug-Metabolizing Enzymes and Drug Transporters in Drug Toxicity 139Ann K. Daly 5.1 Introduction 139 5.2 Drug-Induced Liver Injury 140 5.2.1 Background 140 5.2.2 Polymorphisms Affecting Drug Metabolism and DILI 140 5.2.2.1 Isoniazid 140 5.2.2.2 Diclofenac 146 5.2.2.3 Tolcapone 146 5.2.2.4 Ticlopidine 147 5.2.2.5 Efavirenz 147 5.2.2.6 Troglitazone 147 5.2.3 Polymorphisms Affecting Transporters and DILI 147 5.3 Drug-Induced Skin Injury and Related Hypersensitivity Reactions 149 5.4 Statin-Induced Myopathy 151 5.4.1 Background 151 5.4.2 Cytochromes P450 151 5.4.3 Transporters 152 5.5 Conclusions 154 References 154 6 Acyl Glucuronidation and Acyl-CoA Formation Mechanisms Mediating the Bioactivation and Potential Toxicity of Carboxylic Acid-containing Drugs 167Mark P. Grillo 6.1 Introduction 167 6.2 Phase II Metabolism 171 6.2.1 Glucuronidation 171 6.2.2 Acyl-CoA Thioester Formation 171 6.3 Chemical Stability of Phase II Metabolites 172 6.3.1 Acyl Glucuronide Instability 172 6.3.2 Acyl-CoA Thioester Stability 175 6.4 Phase II Metabolite Chemical Reactivity 176 6.4.1 Acyl Glucuronide Reactivity with Nucleophiles In vitro 176 6.4.2 Acyl-CoA Thioester Reactivity with Nucleophiles In vitro 180 6.5 Phase II Metabolite-Mediated Covalent Binding 183 6.5.1 Acyl Glucuronide-Mediated covalent Binding to protein 183 6.5.2 Acyl-CoA Thioester-Mediated Covalent Binding to Protein 185 6.6 Phase II Metabolite Prediction of Covalent Binding 187 6.6.1 Prediction of Covalent Binding to Protein by Acyl Glucuronides 187 6.6.2 Prediction of Covalent Binding to Protein by Acyl-CoA Thioesters 189 6.7 Studies Directly Comparing Carboxylic Acid Drug Bioactivation by Acyl Glucuronidation and Acyl-CoA Formation 190 6.8 Prediction of Drug-Induced Liver Injury for Carboxylic Acid Drugs 194 6.9 Conclusions 196 References 197 7 Liquid Chromatography-Mass Spectrometry (LC-MS) Quantification of Reactive Metabolites 207Qingping Wang and Chuang Lu 7.1 Introduction 207 7.2 LC-MS Methods Using GSH as a Trapping Reagent 209 7.2.1 LC-MS Approaches at Positive Mode Using Constant Neutral Loss (CNL) Scan or Enhanced Product Ion (EPI) Scan 209 7.2.2 LC-MS Approaches at Negative Mode Using Neutral Loss, Pre-Ion Scan (PIS) and XoPI (Extraction of Product Ion) 212 7.2.3 LC-MS Approaches Using Stable Isotopic-GSH 213 7.2.4 LC-MS Approaches Using Combined XoPI and Stable-Isotopic GSH 214 7.2.5 LC-MS Coupled with Software-Assisted Approach 218 7.2.6 Using GSH Derivatives as Trapping Reagents for Detection and Quantitation 219 7.3 Using Other Trapping Reagents 222 7.4 Identification and Characterization of Rearranged GSH Adducts 222 7.5 Strategies for Optimization and Decision Tree 224 7.6 Summary 226 Acknowledgment 227 Abbreviations 227 References 228 8 Human-Based In Vitro Experimental Approaches for the Evaluation of Metabolism-Dependent Drug Toxicity 235Albert P. Li 8.1 Introduction 235 8.2 Assays for Reactive Metabolites 235 8.2.1 Glutathione Trapping Assay 236 8.2.2 Covalent Binding Assay 236 8.3 Cell-Based Assays for Metabolism-Dependent Toxicity 237 8.4 Primary Human Hepatocyte Assays for Metabolism-Dependent Drug Toxicity 238 8.4.1 In Vitro Screening Assays for Hepatotoxicity 238 8.4.2 Cytotoxic Metabolic Pathway Identification Assay (CMPIA) 238 8.4.3 Metabolic Comparative Cytotoxicity Assay (MCCA) 241 8.4.4 MetMax™ Cryopreserved Human Hepatocytes (MMHH) Metabolic Activation Cytotoxicity Assay (MMACA) 242 8.5 Emerging Hepatocyte Technologies for the Evaluation of Drug Toxicity 242 8.5.1 Human Hepatocytes ROS/ATP Assay for DILI Drugs 242 8.5.2 Long-Term Hepatocyte Cultures 244 8.5.2.1 999Elite™ Long-Term Cultured Human Hepatocytes 244 8.5.2.2 Hepatocyte/Non-Hepatocyte Cocultures 244 8.5.2.3 Human Hepatocyte Spheroids 245 8.5.2.4 Microfluidic 3-Dimensional (3-d) Hepatocyte Cultures 245 8.6 Integrated Discrete Multiple Organ Coculture (IdMOC®) 247 8.7 Conclusion 249 References 251 Part III Drug Transporters and Drug Toxicity 261 9 Mechanism-Based Experimental Models for the Evaluation of BSEP Inhibition and DILI 263William A. Murphy, Chitra Saran, Paavo Honkakoski, and Kim L.R. Brouwer 9.1 Introduction 263 9.1.1 Drug-Induced Liver Injury 263 9.1.2 Bile Acid Homeostasis and Role of Bile Salt Export Pump 264 9.2 Membrane Vesicles to Study BSEP Inhibition 266 9.2.1 Membrane Vesicle Preparations 267 9.2.2 Membrane Vesicle Assays and Data Interpretation 268 9.3 Sandwich-Cultured Hepatocytes to Study BSEP Inhibition 270 9.3.1 B-CLEAR® Assay 270 9.3.2 Uptake and Efflux Studies with Mechanistic Modeling 273 9.4 Other In Vitro Methods to Study BSEP Inhibition 275 9.5 Computational Methods Used to Predict BSEP Inhibition 277 9.6 In Vitro Models as a Predictor of Clinical DILI 278 9.6.1 The C-DILI™ Assay 278 9.7 Preclinical In Vivo Models for the Evaluation of BSEP/Bsep Inhibition and DILI 279 9.8 In Vivo Clinical Biomarkers of BSEP Inhibition and DILI 282 9.8.1 Serum Bile Acids as Clinical Biomarkers 282 9.8.2 Clinical Biomarkers of DILI 283 9.9 Quantitative Systems Toxicology to Predict DILI 284 9.10 Conclusions 287 Funding Information 287 Conflict of Interest 288 Acknowledgments 288 Reference 288 10 Hepatic Bile Acid Transporters in Drug-Induced Cholestasis 307Tao Hu and Hongbing Wang Abbreviations 307 10.1 Introduction 308 10.2 Bile Acid and DIC 308 10.2.1 Bile Acid 309 10.2.1.1 Bile Acid Synthesis 309 10.2.1.2 Bile Acid Transport 310 10.2.2 Cytotoxicity of Bile Acids and DIC 310 10.3 Hepatic Bile Acid Uptake Transporters in DIC 312 10.3.1 Sodium-Taurocholate Cotransporting Polypeptide (NTCP) 312 10.3.1.1 Substrates of NTCP 314 10.3.1.2 Regulation of NTCP 315 10.3.1.3 NTCP and Cholestasis 316 10.3.2 Other Hepatic Bile Acid Uptake Transporters 317 10.4 Hepatic Bile Acid Efflux Transporters in DIC 317 10.4.1 Bile Salt Export Pump (BSEP) 318 10.4.1.1 Substrates of BSEP 318 10.4.1.2 Regulation of BSEP 319 10.4.1.3 Internalization of BSEP 321 10.4.1.4 BSEP and Cholestasis 321 10.4.2 Other Hepatic Bile Acid Efflux Transporters 323 10.4.2.1 MRP2 323 10.4.2.2 MRP3 and MRP4 324 10.5 Bidirectional Bile Acid Transporter OSTα/β 324 10.6 Summary 325 References 326 11 Role of Renal Transporters in Drug–Drug Interactions and Nephrotoxicity 339Yan Zhang and Donald Miller 11.1 Overview of Renal Transporters 339 11.1.1 Basolateral Transporters 340 11.1.2 Apical Transporters 341 11.2 Renal Transporters and Drug–Drug Interactions 343 11.2.1 Impact on the Pharmacokinetics of Drugs 344 11.2.2 Impact on the Drug PD 350 11.3 Renal Transporters and Nephrotoxicity 352 11.3.1 Nephrotoxicity Unrelated to Drug Transporters 353 11.3.2 Nephrotoxicity Related to Drug Transporters 355 11.4 Biomarkers and Nephrotoxicity 359 11.4.1 Biomarkers for Detecting Glomerular Injury 359 11.4.2 Biomarkers for Drug-Induced Injury to Proximal and Distal Tubules 361 11.5 Conclusion 362 References 365 12 Blood–Brain Barrier Transporters and Central Nervous System Drug Response and Toxicity 377Donald W. Miller, Stacey Line, Nur A. Safa, and Yan Zhang 12.1 Over-View of the Brain Barriers 377 12.1.1 Blood–Brain Barrier (BBB) 377 12.1.2 Blood–Cerebrospinal Fluid Barrier (BCSFB) 379 12.1.3 CSF as Predictor of Drug Exposure in the Brain 379 12.1.4 Solute Carriers in the BBB 380 12.1.5 Drug Efflux Transporters in the BBB 380 12.2 General Influence of BBB Transporters on Drug Entry into the Brain 383 12.3 BBB-Transporter Effects on CNS Drug Response 386 12.3.1 Influence of Efflux Transporters on Brain Disposition of Drugs 386 12.3.1.1 Anticancer Agents 386 12.3.1.2 Opioids 388 12.3.2 SLCs and BBB Transport of Drugs 391 12.4 Transporter Considerations Influencing CNS Drug Response 391 12.4.1 Transporter Polymorphisms 391 12.4.1.1 P-gp Polymorphism 391 12.4.1.2 BCRP Polymorphism 393 12.4.1.3 SLC Polymorphism 393 12.4.2 Age-Related Alterations in BBB Transporter Function and Drug Response 394 12.4.3 Disease-Dependent Modulation of BBB Transporters and Drug Response 395 12.4.3.1 Inflammation and Pain 395 12.4.3.2 Epilepsy 396 12.4.4 CNS Toxicity Caused by Drug Interactions at the BBB 398 12.5 Conclusions 400 References 401 13 Ototoxicity and Drug Transport in the Cochlea 413Stefanie Kennon-McGill and Mitchell R. McGill 13.1 Auditory System Anatomy 413 13.1.1 External, Middle, and Inner Ear 413 13.1.1.1 Anatomy of the Inner Ear 414 13.1.1.2 Hair Cell Anatomy 414 13.1.2 Blood–Labyrinth Barrier 415 13.2 Auditory System Physiology 416 13.3 Hearing Loss, Ototoxic Drugs, and Hair Cell Damage 416 13.3.1 Aminoglycosides 417 13.3.2 Platinum Chemotherapeutics 418 13.3.3 Salicylate 419 13.4 Drug Metabolism in the Ear 419 13.4.1 The Importance of Drug Metabolism in the Ear 419 13.4.2 Studies of Drug-Metabolizing Enzymes in Ototoxicity 420 13.4.3 Drug Transporters in the Ear 421 13.5 Conclusion 423 References 423 Part IV Modeling Drug Metabolizing Enzymes-Transporters Interplay for The Prediction of Drug Toxicity 427 14 Application of a PBPK Model Incorporating the Interplay Between Transporters and Drug-Metabolizing Enzymes for the Precise Prediction of Drug Toxicity 429Kazuya Maeda 14.1 Importance of the Consideration of Intracellular Concentration of Drugs in the Tissue for Estimation of Pharmacological/Toxicological Effects of Drugs 429 14.2 Extended Clearance Concept as a Tool to Explain Theoretically Transporter and Drug-Metabolizing Enzyme Interplay 431 14.3 Theoretical Consideration of the Intracellular Concentration of Drugs in the Tissue 433 14.4 The Benefits of Using a PBPK Model for the Accurate Prediction of Pharmacological/Toxicological Effects of Drugs 436 14.5 VCT to Simulate the Distribution of Clinical Outcomes in a Specific Population with Defined Mean and Variability of Parameters in a PBPK Model 440 14.5.1 VCT of Docetaxel to Estimate the Effects on the Risk of Neutropenia of Genetic Polymorphisms in OATP1B3 and MRP2 442 14.5.2 VCT of Oseltamivir and Its Active Metabolite (Ro 64-0802) to Estimate the Effects on Their Brain Exposure of Genetic Polymorphisms in Multiple Uptake/Efflux Transporters 444 14.5.3 VCT of Irinotecan and Its Metabolites to Estimate the Effects of Genetic Polymorphisms in Multiple Uptake/Efflux Transporters on Irinotecan-Induced Side Effects (Neutropenia, Diarrhea) 447 14.6 Conclusions and Future Perspectives 450 References 451 15 The Extended Clearance Model: A Valuable Tool For Drug-Induced Liver Injury Risk Prediction 455Birk Poller, Felix Huth, Vlasia Kastrinou-Lampou, Gerd A. Kullak-Ublick, Michael Arand, and Gian Camenisch 15.1 Introduction 455 15.2 Application of the ECM to Estimate Kpuu Liver 457 15.2.1 Introduction to the ECM: Concepts and Application for the Prediction of Hepatic Clearance and Drug–Drug Interactions 457 15.2.2 Concept of Kpuu Liver 460 15.2.3 Estimation of Kpuu Liver from In Vitro Data Using the ECM 461 15.3 Relevant Concentrations for the DILI Risk Assessment 462 15.3.1 Maximum Plasma Concentrations 464 15.3.2 Maximum Hepatic Inlet Concentrations 464 15.3.3 Maximum Intracellular Hepatocyte Concentrations 465 15.4 Assessing the DIC Risk Using ECM-Based Unbound Intrahepatic Concentrations and Accounting for BSEP Inhibition as a Single Mechanism 465 15.5 Assessing the DILI Risk Using the “1/R-Value Model” to Account for the Inhibition of Multiple Pathways 467 15.5.1 ECM-Based 1/R-Value Model 467 15.5.2 1/R vs Safety Margin Relationship 471 15.6 Discussion and Outlook 473 References 475 Index 481

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Book SynopsisHow to Complete a PhD in the Medical and Clinical Sciences provides fresh insight into the PhD process and a concise framework to aid current and prospective students undertaking research in the medical and clinical sciences.Trade Review‘Intended as a step-by-step guide, the book is a good summary of the major steps, pitfalls along the way, and advice on how to be successful as a student … There are not many books that attempt to do what this one does, and there is not much written about this topic in general, so students should find this a useful resource. Doing a PhD is often fraught with uncertainty, and a written guide to the steps would be helpful for most students, especially as they begin the program.’ Doody’s, November 2017'How to Complete a PhD in the Medical and Clinical Sciences aims (and succeeds) in remaining concise, it examines every aspect of the PhD journey in a comprehensive and precise manner. I would strongly recommend the book to anyone doing or planning to do a PhD in Medical, Clinical, Biomedical or Life Sciences. As well as, frankly, any other subject.' Kristine Bagdassarian, FindAPhD.com Table of ContentsList of contributors, xi About the editors, xv Foreword, xvii Preface, xix Acknowledgements, xxi Chapter 1: Introduction, 1Ashton Barnett-Vanes and Rachel Allen A PhD, 1 Perspective, 2 Why a book? How to use it, 5 References, 6 Chapter 2: Deciding on and finding a PhD, 7Jonathan C.H. Lau and Ming He Background, 7 Routes of entry, 8 How to find one, 11 Choosing a project, 13 Making an application, 16 Interviews, 17 How to fund one, 18 Reference, 22 Further reading, 22 Chapter 3: Anatomy of a PhD: Where you fit in the academic world, 23Laura Lambert and John Tregoning Background: Welcome to the new you, 23 You are here: PhD research versus undergraduate studies, 24 Lab types: A field guide, 25 It’s tricky: The student]supervisor interaction, 27 Check out my massive organogram, 28 Other dull, but important stuff, 29 Conclusion, 31 Reference, 32 Chapter 4: Core techniques, principles and statistics, 33Andrew John Walley, Kyrillos N Adesina Georgiadis, Adel Benlahrech and Fiona Reid Genomics, 33 Metabolomics, 38 Flow cytometry, 40 Statistics, 45 References, 49 Further reading, 49 Chapter 5: Take off: Year 1, 51Ashton Barnett Vanes and Rachel Allen Background, 51 Understanding your team and project, 52 The literature, 53 The research proposal, 55 Starting experiments, 56 Data management and record keeping, 57 The ‘transfer’, 58 Conclusion, 59 Common pitfalls, 59 Chapter 6: Dealing with problems, 63Rachel Allen and David Salman Background, 63 General problems, 64 Academic problems, 66 Common PhD problems, 69 Conclusions, 72 References, 73 Further reading, 73 Chapter 7: Breaking ground: Year 2, 75Ashton Barnett-Vanes and Rebecca Ingram Background, 75 Taking ownership of your project, 75 Shaping the research direction, 76 From preliminary to publishable data, 77 Supervising junior students, 79 The end of Year 2 review/assessment, 80 Conclusion, 82 Common pitfalls, 82 Chapter 8: Presenting and publishing as a PhD student, 85Ashton Barnett-Vanes and Henry D.I. De ’Ath Background, 85 Presentations, 85 How to present, 87 Publications, 89 Writing an original research article, 90 Writing a review article, 93 Narrative reviews, 95 Final steps, 95 Managing the process, 96 Other considerations, 98 Conclusion, 98 References, 98 Further reading, 98 Chapter 9: Landing and writing up: Year 3, 99Manu Chhabra and E. Allison Green Background, 99 An exit strategy, 99 The X Factor results, 100 Before you start writing, 101 Writing your thesis: Part 1, 102 Writing your thesis: Part 2, 105 Conclusion, 111 Common pitfalls, 111 Further reading, 112 Chapter 10: The viva and moving on, 113Rachel Allen and Kate Gowers Background, 113 An examiner’s perspective (Rachel), 113 The viva, 115 Corrections, 117 Career routes, 119 Conclusion, 123 Further reading, 123 Chapter 11: PhDs in veterinary science and medicine, 125Fiona Cunningham, Jonathan Elliott, Fiona Tomley and Kristien Verheyen Background, 125 Is it for me?, 126 Your project, 128 Presenting and publishing your findings, 130 Post]PhD, what’s next for me?, 131 Conclusion, 133 Possible concerns, 133 Acknowledgements, 134 Reference, 134 Chapter 12: International perspectives on medical and clinical science PhDs, 135Celia A. Soares and Paul Langford Background, 135 Choosing a country, 135 Finding a department, 136 ‘Full’ PhDs versus ‘dual]PhDs’, 137 Interviewing in a lab abroad, 139 Funding, 140 Administrative issues, 140 Conclusion, 143 Common pitfalls, 143 Further reading, 144 Chapter 13: What I’m really thinking: The post]doc, 145Adel Benlahrech Background, 145 It is great to be a post]doc!, 145 Is it really that great?, 146 A post]doc’s advice, 146 Conclusion, 149 Further reading, 149 Chapter 14: What I’m really thinking: The Professor, 151Michael Dustin Index, 153

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Book SynopsisTackling One Health from a multi-disciplinary perspective, this book offers in-depth insight into how our health and the health of every living creature and our ecosystem are all inextricably connected. Presents critical population health topics, written by an international group of experts Addresses the technical aspects of the subject Offers potential policy solutions to help mitigate current threats and prevent additional threats from occurring Table of ContentsList of Contributors xiii Foreword by Chadia Wannous and David Nabarro xvii Foreword by Lonnie King xix Preface xxi Section 1 The Science of One Health 1 1 Epidemiology: Science as a Tool to Inform One Health Policy 3Yvette J. Johnson]Walker and John B. Kaneene 1.1 Introduction 3 1.2 Enhancing Our Understanding of Health and Disease 5 1.2.1 Causes of Disease 5 1.2.1.1 Deterministic Models of Disease 6 1.2.1.2 Hill’s Causal Criteria 7 1.2.1.3 Multifactorial Models of Disease Causation 8 1.2.1.4 Breaking the Chain of Transmission 8 1.2.2 Assessing the Impact of Disease 10 1.2.3 Natural Course of Disease 13 1.2.3.1 Reservoirs of Disease 13 1.2.3.2 Humans as a Reservoir 14 1.2.3.3 Domestic Animal Reservoirs 14 1.2.3.4 Wildlife Reservoirs 17 1.2.3.5 Environmental Reservoirs 17 1.3 From Understanding Epidemiology to Public Policy 19 1.3.1 Assessments of Diagnostic Test Reliability 20 1.3.2 Determination of Safety and Effectiveness of New Treatments and Vaccines 20 1.3.3 Assessment of Health at the Level of the Individual, Community, or Ecosystem and Establish Standards of Care for Prevention and Treatment Protocols/Programs 21 1.3.4 Establishing Disease Response Regulations and Control Standards 22 1.4 Examples of the Benefits of Using a One Health Approach 23 1.4.1 Overall Summary of Practical Experiences Applying a One Health Approach 25 References 28 2 Health Impacts in a Changing Climate 31Donald J. Wuebbles 2.1 Introduction 31 2.2 Our Changing Climate 32 2.2.1 Climate Change Effects on Temperature 33 2.2.2 Climate Change Effects on Precipitation 34 2.2.3 Climate Change Effects on Severe Weather 37 2.3 The Basis for a Human Cause for Climate Change 41 2.4 Twenty]first Century Projections of Climate Change 43 2.5 Climate and Health 49 2.5.1 Temperature]Related Death and Illness 49 2.5.2 Air Quality Impacts 50 2.5.3 Vector]Borne Diseases 50 2.5.4 Water]Related Illnesses 52 2.5.5 Food Safety, Nutrition, and Distribution 52 2.5.6 Extreme Weather]Related Impacts 54 2.5.7 Mental Health and Well]being 54 2.5.8 Climate–Health Risk Factors and Populations of Concern 55 2.6 Summary and a Look Forward 55 References 56 3 Food Safety and Security 61Megin Nichols, Lauren Stevenson, Casey Barton Behravesh, and Robert V. Tauxe 3.1 Evolution of Food Production 61 3.2 Foodborne Illness 63 3.3 A One Health Approach to Foodborne Illness Detection and Response 68 3.4 Antibiotic Resistance and Food Safety 75 3.5 Zoonotic Disease and Foodborne Pathogens 78 3.6 Outbreak Response Communication 80 References 83 4 Water Security in a Changing World 89Jeffrey M. Levengood, Ari Hörman, Marja]Liisa Hänninen, and Kevin O’Brien 4.1 Introduction 89 4.2 Waterborne Pathogens and Contaminants : Technologies for Drinking Water Treatment and Management of Water Safety 90 4.2.1 Waterborne Pathogens 90 4.2.2 Antibiotic]Resistant Bacteria in Source and Drinking Water 91 4.2.3 Chemical Hazards in the Drinking Water 93 4.2.4 Pharmaceuticals in Wastewater and Raw Water Sources 93 4.2.5 Water Treatment Methods 93 4.2.5.1 Thermal Treatment 94 4.2.5.2 Chemical Disinfection 94 4.2.5.3 Filtration 95 4.2.5.4 Other Treatment Methods 96 4.2.6 Surveillance for Waterborne Diseases 96 4.2.7 Requirements for Drinking Water Quality 96 4.2.8 Water Safety Plans (WSPs) 97 4.3 The Water/Energy/Food Nexus: Mitigating Global Risks 99 4.3.1 Water/Energy Nexus 99 4.3.1.1 Nuclear 102 4.3.1.2 Coal 103 4.3.1.3 Natural Gas 103 4.3.1.4 Renewables 103 4.3.1.5 Water/Energy Nexus Summary 104 4.3.2 Water/Food Nexus 104 4.3.2.1 Water/Food Nexus Summary 107 4.3.3 Water/Energy/Food Nexus: Summary and Next Steps 107 Acknowledgments 108 References 108 5 One Toxicology, One Health, One Planet 115Daniel Hryhorczuk, Val R. Beasley, Robert H. Poppenga, and Timur Durrani 5.1 Introduction 115 5.1.1 History 115 5.1.2 Toxic Chemicals in Our Environment 117 5.1.3 One Toxicology 118 5.2 Key Concepts 120 5.2.1 Dose]Response Relationships 120 5.2.2 Differences in Susceptibility 120 5.2.3 Periods of Increased Susceptibility 122 5.2.4 Receptors 122 5.2.5 Toxicokinetics and Toxicodynamics 123 5.3 Ecotoxicology and Human Exposures 124 5.3.1 Everyday Toxicology and Ecotoxicology: Contrasts, Complexities, and Challenges 124 5.3.2 Toxicant Fate in the Environment 125 5.3.3 Contrasts in Feasibility: Examinations and Interventions 129 5.3.4 Indirect Effects of Chemicals 132 5.3.5 Direct Immunotoxicity and Indirectly Mediated Immunosuppression 137 5.3.6 Neurotoxicity 138 5.3.7 Endocrine Disruption 138 5.3.8 Reproductive and Developmental Toxicity 140 5.4 Toxicological Risk Assessment and One Health 141 5.4.1 Risk Assessment 141 5.4.2 Regulatory Toxicology 141 5.4.3 One Health and One Toxicology on One Earth 142 5.5 Conclusions 143 References 144 6 Biodiversity and Health 153Dominic A. Travis, Jonathan D. Alpern, Matteo Convertino, Meggan Craft, Thomas R. Gillespie, Shaun Kennedy, Cheryl Robertson, Christopher A. Shaffer, and William Stauffer 6.1 Introduction 153 6.2 Connectivity 155 6.2.1 Biodiversity as an Indicator of Health 155 6.2.2 Social Factors 158 6.3 Grand Challenges, Development Goals, Global Health Security, and Ecosystem Health 159 6.3.1 The Case of Agriculture, Food Security, and Biodiversity 161 6.3.2 The Case of Wildlife Trade, Bushmeat, and Biodiversity 162 6.3.3 The Case of Infectious Diseases and Biodiversity 165 6.3.4 The Case of Climate Change, Conflict, and Human and Animal Migration 166 6.4 Conclusions and a Way Forward 168 6.4.1 The Application of Complexity Science and Technology Tools to Optimize Health and Environmental Outcomes 168 References 170 7 Emerging Infectious Diseases: Old Nemesis, New Challenges 177Ronald C. Hershow and Kenneth E. Nusbaum 7.1 Introduction 177 7.2 Rabies 180 7.2.1 Natural History 180 7.2.2 The Epizoology of Rabies Virus 181 7.2.3 Global Burden 181 7.3 Avian Influenza 182 7.3.1 Natural History 182 7.3.2 Recent Outbreaks 183 7.4 Zika Virus 186 7.5 Ebola Virus Disease (EVD) 188 7.6 Summary 189 Acknowledgments 190 References 190 8 Reigning Cats and Dogs: Perks and Perils of Our Courtship with Companion Animals 195Sandra L. Lefebvre and Robert V. Ellis 8.1 Introduction 195 8.2 Benefits and Hazards of Human]Pet Relationships 197 8.2.1 Physical and Mental Health 197 8.2.1.1 Impacts on Humans 197 8.2.1.2 Impacts on Pets 200 8.2.2 Overweight and Obesity 202 8.2.3 Feeding Practices and Illness 203 8.2.3.1 Human Illness Related to Pet Feeding Practices 203 8.2.3.2 Pet Illness Related to Feeding Practices 205 8.2.4 Infectious Disease Transmission 206 8.2.4.1 Companion Animal]to]Human Transmission 206 8.2.4.2 Human]to]Companion Animal Transmission 216 8.2.5 Pets, People, and Antimicrobial Resistance 216 8.2.6 Social and Community Health 221 8.2.7 Domestic Health and Violence 223 8.3 Interactions Among Humans, Pets, and the Environment 223 8.3.1 Working Dogs 223 8.3.2 Environmental Toxicants 224 8.3.3 Pets and the External Environment 225 8.3.4 Disaster Preparedness 227 8.3.5 Climate Change 228 8.3.6 Zoonotic Disease Surveillance for Both People and Pets 228 8.4 Conclusion 229 Disclaimer 230 References 230 9 Zoological Institutions and One Health 243Thomas P. Meehan and Yvonne Nadler 9.1 Introduction 243 9.2 Zoos, Aquariums, and Field Conservation 243 9.3 Zoos, Aquariums, and the Care of Animals 244 9.4 Social Aspects of Zoos and Aquariums 245 9.5 Zoonotic Disease Challenges: Protecting Visitors, Staff, and Animals 246 9.6 Case Studies in One Health from Zoological Institutions 249 9.6.1 West Nile Virus: A Case Study for the One Health Paradigm 249 9.6.1.1 Emergence of West Nile Virus in North America 249 9.6.1.2 Centers for Disease Control: ArboNET 250 9.6.1.3 A Failure of Early Coordination 251 9.6.1.4 Lessons Learned from the West Nile Virus Outbreak, 1999 252 9.6.1.5 Zoological Institutions as Forerunners to the ‘One Health’ Paradigm 253 9.6.1.6 Zoological Parks as Sentinels for Human Disease 253 9.6.1.7 A Model for Sentinel Surveillance: The Zoological WNV Surveillance Project 254 9.6.1.8 Lessons Learned from the Zoological WNV Surveillance Project 254 9.6.1.9 The Role of Zoological Institutions in Preparing for Pandemics 255 9.6.2 The Emergence of Highly Pathogenic Avian Influenza Virus, 1999 255 9.6.2.1 Consequences of HPAI Detection in a Zoological Institution 256 9.6.2.2 The Association of Zoos and Aquariums Prepares for HPAI 257 9.6.2.3 Lessons Learned from HPAI Surveillance System 258 9.7 Conclusion 259 References 260 Section 2 Four Perspectives on One Health Policy 265 10 One Health Leadership and Policy 267William D. Hueston, Ed G.M. van Klink, and Innocent B. Rwego 10.1 Introduction and Definitions 267 10.2 Grand Challenges in Health (aka “Wicked Problems”) 267 10.3 Implications of Grand Challenges for One Health Leadership 268 10.4 Critical Competencies for One Health Leadership 268 10.5 Policy]Making with One Health in Mind 269 10.6 Integrating One Health Leadership Approaches in Hierarchical Organizations 270 10.7 Demonstrating One Health Leadership and Policy in Action 271 10.8 Case Study 1: National One Health Policy Development in Cameroon and Rwanda 272 10.8.1 Cameroon 272 10.8.2 Rwanda 272 10.9 Case Study 2: The Campaign for Global Elimination of Dog]Mediated Human Rabies 273 10.10 Case Study 3: Antimicrobial Resistance – USA 274 References 276 11 Implementing One Health 277Laura H. Kahn 11.1 Financing One Health Initiatives 277 11.2 Conclusion 279 References 279 12 The Social Cost of Carbon 281William J. Craven 12.1 Introduction 281 12.2 Some Context on Cost]Benefit Analyses 282 12.3 The Social Cost of Carbon (SCC) 282 12.3.1 Looking at Costs 283 12.3.2 Getting the SCC as Good as it Can Get 285 12.4 Current Challenges to Reducing and Mitigating the Effects of Climate Change 287 References 288 13 Complex Problems, Progressive Policy Solutions, and One Health 291John A. Herrmann 13.1 One Health as Prevention 291 13.1.1 Successes 291 13.1.2 Failures 292 13.2 Translating Science: Risk Communication and Science Literacy 293 13.2.1 Communication of Science 294 13.2.2 Liberal Education and the Sciences 295 13.2.3 Community Empowerment and Participatory Democracy 299 13.3 The Economics of One Health 300 13.4 From Here to There 302 References 302 Section 3 Conclusion 305 14 The Long and Winding Road 307John A. Herrmann and Yvette J. Johnson]Walker 14.1 One Health: Many Facets, All Interrelated 307 14.2 One Health Policy Development 310 14.2.1 Policy Basics and Challenges to Enacting One Health]based Policies 310 14.2.2 Microeconomic One Health Dilemmas 311 14.2.3 One Health Research in Emerging Infectious Diseases: Macroeconomic Dilemmas 312 14.2.4 The Long and Winding Road Forward 313 References 321 Index

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Book SynopsisThis updated edition of Painless Evidence-Based Medicine presents basic concepts and application of research statistics in simple and practical manner creating an introductory approach to the complex and technical subject of evidence-based medicine from experienced teachers. A simplified introductory approach to the complex and technical subject of evidence-based medicine from experienced teachers Approaches learning from the vantage point of clinical questions on therapy, diagnosis, prognosis or harm rather than the framework of study designs Provides tables and boxed case studies throughout highlighting key topics, or difficult issues, in an easy to read manner Emphasizes applicability of EBM, encouraging readers to dissect the evidence and how results can be applied to individual patients with different circumstances, varying values and preferences New to the Second Edition are chapters on health screening, clinical practice Table of ContentsList of Contributors vii Foreword to the First Edition xi Foreword to the Second Edition xvii Preface xix 1 Introduction 1 2 Evaluation of Articles on Therapy 12 3 Evaluation of Articles on Diagnosis 38 4 Evaluation of Articles on Harm 58 5 Evaluation of Articles on Prognosis 74 6 Evaluation of Systematic Reviews 87 7 Evaluation of Clinical Practice Guidelines 100 8 Evaluation of Articles on Health Screening 112 9 Literature Searches 122 Index 139

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Book SynopsisWritten to help haematology and general medical trainees evaluate their own knowledge, and particularly useful for those preparing for the Part 1 examination of the Royal College of Pathologists.Trade ReviewThere may be other haematologists in the world who can write detailed single best answer and extended matching questions (SBAs, EMQs)...but I doubt that any one individual can do it as well as Barbara Bain. All questions are well-written, well-researched and include some of the very latest diagnostic and therapeuticadvances... The feedback explaining the reasons for the correct answers is excellent and educational.And that is the point. This book will be a fantastic educational resource for trainees across the world but also for consultants like me who want to update their knowledge in an interactive manner. Just one health warning. Many of these questions are difficult, so no one should expect to get all the answers correct....Recommended for trainees and consultant haematologists without reservation. (British Journal of Haematology, 2016)Table of ContentsPreface vii Normal Ranges and Abbreviations ix Section 1: Single Best Answers Questions 1–50 1 Section 2: Single Best Answers Questions 51–120 29 Section 3: Extended Matching Questions 1–30 67 Section 4: Single Best Answers Answers to Questions 1–120 with Feedback 101 Section 5: Extended Matching Questions Answers and Feedback 155 Index 187

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Book SynopsisTable of ContentsPreface xvi Abacacavir (Ziagen) 435 Abacavir + Lamivudine + Dolutegravir (Triumeq) 381 Acyclovir (Zovirax) 442 Adefovir (Hepsera) 187 Albendazole (Albenza) 3 Amikacin (Amikin) 9 Amoxicillan 11 Amoxicillin-Clavulanate (Augmentin, Augmentin 600ES, Augmentin XR) 32 Amphotericin B (Fungizone) 169 Amphotericin B Colloidal Dispersion – ABCD (Amphotec) 13 Amphotericin B Lipid Complex (Abelcet) 1 Ampicillin 15 Ampicillin-Sulbactam (Unasyn) 394 Anidulafungin (Eraxis) 149 Artemether/Lumefantrine (Coartem) 92 Artesunate 27 Atazanavir (Reyataz) 317 Atazanavir + Cobicistat (Evotaz) 152 Atovaquone (Mepron) 240 Atovaquone/Proguanil (Malarone) 230 Azithromycin (Zithromax, Zmax) 437 Aztreonam (Azactam) 40 Bedaquiline (Sirturo) 337 Benznidazole 51 Bithionol (Bitin) 57 Capreomycin (Capastat) 62 Caspofungin (Cancidas) 60 Cefaclor 66 Cefadroxil (Duricef) 135 Cefamandole (Mandol) 232 Cefazolin (Ancef) 18 Cefdinir (Omnicef) 270 Cefditoren Pivoxil (Spectracef) 343 Cefepime (Maxipime) 234 Cefixime (Suprax) 357 Cefotaxime (Claforan) 87 Cefotetan (Cefotan) 70 Cefoxitin (Mefoxin) 256 Cefpirome (Broact, Cefir, Cefrom, Keiten) 58 Cefpodoxime (Vantin) 406 Ceftaroline fosamil (Teflaro) 365 Ceftazidime (Tazicef, Fortaz ) 165 Ceftazidime and avibactam (Avycaz) 38 Ceftibuten (Cedax) 64 Ceftizoxime (Cefizox) 68 Ceftolozane and Tazobactam (Zerbaxa) 433 Ceftriaxone (Rocephin) 329 Cefuroxime (Zinacef, Ceftin) 72 Cephalexin (Keflex) 212 Chloramphenicol (Chloromycetin) 78 Chloroquine Phosphate (Aralen) 24 Cidofovir (Vistide) 425 Ciprofloxacin (Cipro) 83 Clarithromycin (Biaxin) 52 Clindamycin (Cleocin) 89 Clofazimine (Lamprene) 220 Cobicistat (Tybost) 390 Colistimethate Sodium (Coly-Mycin) 96 Cycloserine (Seromycin) 335 Daclatasvir (Daklinza) 112 Dalbavancin (Dalvance) 114 Dapsone 116 Daptomycin (Cubicin) 107 Darunavir (Prezista) 293 Darunavir + Cobicistat (Prezcobix) 290 Dasabuvir + Ombitasvir + Paritaprevir + Ritonavir (Viekira Pak) 415 Delamanid (Deltyba) 120 Dicloxacillin 124 Diethyl carbamazine/DEC (Hetrazan) 189 Dolutegravir (Tivicay) 375 Doripenem (Doribax) 130 Doxycycline (Vibramycin, Doryx) 132 Efavirenz (Sustiva) 359 Eflornithine (Ornidyl) 274 Elbasvir and Grazoprevir (Zepatier) 431 Elvitegravir (Vitekta) 427 Emtricitabine (Emtriva) 141 Enfuvirtide (Fuzeon) 174 Entecavir (Baraclude) 45 Ertapenem (Invanz) 201 Erythromycin 150 Ethambutol Hydrochloride (Myambutol) 248 Ethionamide (Trecator) 379 Etravirine (Intelence) 196 Famciclovir (Famvir) 157 Fidaxomicin (Dificid) 126 Fluconazole (Diflucan) 127 Flucytosine (Ancobon) 21 Fosamprenavir (Lexiva) 227 Foscarnet (Foscavir) 167 Fosfomycin (Monurol) 246 Ganciclovir Capsules and IV (Cytovene) 106 Gemifloxacin (Factive) 155 Gentamicin (Garamycin) 176 Griseofulvin (Grifulvin V, Grisovulvin, Gris-Peg) 183 Hydroxychloroquine Imipenem-Cilastatin Sodium (Primaxin) 299 Interferon Alpha (Infergen, Intron A) 193 Iodoquinol (Yodoxin) 429 Isavuconazole (Cresemba) 105 Isoniazid 205 Itraconazole (Sporanox) 345 Ivermectin (Stromectol) 353 Kanamycin (Kantrex) 210 Ketoconazole 214 Lamivudine (Epivir) 145 Lamivudine plus Abacavir (Epzicom) 147 Ledipasvir + Sofosbuvir (Harvoni) 185 Levofloxacin (Levaquin) 224 Linezolid (Zyvox) 445 Liposomal Amphotericin B (Ambisome) 7 Lopinavir/Ritonavir (Kaletra) 207 Maraviroc (Selzentry) 333 Mefloquine Hydrochloride (Lariam) 222 Meglumine Antimonite (Glucantime) 182 Melarsoprol B (Mel-B) 238 Meropenem (Merrem) 242 Metronidazole (Flagyl) 159 Micafungin (Mycamine) 250 Miltefosine (Impavido) 191 Minocycline (Minocin, Dynacin) 137 Moxifloxacin (Avelox) 35 Nafcillin 255 Neomycin (Neo-Fradin, Neomycin) 259 Nevirapine (Viramune) 418 Niclosamide (Yomesan) 430 Nifurtimox (Lampit) 219 Nitazoxanide (Alinia) 5 Nitrofurantoin (Furadantin, Macrobid, Macrodantin) 172 Ofloxacin (Floxin) 162 Ombitasvir + Paritaprevir + Ritonavir (Technivie) 363 Oritavancin (Orbactive) 272 Oseltamivir (Tamiflu) 361 Oxacillin 275 Oxamniquine (Vansil) 405 Para-aminosalicylate Sodium (Paser) 277 Peginterferon alpha-2a (Pegasys) 279 Peginterferon alpha-2b (Pegintron) 282 Penicillin (Benzathine Penicillin, Penicillin G, Penicillin V, Procaine Penicillin) 47 Pentamidine (NebuPent, Pentam) 257 Peramivir (Rapivab) 311 Piperacillin (Pipracil) 285 Piperacillin-Tazobactam (Zosyn) 440 Polymixin B Sulfate (Polymixin B) 288 Posaconazole (Noxafil) 264 Praziquantel (Biltricide) 55 Primaquine Phosphate (Primaquine) 298 Pyrantel Pamoate (Antiminth) 23 Pyrazinamide 304 Pyrimethamine (Daraprim) 118 Quinacrine HCl (Atabrine) 28 Quinidine 306 Quinine 308 Raltegravir (Isentress) 203 Ribavirin inhaled (Virazole) 421 Ribavirin oral (Copegus, Rebetol, Ribasphere) 102 Rifabutin (Mycobutin) 252 Rifampin (Rifadin) 320 Rifampin + Isoniazid (Rifamate) 323 Rifampin + Isoniazid + Pyrazinamide (Rifater) 326 Rifapentine (Priftin) 296 Rifaximin (Xifaxan) 427 Rilpivirine (Edurant) 139 Ritonavir (Norvir) 261 Simeprevir (Olysio) 268 Sofosbuvir (Sovaldi) 341 Sofosbuvir + Velpatasvir (Epclusa) 143 Spectinomycin (Trobicin) 387 Spiramycin (Rovamycine) 331 Stibogluconate (Pentostam) 284 Streptomycin 348 Sulfadiazine 355 Suramin Sodium (Germanin) 181 Tedizolid (Sivextro) 339 Telavancin (Vibativ) 413 Telbivudine (Tyzeka) 392 Tenofovir + Emtricitabine + Elvitegravir + Cobicistat (Stribild) 350 Tenofovir + Emtricitabine + Rilpivirine (Complera) 100 Tenofovir Alafenamide + Emtricitabine (Discovy) 122 Tenofovir Alafenamide + Emtricitabine + Elvitegravir + Cobicistat (Genvoya) 178 Tenofovir Alafenamide+ Emtricitabine + Rilpivirine (Odefsey) 266 Tenofovir Alafenamide fumarate (TAF) (Vemlidy) 408 Tenofovir and Emtricitabine (Truvada) 388 Tenofovir Disoproxil Fumarate (Viread) 423 Tenofovir/Emtricitabine/Efavirenz (Atripla) 29 Terbinafine (Lamisil) 217 Tetracycline Hydrochloride 367 Thiabendazole (Mintezole) 244 Ticarcillin-Clavulanate (Timentin) 371 Tigecycline (Tigacyl) 369 Tinidazole (Tindamax) 373 Tobramycin 377 Trimethoprim (Proloprim) 302 Trimethoprim/Sulfamethoxazole (Bactrim, Septra) 42 Valacyclovir (Valtrex) 399 Valganciclovir (Valcyte) 396 Vancomycin-Intravenous 403 Vancomycin-PO (Vancocin) 401 Voriconazole (Vfend) 410 Zanamivir (Relenza) 313 Zidovudine (Retrovir) 315 Zidovudine plus Lamivudine (Combivir) 98 Zidovudine, Lamivudine, and Abacavir (Trizivir) 384 Helpful Formulas, Equations, and Definitions 449 Selected Antimicrobial Toxicities 450 Selected Antimicrobial Coverage 453 Bibliography and References 456

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Book SynopsisWritten by experienced and well-respected physicians and professors, this new all-color volume presents the ultrasonic topographical and pathotopographical anatomy of the body, including the head, neck, chest, anterolateral abdominal wall, abdominal organs, retroperitoneal space, male and female pelvises, and lower extremities. Specific and non-specific ultrasonic symptoms are suggested for normal and abnormal developmental variants, diffuse and local pathotopographical anatomy. This color atlas contains comparative topographical and pathotopographical data and is the first manual of its kind for students and medical specialists in different areas, including those specializing in medical sonography. The original technology was tested at clinics in patients subjected to ultrasonic monitoring. Because of early detection there were no false-positive or false-negative results. The therapy was effective, and, in some cases, the use of the original method of seagalography (optometrTable of ContentsAbstract v Preface ix About the Authors xi Topography and Pathotopography of the Head 1 Topography and Pathotopography of the Neck 23 Topographical and Pathotopographical Anatomy of the Chest 41 Topographical and Pathotopographical Anatomy of the Abdomen 59 Topographical and Pathotopographical Anatomy of the Retroperitoneal Space 89 Topography and Pathotopography of the Pelvis 101 Topography and Pathotopography of Lower Extremity 121 Conclusion 151

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Book SynopsisWritten by an international team of authors specializing in microbiology and infectious disease, this new edition of Evidenced-based Infectious Diseases presents practical, up-to-date information on the care of individual patients suffering from infectious diseases. Each chapter addresses a series of focused clinical questions addressed in a systematic fashion, including a comprehensive literature search, and a rating of the quality of evidence using principles of the GRADE framework. Evidence-Based Infectious Diseases is the ideal reference work for all those involved with microbiology, infectious diseases, and clinical management.Table of ContentsList of Contributors vii Preface xi 1 Introduction to Evidence‐based Infectious Diseases 1Dominik Mertz, Nick Daneman, and Fiona Smaill Part 1 Specific Diseases 11 2 Skin and Soft‐tissue Infections 13Douglas Austgarden and Guilio DiDiodato 3 Bone and Joint Infections 23Nora Renz and Andrej Trampuz 4 Infective Endocarditis 37Bahareh Ghadaki and Deborah Yamamura 5 Meningitis and Encephalitis 53Christopher E. Kandel and Wayne L. Gold 6 Community‐acquired Pneumonia 73Mark Downing and Jennie Johnstone 7 Healthcare‐associated Pneumonia 81Jennie Johnstone and Mark Downing 8 Tuberculosis 87Peter Daley and Marek Smieja 9 Clostridium Difficile Infection in Adults 99Louis Valiquette 10 Urinary Tract Infections 107Thomas Fekete 11 Sexually Transmitted Infections 127Courtney A. Thompson, Darrell H. S. Tan, and Kaede Sullivan 12 Human Immunodeficiency Virus (HIV) 149Ali Amini, Monique Andersson, Ravindra Gupta, and Brian Angus 13 Hepatitis 181Lise Bondy and Michael S. Silverman 14 Influenza 193Ashley Roberts and Joanne M. Langley 15 Critical Care 201Bram Rochwerg and Jocelyn A. Srigley Part 2 Special Populations 215 16 Infection Prevention and Control 217Graham M. Snyder and Eli N. Perencevich 17 Antimicrobial Stewardship 235Alainna J. Jamal and Andrew M. Morris 18 Infections in Neutropenic Hosts 251Eric J. Bow 19 Infections in General Surgery 269Paul A. Moroz and Christine H. Lee 20 Infections in Healthcare Workers 279Gregory W. Rose Index 287

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Book SynopsisEMERGENCY MANAGEMENT OF THE HI-TECH PATIENT IN ACUTE AND CRITICAL CARE Emergency Management of the Hi-Tech Patient in Acute and Critical Care helps practitioners stabilize and care for pediatric and adult patients who have specialized medical devices such as prosthetic valves, cochlear transplants, insulin pumps, orthopedic hardware, and ventriculoperitoneal (VP) shunts. Using a step-by-step approach to acute presentations of patients with clinical hardware, this concise yet comprehensive guide provides specific instructions for the initial evaluation and management of numerous clinical scenarios including device malfunctions, infections, trauma, surgical complications, and more. Encompassing management of both the patient and the device, the guide enables emergency and critical care clinicians to rapidly make appropriate treatment decisions without the immediate need for extensive research, extended discussions with subspecialists, or recalling complex diagnostic aTable of ContentsList of Contributors ix Preface xv Acknowledgments xvii Section I Gastro-intestinal Devices 1 1 Using and Troubleshooting Enteral Feeding Devices 3Courtney E. Nelson and Thane A. Blinman 2 Gastrointestinal Diversions: Colostomies, Ileostomies, Mucous Fistulas, and Spit Fistulas 21Ellen G. Szydlowski and Peter Mattei 3 Management of the Bariatric Surgery Patient in the Emergency Department 27Megan Lavoie and Joy Collins 4 Transjugular Intrahepatic Portosystemic Shunt 37Heather House and Anne Marie Cahill Section II Central Catheters 43 5 Indwelling Central Venous Catheter Devices 45Anna Weiss 6 Vascular Access for Hemodialysis 57Sarah Fesnak, Xenia Morgan, and Kimberly Windt 7 Peritoneal Dialysis Catheters 63Jamie Lovell Section III ENT and OMFS Devices 71 8 Orthopedic Devices 73Carmelle Wallace, Andrew Tyler, and Keith D. Baldwin 9 Spine Devices 95Susan E. Nelson and Keith D. Baldwin 10 Facial Distractors: Cranial Vault, Midface, and Mandibular 109Francesca Drake and Phuong D. Nguyen 11 Management of Facial Fractures in Adults and Children 117Sameer Shakir and Phuong D. Nguyen 12 Cranial Orthotics and Ear Molding 129Meg Ann Maguire and Phuong D. Nguyen 13 Ear, Nose, and Throat Devices 137Eva Delgado and Adva Buzi Section IV CNS Devices 157 14 Cerebral-ventricular Shunts 159Panagiotis Kratimenos, Angela Burd, and Chima Oluigbo 15 Initial Evaluation and Management of Patients with Neurosurgical Devices 169Peter J. Madsen, Chariton Moschopoulos, and Benjamin C. Kennedy Section V Miscellaneous Devices 183 16 Ophthalmic Devices 185Marlet Bazemore and William P. Madigan 17 Breast Implants 189R. Jason VonDerHaar and Liza C. Wu 18 Cutaneous Delivery Systems/Patches 203Desiree M. Seeyave 19 Dental Emergencies Involving Oral Hardware 209Chisom O.A. Agbim and Ioannis Koutroulis Section VI Wound Management Devices 215 20 Emergency Management of Patients with Negative Pressure Wound Therapy Devices (NPWTD) 217David Yamane and Tenagne Haile-Mariam 21 Emergency Management of Patients with Wound Infections 233David Yamane and Tenagne Haile-Mariam Section VII GU Devices 235 22 Emergency Management of Patients with Genitourinary Prostheses 237Katie Wagner, Michael Phillips, and Kelly Chiles Section VIII Cardiac Devices 245 23 Management of Prosthetic Valve Complications 247Massoud Kazzi and Guenevere V. Burke 24 Emergency Management of Patients with Vascular Occlusion Devices, Stents, or Filters 257Amy Caggiula 25 The Emergency Department Approach to the Patient with an Implantable Mechanical Circulatory Support Device 267Robert Shesser 26 Emergency Management of the Patient with an Implantable Pacemaker or Defibrillator 277Michael J. O’Neal Section IX Pulmonary Devices 289 27 Invasive Ventilation: A Discussion of Equipment and Troubleshooting 291Pelton A. Phinizy, Joseph J. Bolton, and John F. Tamasitis 28 Respiratory Medication Devices 313Natalie Napolitano and James B. Fink 29 Secretion Clearance Devices 325Amanda J. Nickel, Daniel Dawson, and Oscar H. Mayer 30 Non-invasive Ventilation 337Oscar H. Mayer and Anthony Mozzone 31 Tracheostomy Tubes 347Joanne Stow, Allison E. Boyd, and Jerry Cabrera Index 373

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Book SynopsisThe Union for International Cancer Control?s (UICC) TNM classification system is the most widely used cancer classification and staging system in the world. It is used to describe the anatomical extent of disease and it is essential to patient care, research and cancer control. This fifth edition of the TNM Supplement: A Commentary of Uniform Use offers practitioners a wealth of material intended to complement the system?s day-to-day use. The volume features: Updated definitions of terms used in cancer staging. New sections on carcinomas of the thymus, sarcomas of the spine and pelvis and soft tissue sarcomas of the head and neck, and comprehensive updates to the head and neck carcinomas, carcinomas of the lung and neuroendocrine tumours sections. Frequently asked questions from the UICC helpdesk. The Supplement may be treated as a companion text to the recent eighth edition of the TNM Classification of MTable of ContentsPreface viii Organizations Associated with the TNM System xiii National Committees xiii Acknowledgements xv Abbreviations xvi Chapter 1 Explanatory Notes – General The General Rules of the TNM System 1 The TNM Clinical and Pathological Classifications 7 Residual Tumour (R) Classification 15 Additional Descriptors 20 Optional Descriptors 24 Unknown Primary 25 Staging of Tumours for Which No TNM Classification is Provided 25 Histopathological Grading 26 References 28 Chapter 2 Explanatory Notes – Specific Anatomical Sites Head and Neck Tumours 34 Digestive System Tumours 54 Lung, Pleural and Thymic Tumours 85 Bone Tumours 104 Soft Tissue Tumours 106 Gastrointestinal Stromal Tumour (GIST) 108 Skin Tumours 110 Breast Tumours 118 Gynaecological Tumours 122 Urological Tumours 131 Ophthalmic Tumours 142 Hodgkin and Non‐Hodgkin Lymphomas 149 References 150 Chapter 3 Site‐Specific Requirements for pT and pN Introduction 157 Head and Neck Tumours 160 Digestive System Tumours 166 Lung and Pleural Tumours 173 Tumours of Bone and Soft Tissues 176 Skin Tumours 179 Breast Tumours 183 Gynaecological Tumours 185 Urological Tumours 188 Adrenal Cortex Tumours 192 Ophthalmic Tumours 193 Hodgkin and Non‐Hodgkin Lymphomas 195 References 196 Chapter 4 New TNM Classifications Recommended for Testing and Other Classifications Introduction 198 General 198 Specific 198 Non Upper Aerodigestive Tract Mucosal Melanoma 199 Primary Liver Carcinoma of Infants and Children/Hepatoblastoma 200 Primary Cutaneous Lymphomas 202 Cutaneous T‐Cell Lymphomas 202 Primary Cutaneous Lymphomas 203 Histopathologic Staging of Lymph Nodes in Mycosis Fungoides and Sézary Syndrome 204 Primary Cutaneous B‐Cell/T‐Cell Lymphoma (Non‐MF/SS Lymphoma) 206 Multiple Myeloma 207 Leukaemia 208 References 208 Chapter 5 Optional Proposals for Testing New Subcategories of TNM All Tumour Sites 210 Head and Neck Tumours 210 Digestive System Tumours 211 Lung Tumours 213 Breast Tumours (ICD‐0‐3 C50) 214 Gynaecological Tumours 215 Urological Tumours 215 References 216 Chapter 6 Frequently Asked Questions General Questions 218 Site‐Specific Questions 229 References 289 Index 291 Plate section facing p. 48

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Book SynopsisA comprehensive resource on the recent developments of stem cell use in wound healing With contributions from experts in the field, Wound Healing offers a thorough review of the most recent findings on the use of stem cells to heal wounds. This important resource covers both the basic and translational aspects of the field. The contributors reveal the great progress that has been made in recent years and explore a wide range of topics from an overview of the stem cell process in wound repair to inflammation and cancer. They offer a better understanding of the identities of skin stem cells as well as the signals that govern their behavior that contributes to the development of improved therapies for scarring and poorly healing wounds. Comprehensive in scope, this authoritative resource covers a wealth of topics such as: an overview of stem cell regeneration and repair, wound healing and cutaneous wound healing, the role of bone marrow derived stems cells, Table of ContentsList of Contributorsvii 1 Stem Cell Regeneration and Repair – Overview 1Clement D. Marshall, Alessandra A. Moore, Michael T. Longaker, and H. Peter Lorenz 2 Cadherins as Central Modulators of Wound Repair 15Melissa Crawford and Lina Dagnino 3 Tight Junctions and Cutaneous Wound Healing 31Thomas Volksdorf and Johanna M. Brandner 4 The Role of Microvesicles in Cutaneous Wound Healing 43Alexandra Laberge and Véronique J. Moulin 5 Wound Healing and Microenvironment 67Elgin Türköz Uluer, Hafize Seda Vatansever, and Feyzan Őzdal Kurt 6 Wound Healing and the Non-cellular Microenvironment 79Hayley S. Ramshaw, Jasreen Kular, and Michael S. Samuel 7 Contribution of Adipose-Derived Cells to Skin Wound Healing 89Barbara Gawronska-Kozak, Joanna Bukowska, Xiying Wu, Amy Lin Strong, Trivia Frazier, Bruce A. Bunnell, and Jeffrey M. Gimble 8 Role of Bone Marrow-Derived Stem Cells in Wound Healing 103Feyzan Özdal Kurt, Hafize Seda Vatansever, and Elgin Türköz Uluer 9 Role of Vitamin D and Calcium in Epidermal Wound Repair 113Daniel D. Bikle, Chia-ling Tu, and Yuko Oda 10 Oral Mucosal Healing 125Luisa A. DiPietro and Megan Schrementi 11 Role of Adipose-Derived Stem Cells in Wound Healing: An Update from Isolation to Transplantation 133Selami Demirci, Ayşegül Doğan, and Fikrettin Şahin 12 The Hair Follicle as a Wound Healing Promoter and Its Application in Clinical Practice 149Francisco Jimenez, María Luisa Martínez, Eduardo Escario, and Ander Izeta 13 Impaired Wound Healing in Diabetic Ulcers: Accelerated Healing Through Depletion of Ganglioside 167Duncan Hieu M. Dam, Sophia A. Jelsma, and Amy S. Paller 14 Inflammation in Wound Repair: Role and Function of Inflammation in Wound Repair 177Amanda S. MacLeod and Jeffery T. Kwock 15 Inflammation, Wound Healing, and Fibrosis 195Shibnath Ghatak, Vincent C. Hascall, Ricardo Moreno Rodriguez, Roger R. Markwald, and Suniti Misra 16 The Potential Role of Photobiomodulation and Polysaccharide-Based Biomaterials in Wound Healing Applications 211Heidi Abrahamse, Sathish Sundar Dhilip Kumar, and Nicolette Nadene Houreld 17 Is Understanding Fetal Wound Repair the Holy Grail to Preventing Scarring? 225Olivier A. Branford and Kerstin J. Rolfe 18 Inflammation and Cancer 239Suniti Misra, Vincent C. Hascall, Roger R. Markwald, Paul E. O’Brien, and Shibnath Ghatak Index 275

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Book SynopsisThorough Overview Identifies and Addresses Critical Gaps in the Treatment of Several Chronic Diseases With increasing numbers of patients suffering from Immune-Mediated Inflammatory Diseases (IMIDs), and with the increasing reliance on biopharmaceuticals to treat them, it is imperative that researchers and medical practitioners have a thorough understanding of the absorption, distribution, metabolism and excretion (ADME) of therapeutic proteins as well as translational pharmacokinetic/pharmacodynamic (PK/PD) modeling for them. This comprehensive volume answers that need to be addressed. Featuring eighteen chapters from world-renowned experts and opinion leaders in pharmacology, translational medicine and immunology, editors Honghui Zhou and Diane Mould have curated a much-needed collection of research on the advanced applications of pharmacometrics and systems pharmacology to the development of biotherapeutics and individualized treatment strategies for tTable of ContentsList of Contributors xvii About the Editors xxi Foreword xxiii Preface xxvii 1 Disease Interception in Autoimmune Diseases: From a Conceptual Framework to Practical Implementation 1 Anish Suri 1.1 Introduction to Disease Interception 1 1.2 Disease Interception in Autoimmune Diseases 3 1.3 Progress in Modulation of the Adaptive Immune Response in Autoimmune Inflammatory Diseases 5 1.4 The Complex Interplay between the Specificity of the Pathogenic Immune Repertoire and Its Sculpting by the Environment – Implications for Disease Interception 8 1.5 Clinical Application and Concluding Remarks 14 Acknowledgments 15 References 15 2 The Role of Biomarkers in Treatment Algorithms for Ulcerative Colitis (UC) 25 Reena Khanna and Brian G. Feagan 2.1 Background 25 2.2 Histology 32 2.2.1 Tissue Markers 33 2.3 Treatment Algorithms 34 2.3.1 Differentiating Inflammatory and Noninflammatory Disease 34 2.4 Assessing Response to Therapy 35 2.5 Predicting Relapse 35 2.6 Summary 35 References 35 3 Mechanism and Physiologically Based PK/PD Model in Assisting Translation from Preclinical to Clinical: Understanding PK/PD of Therapeutic Proteins at Site-of-Action 43 Xi Chen and Weirong Wang 3.1 Introduction 43 3.2 Biologic Distribution to Tissue Site of Action 44 3.3 Target Engagement of Biologics at Site of Action 50 3.4 Translational Application of Mechanistic PBPK Modeling 54 3.5 Conclusion 59 References 59 4 Application of Minimal Anticipated Biological Effect Level (MABEL) in Human Starting Dose Selection for Immunomodulatory Protein Therapeutics – Principles and Case Studies 65 Haiqing Wang, Zheng Yang, and Rong Shi 4.1 Introduction 65 4.2 Safety and Immune-Related Toxicities of Immunomodulatory Protein Therapeutics 66 4.3 Uncertainties of Toxicology Approach in FIH Safe Starting Dose Selection for Immunomodulatory Protein Therapeutics 68 4.4 Incorporating Mabel Approach in FIH Starting Dose Selection for High-Risk Immunomodulatory Protein Therapeutics 71 4.5 Case Studies of Mabel Calculation 75 4.6 Discussion and Conclusion 85 References 87 5 Model-Based Meta-Analysis Use in the Development of Therapeutic Proteins 93 Timothy J. Taylor, Bill Frame, and Angela D. Taylor 5.1 Introduction 93 5.2 Types of MBMA and Database Considerations 94 5.3 Data Analytic Models Useful for MBMA 96 5.4 Example 1: MBMA in Inflammatory Bowel Disease 97 5.5 MBMA Literature Search 99 5.6 Kinetic-Pharmacodynamic Models 100 5.7 MBMA Implications for Inflammatory Bowel Disease 116 5.8 Example 2: MBMA in Rheumatoid Arthritis 117 5.9 Conclusion 119 References 120 6 Utility of Joint Population Exposure–Response Modeling Approach to Assess Multiple Continuous and Categorical Endpoints in Immunology Drug Development 125 Chuanpu Hu and Honghui Zhou 6.1 Introduction 125 6.2 Latent Variable Indirect Response Models 126 6.3 Residual Correlation Modeling Between a Continuous and a Categorical Endpoint 128 6.4 Structural Correlation Modeling Between a Continuous Endpoint and a Categorical Endpoint 134 6.4.1 Application Example: Rheumatoid Arthritis 134 6.5 Conclusion 145 References 145 7 Modeling Approaches to Characterize Target-Mediated Pharmacokinetics and Pharmacodynamics for Therapeutic Proteins 149 Leonid Gibiansky and Ekaterina Gibiansky 7.1 Introduction 149 7.2 Target-Mediated Drug Disposition Model 150 7.3 Data and Practical Considerations 152 7.4 What to Expect from the Concentration–Time Course 154 7.5 Approximations of the TMDD Model 157 7.6 Identifiability of Model Parameters 166 7.7 Summary 167 References 168 8 Tutorial: Numerical (NONMEM) Implementation of the Target-Mediated Drug Disposition Model 173 Leonid Gibiansky and Ekaterina Gibiansky 8.1 Introduction 173 8.2 Notations and Data 174 8.3 NONMEM Code for TMDD Model and Approximations 174 8.4 How to Select Correct Approximation 179 8.4.2 Approach Based on Biological Considerations 180 8.5 Numerical Implementation 181 8.5.1 Choice of ADVAN Subroutines 181 8.5.2 Parallel Computing 181 8.6 Summary 182 References 182 9 Translational Considerations in Developing Bispecific Antibodies: What Can We Learn from Quantitative Pharmacology? 187 Pradeep B. Lukka, Santosh Wagh, and Bernd Meibohm 9.1 Introduction 187 9.2 Quantitative Pharmacokinetic Considerations of BsAbs 187 9.3 Preclinical Considerations 189 9.4 Translational Considerations 196 9.5 Immunogenicity 197 9.6 Clinical Development of BsAbs 198 9.7 Conclusion 200 References 202 10 Application of Pharmacometrics and Systems Pharmacology to Current and Emerging Biologics in Inflammatory Bowel Diseases 209 Sihem Ait-Oudhia, Yi Ting (Kayla) Lien, Sumit Basu, Lawrence Lesko, and Stephan Schmidt 10.1 Introduction 209 10.2 Pharmacological Approaches for the Treatment of IBD 215 10.3 Mathematical Models in IBD 224 10.4 Role of FDA in the Drug Development of Biologics in the Treatment of IBD 228 10.5 Summary 231 References 231 11 Pharmacokinetics-Based Dosing for Therapeutic Monoclonal Antibodies in Inflammatory Bowel Disease 243 Niels Vande Casteele and William J. Sandborn 11.1 Inflammatory Bowel Disease 243 11.2 Population Pharmacokinetics 244 11.3 Exposure–Response 246 11.4 Exposure-Based Dosing Strategies 247 11.5 Discussion 249 References 251 12 Pharmacokinetics-Based Dosing Strategies for Therapeutic Proteins in Inflammatory Bowel Disease 255 Diane R.Mould, Richard N. Upton, and Jessica Wojciechowski 12.1 Introduction 255 12.2 The Need for Understanding and Controlling Variability in Exposure 256 12.3 History of Dose Individualization 258 12.4 Bayesian Methods for Dose Individualization 260 12.5 Clinical Need for Improved Dosing with mAbs 265 12.6 Expectations for Bayesian Adaptive Dosing 268 12.7 Summary and Conclusions 277 References 278 13 Quantitative Pharmacology Approach to Select Optimal Dose and Study the Important Factors in Determining Disposition of Therapeutic Monoclonal Antibody in Pediatric Subjects – Some Considerations 285 Deni Hardiansyah and Chee M. Ng 13.1 Introduction 285 13.2 Pharmacokinetics of Therapeutic Monoclonal Antibody in Pediatric Population 289 13.3 Quantitative Pharmacology Considerations to Select Optimal Pediatric Dose of mAbs Based on Adult PK Studies 291 13.4 Using mPBPK Model to Study the Effects of FcRn Developmental Pharmacology on the PK of mAbs in Pediatric Subjects 299 References 307 14 Quantitative Pharmacology Assessment Strategy Therapeutic Proteins in Pediatric Subjects – Challenges and Opportunities 315 Jeremiah D. Momper, Andrew Mulberg, Nitin Mehrotra, Dan Turner, William Faubion, Laurie Conklin, Karim Azer, and Marla C. Dubinsky 14.1 Introduction 315 14.2 Extrapolation of Efficacy 315 14.3 Initiation of Pediatric Trials 321 14.4 Trial Design Considerations 322 14.5 Challenges in Pediatric Trials for First-in-Class vs. Follow-on Drug-in-Class 330 References 331 15 Case Examples of Using Quantitative Pharmacology in Developing Therapeutic Proteins for Plaque Psoriasis – Guselkumab 337 Zhenling Yao, Yaowei Zhu, Chuanpu Hu, Yang Chen, Shu Li, Bruce Randazzo, Zhenhua Xu, Amarnath Sharma, and Honghui Zhou 15.1 Introduction 337 15.1.1 Pathogenesis of Plaque Psoriasis 337 15.1.2 Current Treatment Paradigms for Psoriasis 338 15.2 Understanding of Exposure–Response (ER) Relationship of Guselkumab in Psoriasis 339 15.3 Dose Selection for Guselkumab in Psoriasis 342 15.4 Quantitative Pharmacology in Post-submission Support 358 15.5 Conclusion 359 References 360 16 Vedolizumab—A Case Example of Using Quantitative Pharmacology in Developing Therapeutic Biologics in Inflammatory Bowel Disease 363 Maria Rosario, Nathanael L. Dirks, Diane R.Mould, Catherine Scholz, Timothy Wyant, Asit Parikh, and Irving Fox Abbreviations 363 16.1 Introduction 364 16.2 Dose Selection for Adult Patients in Phase 3 Trials 365 16.3 Pharmacokinetic Profile of Vedolizumab 366 16.4 Population Pharmacokinetics in Phase 1 and 2 Trials 368 16.5 Comparison of Simulated vs. Measured Vedolizumab Trough Concentrations 372 16.6 Population Pharmacokinetics in Phase 3 Trials 372 16.7 Dose Selection for Pediatric Populations 374 16.8 Exposure–Response Analysis 376 16.9 Logistic Regression Analyses 378 16.10 Exposure–Response: Causal Inferences 381 16.11 Conclusion 384 Disclosure 384 References 384 17 Case Examples of Using Quantitative Pharmacology in Developing Therapeutic Proteins in Systemic Lupus Erythematosus – Belimumab 389 Herbert Struemper 17.1 Introduction 389 17.2 Overview of Supporting Data and Methods 390 17.3 Body Size Characterizations and Impact on Switching from Weight Proportional to Fixed Dosing 390 17.4 The Yin and Yang of FcRn – Opposing Effect of Albumin and IgG on mAb Clearance 392 17.5 Lost in Filtration – Renal Contributions to mAb Clearance 395 17.6 Conclusion 397 References 398 18 Case Examples of Using Quantitative Pharmacology in Developing Therapeutic Proteins in Multiple Sclerosis – Peginterferon Beta-1a, Daclizumab Beta, Natalizumab 401 Xiao Hu, Yaming Hang, Lei Diao, Kumar K.Muralidharan, and Ivan Nestorov 18.1 Introduction 401 18.2 Application of Quantitative Clinical Pharmacology for Dosing Regimen Recommendation of Peginterferon Beta- 1a 403 18.3 Population PK/PD Analyses of Daclizumab Beta and Phase 3 Dose Selection 414 18.4 Model-Based Approach for the Clinical Development of Subcutaneous Natalizumab 419 18.5 Summary 431 References 431 Index 437

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Book SynopsisAn incisive and contemporary discussion of epigenetic phenomena applied to human health and disease Epigenetics and Health: A Practical Guide delivers a thorough and insightful exploration of the basic principles of gene function, gene regulation, and gene expression. The author explains how epigenetic modifications alter gene expression and demonstrate the role played by environmental factorsincluding nutrition, exercise, toxins, and stressin gene regulation, as well as their potential health consequences. The book presents current methods for analyzing epigenetic variation, including NGS applications and bioinformatic analysis. Readers will be encouraged to question, analyze, and critically appraise the literature on epigenetics to further develop their understanding. They'll also find: Explorations of epigenetic mechanisms, homeostasis, and the potential for manipulating the epigenome Practical discussions of methods for epigenetic analysesTable of ContentsPreface Chapter 1: How do genes work? Chapter 2: What is Epigenetics? Chapter 3: Epigenetic mechanisms, homeostasis and potential for manipulating the epigenome Chapter 4: Methods for epigenetic analyses Chapter 5: Aging and epigenetic variation Chapter 6: Cancer Epigenetics Chapter 7: Epigenetics and Mental health Chapter 8: Implications of epigenetic research and Getting Started

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Book SynopsisNeonatal Haematology This unique handbook contains comprehensive coverage of neonatal haematology and aids diagnosis via high-quality images, diagnostic algorithms, case studies, and tables. With illustrations accompanying the diagnosis at each stage and clear explanations provided throughout, the book is ideal for trainees and experts alike. Authored by two of the world's leading haematologists, Professor Irene Roberts and Professor Barbara Bain, this book provides a depth of knowledge that is unequalled in other texts. To aid in reader comprehension, it is neatly organised by clinical problems and covers sample topics such as: Red cells: morphology, membrane, enzymes, and changes over the first 4 weeks of life Haemolytic anaemias: causes of neonatal haemolysis, diagnostic clues, and immune haemolysis (haemolytic disease of the newborn) Neonatal anaemia due to blood loss: causes of blood loss, diagnostic clues, feto-maternal haemorrhage, and twin-to-twin transfusion Haematological siTable of ContentsPreface viii Abbreviations x 1 The full blood count and blood film in healthy term and preterm neonates 1 Introduction 1 Brief outline of the ontogeny of haemopoiesis 1 Properties of fetal haemopoietic stem and progenitor cells 2 Red blood cell production and development in the fetus and neonate 5 Erythropoietin production in the fetus and neonate 6 Haemoglobin synthesis and red blood cell production in the fetus and newborn 6 Red blood cell lifespan and the red blood cell membrane in the fetus and neonate 9 Red blood cell metabolism in the fetus and neonate 10 Iron metabolism in the fetus and neonate 11 Normal values for red blood cell parameters in the fetus and neonate 12 Leucocytes in the fetus and newborn 17 Leucocyte production and function in the fetus and neonate 18 Platelets and megakaryocytes in the fetus and neonate 23 Developmental megakaryopoiesis and thrombopoiesis 23 Platelet numbers in the neonate and fetus – normal values 24 Neonatal platelet function 25 Practical problems in interpreting neonatal blood counts and films 25 Sample quality/artefacts 25 Site of sampling 26 Gestational age and postnatal age 27 Pregnancy-associated complications and mode of delivery 28 References 28 2 Red cell disorders: Anaemia, jaundice, polycythaemia and cyanosis 38 Neonatal anaemia 38 Definition and clinical significance of neonatal anaemia 38 Neonatal anaemia due to reduced red cell production 39 Neonatal anaemia due to increased red cell destruction 47 Neonatal anaemia due to haemoglobinopathies and other microcytic anaemias 67 Neonatal anaemia due to blood loss 76 Anaemia of prematurity 81 A simple diagnostic approach to neonatal anaemia 83 Neonatal polycythaemia 85 Haematological causes of cyanosis 86 Principles of red cell transfusion in neonates 86 Illustrative cases 88 Abbreviations used in the illustrative cases 110 References 110 3 Neonatal infection and leucocyte disorders 128 Leucocyte abnormalities in neonatal systemic disease 128 Increases in leucocyte numbers 128 Neonatal infection and its differential diagnosis: clues from the blood count and blood film 135 Storage disorders: diagnostic clues from the blood film 144 Neonatal neutropenia 145 Definition and causes of neutropenia 145 Immune neutropenia 148 Inherited congenital or neonatal neutropenia 150 Haematological features of neonates with Down syndrome 154 Congenital leukaemia 154 Leukaemia and preleukaemia in neonates with Down syndrome 156 Acute leukaemia in neonates without Down syndrome 160 Juvenile myelomonocytic leukaemia and Noonan syndrome myeloproliferative disorder 168 Illustrative cases 169 Abbreviations used in the illustrative cases 176 References 176 4 Disorders of platelets and coagulation, thrombosis and blood transfusion 190 Thrombocytopenia overview 190 Causes of neonatal thrombocytopenia: a practical classification based on age at onset 192 Fetal thrombocytopenia 194 Early-onset neonatal thrombocytopenia (presenting at <72 hours of age) 194 Late-onset neonatal thrombocytopenia (presenting at >72 hours of age) 196 Conditions leading to clinically significant thrombocytopenia in the neonate 197 Fetal/neonatal alloimmune thrombocytopenia 197 Neonatal thrombocytopenia due to maternal autoimmune disease 200 Thrombocytopenia due to congenital infections 201 Neonatal thrombocytopenia associated with chromosomal abnormalities 205 Inherited thrombocytopenia 206 Investigation of neonatal thrombocytopenia 215 Management of neonatal thrombocytopenia 215 Indications for platelet transfusion 216 Platelet function disorders 217 Inherited platelet function disorders with normal platelet counts presenting in the neonate 218 Thrombocytosis 218 Abnormalities of coagulation 220 Developmental haemostasis 220 Laboratory investigation of coagulation disorders in the neonate 220 Acquired coagulation abnormalities 221 Inherited coagulation disorders 223 Thrombosis 224 Screening tests for thrombophilia in neonates 224 Acquired thrombotic abnormalities 225 Inherited thrombotic abnormalities 225 General principles of neonatal platelet and plasma component transfusion 226 Platelet transfusion 226 Fresh frozen plasma 226 Cryoprecipitate 227 Prothrombin complex and recombinant factor VIIa 227 Illustrative cases 227 Abbreviations used in the illustrative cases 233 References 234 Index 254

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Book SynopsisThe Essential Guide to Recognizing and Treating Acute Endocrine and Metabolic Illness Endocrinology covers some of the most common conditions and serious public health challenges facing medicine today, and endocrine and metabolic emergencies constitute a large proportion of the clinical workload. Endocrine and Metabolic Medical Emergencies: A Clinician's Guide provides a singular reference to help endocrinologists, acute and general medicine clinicians, hospitalists and critical care physicians, and general practitioners recognize the symptoms of endocrine emergencies and provide the highest standards of care. Already the definitive and most comprehensive guide to endocrine emergency care, this new second edition: provides acute care guidance for a range of both common and unusual endocrine emergencies; details the effects of acute medical and critical illness on metabolic and endocrine systems, and their impacts on endocrine investigations; discusses special paTable of ContentsNotes on Contributors x Foreword xv Preface xvi List of Abbreviations xviii Part I General Aspects of AcuteMedical Emergencies 1 Introduction: AcuteMedical Care: A Crisis with Solutions 3GlennMatfin 1 Early Management of AcuteMedical Emergencies 10Paul J. Frost and Matt P.Wise Part II General Endocrine and Metabolic Aspects of Acute and Critical Illness 21 Introduction: Endocrine Testing and Responses in Acute and Critical Illness 23David B. Sacks 2 Endocrine Testing in Acute and Critical Illness 28Reza Morovat 3 Endocrine Responses to Critical Illness: Novel Insights and Therapeutic Implications 60Jan Gunst, Eva Boonen, and Greet Van den Berghe Part III Special Populations 83 4 Endocrine and Metabolic Emergencies in Pregnancy 85Anita Banerjee and CatherineWilliamson 5 Endocrine and Metabolic Emergencies in Inherited Metabolic Diseases: Acute Presentations in Adulthood 98Elaine Murphy and Robin H. Lachmann 6 Endocrine and Metabolic Emergencies in Transitional Care 110Mabel Yau andMark A. Sperling 7Emergency Perioperative Diabetes and Endocrine Management 129Glenn Matfin, Kate Evans, and Ketan Dhatariya 8 Endocrine and Metabolic Emergencies in HIV/AIDS 151Katherine Samaras 9 Endocrine and Metabolic Emergencies in Late-Effects Patients: Consequences of Cancer Therapy 160Helena Gleeson and Andrew Toogood 10 Endocrine and Metabolic Emergencies in Transplantation 171Robert A. Wermers and Pankaj Shah 11 Endocrine and Metabolic Changes with Aging: Endocrin-Aging: Recognizing and Managing Care in Older Frail Persons 182Angela M. Abbatecola and John E.Morley Part IV Pituitary Disorders 195 Introduction: Emergency Management of Pituitary Disorders 197Edward R. Laws and Ursula B. Kaiser 12 Hypopituitarism 203Nicholas A. Tritos and Anne Klibanski 13 Pituitary Apoplexy 218Claire Briet and Philippe Chanson 14 Macroprolactinomas 231Mark E. Molitch Part V Thyroid Disorders 243 Introduction: Emergency Management of Thyroid Disorders 245Hossein Gharib 15 Myxedema Coma 252Natasha Kasid and James V. Hennessey 16 Life-Threatening Thyrotoxicosis: Thyroid Storm and Adverse Effects of Antithyroid Drugs 262Alicia L.Warnock, David S. Cooper, and Henry B. Burch 17 Amiodarone-Induced Thyrotoxicosis 284Fausto Bogazzi, Luca Tomisti, Luigi Bartalena, and Enio Martino 18 Thyrotoxic Periodic Paralysis 296Mark Vanderpump 19 Sight-Threatening Graves’Orbitopathy 305Rebecca S. Bahn and James A. Garrity Part VI Adrenal Disorders 313 Introduction: Emergency Management of Adrenal Disorders 315Anand Vaidya 20 Acute Adrenal Insufficiency 321Glenn Matfin 21 Acute Medical Aspects Related to Florid Cushing’s Syndrome 345Krystallenia I. Alexandraki and Ashley B. Grossman 22 Endocrine Hypertensive Emergencies 355Graeme Eisenhofer, Andrzej Januszewicz, Christina Pamporaki, and Jacques W. M. Lenders Part VII Calcium, Phosphate, and Metabolic Bone Diseases 375 Introduction: Emergency Management of Calcium, Phosphate, and Metabolic Bone Diseases 377John P. Bilezikian 23 Hypocalcemia 380Glenn Matfin 24 Hypercalcemia 400Glenn Matfin 25 Acute Medical Aspects Related to Phosphate Disorders 422Anda R. Gonciulea and Suzanne M. Jan de Beur 26 Acute Medical Aspects Related to Osteoporosis and Its Therapy 433Dima L. Diab and Nelson B.Watts 27 Acute Medical Aspects Related to Paget’s Disease of Bone 447Ethel S. Siris and Dorothy A. Fink 28 Acute Medical Aspects Related to Kidney Stones 454Hasan Fattah and David S. Goldfarb Part VIII Neuroendocrine Tumors 465 Introduction: Emergency Management of Neuroendocrine Tumors 467Kjell Oberg 29 Acute Endocrine and Metabolic Emergencies Related to Neuroendocrine Tumors 472Gregory Kaltsas, Krystallenia I. Alexandraki, and Ashley B. Grossman Part IX Glucose Disorders 485 Introduction: Emergency Management of Glucose Disorders 487Gerry Rayman 30 Management of Diabetes and/or Hyperglycemia in Non-Critical Care Hospital Settings 491Rodolfo J. Galindo and Guillermo E. Umpierrez 31 Hypoglycemia 506Elizabeth M. Lamos, Lisa M. Younk, and Stephen N. Davis 32 Severe Hyperglycemia, Diabetic Ketoacidosis, and Hyperglycemic Hyperosmolar State 531Ketan Dhatariya and GlennMatfin 33 Short-Term Intensive Insulin Therapy in Patients with Newly Presenting Type Diabetes 548Wen Xu, David Owens, and JianpingWeng 34 Management of Concentrated Insulins in Acute Care Settings 560Nuha El Sayed, Megan J. Ritter, and Alissa R. Segal 35 Management of Insulin Pumps in Hospitalized Patients 571Bithika M. Thompson, Patricia A. Mackey, and Curtiss B. Cook 36 Management of Diabetes and/or Hyperglycemia during Enteral and Parenteral Nutrition 584Aidar R. Gosmanov and Niyaz R. Gosmanov 37 Management of Diabetes and/or Hyperglycemia in Hospitalized Patients with Renal Insufficiency 598Glenn Matfin 38 Management of Glucocorticoid-Induced Diabetes and/or Hyperglycemia 616Han Na Kim and NestorasMathioudakis 39 Management of Diabetes and/or Hyperglycemia in Acute Coronary Syndrome, Acute Stroke, and Acute Heart Failure 632Miles Fisher 40 Acute Diabetic Foot 648Glenn Matfin Part X Sodium Disorders 673 Introduction: Emergency Management of Sodium Disorders 675Richard H. Sterns 41 Emergency Management of Acute and Chronic Hyponatremia 679Joseph G. Verbalis 42 Emergency Management of Acute and Chronic Hypernatremia 700Aoife Garrahy and Christopher Thompson Part XI Obesity and Clinical Lipidology 717 Introduction: Emergency Management Related to Obesity and Clinical Lipidology 719Robert H. Eckel 43 Acute Emergencies Related to Bariatric Surgery 723Michael A. Via and Jeffrey I. Mechanick 44 Chylomicronemia Syndrome: Very Severe Hypertriglyceridemia and Acute Pancreatitis 742Anthony S. Wierzbicki 45 Statin-Related Myopathy and Rhabdomyolysis 760Connie B. Newman and Jonathan A. Tobert Index 775

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Book SynopsisCardiac Problems in Pregnancy offers clinicians the most detailed and comprehensive guide to diagnosing and managing pregnancy-associated cardiovascular diseases currently available. Covering a wide spectrum of congenital and acquired cardiovascular conditions, its extensive contents examine diseases of the heart with an expert awareness of the implications of pregnancy and the attendant physiological changes it brings. Such guidance is vitally required in an age in which congenital and acquired heart diseases are the leading causes of non-obstetrical maternal morbidity and mortality. Featuring 36 new or extensively revised chapters, this fourth edition of the book complements coverage of the latest research and clinical advances with a complete and up-to-date bibliography of literature on pregnancy in women with cardiovascular conditions. It also serves as a practical, step-by-step companion for those caring for heart disease patients during pregnancy, labor, and theTable of ContentsAbout the Editor ix List of Contributors x Preface xiii Acknowledgments xiv Part I Physiologic Changes During Normal Pregnancy and the Puerperium 11 Hemodynamic and Cardiac Function 3Ofer Havakuk and Uri Elkayam Part II Cardiac Evaluation of the Pregnant Woman 17 2 Cardiovascular Evaluation During Pregnancy 19Uri Elkayam 3 Cardiovascular Imaging in the Pregnant Patient 32Patrick Colletti and Uri Elkayam Part III Cardiac Disorders and Pregnancy 41 4 Risk Assessment Prior and During Pregnancy 43Samuel C. Siu and Candice K. Silversides 5 Congenital Heart Disease and Pregnancy 60Candice K. Silversides, Jack M. Colman, and Samuel C. Siu 6 Native Valvular Heart Disease and Pregnancy 75Uri Elkayam 7 Pregnancy in the Patient with Prosthetic Heart Valves 90Uri Elkayam 8 Myocarditis and Pregnancy 107Avraham Shotan and Andrei Keren 9 Pericardial Disorders and Pregnancy 116Marla A. Mendelson 10 Peripartum Cardiomyopathy 128Sorel Goland and Uri Elkayam 11 Dilated Cardiomyopathy and Pregnancy 155Kathleen Stergiopoulos and Fabio V. Lima 12 Hypertrophic Cardiomyopathy and Pregnancy 167Iris M. van Hagen, Uri Elkayam, Sorel Goland, and Jolien W. Roos-Hesselink 13 Left Ventricular Noncompaction 181Radha J. Sarma 14 Acute Myocardial Infarction and Pregnancy 201Uri Elkayam and Ofer Havakuk 15 Cardiac Arrhythmias and Pregnancy 220Danna Spears and Uri Elkayam 16 Pulmonary Arterial Hypertension and Pregnancy 252Dianne Zwicke, Sara Paulus, and Vinay Thohan 17 Infective Endocarditis 261Ramin Ebrahimi, Michael Shenoda, Sheila Sahni, and David Fisk Part IV Vascular Disease in Pregnancy 275 18 Vascular Dissections and Aneurysms During Pregnancy 277Afshan B. Hameed 19 Marfan Syndrome and Pregnancy 285Sorel Goland and Uri Elkayam 20 Non-Marfan Aortopathies and the Pregnant Patient 305John Bois and Heidi Connolly 21 Takayasu’s Arteritis and Pregnancy 319Abha Khandelwal 22 Thromboembolic Disease in Pregnancy 326Courtney C. Bilodeau and Karen Rosene-Montella 23 Amniotic Fluid Embolism and Pregnancy 334Irene A. Stafford, Steven L. Clark, and Gary A. Dildy 24 Hypertension During Pregnancy 339Chonyang L. Albert and Leslie Cho 25 Syncope in Pregnancy 349Paul S. Gibson Part V Cardiac Surgery and Catheter Based Interventions During Pregnancy 359 26 Cardiac Surgery During Pregnancy 361Anita Nguyen and Hartzell V. Schaff 27 Catheter-Based Interventions in Women with Heart Disease During Pregnancy 370Anil Mehra, Gassan Muadi, Pavan Reddy, and Uri Elkayam 28 Analgesia and Anesthesia During Pregnancy, Labor, and Delivery 389Katherine W. Arendt 29 Cardiopulmonary Resuscitation of Pregnant Women 397Joan Briller 30 Pregnancy After Cardiac Transplantation 419Serban Constantinescu, Dawn P. Armenti, Lisa A. Coscia, Lynn R. Punnoose, John M. Davison, and Michael J. Moritz Part VI Cardiovascular Drug Therapy During Pregnancy 433 31 Pharmacokinetics of Drugs in Pregnancy and Lactation 435Irving Steinberg 32 Cardiovascular Drugs in Pregnancy and Lactation 456Petronella G. Pieper, Uri Elkayam, Joy Eskandar, and Titia P.E. Ruys 33 Tocolytic Therapy in the Cardiac Patient 491Joseph G. Ouzounian 34 Fertility Control in the Cardiac Patient 497Joan Briller, Mark R. Johnson, and Jolien W. Roos-Hesselink Part VII Labor and Delivery 513 35 Management of Labor and Delivery in a Cardiac Patient 515Rohan D’Souza and Mathew Sermer 36 Cardiac Effects of Drugs Used for Induction of Labor and Prevention and Treatment of Postpartum Hemorrhage 530Mark R. Johnson Index 537

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Book SynopsisThe essential guide for understanding and treating women with inherited bleeding disorders, revised and updated Now in its second edition, Inherited Bleeding Disorders in Women includes the most recent developments and research in the field. This important guide offers the most current information available for the effective management of these complex and difficult to diagnose disorders. Treating women with inherited bleeding disorders can be challenging and requires close collaboration among practitioners in different specialties. This important guide is written by a team of international experts who offer advice and practical suggestions for treating women with inherited bleeding disorders. Inherited Bleeding Disorders in Womencomprehensively covers obstetric and gynecological issues for carriers of hemophilia, women with von Willebrand disease, rare bleeding disorders and inherited platelet disorders. This important resource: OfferTable of ContentsPreface to Second Edition ix Preface to First Edition xi List of Contributors xiii 1 Hematological Assessment of a Patient with an Inherited Bleeding Disorder 1 Sue Pavord and Henna Wong 1.1 Introduction 1 1.2 Normal Hemostasis 1 1.3 Defects of Hemostasis 5 1.4 Clinical Presentation of Bleeding 5 1.5 Diagnosis 6 1.6 Approach to a Female with a Bleeding History 6 1.7 Summary 10 References 11 2 Bleeding Assessment Tools 13Sarah H. O’Brien and Paula D. James 2.1 Introduction 13 2.2 Evolution of Vicenza‐Based Bleeding Assessment Tools 13 2.3 Women’s Studies Using Vincenza‐Based Bleeding Tools 22 2.4 Tools to Evaluate Menstrual Blood Loss 23 2.5 Young Women’s Hematology and Bleeding Assessment Tools 25 2.6 Clinical Utility of Bleeding Assessment Tools 25 2.7 Conclusion 26 References 27 3 Physiology of Menstruation 29Jane J. Reavey, Jacqueline A. Maybin, and Hilary O.D. Critchley 3.1 Introduction 29 3.2 Normal Menstruation 29 3.3 Neuroendocrine Hormones 30 3.4 Menarche 31 3.5 Ovarian Follicle Development and Endocrine Function 31 3.6 Endometrium 33 3.7 Secretory Phase 34 3.8 Menstruation 35 3.9 Control of Bleeding 37 3.10 Endometrial Repair 38 3.11 Proliferative Phase 40 3.12 Summary 40 References 41 4 Gynecology 45Joanna S. Davies and Rezan A. Kadir 4.1 Introduction 45 4.2 Heavy Menstrual Bleeding 48 4.3 Management of Acute Episodes of Heavy Menstrual Bleeding 58 4.4 Ovulation Bleeding 59 4.5 Endometriosis 59 4.6 Other Gynecological Conditions 60 4.7 Conclusion 61 References 61 5 Carriers of Hemophilia A and Hemophilia B 65Roseline d’Oiron 5.1 Inheritance 65 5.2 Screening for the Genetic Status of Carriers of Hemophilia 65 5.3 Confusion Between Genetic and Coagulation Testing 66 5.4 When to Perform Genetic Testing 67 5.5 What Reasons might Contribute to Delayed Genetic Diagnosis of Carriership? 68 5.6 Bleeding Disorders in Carriers of Hemophilia 68 5.7 Quality of Life of Carriers of Hemophilia 73 5.8 Carriers of Hemophilia A and B and Pregnancy 73 5.9 How to Improve Care for Carriers of Hemophilia 77 References 79 6 Von Willebrand Disease 83Carolyn M. Millar 6.1 Introduction 83 6.2 Structure and Function of Von Willebrand Factor 83 6.3 Von Willebrand Factor Levels and Prevalence of Von Willebrand Disease 84 6.4 VWF Levels, the Menstrual Cycle and Pregnancy 84 6.5 Von Willebrand Disease Classification and Inheritance 85 6.6 Clinical Presentation 87 6.7 Menorrhagia and Postpartum Hemorrhage 87 6.8 Diagnosis and Laboratory Testing 88 6.9 Management of Von Willebrand Disease 90 6.10 Management of Gynecological Bleeding 91 6.11 Obstetric Management of Von Willebrand Disease 92 6.12 Neonatal Management 94 6.13 Cases 94 References 96 7 Factor XI Deficiency 101Bethan Myers and Rezan A. Kadir 7.1 Factor XI Structure and Function in Coagulation 101 7.2 Incidence and Inheritance of Factor XI Deficiency 101 7.3 Bleeding Manifestations and Diagnosis of Factor XI Deficiency 103 7.4 Factor XI Deficiency and Gynecological Issues 103 7.5 Factor XI Deficiency and Pregnancy 105 7.6 Neuroaxial Analgesia and Anesthesia 108 7.7 Management of Postpartum Period 108 7.8 Treatment Options 109 7.9 Neonatal Bleeding 111 7.10 Conclusions and Recommendations 111 References 112 8 Rare Bleeding Disorders 117Danijela Mikovic, Marzia Menegatti, and Flora Peyvandi 8.1 Introduction 117 8.2 Clinical Symptoms 118 8.3 Gynecological and Obstetrical Manifestations in Women with Rare Bleeding Disorders 119 8.4 Laboratory Diagnosis 122 8.5 Differential Diagnosis in Women with Menorrhagia 123 8.6 Treatment 124 8.7 Conclusion 128 References 129 9 Inherited Platelet Defects 133Mike Makris and Clare Samuelson 9.1 Introduction 133 9.2 Normal Platelet Function 133 9.3 Presentation 136 9.4 Investigation 137 9.5 Syndromic and Non‐Syndromic Inherited Platelet Disorders with Recognized Causative Genes 143 9.6 Prenatal Diagnosis 143 9.7 Management 144 9.8 Future Directions 147 9.9 Case Histories 147 9.10 Conclusion 148 References 149 10 Genetic and Laboratory Diagnosis 153Anne C. Goodeve 10.1 Introduction 153 10.2 Phenotypic Analysis of Hemophilia A 154 10.3 Phenotypic Analysis of Hemophilia B 156 10.4 Phenotypic Analysis of von Willebrand Disease 157 10.5 Phenotypic Analysis of Inherited Bleeding Disorders 157 10.6 Genetic Analysis of Hemophilia A 160 10.7 Genetic Analysis of Hemophilia B 162 10.8 Genetic Analysis of von Willebrand Disease 163 10.9 Guidelines 164 10.10 Summary 164 References 164 11 Antenatal Diagnosis 167Rezan A. Kadir, Irena Hudecova, and Claudia Chi 11.1 Introduction 167 11.2 Genetic Counseling 167 11.3 Prenatal Diagnosis 170 11.4 Prenatal Diagnosis of Hemophilia 177 11.5 Prenatal Diagnosis of von Willebrand Disease 180 11.6 Prenatal Diagnosis of Rare Bleeding Disorders 180 11.7 Preimplantation Genetic Diagnosis 181 11.8 Views about and Experiences of Prenatal Diagnosis of Women in Families Affected with Inherited Bleeding Disorders 183 11.9 Termination of Pregnancy 185 References 186 12 Analgesia and Anesthesia for Pregnant Women with Inherited Bleeding Disorders 191Anne‐Sophie Bouthors, Adrian England, and Rezan A. Kadir 12.1 Introduction 191 12.2 Non‐Pharmacological Methods 192 12.3 Pharmacological Methods 192 12.4 Conclusion 201 References 202 13 The Newborn 205Manuel Carcao and Vanessa Bouskill 13.1 Introduction 205 13.2 Developmental Hemostasis 205 13.3 Laboratory Hemostatic Evaluation of the Neonate 208 13.4 When to Suspect a Congenital Bleeding Disorder in a Newborn 209 13.5 Congenital Bleeding Disorders and Their Presentation in Newborns 213 13.6 Management of Bleeding in Neonates with Congenital Bleeding Disorders 218 13.7 Conclusion 221 References 222 14 Women with Inherited Bleeding Disorders in Different Cultural Settings 225Tahira Zafar, Jameela Sathar, Ali T. Taher, Fadi G. Mirza, and Christine A. Lee 14.1 Introduction 225 14.2 Pakistan 225 14.3 Malaysia 227 14.4 Lebanon 229 14.5 Discussion 231 References 232 Index 235

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Book SynopsisA FRESH EXAMINATION OF PRECISION MEDICINE'S INCREASINGLY PROMINENT ROLE IN THE FIELD OF ONCOLOGY Precision medicine takes into account each patient's specific characteristics and requirements to arrive at treatment plans that are optimized towards the best possible outcome. As the field of oncology continues to advance, this tailored approach is becoming more and more prevalent, channelling data on genomics, proteomics, metabolomics and other areas into new and innovative methods of practice. Precision Medicine in Oncology draws together the essential research driving the field forward, providing oncology clinicians and trainees alike with an illuminating overview of the technology and thinking behind the breakthroughs currently being made. Topics covered include: Biologically-guided radiation therapyInformatics for precision medicineMolecular imagingBiomarkers for treatment assessmentBig dataNanoplatforms Casting a spotlight on this emerging knowledge base and its impact upon the manaTable of ContentsList of Contributors xiii Preface xv List of Abbreviations xvii 1 Genomic Strategies for Personalized Cancer TherapyArkadiusz Z. Dudek, Kate Baxstrom, Sushma Bharadwaj, Anne Blaes, Amit Kulkarni, Emil Lou, Vijeyaluxmy Nehru, Emma Rabinovich, Ardaman Shergill, and Maya Viner 1.1 Introduction 1 1.1.1 Definition of Precision Medicine in Oncology 1 1.1.2 DNA and RNA Sequencing Techniques 2 1.2 Precision Medicine in Specific Tumors 3 1.2.1 Lung Cancer 3 1.2.1.1 Adenocarcinoma 4 1.2.1.2 Squamous Cell Carcinoma 4 1.2.1.3 Small-Cell Lung Carcinoma (SCLC) 4 1.2.1.4 Epidermal Growth Factor Receptor (EGFR) Mutations 4 1.2.1.5 Anaplastic Lymphoma Kinase (ALK) 5 1.2.1.6 BRAF, ROS1, MET 5 1.2.1.7 KRAS 6 1.2.1.8 Other: RET, NTRK 6 1.2.2 Head and Neck Cancers 6 1.2.2.1 HPV-Positive Cancers 7 1.2.2.2 HPV-Negative Cancers 8 1.2.2.3 Targeting the Epidermal Growth Factor Receptor (EGFR) Pathway 8 1.2.2.4 Thyroid Cancers 8 1.2.2.5 Other Targets 8 1.2.3 Hematological Malignancies 9 1.2.3.1 Lymphoma 9 1.2.3.2 Leukemia 10 1.2.3.3 Myelodysplastic Syndrome 11 1.2.4 Gynecologic Malignancies 11 1.2.4.1 Cervical 11 1.2.4.2 Uterine 11 1.2.4.3 Ovarian 12 1.2.5 Melanoma 13 1.2.6 Gastrointestinal Malignancies 16 1.2.6.1 Gastroesophageal Cancers 17 1.2.6.2 Colorectal Cancers 17 1.2.7 Breast Cancer 19 1.2.7.1 Basal-Like, or Triple Negative Breast Cancer 19 1.2.7.2 Luminal A/B, or Hormone Positive 20 1.2.7.3 HER2 Positive Breast Cancer 20 1.2.7.4 Immunotherapy 20 1.2.7.5 Germline Testing in Breast Cancer 21 1.2.7.6 Conclusion 21 1.2.8 Genitourinary Malignancies 21 1.2.8.1 Prostate Cancer 21 1.2.8.2 Renal Cell Cancer (RCC) 23 1.2.8.3 Urothelial Cancers 23 1.2.9 Pediatric Cancers 24 1.2.9.1 Introduction 24 1.2.9.2 Leukemia and Lymphoma 24 1.2.9.3 Central and Peripheral Nervous System Tumors 25 1.2.9.4 Bone and Soft Tissue Sarcomas 26 1.2.9.5 Other Embryonal Tumors 26 1.2.9.6 Conclusion 27 1.2.10 Cancers of Unknown Primary Origin 27 1.2.10.1 Diagnosis 27 1.2.10.2 Gene Expression Profiling 28 1.2.10.3 Mutational Testing with Next-Generation Sequencing (NGS) 28 1.2.10.4 Treatment 28 1.3 Biomarkers for Immunotherapy of Cancer 28 1.3.1 PD-L1 29 1.3.2 Soluble PD-L1 (sPD-L1) 29 1.3.3 Combined Positive Score (CPS) 30 1.3.4 Tumor Microenvironment 30 1.3.5 Tumor Mutational Burden (TMB) 30 1.3.6 Microsatellite Instability (MSI) 31 1.3.7 MMR Deficiency 31 1.3.8 Peripheral Blood Absolute Neutrophil Count/Absolute Lymphocyte Count 31 1.3.9 Microbiome 31 1.4 Clinical Trial Design in the Era of Precision Oncology 32 1.5 Ethical, Legal, and Social Issues of Precision Oncology 33 1.5.1 Ethical Issues 33 1.5.2 Legal Issues 34 1.5.3 Social Issues 35 1.6 Databases, Data Sharing, and Challenges of Precision Oncology 36 References 37 2 Blood-Based Biomarkers for the Diagnosis and Prognosis of Cancer 61Shreetama Bandyopadhayaya and Chandi C. Mandal 2.1 Introduction 61 2.2 Importance of Blood-Based Biomarkers 61 2.3 Circulating Proteins as Biomarkers 62 2.4 Circulating Long Non-coding RNAs as Biomarkers 64 2.5 Circulating miRNAs as Biomarkers 65 2.6 Circulating Autoantibodies as Biomarkers 67 2.7 Circulating Tumor DNA as Biomarkers 69 2.8 Metabolites as Biomarkers 70 2.9 Lipids as Biomarkers 72 2.10 Exosomes as Biomarkers 74 2.11 Conclusion 77 References 77 3 Application of Circulating Cell-free DNA for Personalized Cancer Therapy 83Indranil Chattopadhyay 3.1 Introduction 83 3.2 Drawbacks and Challenges of Invasive Tumor Tissue in Treatment and Diagnosis of Cancer 84 3.3 Importance of Noninvasive Biomarkers in Treatment and Diagnosis of Cancer 84 3.4 Liquid Biopsy: cfDNA and ctDNA 85 3.4.1 Biogenesis of ctDNA: Mechanisms of Release, Characteristics, Quantity, and Quality 85 3.4.2 Role of Preanalytical Factors that Affect cfDNA Measurements 86 3.5 Practical Approach to Estimate ctDNA in Liquid Biopsy 86 3.5.1 Isolation of cfDNA and ctDNA 86 3.5.2 Analysis of ctDNA by Real-Time Quantitative PCR 86 3.5.3 Analysis of ctDNA by Digital PCR (dPCR) 87 3.5.4 Analysis of ctDNA by Beads, Emulsion, Amplification, and Magnetics (BEAMing) 87 3.5.5 Analysis of ctDNA by Next-Generation Sequencing (NGS) 87 3.6 Clinical Application of ctDNA Detection in Various Cancers 88 3.6.1 Clinical Applications of ctDNA in Lung Cancer 88 3.6.2 Clinical Application of ctDNA in Head and Neck Cancer 89 3.6.3 Clinical Utility of Circulating Tumor DNA in Pancreatic Cancer 90 3.6.4 Clinical Utility of Circulating Tumor DNA in Early and Metastatic Breast Cancer 90 3.6.5 Clinical Utility of Circulating Tumor DNA in Colorectal Cancer 91 3.6.6 Clinical Utility of Circulating Tumor DNA in Melanoma 91 3.7 Clinical Utility of Methylation in ctDNA in Personalized Oncology 92 3.8 Conclusion 92 References 93 4 Prognostic Implications of EGFR, p53, p16, Cyclin D1, and Bcl-2 in Head and Neck Squamous Cell Carcinoma (HNSCC) 99Zane Deliu, Ardaman Shergill, Anne Meier, Phyo Thazin Myint, Sarah Khan, Paramjeet Khosla, and Lawrence Feldman 4.1 Introduction 99 4.2 Epidermal Growth Factor Receptor (EGFR) 99 4.2.1 EGFR Structure and Ligands 99 4.2.2 Physiology 100 4.2.3 EGFR Expression and Genetic Changes 100 4.2.3.1 EGFR Expression in HNSCC 100 4.2.3.2 Normal Adjacent Oral Mucosa and Pre-malignant Lesions 101 4.2.4 EGFR Genetic Changes: Gene Copy Numbers, Amplifications, and Mutations in HNSCC 101 4.2.4.1 Association of EGFR Expression or Genetic Changes with HPV Infection 101 4.2.5 EGFR as a Prognostic and Predictive Marker 102 4.2.5.1 EGFR as a Prognostic Marker 102 4.2.5.2 EGFR as a Predictive Marker 102 4.2.6 Future Perspectives 103 4.2.6.1 EGFR in Immuno-SPECT or PET Imaging 103 4.2.6.2 Molecular Profiling for Precision Medicine 104 4.3 TP53 Mutations in Head and Neck Cancer 104 4.3.1 Pathogenesis and Prevalence 104 4.3.2 Risk Factors 104 4.3.3 TP53 Structure and Physiology 105 4.3.3.1 TP53 Structure 105 4.3.3.2 TP53 as a Tumor Suppressor Gene 105 4.3.4 TP53 Gain of Function Properties 105 4.3.5 TP53 as a Prognostic and Predictive Marker 106 4.3.6 Therapeutic Strategies Targeting TP53 106 4.4 P16 and Cyclin D1 Mutations in Head and Neck Cancer 107 4.4.1 Cyclin D1 107 4.4.2 P16 108 4.5 Bcl-2 Mutations in Head and Neck Cancer 109 4.5.1 Bcl-2 109 4.5.1.1 Physiological Role of Bcl-2 109 4.5.2 Bcl-2 Family of Proteins 109 4.5.3 Significance of Bcl-2 Overexpression 110 4.5.4 Association with Chemoresistance and Radioresistance 111 4.5.5 Role of Bcl-2 as a Marker of Prognosis 111 4.5.6 Chemotherapeutics Targeting Bcl-2 112 4.5.7 Bcl-2 Summary 113 4.6 Conclusion 113 References 114 5 Immunotherapy and Cancer 133Maaly Bassiony, Adedoyin Victoria Aluko, and James A. Radosevich 5.1 Introduction 133 5.2 What Is Cancer Immunotherapy? 134 5.3 How Does Immunotherapy Work? 135 5.4 Timing of Immunotherapy 135 5.5 Combination Immunotherapy 136 5.6 Side Effects of Immunotherapy 137 5.7 Types of Cancer Immunotherapy Treatments 137 5.7.1 Immune Checkpoint Inhibitors 137 5.7.2 Monoclonal Antibodies and Tumor-Agnostic Therapies 138 5.7.3 Adoptive T Cell Therapy 138 5.8 Cancer Vaccines 139 5.9 Oncolytic Viral Immunotherapy (OVIs) 140 5.10 Non-specific Immunotherapies 141 5.11 Immunotherapy by Cancer Type 141 5.11.1 Skin Cancer 141 5.11.2 Lung Cancer 142 5.11.3 Breast Cancer 142 5.11.4 Kidney and Prostate Cancers 143 5.11.5 Brain Cancer 145 5.11.6 Colorectal Cancer 146 5.11.7 Bladder Cancer 147 5.11.8 Cervical Cancer 147 5.11.9 Leukemia 147 5.11.10 Liver Cancer 148 5.12 Proven Studies 150 5.13 Cancer Immunity Pathway 150 5.14 Recent Developments in Immunotherapy 150 5.15 Neoantigens for Cancer Immunotherapy 151 5.16 Discussion 152 References 153 6 Predictive and Prognostic Markers for Cancer Medicine 157Elif Zeynep Yilmaz and Ebru Esin Yoruker 6.1 Introduction 157 6.2 Historical Development of Cancer Markers 157 6.3 Characteristics of the Ideal Cancer Markers 158 6.3.1 Ideal Source of Cancer Markers 159 6.3.2 Kinetics of Cancer Markers 162 6.3.3 Sensitivity and Specificity for Evaluation of Cancer Markers 163 6.4 Utilization of Cancer Markers in Most Common Cancers 163 6.4.1 Colorectal Cancer 166 6.4.1.1 CEA 166 6.4.1.2 KRAS/NRAS 167 6.4.1.3 MSI 168 6.4.1.4 PD-1/PD – L1 168 6.4.1.5 BRAF 169 6.4.1.6 Oncotype DX Colon Cancer Test 169 6.4.1.7 ColoPrint 169 6.4.1.8 CTC 169 6.4.2 Breast Cancer 169 6.4.2.1 ER/PR 170 6.4.2.2 HER2 171 6.4.2.3 Oncotype DX 171 6.4.2.4 MammaPrint 171 6.4.2.5 uPA/PAI-1 172 6.4.3 Ovarian Cancer 172 6.4.4 Lung Cancer 172 6.4.4.1 EGFR 173 6.4.4.2 ALK Rearrangements 173 6.4.4.3 ROS1 Rearragements 174 6.4.5 Urological Cancers 174 6.4.5.1 Prostate Cancer 174 6.4.5.2 Renal Cancer 175 6.5 Classification and Techniques for Studying of Cancer Markers 176 6.5.1 Circulating Tumor Cells as Cancer Markers 176 6.5.2 DNA-Based Cancer Markers 177 6.5.2.1 Microsatellite Alterations 177 6.5.2.2 cfDNA Integrıty 177 6.5.2.3 DNA Methylation 178 6.5.2.4 Mutations and Single Nucleotide Polymorphisms (SNPs) 178 6.5.3 RNA-Based Tumor Markers 180 6.5.3.1 mRNAs 180 6.5.3.2 Noncoding RNAs 180 6.5.4 Protein-Based Tumor Markers 181 6.6 Clinical Validation of Cancer Markers 185 6.7 Conclusions and Future Perspectives 186 References 187 7 Dual Energy Imaging in Precision Radiation Therapy 203John C. Roeske, Maksat Haytmyradov, Roberto Cassetta, and Murat Surucu 7.1 Introduction and Overview 203 7.2 Historical Perspective 203 7.2.1 X-Ray Production 204 7.2.2 X-Ray Interactions in Matter 205 7.2.3 Planar Image Formation 205 7.2.4 Computed Tomography 206 7.2.5 X-Ray Imaging in Radiation Oncology 207 7.2.6 Dual Energy Imaging in Radiation Therapy 207 7.3 Planar Dual Energy Imaging 208 7.3.1 Theory 209 7.3.2 Planar Dual Energy Imaging Methods 210 7.3.3 Applications in Radiation Therapy 210 7.3.3.1 Image-Guided Radiation Therapy 211 7.3.3.2 Markerless Tumor Tracking 211 7.3.3.3 Megavoltage Dual Energy Imaging 214 7.4 Dual Energy Computed Tomography 214 7.4.1 Theory 215 7.4.2 Dual Energy Scanning Methods 216 7.4.3 Applications in Radiation Therapy 218 7.4.3.1 Brachytherapy Planning 218 7.4.3.2 Proton Planning 218 7.4.3.3 Normal Tissue Segmentation 220 7.4.3.4 Assessment of Therapy Response 221 7.4.3.5 Dual Energy Cone Beam Computed Tomography 222 7.5 Summary and Future Directions 222 Acknowledgement 223 References 224 8 The Role of Big Data in Personalized Medicine 229Jean-Emmanuel Bibault and Lei Xing 8.1 Introduction 229 8.2 The Concept of Big Data and the Specificities of Healthcare 230 8.2.1 Volume: How Big Is Big Data? 230 8.2.2 Variety: Where Does Big Data Come from? 231 8.2.3 Velocity: How Fast Is Big Data Generated and Interpreted? 232 8.2.4 Variability: How Does Big Data Change? 232 8.2.5 Veracity: How Accurate Is Big Data? 232 8.2.6 Value: Why Is Big Data Important? 232 8.3 Sources of Data 233 8.3.1 Genomics, Epigenomics, and Transcriptomics 233 8.3.2 Proteomics and Metabolomics 234 8.3.3 Medical Imaging and Radiomics 235 8.3.4 Clinical Informatics 236 8.4 Big Data Analytical Techniques 236 8.4.1 Machine Learning 236 8.4.2 Deep Learning 237 8.4.3 Natural Language Processing 238 8.5 Challenges in Big Data Analytics 239 8.5.1 Implementing a Big Data Approach 239 8.5.2 Developing an Information-Sharing Culture 239 8.5.3 Security Measures 240 8.5.4 Ethics in Big Data Analysis 240 8.5.4.1 Consent in the Era of Big Data 240 8.5.4.2 Privacy 240 8.5.4.3 Anonymization 241 8.5.4.4 Ownership 241 References 241 Index 249

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Book SynopsisWritten by an experienced and well-respected physician and professor, this new volume, building on the previous volume, Ultrasonic Topographical and Pathotopographical Anatomy, also available from Wiley-Scrivener, presents the ultrasonic topographical and pathotopographical anatomy of the head and neck, offering further detail into these important areas for use by medical professionals. This atlas of topographic and pathotopographic human anatomy is a fundamental and practically important book designed for doctors of all specializations and students of medical schools. Here you can find almost everything that is connected with the topographic and pathotopographic human anatomy, including original graphs of logical structures of topographic anatomy and development of congenital abnormalities, topography of different areas in layers, pathotopography, computer and magnetic resonance imaging (MRI) of topographic and pathotopographic anatomy. Also you can find here new theoTable of ContentsAbout the Author vii Introduction ix Part 1 The Head 1 Topographic Anatomy of the Head 1 Cerebral Cranium 1 Basis Cranii Interna 15 The Brain 18 Surgical Anatomy of Congenital Disorders 41 Pathotypography of the Cerebral Part of the Head 42 Facial Head Region 47 The Lymphatic System of the Head 89 Congenital Face Disorders 92 Pathotypography of the Facial Part of the Head 94 Attachment 1: Neurocranial Part Topography 102 Attachment 2: Facial Part Topography 103 Part 2 The Neck 105 Topographic Anatomy of the Neck 105 Fasciae, Superficial and Deep Cellular Spaces and their Relationship with Spaces Adjacent Regions 107 Triangles of the Neck 113 Organs of the Neck 135 Pathography of the Neck 144 Attachment 3: Topography of the Neck 155 Appendix A: Adult 157 Appendix B: Child 165

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Book SynopsisHighly commendedat the British Medical Association (BMA)Awards 2019, thisnew volume from the International Society of Neuropathology series addresses infections of the nervous system, written by expert editors. An expansive and inclusive contents list including rare disorders presented in easily referable chapters, containing; definitions, microbiological characteristics, epidemiology, clinical features, lab tests, pathology, genetics and treatment.Table of ContentsList of Contributors ix 1 Introduction and Classification of Infections of the CNS According to the Agent 1Fabrice Chrétien, Kum Thong Wong, Leroy R. Sharer, Catherine (Katy) Keohane, and Françoise Gray 2 Sepsis‐Associated Encephalopathy 11Franck Verdonk, Aurelien Mazeraud, Fabrice Chrétien, and Tarek Sharshar 3 Variation of CNS Infections According to the Host 21Leroy R. Sharer, Catherine (Katy) Keohane, and Françoise Gray 4 Clinical Approach to the Adult Patient with CNS Infection 29Michel Wolff, Romain Sonneville, and Tarek Sharshar 5 Herpes Simplex Virus Infections of the CNS 43Bette K. Kleinschmidt‐DeMasters, Catherine (Katy) Keohane, and Françoise Gray 6 Varicella‐Zoster Virus and Epstein‐Barr Virus Infections of the CNS 55Catherine (Katy) Keohane and Françoise Gray 7 Cytomegalovirus Infections of the CNS 65Homa Adle‐Biassette and Natacha Teissier 8 Adenovirus Meningoencephalitis 77Harry V. Vinters and Xinhai R. Zhang 9 Polyomavirus Infections of the CNS 83Susan Morgello 10 Measles Virus Infection of the CNS 95Catherine (Katy) Keohane, Leroy R. Sharer, and Françoise Gray 11 Rubella Virus 105Bette K. Kleinschmidt‐DeMasters 12 Henipavirus Encephalitis 113Kum Thong Wong and Kien Chai Ong 13 Rabies 121Guilherme Dias de Melo, Perrine Parize, Grégory Jouvion, Laurent Dacheux, Fabrice Chrétien, and Hervé Bourhy 14 Flaviviruses 1: General Introduction and Tick‐Borne Encephalitis 131Herbert Budka 15 Flaviviruses 2: West Nile, St. Louis Encephalitis, Murray Valley Encephalitis, Yellow Fever, and Dengue 147Edward S. Johnson and Juan M. Bilbao 16 Flaviviruses 3: Zika Virus Infection of the CNS 163Leila Chimelli 17 Flaviviruses 4: Japanese Encephalitis 169Shankar Krishna Susarla, Anita Mahadevan, Bishan Radotra, Masaki Takao, and Kum Thong Wong 18 CNS Disorders Caused by Hepatitis C and Hepatitis E Viruses 177Melissa Umphlett, Clare Bryce, and Susan Morgello 19 Alphaviral Equine Encephalomyelitis (Eastern, Western, and Venezuelan) 183Kum Thong Wong 20 Chikungunya Virus 189Cássia Shinotsuka, Michael Blatzer, Grégory Jouvion, and Fabrice Chrétien 21 Poliovirus Infection and Postpolio Syndrome 195Catherine (Katy) Keohane, Leila Chimelli, and Aisling Ryan 22 Enterovirus A71 Infection 205Kum Thong Wong, Kien Chai Ong, Thérèse Couderc, and Marc Lecuit 23 Human Immunodeficiency Virus Infection of the CNS 215Françoise Gray and Leroy R. Sharer 24 HTLV‐1 and Neurological‐Associated Disease 231Antoine Gessain, Olivier Cassar, and Philippe V. Afonso 25 Parechovirus A 243Clayton A. Wiley 26 Acute Disseminated Encephalomyelitis and Acute Hemorrhagic Leukoencephalomyelitis 251Romana Höftberger and Hans Lassmann 27 Miscellaneous Inflammatory Disorders of the CNS of Possible Infectious Origin 259Mari Perez‐Rosendahl, Jamie Nakagiri, Xinhai R. Zhang, and Harry V. Vinters 28 Mycoplasmal and Rickettsial Infections of the CNS 267Roy H. Rhodes 29 Pathogenesis and Pathophysiology of Bacterial Infections of the CNS 279Loic Le Guennec and Sandrine Bourdoulous 30 Pyogenic Infections of the CNS 1: Acute Bacterial Meningitis 295Loic Le Guennec and Sandrine Bourdoulous 31 Pyogenic Infections of the CNS 2: (Brain Abscess, Subdural Abscess or Empyema, Epidural Abscess, Septic Embolism, and Suppurative Intracranial Phlebitis) 309Arnault Tauziede‐Espariat, Alexandre Roux, Megan Still, Marc Zanello, Gilles Zah‐Bi, Ghazi Hmeydia, Catherine Oppenheim, Michel Wolff, Johan Pallud, and Fabrice Chrétien 32 Pyogenic Infections of the CNS 3: Following Neurosurgical Procedures 319Alexandre Roux, Megan Still, Marc Zanello, Gilles Zah‐Bi, Arnault Tauziede‐Espariat, Ghazi Hmeydia, Catherine Oppenheim, Michel Wolff, Fabrice Chrétien, and Johan Pallud 33 CNS Involvement in Tropheryma whipplei Infection 331Emmanuèle Lechapt‐Zalcman 34 Cerebral Actinomycosis 337Arnault Tauziede‐Espariat 35 Cerebral Nocardiosis 343Arnault Tauziede‐Espariat and Leroy R. Sharer 36 CNS Tuberculosis 349Michael A. Farrell, Eoin R. Feeney, and Jane B. Cryan 37 Non‐Tuberculous Mycobacterial Infections 357Leroy R. Sharer 38 Spirochetal Infections of the CNS 363Françoise Gray and Catherine (Katy) Keohane 39 Neurobrucellosis 379Marine Le Dudal, Fabrice Chrétien, and Grégory Jouvion 40 Legionellosis 383Edward S. Johnson 41 Neurosarcoidosis 393Michael A. Farrell and Alan Beausang 42 Hypertrophic Pachymeningitis 403Françoise Gray and Leroy R. Sharer 43 Toxin‐Induced Neurological Diseases 411Pierre L. Goossens, Cédric Thépenier, and Michel R. Popoff 44 Fungal Infections of the CNS 419Michael Blatzer, Fanny Lanternier, Jean‐Paul Latgé, Anne Beauvais, Stéphane Bretagne, Fabrice Chrétien, and Grégory Jouvion 45 Cerebral Malaria 437Patrícia Reis, Vanessa Estato, and Hugo Caire de Castro Faria Neto 46 Toxoplasma Infection of the CNS 449Stéphane Bretagne, Catherine (Katy) Keohane, and Homa Adle‐Biassette 47 Other Protozoal Infections 463Leila Chimelli and Catherine (Katy) Keohane 48 Helminth Infections of the CNS 475Marine Le Dudal, Stéphane Bretagne, David Hardy, Fabrice Chrétien, and Grégory Jouvion Appendix: CASE EXAMPLE: Schistosoma mekongi Neuroschistosomiasis 500Edward S. Johnson 49 Brain Myiasis 503Arnault Tauziede‐Espariat 50 Emerging CNS Infections 505Kum Thong Wong Index 515

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Book SynopsisDeveloped by the American Cancer Society this new textbook designed for a wide range of learners and practitioners is a comprehensive reference covering the diagnosis of cancer, and a range of related issues that are key to a multidisciplinary approach to cancer and critical to cancer control and may be used in conjunction with the book, The American Cancer Society''s Oncology in Practice: Clinical Management. Edited by leading clinicians in the field and a stellar contributor list from the US and Europe, this book is written in an easy to understand style by multidisciplinary teams of medical oncologists, radiation oncologists and other specialists, reflecting day-to-day decision-making and clinical practice. Input from pathologists, surgeons, radiologists, and other specialists is included wherever relevant and comprehensive treatment guidelines are provided by expert contributors where there is no standard recognized treatment. This book is an ideal resource for anyonTable of ContentsEditorial Board and Reviewers viii List of Contributors ix Introduction xv Section 1 | Cancer Causes, Prevention, and Early Detection 1 1 Descriptive Epidemiology 3Rebecca L. Siegel, Kimberly D. Miller, and Ahmedin Jemal 2 Fundamentals of Cancer Epidemiology 15Susan M. Gapstur and Eric J. Jacobs 3 Socioeconomic Inequalities in Cancer Incidence and Mortality 23Gopal K. Singh and Ahmedin Jemal 4 The Global Burden of Cancer 33Ahmedin Jemal and Lindsey A. Torre 5 Counseling and Testing for Inherited Predisposition to Cancer 45Emily Glogowski, Kasmintan A. Schrader, Kelly L. Stratton, and Kenneth Offit 6 Tobacco 58Thomas J. Glynn, Richard D. Hurt, and J. Lee Westmaas 7 Microbial Carcinogens 72Edgar P. Simard and Ahmedin Jemal 8 Environmental and Occupational Carcinogens 81Elizabeth Ward 9 Nutrition and Physical Activity for Cancer Prevention 92Stacey Fedewa, Rebecca L. Siegel, Colleen Doyle, Marji L. McCullough, and Alpa V. Patel 10 Sun Protection 99Andrew C. Walls and Martin A. Weinstock 11 Screening and Early Detection 110Robert A. Smith, Otis W. Brawley, and Richard C. Wender Section 2 | Cancer Biology 137 12 The Principles and Drivers of Cancer 139Charles Saxe and William C. Phelps Section 3 | Diagnosis 153 13 Imaging in Oncology 155Andreas G. Wibmer, Andreas M. Hötker, Maura Miccò, David M. Panicek, and Hedvig Hricak 14 The Pathologic Evaluation of Neoplastic Diseases 164John D. Pfeifer and Mark R. Wick 15 Cancer Staging 184Frederick L. Greene and Lauren A. Kosinski Section 4 | Treatment Modalities 191 16 Surgical Oncology Overview 193M. Andrew Sicard and Benjamin D. Li 17 Radiotherapy 204Curtiland Deville, Jr., Gaurav Shukla, Ramesh Rengan, and Charles R. Thomas, Jr. 18 Cytotoxic Chemotherapy 220R. Donald Harvey and Fadlo R. Khuri 19 Hormonal Therapy for Cancer 236Amelia B. Zelnak and Bradley C. Carthon 20 Immunotherapy of Cancer 244Diwakar Davar, Ahmad A. Tarhini, and John M. Kirkwood 21 Targeted Therapies 267Elizabeth Kessler, Paul Brittain, S. Lindsey Davis, Stephen Leong, S. Gail Eckhardt, and Christopher H. Lieu 22 Hematopoietic Stem Cell Transplantation for Cancer 284Joshua F. Zeidner, Christopher G. Kanakry, and Leo Luznik 23 Diet, Physical Activity, and Weight Control for Cancer Patients and Survivors 293Wendy Demark]Wahnefried, Laura Q. Rogers, Catherine M. Alfano, Cynthia A. Thomson, Kerry S. Courneya, Jeffrey A. Meyerhardt, Nicole L. Stout, Elizabeth Kvale, Heidi Ganzer, Ted Gansler, and Jennifer A. Ligibel 24 Clinical Trials 306Olwen M. Hahn and Richard L. Schilsky 25 Complementary and Alternative (Integrative) Oncology 315Gabriel Lopez, Richard Lee, M. Kay Garcia, Alejandro Chaoul, and Lorenzo Cohen Section 5 | Geriatric Oncology 323 26 Geriatric Oncology 325Arvind M. Shinde, Sumanta K. Pal, and Arti Hurria Section 6 | Symptom Management, Palliative Care, Complications and Toxicities of Treatment, Patient]Reported Outcomes, etc. 333 27 Palliative and Supportive Care 335Rony Dev and Eduardo Bruera 28 Sexuality and Fertility 359Jeanne Carter, Shari B. Goldfarb, Yukio Sonoda, Christian J. Nelson, Maura N. Dickler, and John P. Mulhall 29 Psychiatric Issues in Cancer Patients 379Andrew J. Roth and Adrienne Jaeger 30 Oncologic Emergencies 393Mark A. Lewis, William J. Hogan, and Timothy J. Moynihan 31 Patient]Reported Outcomes in Cancer: Application and Utility in Clinical Practice and Research 409Kevin D. Stein, Tenbroeck Smith, Joseph E. Bauer, Deborah L. Driscoll, and Dexter L. Cooper 32 Survivorship Care 419Emily Tonorezos, Shrujal S. Baxi, Victoria Blinder, Darren R. Feldman, Danielle Novetsky Friedman, Matthew Matasar, Talya Salz, Armin Shahrokni, and Kevin C. Oeffinger Index 437

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Book SynopsisResearch has shown that a range of adult psychiatric disorders and mental health problems originate at an early age, yet the psychiatric symptoms of an increasing number of children and adolescents are going unrecognized and untreatedthere are simply not enough child psychiatric providers to meet this steadily rising demand. It is vital that advanced practice registered nurses (APRNs) and primary care practitioners take active roles in assessing behavioral health presentations and work collaboratively with families and other healthcare professionals to ensure that all children and adolescents receive appropriate treatment. Child and Adolescent Behavioral Health helps APRNs address the mental health needs of this vulnerable population, providing practical guidance on assessment guidelines, intervention and treatment strategies, indications for consultation, collaboration, referral, and more. Now in its second edition, this comprehensive and timely resource has been fullTrade ReviewSecond Place in the Child Health Category, 2021 American Journal of Nursing Book of the Year Awards Table of ContentsAbout the Editors ix List of Contributors xi Forward xv Forward xvi Preface to Second Edition xvii Acknowledgment xix About the Companion Website xxi 1 Child, Adolescent, and Family Development 1Stephanie Wright and Edilma L. Yearwood 2 Temperament and Self-Regulation 23Pamela Galehouse and Marie Foley 3 Neurobiology and Neurophysiology of Behavioral/Psychiatric Disorders 41Susan J. Boorin and Norman L. Keltner 4 Integration of Physical and Psychiatric Assessment 58Veronica C. Doran and Jamesetta A. Newland 5 Child Sexual Development 90Gabrielle Abelard and Emma Dundon 6 Adolescent Sexual Behaviors 98Bridgette M. Brawner and Anne M. Teitelman 7 Assessing and Managing the Needs of LGBTQ Youth 110Liam C. Hein and Jose A. Parés-Avila 8 Adverse Childhood Experiences: Providing Trauma-informed Care to Promote Resilience in Children and Their Families in Health Settings 123Freida H. Outlaw, Lisa Milam, and Patricia K. Bradley 9 Psychopharmacology: Issues in Prescribing Psychiatric Medication to Children and Adolescents 136Geraldine S. Pearson and Crystal Marie Bennett 10 Attention Deficit Hyperactivity Disorder 162Geraldine S. Pearson and Cherry Leung 11 Anxiety Disorders 173Geraldine S. Pearson and Kathleen Kenney-Riley 12 Mood Dysregulation Disorders 184Mikki Meadows-Oliver and Edilma L. Yearwood 13 Deliberate Self-harm: Nonsuicidal Self-injury and Suicide in Children and Adolescents 207Edilma L. Yearwood and Eve Bosnick 14 Perceptual Alterations Disorders 227Heeyoung Lee and Eunjung Kim 15 Feeding and Eating Disorders in Children and Adolescents 242Janiece E. DeSocio and Joan B. Riley 16 Autism Spectrum Disorder 267Judith Coucouvanis and Donna Hallas 17 Learning and Intellectual Disabilities 290Linda M. Finke and Patricia Ryan-Krause 18 Nonpharmacological Treatment Modalities: Play and Group Therapies 305Edilma L. Yearwood and Allison Grady 19 Individual and Family Therapies 321Kathleen Scharer 20 Cognitive Behavioral Interventions in Child and Adolescent Mental Health Treatment 340Pamela Lusk and Jessica Lee Kozlowski 21 Disorders Specific to Infants and Young Children 357Joan A. Kearney and Shannon D’Alton 22 Juvenile Justice Populations 380Elizabeth Bonham and Moriah Freeman 23 Substance Use 397Caroline R. McKinnon, Deborah Johnson, and Linda Stephan 24 Child and Adolescent Victims of Trauma 425Dawn Bounds, Necole Leland, and Angela F. Amar 25 Children in Out-of-Home Placement 444Julie E. Bertram and Betty Boyle-Duke 26 Chronic and Palliative Care Pediatric Populations 458Geraldine S. Pearson and Deborah Fisher 27 Collaborative Treatment with Primary Care 472Madeleine M. Lloyd and Jamesetta A. Newland 28 Legal and Ethical Issues 483Margaret Hardy and Sarah B. Vittone 29 Evidence-based Nursing Practice 503Donna Hallas and Pamela Lusk 30 Cultural Influences on Child and Adolescent Mental Health: Needs of Immigrant, Refugee, Displaced, and Culturally Vulnerable Youth 512Edilma L. Yearwood and Mikki Meadows-Oliver 31 Conducting Behavioral Health Research with Children and Using Research Methods 526Elizabeth Burgess Dowdell and Judith Fry-McComish 32 Advanced Practice Registered Nurses Interfacing with the School System 540Melissa M. Gomes and Naomi A. Schapiro 33 Child and Adolescent Mental Health Policy 555Sally Raphel and Eileen K. Fry-Bowers Index 570

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Book SynopsisThe third medical atlas in this new series on the human body and filled with detailed pictures, this atlas details the topographical and pathotopographical anatomy of the chest, abdomen, lumbar region, and retroperitoneal space, a useful reference for medical professionals and students alike. Written by an experienced and well-respected physician and professor, this new volume, building on the previous volume, Ultrasonic Topographical and Pathotopographical Anatomy, and its sequel, Topographical and Pathotopographical Medical Atlas of the Head and Neck, also available from Wiley-Scrivener, presents the ultrasonic topographical and pathotopographical anatomy of the chest, abdomen, lumbar region, and retroperitoneal space, offering further detail into these important areas for use by medical professionals. This series of atlases of topographic and pathotopographic human anatomy is a fundamental and practically important series designed for doctors ofTable of ContentsPreface viiPart 1: The Chest 1Part 2: Abdomen 51Part 3: Lumbar Region and Retroperitoneal Space 111Part 4: Pathotography Chest 139About the Author 179

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Book SynopsisA comprehensive primer and reference, this book provides pharmacists and health practitioners the relevant science and policy concepts behind biologics, biosimilars, and biobetters from a practical and clinical perspective. Explains what pharmacists need to discuss the equivalence, efficacy, safety, and risks of biosimilars with physicians, health practitioners, and patients about Guides regulators on pragmatic approaches to dealing with these drugs in the context of rapidly evolving scientific and clinical evidence Balances scientific information on complex drugs with practical information, such as a checklist for pharmacists Table of ContentsList of Contributors vii Foreword ix Preface xi 1 Innovator Biologics, Biosimilars, and Biobetters: Terminology, Nomenclature, and Definitions 1 2 Approved Biologic Medicines and Biosimilars in Major Regulatory Jurisdictions 17 3 Status of Biologic Drugs in Modern Therapeutics-Targeted Therapies vs. Small Molecule Drugs 31 4 Major Classes of Biotherapeutics 47 5 Drug Targets for Biologics 71 6 Pivotal Biology, Chemistry, Biochemistry, and Biophysical Concepts of Biologics and Biosimilars 89 7 Biosimilarity and Interchangeability of Biologic Drugs-General Principles, Biophysical Tests, and Clinical Requirements to Demonstrate Biosimilarity 109 8 Pharmacokinetics of Biologics 125 9 Pharmacogenomics of Biologics 147 10 International Regulatory Processes and Policies for Innovator Biologics, Biosimilars, and Biobetters 159 11 Pharmacovigilance of Innovator Biologics and Biosimilars 177 12 Pharmacoeconomics of Biologic Medicines and Biosimilars 195 13 New Emerging Biotherapies: Cutting-Edge Research to Experimental Therapies 213 14 Optimizing Use of Biologic Medicines Using a Quality Use of Medicines Approach 237 15 Knowledge Areas and Competency Standards on Biologic Medicines for Pharmacists and Pharmacy Students 253 16 A Checklist for Pharmacists on Biologics and Biosimilars: Tips to Enhance Patient-Centered Discussions 267 Index 295

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Book SynopsisExplains the advantages of using medaka in experimental designs, to facilitate research, and to stimulate progress by adopting medaka as a model animal The second volume of Medaka: Biology, Management, and Experimental Protocols, together with the first volume, helps to familiarize scientists with the advantages of using medaka in experimental designs, to facilitate research using medaka, and to stimulate progress by adopting medaka as a model animal. The second edition expands on the first by providing additional information and current protocols that have been recently developed, or modified, to successfully raise medaka fish under stable culture conditions in the laboratory. This volume explores new technologies developed after 2009, using the fish as a molecular tool in the fields of life science, evolution, ecology, and toxicology. The authorsnoted experts in the fieldprovide the latest information that spans the varied research disciplines and addreTable of ContentsList of Contributors xv Preface xxi 1 Medaka Management 1 1.1 Introduction 1 1.2 Medaka Management for Scientific Research 1 1.2.1 Outline of medaka life‐cycle in the wild 2 1.2.2 Preparation of normal rearing conditions of medaka in the laboratory and procedures for breeding 2 1.2.2.1 Breeding system set‐up 2 1.2.2.2 Obtaining medaka 3 1.2.2.3 Collecting eggs in a laboratory setting 3 1.2.2.4 Daily care and maintenance of eggs 4 1.2.2.5 Rearing medaka from the larval stage to adulthood 4 1.2.2.6 Anesthesia and euthanasia 4 1.3 Standardized Culture and Growth Curve 7 1.3.1 Characteristics and selection of strains 7 1.3.2 Management of medaka eggs and fish 8 1.3.2.1 Mating 8 1.3.2.2 Management of embryos 8 1.3.2.3 Management of embryos before hatching 13 1.3.2.4 Rearing from the larval stage to adulthood (to induce earlier maturation) 14 1.3.3 Maintenance of breeding tanks during breeding 23 1.3.3.1 Judgment of water quality 23 1.3.3.2 Maintenance of breeding water 24 1.3.4 Anesthesia 25 1.3.4.1 Behavior under each anesthesia stage 26 1.3.4.2 Difference in sensitivity to anesthesia among strains 26 1.3.4.3 Growth stage specificity in sensitivity to MS‐222 27 1.3.4.4 Eugenol is recommended as an anesthetic reagent 28 1.3.4.5 Euthanasia 28 1.3.4.6 Important reminders for euthanasia 29 2 Medaka and Oryzias Species as Model Organisms and the Current Status of Medaka Biological Resources 31 2.1 Introduction 31 2.2 Common and Unique Futures of Medaka and Related Species as Model Organisms 31 2.3 Phylogenetic Relationships of Medaka and Related Species 35 2.3.1 The javanicus species group 35 2.3.2 The latipes species group 40 2.3.3 The celebensis species group 42 2.4 BAC Resources of Species Related to Medaka 43 2.5 National Bio‐Resource Project Medaka (NBRP Medaka) 43 2.5.1 Support for visiting researchers 45 3 Looking at Adult Medaka 49 3.1 General Morphology 49 3.1.1 Secondary sexual characters 49 3.1.1.1 Dorsal fin 49 3.1.1.2 Anal fin 49 3.1.1.3 Papillar processes 50 3.1.1.4 Urogenital papillae 50 3.1.2 Body color 51 3.1.2.1 Pigment cells (chromatophores) 51 3.1.2.2 Structures of the chromatophores 51 3.1.2.3 Chromatophores in medaka 51 3.1.2.4 Chromatophore distribution in medaka 55 3.1.2.5 See‐through medaka 56 3.2 Anatomy and Histology 56 3.2.1 Observations of internal organs 56 3.2.1.1 Observations of internal organs in the live see‐through medaka 56 3.2.1.2 Dissection of adult medaka 58 3.2.2 Horizontal and sagittal sections of juvenile medaka 58 3.2.3 Nervous system 58 3.2.3.1 Adult central nervous system 58 3.2.3.2 Adult peripheral nervous system 67 3.2.4 Endocrine system 74 3.2.4.1 Hypothalamo‐pituitary system 76 3.2.4.2 Pineal organ (epiphysis) 78 3.2.4.3 Thyroid gland 79 3.2.4.4 Heart 81 3.2.4.5 Interrenal gland and chromaffin cells 81 3.2.4.6 Gonads 81 3.2.4.7 Endocrine pancreas (islets of Langerhans) 81 3.2.4.8 Gastrointestinal tract 81 3.2.4.9 Ultimobranchial gland 82 3.2.4.10 Corpuscle of Stannius 82 3.2.4.11 Urophysis 83 3.2.4.12 Thymus 83 3.2.5 Gonads 83 3.2.5.1 Ovary 83 3.2.5.2 Testis 85 3.2.6 Kidney 85 3.2.6.1 Pronephros 86 3.2.6.2 Mesonephros 86 3.2.6.3 Histology of the kidney 86 Column 3.1 How to make sections of a mature ovary for histological analysis 88 4 Looking at Medaka Embryos 97 4.1 Development of Various Tissues and Organs 97 4.1.1 Developmental stages 97 4.1.1.1 Stage 0: unfertilized egg (Figure 4-1) 97 4.1.1.2 Stage 1: activated egg stage (3 minutes) (Figure 4-1) 99 4.1.1.3 Stage 2: blastodisc stage (Figure 4-1) 99 4.1.1.4 Stage 3: two‐cell stage (1 hour 5 minutes) (Figure 4-1) 99 4.1.1.5 Stage 4: four‐cell stage (1 hour 45 minutes) (Figure 4-1) 100 4.1.1.6 Stage 5: eight‐cell stage (2 hours 20 minutes) (Figure 4-1) 100 4.1.1.7 Stage 6: 16‐cell stage (2 hours 55 minutes) (Figure 4-2) 100 4.1.1.8 Stage 7: 32‐cell stage (3 hours 30 minutes) (Figure 4-2) 100 4.1.1.9 Stage 8: early morula stage (4 hours 5 minutes) (Figure 4-2) 100 4.1.1.10 Stage 9: late morula stage (5 hours 15 minutes) (Figure 4-2) 100 4.1.1.11 Stage 10: early blastula stage (6 hours 30 minutes) (Figure 4-2) 100 4.1.1.12 Stage 11: late blastula stage (8 hours 15 minutes) (Figure 4-2) 102 4.1.1.13 Stage 12: pre‐early gastrula stage (10 hours 20 minutes) (Figure 4-3) 102 4.1.1.14 Stage 13: early gastrula stage (13 hours) (Figure 4-3) 102 4.1.1.15 Stage 14: pre‐mid‐gastrula stage (15 hours) (Figure 4-3) 102 4.1.1.16 Stage 15: mid‐gastrula stage (17 hours 30 minutes) (Figure 4-3) 102 4.1.1.17 Stage 16: late gastrula stage (21 hours) (Figure 4-3) 102 4.1.1.18 Stage 17: early neurula stage (1 day 1 hour) (Figure 4-3) 103 4.1.1.19 Stage 18: late neurula stage (1 day 2 hours) (Figure 4-4) 104 4.1.1.20 Stage 19: two‐somite stage (1 day 3 hours 30 minutes) (Figure 4-4) 104 4.1.1.21 Stage 20: four‐somite stage (1 day 7 hours 30 minutes) (Figure 4-4) 104 4.1.1.22 Stage 21: six‐somite stage (1 day 10 hours) (Figure 4-4) 104 4.1.1.23 Stage 22: nine‐somite stage (1 day 14 hours) (Figure 4-4) 104 4.1.1.24 Stage 23: 12‐somite stage (1 day 17 hours) (Figure 4-4) 104 4.1.1.25 Stage 24: 16‐somite stage (1 day 20 hours) (Figure 4-5) 106 4.1.1.26 Stage 25: 18–19‐somite stage (2 days 2 hours) (Figure 4-5) 107 4.1.1.27 Stage 26: 22‐somite stage (2 days 6 hours) (Figure 4-5) 107 4.1.1.28 Stage 27: 24‐somite stage (2 days 10 hours) (Figure 4-5) 107 4.1.1.29 Stage 28: 30‐somite stage (2 days 16 hours) (Figure 4-5) 107 4.1.1.30 Stage 29: 34‐somite stage (3 days 2 hours) (Figure 4-5) 108 4.1.1.31 Stage 30: 35‐somite stage (3 days 10 hours) (Figure 4-6) 108 4.1.1.32 Stage 31: gill blood vessel formation stage (3 days 23 hours) (Figure 4-6) 108 4.1.1.33 Stage 32: somite completion stage (4 days 5 hours) (Figure 4-6) 108 4.1.1.34 Stage 33: stage at which notochord vacuolization is completed (4 days 10 hours) (Figure 4-6) 108 4.1.1.35 Stage 34: pectoral fin blood circulation stage (5 days 1 hour) (Figure 4-6) 110 4.1.1.36 Stage 35: stage at which visceral blood vessels form (5 days 12 hours) (Figure 4-6) 110 4.1.1.37 Stage 36: heart development stage (6 days) (Figure 4-7) 110 4.1.1.38 Stage 37: pericardial cavity formation stage (7 days) (Figure 4-7) 110 4.1.1.39 Stage 38: spleen development stage (8 days) (Figure 4-7) 110 4.1.1.40 Stage 39: hatching stage (9 days) (Figure 4-7) 110 4.1.1.41 Stage 40: first larval stage (Figure 4-8) 112 4.1.1.42 Stage 41: second larval stage (Figure 4-8) 113 4.1.1.43 Stage 42: third larval stage (Figure 4-8) 113 4.1.1.44 Stage 43: first juvenile stage (Figure 4-8) 113 4.1.1.45 Stage 44: second juvenile stage (Figure 4-8) 113 4.1.1.46 Stage 45 (Figure 4-8) 113 4.1.2 Brain 113 4.1.2.1 Gastrula step (stages 13–17) 114 4.1.2.2 Neurula step (stages 17–18) 114 4.1.2.3 Neural rod step (stages 19–22) 116 4.1.2.4 Neural tube step (stages 23–27) 116 4.1.2.5 Late embryonic brain step (stages 28–34) 117 4.1.2.6 Larval brain step (stages 35–42) 119 4.1.3 Hatching gland 119 4.1.3.1 Origin of fish hatching gland cells 119 4.1.3.2 Secretion of hatching enzymes from hatching gland cells 122 4.1.4 Eye development 124 4.1.4.1 Specification of the anterior neural plate 124 4.1.4.2 Eye field determination and establishment of retinal identity 125 4.1.4.3 Splitting of the retinal anlage into two retinal primordia 125 4.1.4.4 Morphogenesis I: evagination of the optic vesicle 125 4.1.4.5 Morphogenesis II: formation of the optic cup 127 4.1.4.6 Retinal differentiation I: central retina 127 4.1.4.7 Retinal differentiation II: Ciliary Marginal Zone 127 4.1.4.8 Retinotectal projection 128 4.1.5 Branchial arch and jaws 128 4.1.5.1 Skeletal development 128 4.1.5.2 Muscle development 130 4.1.6 Vasculature 131 4.1.6.1 Vascular anatomy of the developing medaka 131 4.1.6.2 Origin of the medaka endothelial lineage 142 4.1.6.3 Abbreviations 142 4.1.6.4 Acknowledgment 143 4.1.7 Blood cells (hematopoiesis) 143 4.1.7.1 Overview 143 4.1.7.2 Observation of embryonic and adult blood cells 144 4.1.8 Heart 146 4.1.8.1 Overview 146 4.1.8.2 Heart architecture 146 4.1.8.3 Heart morphogenesis 147 4.1.8.4 Observation of the developing heart 156 4.1.9 Kidney 159 4.1.9.1 Overview 159 4.1.9.2 Nephrogenesis 159 4.1.9.3 Pronephros 160 4.1.9.4 Mesonephros 160 4.1.10 Thymus 160 4.1.10.1 Overview 160 4.1.10.2 Early development of the thymus 160 4.1.10.3 Cortex and medulla 161 4.1.10.4 Involution of the thymus 162 4.1.11 Gut and liver 162 4.1.12 Bones 164 4.1.12.1 Vertebral column 164 Column 4.1 Key words in bone formation 172 4.1.13 Fins 173 4.1.13.1 Overview 173 4.1.13.2 Fin anatomy 173 4.1.13.3 Embryonic fin development (from fertilization to stage 39 [hatching stage]) 174 4.1.13.4 Fin development after hatching (after stage 39) 175 4.1.13.5 Gene expression during fin development 175 4.1.14 Gonads 176 4.1.14.1 Overview 176 4.1.14.2 PGC specification 177 4.1.14.3 Formation of gonadal primordium (Figure 4-60b) 177 4.1.14.4 Sexual dimorphism in germ cell proliferation (Figure 4-61) 179 4.1.14.5 Posthatching period in XX gonads 180 4.1.14.6 Posthatching period in XY gonads 180 4.2 Medaka EGG Envelope and Hatching Enzyme 181 4.2.1 Overview 181 4.2.2 Preparation of a hatching enzyme solution from hatching liquid 182 4.2.2.1 Procedure 182 4.2.3 Simple method for preparing hatching enzyme solution 183 4.2.3.1 Procedure 183 4.2.4 Solubilization of the egg envelope using hatching enzyme 183 Column 4.2 Easy method for preparation of a small amount of hatching enzyme solution (see website for figure) 184 4.3 Observation of Embryos (Embedding Embryos) 185 4.3.1 Anesthesia of embryos using MS‐222 185 4.3.1.1 Equipment and reagents 185 4.3.2 Observation of embryos (mounting) 185 4.3.2.1 Living embryos 185 4.3.2.2 Processed embryos 188 4.4 Whole‐Mount In Situ Hybridization (see section 4.1.8.4 for a similar protocol) 189 4.4.1 Fixation and storage 189 4.4.1.1 Procedure 1 189 4.4.2 Rehydration, proteinase K treatment, and postfixation at RT 190 4.4.2.1 Procedure 2 190 4.4.3 Hybridization and washing 190 4.4.3.1 Procedure 3 190 4.4.4 Immunoreaction and washing antibodies 191 4.4.4.1 Procedure 4 191 4.4.5 Staining 191 4.4.5.1 Procedure 5 191 4.5 Embedding in a Plastic Resin (Technovit 7100) 192 4.5.1 Equipment and reagents 192 4.5.2 Agarose mounting (Figure 4-68) 192 4.5.2.1 Procedure 1 192 4.5.3 Dehydration and infiltration (Figure 4-68) 192 4.5.3.1 Procedure 2 192 4.5.4 Polymerization (Figure 4-68) 193 4.5.4.1 Procedure 3 193 Column 4.3 Pigment Cells (Figure 4-69) 194 Column 4.4 Kupffer’s Vesicle 195 5 Reproductive Behavior of Wild Japanese Medaka 205 5.1 Wild Japanese Medaka 205 5.2 Reproductive Behavior of Wild Medaka 206 5.2.1 Aggressive behavior 207 5.2.2 Spawning behavior 207 5.2.3 Egg deposition behavior 210 5.2.4 Egg discarding behavior 210 5.2.5 School and aggregation 211 5.3 Conclusion 211 6 Cryopreservation and Transplantation of Medaka Germ Cells 215 6.1 Introduction 215 6.2 Cryopreservation of Medaka Testes 215 6.2.1 Solutions 216 6.2.2 Materials 217 6.2.3 Procedures 217 6.3 Transplantation of Thawed Testicular Cells into Recipient Larvae 218 6.3.1 Solutions 218 6.3.2 Materials 219 6.3.3 Procedures 219 Column 6.1 Production of triploid medaka 222 7 Genome Editing 225 7.1 Introduction 225 7.2 Outline of Targeted Genome Editing Using Nucleases 225 7.3 Preparation of CRISPR/Cas9 Genome Editing Tools 226 7.3.1 Materials 227 7.3.2 Production of custom‐designed sgRNA 228 7.3.2.1 Preparation of the bsai‐digested sgRNA backbone 228 7.3.2.2 Design and production of customized sgRNA 228 7.3.3 Production of capped RNA encoding a Cas9 nuclease 232 7.4 Preparation of Custom‐Designed TALENs 234 7.4.1 Materials 234 7.4.2 Preparation of the TALEN assembly system 236 7.4.2.1 Preparation of TAL modules (HD1‐6, NG1‐6, NI1‐6, and NN1‐6) 236 7.4.2.2 Preparation of array backbone plasmids (pFUS vectors) 236 7.4.2.3 Preparation of last repeat modules (LR‐HD, NG, NI, and NN) 237 7.4.2.4 Preparation of TALEN backbone plasmids (pCS2TAL3DD and RR vectors) 238 7.4.3 Design and construction of custom‐designed TALENs 239 7.4.3.1 Design of TALEN using TALE‐NT 239 7.4.3.2 First assembly: construction of 6‐modules array vectors 240 7.4.3.3 Second assembly: construction of TALEN expression vectors 242 7.5 Heteroduplex Mobility Assay – A Simple Method to Detect Targeted Genome Modification 244 7.5.1 Materials 246 7.5.2 Procedure 246 7.5.2.1 Identification of the wild type, heterozygotes, and homozygotes 246 7.5.2.2 Evaluation of the efficiency of targeted genome modifications 246 7.6 How to Establish Gene Knock‐out Strains 247 7.6.1 Design and synthesis of genome‐editing tools 247 7.6.2 Evaluation of genome‐editing activity with fertilized medaka eggs 247 7.6.3 Microinjection of the selected genome‐editing tool(s) 248 7.6.4 Selection of founder fish by genotyping F1 embryos 249 7.6.5 Selection of F1 fish carrying the same mutation and the establishment of mutant strain 249 7.6.6 Selection of homozygous mutant fish in the F2 family 251 7.7 How to Establish Gene Knock‐in Strains 252 7.7.1 Design and synthesis of CRISPR/Cas9 components 253 7.7.2 Evaluation of genome‐editing activity with fertilized medaka eggs 253 7.7.3 Construction of donor plasmid with homology arms (Ca. 0.5 kbp) and bait sequences 253 7.7.4 Microinjection for establishing knock‐in strains 254 7.7.5 Selecting G0 founders harboring the insert gene in the genomic target site 254 Column 7.1 Utilization of crRNA, tracrRNA, Cas9 Protein 255 7.A Simple Genomic DNA Preparation by an Alkaline Lysis Method 256 7.A.1 Materials 256 7.A.2 Procedure 256 8 Photo‐Inducible Gene Expression in Medaka 261 8.1 Outline of IR‐LEGO 261 8.2 Practical Strategies of IR‐LEGO in Medaka Study 262 8.2.1 Selection of heat shock promoters and application studies 262 8.3 Laser Irradiation Conditions and Sample Preparation 265 8.4 Caution in Maintaining Strains 267 8.5 Other Uses of IR‐LEGO 267 8.6 Summary and Future Prospects 268 9 Screening and Testing Methods of Endocrine‐Disrupting Chemicals Using Medaka 271 9.1 Applied Toxicity Tests for Endocrine Disruptors 271 9.2 Detection of Androgenic and Antiandrogenic Chemicals Using Medaka 275 9.2.1 The formation of papillary processes on anal fin rays as an indicative phenotype for exposure of androgenic and/or antiandrogenic chemicals 275 9.2.2 Candidate biomarkers for assessing the action of androgenic and antiandrogenic chemicals 276 9.2.3 Visualization of androgenic and antiandrogenic activity as green fluorescence with spiggin‐GFP medaka 276 10 Application of the Seawater Medaka Oryzias melastigma (McClelland) for Marine Ecotoxicology 281 10.1 Background and Development of Oryzias melastigma for Marine Ecotoxicology 281 10.2 Marine Medaka Developmental Staging 283 10.3 Standard Breeding and Rearing Conditions 284 10.3.1 Seawater 285 10.3.2 Temperature 285 10.3.3 Photoperiod 285 10.3.4 Feeding 286 10.3.5 Embryo collection and rearing 286 10.3.6 Hatching and larvae collection 287 10.3.7 Larvae rearing 288 10.3.8 Larvae feeding 288 10.4 Raising Marine Medaka for Experimental Use 289 10.4.1 Experiments using adult fish 289 10.4.2 Experiments using larvae 289 10.5 Troubleshooting 289 10.5.1 Mass mortality 289 10.5.2 Low egg production 289 10.5.3 Extensive algal growth 290 10.6 How to Obtain Marine Medaka O. melastigma 290 10.7 Experimental Protocols Using Marine Medaka 290 10.8 Immunotoxicity Assessment: Bacteria Challenge Assays 290 10.8.1 SOP for adult bacterial challenge assay 291 10.8.2 SOP for larval bacterial challenge assay 292 10.8.3 Age selection for larval bacterial challenge 293 10.9 Fish Dissection and the Whole Adult Histoarray 294 10.9.1 SOP for fish dissection 295 10.9.2 SOP for adult medaka histoarray 295 10.10 Embryo Chip 297 10.10.1 SOP for embryo and larvae histoarray 297 10.A Materials for SOP for Adult Medaka Histoarray (see section 10.9.2) 299 11 Telomerase and Telomere Biology in Medaka 303 11.1 Introduction 303 11.2 SOP for Quantification of Telomerase Activity Using the Real‐Time Quantitative Telomeric Repeat Amplification Protocol (RTQ‐TRAP) 308 11.2.1 Procedures for sample extraction 308 11.2.2 Procedures for determination of protein concentration 308 11.2.3 Procedures for RTQ‐TRAP linearity test 308 11.2.4 Calculation of telomerase activity 309 11.3 SOP for Quantification of Telomere Length Using Southern Blotting Analysis 309 11.3.1 Procedures for genomic DNA extraction and digestion with restriction enzymes 309 11.3.2 Procedures for probe preparation 311 11.3.3 Procedures for electrophoresis and southern blotting 311 11.3.4 Procedures for hybridization and detection 312 11.3.5 Procedures for computerized telomere analysis 312 11.4 SOP for Quantification of Telomere Length Using Fluorescence In Situ Hybridization 313 11.4.1 Procedures for fluorescence in situ hybridization 313 11.4.2 Procedures for confocal microscopy detection 313 11.4.3 Procedures for ImageJ analysis 314 12 Assessments of Medaka Skeletal Toxicity 317 12.1 Introduction 317 12.2 Methods 318 12.2.1 Embryonic exposures: dioxin 319 12.2.2 Embryonic exposure: dithiocarbamates 319 12.2.3 Whole‐mount alcian blue staining of hatchlings/larvaea 320 12.2.4 Whole‐mount Alizarin red S staining of hatchlings/larvaec 320 12.2.5 In vivo Alizarin complexone fluorescent staining for mineralized bone matrix 321 12.2.6 In vivo calcein fluorescent staining for mineralized bone matrix 321 12.2.7 Confocal imaging of embryo/hatchling medaka 321 12.2.8 Morphological assessments 323 12.3 Results and Discussion 324 12.3.1 Dithiocarbamates 324 12.3.2 Dioxin 325 Appendix A Solutions 329 Attributions 331 Index 335

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Book SynopsisA ComprehensiveGuidetoRadiographic Sciences and Technologyisa concisereview ofradiographic physics andimaging,perfectforstudents preparingfor certification examinations such as the American Registry for Radiologic Technologists (ARRT). Aligned with the core radiographic science components of the current American Society of Radiologic Technologists (ASRT) curriculum, this up-to-date resourcecovers topics includingradiation production and characteristics,imaging equipment,digital image acquisition and display,radiation protection,basic principles of computed tomography, and quality control. The guide beginswith an overview of theradiographic sciences and technology,followed by detailed descriptionsofthe major components of digital radiographic imaging systems.Subsequent sections discussthe essential aspects of diagnostic radiography and computed tomography, includingbasic physics, imaging modalities, digital image processing, quality control, imaging informatics,andbasic concepts of radiobiology and radiation protection.Throughoutthe book, concisechapterssummarisethe critical knowledgerequiredfor effective and efficient imaging of the patientwhileemphasisingthe important,yet commonly misunderstood,relationship between radiation dose and image quality.Written by an internationallyrecognisedexpert in the field, thisinvaluable reference and guide: Provides easy access to basic physics, techniques, equipment, and safety guidelines for radiographic imagingReflects the educational requirements of the American Society of Radiologic Technologists (ASRT), the Canadian Association of Medical Radiation Technologists (CAMRT), theCollegeof Radiographers(CoR), and otherradiography societies and associationsworldwideOffers a range of pedagogical tools such as chapter outlines, key term definitions, bulleted lists, practical examples, and links tocurrentreferences and additional resourcesIncludes charts, diagrams, photographs, and x-ray images A ComprehensiveGuidetoRadiographic Sciences and Technologyis required reading forstudents in programs using ionizing radiation, those preparing for the ARRT and other global radiography certificationexams, andpractisingtechnologists wanting to refresh their knowledge.Table of ContentsForeword xiii Preface xiv Acknowledgments xvii Section 1: Introduction Chapter 1 Radiographic sciences and technology: an overview 3 RADIOGRAPHIC IMAGING SYSTEMS: MAJOR MODALITIES AND COMPONENTS 4 RADIOGRAPHIC PHYSICS AND TECHNOLOGY 5 Essential physics of diagnostic imaging 5 Digital radiographic imaging modalities 5 Radiographic exposure technique 6 Image quality considerations 6 Computed tomography – physics and instrumentation 7 Quality control 8 Imaging informatics at a glance 9 RADIATION PROTECTION AND DOSE OPTIMIZATION 10 Radiobiology 10 Radiation protection in diagnostic radiography 10 Technical factors affecting dose in radiographic imaging 11 Radiation protection regulations 12 Optimization of radiation protection 13 Bibliography 13 Chapter 2 Digital radiographic imaging systems: major components 14 FILM‐SCREEN RADIOGRAPHY: SHORT REVIEW OF PRINCIPLES 14 DIGITAL RADIOGRAPHY MODALITIES: MAJOR SYSTEM COMPONENTS 18 Computed radiography 19 Flat‐panel digital radiography 19 Digital fluoroscopy 19 Digital mammography 21 Computed tomography 21 IMAGE COMMUNICATION SYSTEMS 22 Picture archiving and communication system 23 References 23 Section 2: Basic Radiographic Sciences and Technology Chapter 3 Basic physics of diagnostic radiography 27 STRUCTURE OF THE ATOM 28 Nucleus 28 Electrons, quantum levels, binding energy, electron volts 28 ENERGY DISSIPATION IN MATTER 29 Excitation 29 Ionization 30 TYPES OF RADIATION 30 Electromagnetic radiation 31 Particulate radiation 32 X‐RAY GENERATION 32 X‐RAY PRODUCTION 32 Properties of x‐rays 33 Origin of x‐rays 33 Characteristic radiation 33 Bremsstrahlung radiation 34 X‐RAY EMISSION 34 X‐RAY BEAM QUANTITY AND QUALITY 35 Factors affecting x‐ray beam quantity and quality 36 INTERACTION OF RADIATION WITH MATTER 39 Mechanisms of interaction in diagnostic x-ray imaging 40 RADIATION ATTENUATION 43 Linear attenuation coefficient 43 Mass attenuation coefficient 43 Half value layer 44 RADIATION QUANTITIES AND UNITS 45 Bibliography 45 Chapter 4 X‐ray tubes and generators 46 PHYSICAL COMPONENTS OF THE X‐RAY MACHINE 47 COMPONENTS OF THE X‐RAY CIRCUIT 48 The power supply to the x‐ray circuit 49 The low‐voltage section control console) 49 The high‐voltage section 50 TYPES OF X‐RAY GENERATORS 51 Three‐phase generators 52 High‐frequency generators 52 Power ratings 53 THE X‐RAY TUBE: STRUCTURE AND FUNCTION 53 Major components 54 SPECIAL X‐RAY TUBES: BASIC DESIGN FEATURES 57 Double‐bearing axle 58 HEAT CAPACITY AND HEAT DISSIPATION CONSIDERATIONS 58 X‐RAY BEAM FILTRATION AND COLLIMATION 58 Inherent and added filtration 59 Effects of filtration on x‐ray tube output intensity 59 Half‐value layer 60 Collimation 60 References 60 Chapter 5 Digital image processing at a glance 61 DIGITAL IMAGE PROCESSING 61 Definition 62 Image formation and representation 62 Processing operations 63 CHARACTERISTICS OF DIGITAL IMAGES 63 GRAY SCALE PROCESSING 64 Windowing 67 CONCLUSION 69 References 69 Chapter 6 Digital radiographic imaging modalities: principles and technology 70 COMPUTED RADIOGRAPHY 71 Essential steps 71 Basic physical principles 71 Response of the IP to radiation exposure 73 The standardized exposure indicator 73 FLAT‐PANEL DIGITAL RADIOGRAPHY 76 What is FPDR? 76 Types of FPDR systems 76 Basic physical principles of indirect and direct flat‐panel detectors 76 The fill factor of the pixel in the flat‐panel detector 78 Exposure indicator 79 Image quality descriptors for DR systems 79 Continuous quality improvement for DR systems 79 DIGITAL FLUOROSCOPY 80 Digital fluoroscopy modes 80 II‐Based digital fluoroscopy characteristics 80 Flat‐panel digital fluoroscopy characteristics 83 DIGITAL MAMMOGRAPHY 85 Screen‐film mammography – basic principles 85 Full‐field digital mammography –major elements 86 DIGITAL TOMOSYNTHESIS AT A GLANCE 87 Imaging system characteristics 87 Synthesized 2D digital mammography 89 References 90 Chapter 7 Image quality and dose 91 THE PROCESS OF CREATING AN IMAGE 92 IMAGE QUALITY METRICS 93 Contrast 93 Contrast resolution 94 Spatial resolution 96 Noise 98 Contrast‐to‐noise ratio 101 Signal‐to‐noise ratio 101 ARTIFACTS 102 IMAGE QUALITY AND DOSE 103 Digital detector response to the dose 103 Detective quantum efficiency 104 References 105 Section 3: Computed Tomography: Basic Physics and Technology Chapter 8 The essential technical aspects of computed tomography 109 BASIC PHYSICS 110 Radiation attenuation 111 TECHNOLOGY 116 Data acquisition: principles and components 117 Image reconstruction 118 Image display, storage, and communication 120 MULTISLICE CT: PRINCIPLES AND TECHNOLOGY 121 Slip‐ring technology 122 X‐ray tube technology 122 Interpolation algorithms 123 MSCT detector technology 124 Selectable scan parameters 125 Isotropic CT imaging 127 MSCT image processing 127 IMAGE POSTPROCESSING 128 Windowing 128 3‐D image display techniques 129 IMAGE QUALITY 130 Spatial resolution 130 Contrast resolution 131 Noise 131 RADIATION PROTECTION 131 CT dosimetry 132 Factors affecting patient dose 132 Optimizing radiation protection 133 CONCLUSION 134 References 134 Section 4: Continuous Quality Improvement Chapter 9 Fundamentals of quality control 139 INTRODUCTION 139 DEFINITIONS 140 ESSENTIAL STEPS OF QC 141 QC RESPONSIBILITIES 142 STEPS IN CONDUCTING A QC TEST 142 THE TOLERANCE LIMIT OR ACCEPTANCE CRITERIA 143 PARAMETERS FOR QC MONITORING 145 Major parameters of imaging systems 145 QC TESTING FREQUENCY 145 TOOLS FOR QC TESTING 146 THE FORMAT OF A QC TEST 146 PERFORMANCE CRITERIA/TOLERANCE LIMITS FOR COMMON QC TESTS 147 Radiography 147 Fluoroscopy 150 REPEAT IMAGE ANALYSIS 151 Corrective action/Reasons for rejection 151 COMPUTED TOMOGRAPHY QC TESTS FOR TECHNOLOGISTS 152 The ACR CT accreditation phantom 152 The ACR action limits for tests done by technologists 153 Artifact evaluation 155 References 156 Section 5: PACS and Imaging Informatics Chapter 10 PACS and imaging informatics at a glance 159 INTRODUCTION 159 PACS CHARACTERISTIC FEATURES 160 Definition 160 Core technical components 160 IMAGING INFORMATICS 163 Enterprise imaging 164 Cloud computing 164 Big data 164 Artificial intelligence 164 Machine learning 165 Deep learning 165 APPLICATIONS OF AI IN MEDICAL IMAGING 165 AI in CT image reconstruction 166 Ethics of AI in radiology 166 References 166 Section 6: Radiation Protection Chapter 11 Basic concepts of radiobiology 171 WHAT IS RADIOBIOLOGY? 172 BASIC CONCEPTS OF RADIOBIOLOGY 173 Generalizations about radiation effects on living organisms 173 Relevant physical processes 174 Radiosensitivity 175 Dose–response models 176 Radiation interactions in tissue: target theory, direct and indirect action 177 DNA and chromosome damage 178 EFFECTS OF RADIATION EXPOSURE TO THE TOTAL BODY 179 Hematopoietic of bone marrow syndrome 180 Gastrointestinal syndrome 180 Central nervous system (CNS) syndrome 180 DETERMINISTIC EFFECTS 180 STOCHASTIC EFFECTS 181 Tissue effects 181 Life‐span shortening 181 Radiation‐induced cancers 181 Hereditary effects 182 RADIATION EXPOSURE DURING PREGNANCY 183 References 183 Chapter 12 Technical dose factors in radiography, fluoroscopy, and CT 185 DOSE FACTORS IN DIGITAL RADIOGRAPHY 186 The x‐ray generator 186 Exposure technique factors 187 X‐ray beam filtration 187 Collimation and field size 188 The SID and SSD 188 Patient thickness and density 188 Scattered radiation grid 189 The sensitivity of the image receptor 190 DOSE FACTORS IN FLUOROSCOPY 190 Fluoroscopic exposure factors 190 Fluoroscopic equipment factors 191 CT RADIATION DOSE FACTORS AND DOSE OPTIMIZATION CONSIDERATIONS 194 Dose distribution in the patient 194 CT dose metrics 195 Factors affecting the dose in CT 196 Dose optimization overview 197 References 198 Chapter 13 Essential principles of radiation protection 200 INTRODUCTION 201 WHY RADIATION PROTECTION? 201 Categories of data from human exposure 201 Radiation dose–risk models 201 Summary of biological effects 202 Radiation protection organizations/reports 202 OBJECTIVES OF RADIATION PROTECTION 203 RADIATION PROTECTION PHILOSOPHY 203 Justification 203 Optimization 204 Dose limits 204 Personal actions 205 Time 205 Shielding 206 Distance 206 RADIATION QUANTITIES AND UNITS 206 Sources of radiation exposure 207 Quantities and units 207 PERSONNEL DOSIMETRY 209 OPTIMIZATION OF RADIATION PROTECTION 211 Regulatory and guidance recommendations 211 Diagnostic reference levels (DRLs) 212 Gonadal shielding: past considerations 213 X‐ray room shielding 214 CURRENT STATE OF GONADAL SHIELDING 215 References 215 Index 217

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Book SynopsisSARCOPENIA An in-depth examination of sarcopenia's underexplored yet widespread impact within the field of gerontologySarcopenia is common in older men and women, and yet awareness of its clinical relevance is still relatively low. Only formally included in the International Classification of Diseases in 2016, the condition may impact societies with serious health-related and financial consequences unless consistent, effective methods of identification and management are adopted.This second edition of Sarcopenia provides geriatricians and other healthcare professionals with a revised and expanded examination of this understudied and underdiagnosed condition. Edited by two leading authorities on the subject, it covers the epidemiology and diagnosis of sarcopenia, as well as treatment options and possible prevention strategies. Eight newly written chapters build upon existing knowledge with fresh data on topics including sarcopenia's biomarkers and its impacTable of ContentsList of Contributors vii Preface xiii 1 Definitions of Sarcopenia 1Alfonso J. Cruz‐Jentoft, Beatriz Montero‐Errasquin and John E. Morley 2 Epidemiology of Muscle Mass Loss with Age 11Marjolein Visser 3 The Role of Mitochondria in Age‐Related Sarcopenia 19Luigi Ferrucci, Marta Zampino, Paul Coen and Bret H. Goodpaster 4 Motor Unit Remodeling 35Ben Kirk and Mathew Piasecki 5 Nutrition, Protein Turnover and Muscle Mass 45Stéphane Walrand, Christelle Guillet and Yves Boirie 6 Recognizing Persons at Risk for Sarcopenia 63John E. Morley 7 Adverse Outcomes and Functional Consequences of Sarcopenia 71Jean Woo 8 A Lifecourse Approach to Sarcopenia 77Richard Dodds and Avan Aihie Sayer 9 Acute Sarcopenia 95Beatrice Gasperini, Stefano Volpato and Antonio Cherubini 10 Sarcopenia, Frailty, and Intrinsic Capacity 115Jurgen M. Bauer and Cornel Sieber 11 Osteosarcopenia 127Ben Kirk, Jesse Zanker, Steven Phu and Gustavo Duque 12 Sarcopenic Obesity 147Mauro Zamboni, Federica Macchi, Nicole Nori and Andrea P. Rossi 13 Sarcopenia and Cognitive Impairment 157Liang‐Kung Chen 14 Sarcopenia and Other Chronic Organ Diseases 175Hidenori Arai 15 Imaging of Skeletal Muscle 185Thomas F. Lang 16 Measurements of Muscle Mass, Equations and Cut‐off Points 199Marjolein Visser and Laura Schaap 17 Deuterated Creatine Dilution to Assess Muscle Mass (D3‐Cr Muscle Mass) in Humans: Methods, Early Results, and Future Directions 227Peggy M. Cawthon and William J. Evans 18 Measurement of Muscle Strength and Power 239Michael Drey, Sandra Helmers and Jürgen M. Bauer 19 Measurements of Physical Performance 253Laura Orlandini, Yves Rolland and Matteo Cesari 20 Biomarkers for Physical Frailty and Sarcopenia: A “Two‐Body Problem” 271Anna Picca, Riccardo Calvani and Emanuele Marzetti 21 Quality of Life and Sarcopenia 279Charlotte Beaudart, Jean‐Yves Reginster, Olivier Bruyère and Anton Geerinck 22 Exercise Interventions to Prevent and Improve Sarcopenia 305Mark D. Peterson and Jose A. Serra 23 Nutritional Approaches to Treat Sarcopenia 335Tommy Cederholm, Jurgen M. Bauer and Alfonso J. Cruz‐Jentoft 24 Beta‐hydroxy‐beta‐methylbutyrate (HMB) and Sarcopenia 355Francesco Landi, Riccardo Calvani, Anna Picca and Emanuele Marzetti 25 The Future of Drug Treatments 367Francesco Landi, Graziano Onder and Rolland Yves 26 Sarcopenia: Is It Preventable? 403Stany Perkisas, Keliane Liberman, Ivan Bautmans and Maurits Vandewoude 27 Financial Impact of Sarcopenia 421Kristina Norman 28 Sarcopenia Management for Clinicians 433Renuka Visvanathan and Solomon Yu Index 441

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Book SynopsisExplore this concise and clinically focused approach to the field of blood banking and transfusion therapy TheFifth Edition ofTransfusion Medicinedeliversa succinct, thorough, clinically focused, practicaland authoritative treatment of a full range of topics in transfusion therapy.Thisranges fromissues with the blood supply,recruitmentof both whole blood and apheresis donors,blood collection and storage, blood testing,blood safety,andtransmissible diseases.This edition has been fully updated and revised to include exciting cellular therapies for cancer,transplantation of both hematopoietic cells and solid organs, infectiousdiseasesand regenerative medicine. TheFifthEditionincludes newauthors with highly relevant content that provides a solid grounding for readers in the field. The book: Is an approachable comprehensive guide to the field of blood banking and transfusionmedicine Provides complete andtimely perspectiveoncruciTable of ContentsContributors vii Preface ix Chapter 1 History 1Jeffrey McCullough Chapter 2 The Blood Supply 11Jeffrey McCullough Chapter 3 Recruitment of Blood Donors 25Thomas Watkins Chapter 4 Blood Donor Medical Assessment, Collection, and Complications 37Gary Bachowski Chapter 5 Preparation, Storage, and Characteristics of Whole Blood, Blood Components, and Plasma Derivatives 59Alesia Kaplan Chapter 6 Production of Components by Apheresis 90Thomas Gniadek Chapter 7 Laboratory Testing of Donated Blood 111Nancy Van Buren Chapter 8 Blood Groups 135Sarah J. Ilstrup Chapter 9 Laboratory Detection of Blood Groups and Provision of Red Cells 168Ulrike F. Koenigbauer Chapter 10 Clinical Uses of Blood Components 197Vincent Laroche and Isabelle Blais‐Normandin Chapter 11 Transfusion Therapy in Specific Clinical Situations 257James Stubbs, Allan Klompas, and Leanne Thalji Chapter 12 Patient Blood Management 325Jeffrey McCullough Chapter 13 Pediatric Transfusion Medicine 343Stephanie Kinney Chapter 14 Pathogen Reduced Blood Products 359Jeffrey McCullough Chapter 15 Techniques of Blood Transfusion 376Randal Covin Chapter 16 Complications of Transfusion 39Scott Koepsell Chapter 17 Transfusion‐Transmitted Diseases 422Jeffrey McCullough Chapter 18 The HLA System in Transfusion Medicine and Transplantation 453S. Yoon Choo Chapter 19 Cellular Engineering: Hematopoietic Transplant, Immune Cell Therapy, and Regenerative Medicine 477David H. McKenna and David F. Stroncek Chapter 20 Therapeutic Apheresis 500Ramkrishna L. Reddy Chapter 21 Quality Programs in Blood Banking and Transfusion Medicine 541Kristin M. Mascotti Index 556

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Book SynopsisLearn how to improve the quality of health care offered by your institution using data you already have Improving Health Care Quality: Case Studies with JMP teaches readers how to systematically identify problems, collect and interpret data, and solve issues in the real world. Relying on JMP software, the authors walk readers through the process of applying quality improvement techniques to real-life health care problems. The case studies provided in the book vary significantly and provide a wide-ranging view of the application of quality improvement techniques in the health care field. Studies regarding length of stay of diabetes patients to benchmarking the costs of hip replacement all serve to illuminate and explain the underlying concepts of statistical analysis. The authors break each case study down into several sections, including: Background and Task Data and Data Management Analysis Summary Table of ContentsForeword xv Preface xvii Acknowledgments xix Acronyms and Synonyms xxi About the Companion Website xxiii 1 Introduction 1 1.1 Key Concepts 1 1.2 Quality Improvement in Healthcare 1 1.3 Understanding Variability: The Key to QI 2 1.4 Quality Improvement Frameworks 3 1.4.1 Define–Measure–Analyze–Improve–Control (DMAIC) 4 1.4.2 Plan–Do–Check–Act (PDCA) 4 1.4.3 Choosing a Framework 5 1.5 Statistical Tools for Quality Improvement 6 1.5.1 Data Visualization 8 1.5.2 Subgrouping Data 8 1.5.3 Control Charts 9 1.5.4 The Importance of Assumptions 10 1.6 Using this Casebook 11 1.7 Summary 12 1.7.1 Exercises 13 1.7.2 Discussion Questions 14 References 14 2 Improving Patient Satisfaction 17 2.1 Key Concepts 17 2.2 DMAIC 17 2.3 PDCA 17 2.4 Background 17 2.5 The Task 18 2.6 The Data: ComplaintData.xlsx and PatientFeedback.jmp 18 2.7 Data Management 19 2.8 Analysis 20 2.8.1 Complaint Data 20 2.8.2 Patient Satisfaction Data 21 2.9 Summary 26 2.9.1 Statistical Insights 26 2.9.2 Implications and Next Steps 27 2.9.3 Summary of Tools and JMP Features 27 2.9.4 Exercises 27 2.9.5 Discussion Questions 28 Reference 29 3 Length of Stay and Readmission for Hospitalized Diabetes Patients 31 3.1 Key Concepts 31 3.2 DMAIC 31 3.3 PDCA 31 3.4 Background 31 3.5 The Task 32 3.6 The Data: HospitalReadmission.jmp 32 3.7 Data Management 32 3.8 Analysis 32 3.9 Summary 39 3.9.1 Statistical Insights 39 3.9.2 Implications and Next Steps 39 3.9.3 Summary of Tools and JMP Features 40 3.9.4 Exercises 40 3.9.5 Discussion Questions 41 4 Identify and Communicate Opportunities for Reducing Hospital Length of Stay Using JMP® Dashboards 43 4.1 Key Concepts 43 4.2 DMAIC 43 4.3 PDCA 43 4.4 Background 43 4.5 The Task 44 4.6 The Data: HospitalReadmission.jmp 44 4.7 Data Management 44 4.8 Analysis 44 4.8.1 Creating Dashboards with Combine Windows 44 4.8.2 Creating Dashboards with Dashboard Builder 45 4.8.3 Saving and Sharing JMP Dashboards 48 4.9 Summary 48 4.9.1 Statistical Insights 48 4.9.2 Implications and Next Steps 52 4.9.3 Summary of Tools and JMP Features 52 4.9.4 Exercises 53 4.9.5 Discussion Questions 53 References 53 5 Variability in the Cost of Hip Replacement 55 5.1 Key Concepts 55 5.2 DMAIC 55 5.3 PDCA 55 5.4 Background 55 5.5 The Task 56 5.6 The Data: SouthernTier_HipReplacement.csv 56 5.7 Data Management 56 5.7.1 Initial Data Review 57 5.7.2 Adjusting JMP Column Properties 58 5.7.3 Deleting Unneeded Columns 59 5.7.4 Shortening Character Columns 60 5.8 Analysis 61 5.8.1 Descriptive Analysis 62 5.8.2 Assessing Variability 63 5.9 Summary 67 5.9.1 Statistical Insights 67 5.9.2 Implications and Next Steps 67 5.9.3 Summary of Tools and JMP Features 68 5.9.4 Exercises 68 5.9.5 Discussion Questions 69 References 70 6 Benchmarking the Cost of Hip Replacement 71 6.1 Key Concepts 71 6.2 DMAIC 71 6.3 PDCA 71 6.4 Background 71 6.5 The Task 72 6.6 The Data: HipNYSPARCS_SouthernTier.jmp 72 6.7 Data Management 72 6.8 Analysis 73 6.8.1 Descriptive Analysis 73 6.8.2 Statistical Test of Hypothesis 73 6.8.3 Confidence Interval for Mean Total Cost 75 6.9 Summary 75 6.9.1 Statistical Insights 75 6.9.2 Implications and Next Steps 76 6.9.3 Summary of Tools and JMP Features 76 6.9.4 Exercises 76 6.9.5 Discussion Questions 77 References 78 7 Nursing Survey 79 7.1 Key Concepts 79 7.2 DMAIC 79 7.3 PDCA 79 7.4 Background 79 7.5 The Task 80 7.6 The Data: NursingResearch_Survey_Responses.jmp 80 7.7 Data Management 81 7.7.1 Initial Data Review 81 7.7.2 Recoding the Primary Role Column 83 7.8 Analysis 85 7.8.1 Descriptive Analysis 85 7.8.2 One-Sample Test of Proportion 87 7.8.3 Test for Difference of Two Proportions 88 7.9 Summary 90 7.9.1 Statistical Insights 90 7.9.2 Implications and Next Steps 90 7.9.3 Summary of Tools and JMP Features 91 7.9.4 Exercises 91 7.9.5 Discussion Questions 92 References 93 8 Determining the Sample Size for a Nursing Research Study 95 8.1 Key Concepts 95 8.2 DMAIC 95 8.3 PDCA 95 8.4 Background 95 8.5 The Task 96 8.6 The Data 96 8.7 Study Design and Data Collection Methodology 96 8.8 Analysis 97 8.8.1 Analysis Plan 97 8.8.2 The Basics of Sample Size Determination 98 8.8.3 Sample Size Determination for the Bee Sting Study 99 8.9 Summary 101 8.9.1 Statistical Insights 101 8.9.2 Implications and Next Steps 102 8.9.3 Summary of Tools and JMP Features 103 8.9.4 Exercises 104 8.9.5 Discussion Questions 104 References 105 9 Mapping California Ambulance Diversion 107 9.1 Key Concepts 107 9.2 DMAIC 107 9.3 PDCA 107 9.4 Background 107 9.5 The Task 108 9.6 The Data: ED_ambulance_diversion_trend.xlsx and CA_healthcare_facility_locations.xlsx 108 9.7 Data Management 108 9.7.1 Merging the Data Tables 109 9.7.2 Reviewing the Merged File 109 9.7.3 Extracting General Acute Care Hospital Data 112 9.8 Analysis 112 9.8.1 Descriptive Analysis 112 9.8.2 Geographic Distribution of Total Diversion Hours 113 9.9 Summary 116 9.9.1 Statistical Insights 116 9.9.2 Implications and Next Steps 116 9.9.3 Summary of Tools and JMP Features 117 9.9.4 Exercises 117 9.9.5 Discussion Questions 118 References 118 10 Monitoring Ambulance Diversion Hours 119 10.1 Key Concepts 119 10.2 DMAIC 119 10.3 PDCA 119 10.4 Background 119 10.5 The Task 120 10.6 The Data: CedarsSinai_Diversion_Hours.jmp 120 10.7 Data Management 121 10.8 Analysis 121 10.8.1 Descriptive Analysis 121 10.8.2 Control Chart Basics 122 10.8.3 Ambulance Diversion Process 123 10.8.4 Setting the Control Limits 123 10.8.5 Monitoring Ambulance Diversion with IR Charts 126 10.9 Summary 130 10.9.1 Statistical Insights 130 10.9.2 Implications and Next Steps 130 10.9.3 Summary of Tools and JMP Features 131 10.9.4 Exercises 131 10.9.5 Discussion Questions 132 References 132 11 Ambulatory Surgery Start Times 133 11.1 Key Concepts 133 11.2 DMAIC 133 11.3 PDCA 133 11.4 Background 133 11.5 The Task 134 11.6 The Data: ASU.jmp 134 11.7 Data Management 134 11.8 Analysis 135 11.8.1 Case 1 Analysis 138 11.8.2 Case 2 Analysis 140 11.9 Summary 141 11.9.1 Statistical Insights 141 11.9.2 Implications and Next Steps 143 11.9.3 Summary of Tools and JMP Features 144 11.9.4 Exercises 144 11.9.5 Discussion Questions 145 Reference 145 12 Pre-Op TJR Process Improvement – Part 1 147 12.1 Key Concepts 147 12.2 DMAIC 147 12.3 PDCA 147 12.4 Background 147 12.5 The Task 148 12.6 The Data: TJR.xlsx 148 12.7 Data Management 150 12.8 Analysis 153 12.9 Summary 159 12.9.1 Statistical Insights 159 12.9.2 Implications and Next Steps 161 12.9.3 Summary of Tools and JMP Features 161 12.9.4 Exercises 161 12.9.5 Discussion Questions 162 Reference 163 13 Pre-Op TJR Process Improvement – Part 2 165 13.1 Key Concepts 165 13.2 DMAIC 165 13.3 PDCA 165 13.4 Background 165 13.5 The Task 166 13.6 The Data: TJR.jmp 166 13.7 Data Management 166 13.8 Analysis 167 13.9 Summary 173 13.9.1 Statistical Insights 173 13.9.2 Implications and Next Steps 174 13.9.3 Summary of Tools and JMP Features 174 13.9.4 Exercises 174 13.9.5 Discussion Questions 175 References 175 14 Pre-Op TJR Process Improvement – Part 3 177 14.1 Key Concepts 177 14.2 DMAIC 177 14.3 PDCA 177 14.4 Background 177 14.5 The Task 178 14.6 The Data: TJR.jmp 178 14.7 Data Management 179 14.8 Analysis 179 14.9 Summary 187 14.9.1 Statistical Insights 187 14.9.2 Implications and Next Steps 188 14.9.3 Summary of Tools and JMP Features 190 14.9.4 Exercises 190 14.9.5 Discussion Questions 191 References 191 Index 193

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Book SynopsisOffers clear and concise instruction on running, reporting and interpreting immunophenotyping studies Written by two well-known haematology educators and experts on the topic, Immunophenotyping for Haematologists contains an introduction to running, reporting and interpreting immunophenotyping studies. The book offers a unique approach to the topic by putting the focus on clinical and laboratory haematologists who are not routinely involved in running and reporting on immunophenotyping studies. Immunophenotyping using flow cytometry has become the method of choice in identifying and sorting cells within complex populations, for example, the analysis of immune or neoplastic cells in a blood sample. The text reviews the purpose and principles of immunophenotyping and includes an introduction and explanation of the principles and the role of immunophenotyping. The authors examine immunophenotypic characteristics of the disease groups commonly encountered andTable of ContentsPreface and Acknowledgement vii Abbreviations Used in the Book ix Part 1 Purpose and Principles of Immunophenotyping 1 Part 2 Immunophenotyping for Haematologists 11 Part 3 Immunophenotyping in the Diagnosis and Monitoring of Haematological Neoplasms and Related Conditions with Tables and Figures for Quick Reference 47 Part 4 Test Yourself 89 Index 127

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Book SynopsisFlow Cytometry of Hematological Malignancies Flow cytometric analysis is often integral to the swift and accurate diagnosis of leukemias and lymphomas of the blood, bone marrow, and lymph nodes. However, in the fast-moving and expanding field of clinical hematology, in can be challenging to remain up to speed with the latest biological research and technological innovations. Flow Cytometry of Hematological Malignancies has been designed to provide all those working in hematological oncology with a practical, cutting-edge handbook, featuring clear and fully illustrated guidance on all aspects of cytometry's role in diagnosis and analysis. This essential second edition includes: Explorations of more than 70 antigens Full-color illustrations throughout New descriptions of recently discovered markers WHO classifications of hematological neoplastic diseases Helpful tips for result interpretation and analysis Featuring all this andTable of ContentsForeword to the Second Edition xiby Michael J. Borowitz Foreword to the First Edition xiiby Maryalice Stetler-Stevenson Foreword to the First Edition xiiiby Bruno Brando Preface to the Second Edition xv Preface to the First Edition xvi Abbreviations xvii 1 Antigens 1 Clustered (CD) Antigens CD1 3 CD2 5 CD3 8 CD4 17 CD5 21 CD7 24 CD8 26 CD10 30 CD11b 35 CD11c 38 CD13 40 CD14 44 CD15 46 CD16 49 CD19 52 CD20 55 CD22 59 CD23 61 CD24 64 CD25 66 CD26 67 CD27 69 CD28 70 CD30 71 CD33 73 CD34 77 CD38 79 CD43 81 CD45 82 CD45 Isoforms 87 CD49 90 CD56 93 CD57 96 CD61 97 CD62L 98 CD64 99 CD65 101 CD66c 102 CD71 103 CD79 104 CD81 107 CD103 108 CD117 110 CD123 112 CD138 113 CD200 114 CD305 116 CD307 (IRTA) Antigen Family 117 CD371 118 Non clustered (or primarily known with other names) antigens Bcl‐2 Protein 119 Chemokines and Chemokine Receptors 121 CRLF2 128 Cytotoxic Proteins 129 HLA‐DR 130 Immunoglobulins 132 KIR, CD158 isoforms 136 Myeloperoxidase (MPO) 139 NG2 140 PCA‐1 141 ROR1 141 SLAM Molecules and SLAM‐associated Protein (SAP) 142 SOX11 144 T‐cell Receptor (TCR) 145 Terminal Deoxy‐nucleotidyl‐transferase (TdT) 148 Toll‐like Receptors (TLR) 150 VS38 151 ZAP‐70 152 2 Diseases 155 Myeloproliferative neoplasms 157 Chronic myeloid leukemia (CML) 157 Myeloproliferative neoplasms other than CML 160 Chronic neutrophilic leukemia (CNL) 160 Polycythemia vera (PV) 160 Primary myelofibrosis (PMF) 160 Essential thrombocythemia (ET) 160 Chronic eosinophilic leukemia (CEL) 161 Mastocytosis 162 Acute mast‐cell leukemia (AMCL) 162 Chronic mast‐cell leukemia (CMCL) 163 Myelomastocytic leukemia (MML) 163 Myelodysplastic/myeloproliferative neoplasms 164 Chronic myelomonocytic leukemia (CMML) 164 Other myelodysplastic/myeloproliferative neoplasms and related conditions 167 Juvenile myelomonocytic leukemia (JMML) 167 Atypical CML bcr/abl negative (ACML) 167 RAS‐associated autoimmune leukoproliferative disorder (RALD) 167 Myelodysplastic syndromes 168 Myeloid neoplasms with germline predisposition 171 Acute myeloid leukemias 172 AMLs with recurrent genetic anomalies 173 AMLs with chromosomal anomalies 173 AMLs with gene mutations 180 Relationships between genotype and phenotype in cases of AML not recognized as separate entities in WHO 2017 181 AMLs with myelodysplasia‐related changes (AML‐MRC) 182 AMLs not otherwise specified 182 AML with minimal differentiation 182 AML without maturation 183 AML with maturation 183 Acute myelomonocytic leukemia (AMMoL) 183 Acute monoblastic and monocytic leukemia (AMoL) 184 Pure erythroid leukemia (PEL) 185 Acute megakaryoblastic leukemia (AMKL) 186 Acute basophilic leukemia (ABL) 188 Myeloid proliferations associated with Down syndrome 188 Transient abnormal myelopoiesis (TAM) 189 AMLs in patients with Down syndrome 189 Blastic plasmacytoid dendritic cell neoplasm (BPDCN/PDCL) 189 Acute leukemias with ambiguous lineage attribution (ALAL) 192 Acute undifferentiated leukemias (AUL) 192 Mixed phenotype acute leukemias (MPAL) 192 Neoplastic diseases of B and T lymphatic precursors 194 B lymphoblastic leukemia/lymphoma, not otherwise specified (B‐ALL/LBLnos) 195 B lymphoblastic leukemia/lymphoma with recurrent genetic anomalies 197 Relationships between genotype and phenotype in cases of B‐ALL not recognized as separate entities in WHO 2017 201 T lymphoblastic leukemia/lymphoma (T‐ALL/LBL) 202 Early T‐cell precursor lymphoblastic leukemia (ETP‐ALL) 205 NK lymphoblastic leukemia/lymphoma (NK‐ALL/LBL) 205 Neoplastic diseases of mature B cells 206 Chronic lymphocytic leukemia/small lymphocytic lymphoma (B‐CLL/SLL) 206 Familial B‐CLL 215 Richter syndrome 215 Monoclonal B‐cell lymphocytosis (MBL) 216 CLL‐like monoclonal B lymphocytosis 216 Non‐CLL‐like monoclonal B lymphocytosis 216 B‐cell prolymphocytic leukemia (B‐PLL) 216 Lymphoplasmacytic lymphoma (LPL) 218 Heavy chain disease (HCD) 221 γ heavy chain disease 222 μ heavy chain disease 222 α heavy chain disease 222 Hairy cell leukemia (HCL) 222 Hairy cell leukemia, variant (HCL‐v) 226 Hairy cell leukemia, Japanese variant (HCL‐J) 227 Splenic diffuse red pulp lymphoma (SDRPL) 227 Marginal zone lymphomas (MZL) 228 Nodal marginal zone lymphoma (NMZL) 229 Splenic marginal zone lymphoma (SMZL) 230 Extranodal marginal zone lymphoma (EMZL/MALToma) 232 Clonal B‐cell lymphocytosis with MZL‐like phenotype (CBL‐MZ) 233 Follicular lymphoma (FCL) 234 Testicular follicular lymphoma 237 Duodenal type follicular lymphoma 237 Pediatric type follicular lymphoma 237 Primitive cutaneous follicular lymphoma (PCFL) 237 Large B‐cell lymphoma with IRF4 rearrangement 237 Mantle‐cell lymphoma (MCL) 237 Blastic mantle‐cell lymphoma (BMCL) 240 Leukemic non nodal mantle‐cell lymphoma 240 DLBCL not otherwise specified (DLBCLnos) 240 CD5(+) diffuse large cell lymphoma (CD5(+) DLBCL) 243 T‐cell/histiocyte‐rich B‐cell lymphoma (THRLBCL) 243 Primary DLBCL of the CNS (PCNSL) 244 Primary cutaneous DLBCL, “leg type” 244 EBV(+) DLBCLnos 244 DLBCL associated with chronic inflammation (PAL) 245 Fibrin associated DLBCL 245 Lymphomatoid granulomatosis (LYG) 245 Primary mediastinal B‐cell lymphoma (PMBCL) 245 Intravascular large B‐cell lymphoma (IVBCL) 246 ALK‐positive large cell lymphoma (ALK(+) LBCL) 246 Plasmablastic lymphoma (PBL) 247 Primary effusion lymphoma (PEL) 247 HHV8‐associated lymphoproliferative disorders 247 HHV8‐positive DLBCL 248 HHV8‐positive germinotropic lymphoproliferative disorder 248 Burkitt lymphoma (BL) 248 Burkitt leukemia with immature phenotype 250 Burkitt‐like lymphoma with 11q aberrations 251 High‐grade B‐cell lymphoma (HGBL) 251 Plasma cell neoplasms 251 Monoclonal gammopathies of undetermined significance (MGUS) 253 Multiple myeloma (MM) 253 Plasma cell leukemia (PCL) 257 Neoplastic diseases of mature T and NK cells 258 T‐cell prolymphocytic leukemia (T‐PLL) 258 T‐cell large granular lymphocytic leukemia (T‐LGL) 261 Chronic lymphoproliferative disorders of NK cells (CLPD‐NK/CNKL) 263 Aggressive NK‐cell leukemia (ANKL) 266 Adult T‐cell leukemia/lymphoma (ATLL) 266 Extranodal NK/T-cell lymphoma, “nasal type” (ENKTL) 269 Intestinal T‐cell lymphomas (ITCL) 270 Enteropathy‐associated T‐cell lymphoma (EATCL) 270 Monomorphic epitheliotropic intestinal T‐cell lymphoma (MEITL) 272 Indolent gastro‐intestinal T lymphoproliferative disorder (indolent GI T‐LPD) 273 Hepatosplenic T‐cell lymphoma (HSTCL) 273 Subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) 275 Mycosis fungoides (MF) 275 Sezary syndrome (SS) 277 Primary cutaneous CD30(+) lymphoproliferative disorders 279 Lymphomatoid papulosis (LyP) 279 Primary cutaneous anaplastic T‐cell lymphoma (pcALCL) 279 Primary cutaneous peripheral T‐cell lymphoma (PTCL) 280 Primary cutaneous TCRγδ(+) T‐cell lymphoma (PCGD‐TCL) 280 Primary cutaneous CD8(+) aggressive epidermotropic cytotoxic T‐cell lymphoma (PCAETL) 280 Primary cutaneous acral CD8(+) T‐cell lymphoma (PCATCL) 280 Primary cutaneous lymphoma of the medium/small CD4(+) T cells (PCSM‐TCL) 281 Peripheral T‐cell lymphoma, not otherwise specified (PTCLnos) 281 Nodal lymphomas of follicular T‐helper derivation 283 Angioimmunoblastic T‐cell lymphoma (AITL) 283 Follicular T‐cell lymphoma (FTCL) 285 Nodal PTCL with follicular T‐helper phenotype 285 Anaplastic large cell lymphoma ALK(+) (ALCL ALK(+)) 285 Anaplastic large cell lymphoma ALK(‐) (ALCL ALK(‐)) 288 Breast implant–associated anaplastic large cell lymphoma (biaALCL) 288 Hodgkin lymphomas 289 Classic Hodgkin lymphoma (CHL) 289 Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) 290 Neoplastic diseases of histiocytic and dendritic cells 291 Histiocytic sarcoma (HS) 292 Langerhans cell histiocytosis (LCH) 292 Indeterminate dendritic cell tumor (IDCT) 292 Interdigitating dendritic cell sarcoma (IDCS) 292 Follicular dendritic cell sarcoma (FDCS) 292 Erdheim–Chester disease (EDC) 292 3 Appendix 293 Acute leukemias not recognized by the 2017 WHO classification 294 Acute leukemia of myeloid/NK precursors (M/NK‐AL) 294 Acute leukemia of myeloid dendritic cells (MDCL) 294 Acute leukemia of Langerhans cells 294 Composite lymphomas 294 Hypereosinophilic syndrome (HES), lymphocyte variant 295 Indolent T lymphoblastic proliferations (iT‐LBP) 295 Polyclonal lymphocytoses of B lymphocytes 298 Persistent polyclonal B‐cell lymphocytosis (PPBL) 298 Persistent polyclonal CD5(+) B‐cell lymphocytosis 298 Persistent polyclonal B‐cell lymphocytosis, Japanese (hairy) variant 298 Polyclonal plasmacytoses 299 Small round (blue) cell tumors (SR(B)CT) 300 References 301 Index 429

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Book SynopsisBlood and Marrow Transplantation Long Term Management Hematopoietic cell transplantation (HCT) provides curative therapy for a variety of diseases. Over the past several decades, significant advances have been made in the field of HCT, to the point where HCT has become an integral part of treatment modality for a variety of hematologic malignancies and some nonmalignant diseases. HCT remains an important treatment option for a wide variety of hematologic and nonhematologic disorders, despite recent advances in the field of immunologic therapies. Factors driving this growth include expanded disease indications, greater donor options (expanding unrelated donor registries and haploidentical HCT), and accommodation of older and less fit recipients.The development of less toxic pretransplant conditioning regimens, more effective prophylaxis of graft-versus-host disease (GVHD), improved infection control, and other advances in transplant technology have resulted in a rapidly groTable of ContentsForeword by Professor John Barrett vii Foreword by Professor John Goldman viii List of Contributors ix Section 1 Late effects concepts 1 1 Introduction to long‐term survivorship after hematopoietic cell transplantation 3Bipin N. Savani and André Tichelli 2 International Blood and Marrow Registries: trends on long‐term data collection 6Rachel Phelan, Jakob R. Passweg, Helen Baldomero, Minako Iida, Yoshiko Atsuta, Shinichiro Okamoto, Mahmoud Aljurf, Feras Alfraih, and Bronwen E. Shaw 3 Long‐term follow‐up program and transplant clinic setup 14André Tichelli, Bipin N. Savani, Shahrukh K. Hashmi, Navneet S. Majhail, and Alicia Rovó 4 Telemedicine in patient care of long‐term transplant survivors 25Catherine J. Lee, Mihkaila Wickline, and Mary E.D. Flowers 5 Long‐term follow‐up calendar 33André Tichelli, Bipin N. Savani, Shahrukh K. Hashmi, Navneet S. Majhail, and Alicia Rovó 6 Late effects post‐allogeneic hematopoietic stem cell transplantation 38Shahrukh K. Hashmi and Yoshihiro Inamoto 7 Late effects post‐autologous hematopoietic stem cell transplantation 47Rajshekhar Chakraborty and Betty K. Hamilton 8 Long‐term follow‐up of children 58Paul A. Carpenter 9 Graft‐versus‐host disease and late effects after hematopoietic stem cell transplantation 73David Michonneau, Aurélien Sutra del Galy, and Gérard Socié 10 Screening and prevention guidelines for hematopoietic cell transplant survivors 80Neel S. Bhatt, J. Douglas Rizzo, and Navneet S. Majhail 11 Biology of survivorship after blood or marrow transplantation 92Smita Bhatia Section 2 Specific late effects 101 12 Second malignancies 103Aurélien Sutra del Galy, David Michonneau, and Gérard Socié 13 Anti‐infective prophylaxis, immunization and prevention of late infectious complications 112Per Ljungman 14 Seasonal respiratory viral infections 119Nosha Farhadfar, Zeina Al‐Mansour, and John R. Wingard 15 Monitoring and management of hepatitis B, C, and HIV infection before and after transplantation 132Enric Carreras and Montserrat Rovira 16 Skin chronic GVHD 140Attilio Olivieri, Anna Campanati, Gaia Goteri, and Andrea Bacigalupo 17 Ocular complications 166Alicia Rovó, André Tichelli, and Yoshihiro Inamoto 18 Management of oral and dental complications 176Hildegard T. Greinix 19 Thyroid disease: monitoring and management guidelines 183Juliana Matthews, Leslee Matheny, and Shubhuda Jagasia 20 Pretransplant considerations in gender, reproductive, and sexual health 189Dana Shanis, Jeanne Murphy, Kate Debiec, Betty K. Hamilton, Shawna Boyle, and Pamela Stratton 21 Posttransplant Considerations in Gender, Reproductive, and Sexual Health 198Jeanne Murphy, Dana Shanis, Kate Debiec, Betty K. Hamilton, Shawna Boyle, and Pamela Stratton 22 Fertility issues, fertility preservation, and pregnancy outcome in long‐term survivors 211Alicia Rovó, Alison W. Loren, André Tichelli, and Nina Salooja 23 Sexual Dysfunction in Long‐Term Survivors 221Rebecca L. Hunter, Sarah Thilges, Janna Gordon, Kristy Luke, Karla Cavazos, Emilee Moeke, Colleen Bruen, and Sunita Nathan 24 Late non‐infectious pulmonary complications 231Ayman O. Soubani 25 Cardiac and arterial complications 241Alicia Rovó and André Tichelli 26 Cardiovascular risk factors 251Kimberley Doucette and Minoo Battiwalla 27 Gastrointestinal complications 260Sumona Bhattacharya, Steven Pavletic, and Theo Heller 28 Hepatic Complications 271Christy Ann L. Gilman, Christopher Koh, Steven Pavletic, and Theo Heller 29 Renal complications 278Insara Jaffer Sathick and Sangeeta Hingorani 30 Posttransplantation bone disease: prevalence, surveillance, prevention, and management 287Christine N. Duncan 31 Late neurologic complications 300Enrico Maffini 32 Neurocognitive dysfunction 312David Buchbinder and Angela Scherwath 33 Psychological Distress 330Anna Barata, Aasha I. Hoogland, and Heather S. L. Jim 34 Evaluation and management of fatigue in survivors of allogeneic hematopoietic stem cell transplantation 337Sandra A. Mitchell 35 Social Issues 349Sanghee Hong and Navneet S. Majhail 36 Health‐related quality of life in adult and pediatric survivors 355Sandra A. Mitchell, Lori Wiener, Jenny Hoag, Abigail Fry, and Margaret F. Bevans Section 3 Supportive care and patients reported outcomes 381 37 Immunosuppressive agents and monitoring in long‐term survivors 383Kathryn A. Culos and Katie S. Gatwood 38 Nutritional support and nutritional supplementation 393Shigeo Fuji 39 Daily routines and healthy lifestyle guidelines 397Melissa Logue 40 Prevalent psychosocial adjustment issues and solutions: lifestyle and social challenges 402Katrina M. Stokes 41 Complementary and alternative medicine in HSCT 406Ibrahim N. Muhsen, Bipin N. Savani,, and Shahrukh K. Hashmi 42 Impact of adherence in outcome of long‐term survivors 413Corien Eeltink and Annika Kisch 43 Prominent role of allied health professionals 418Catherine E. Lucid 44 Patient reported outcomes 420Hélène Schoemans 45 Caregivers of long‐term survivors 428Angela Moreschi Woods 46 Patient’s perspective: memoir of a recovered lymphomaniac 434Michael Brown Appendix 1 Commonly used transplant‐related medications in long‐term survivors 442Kathryn A. Culos and Katie S. Gatwood Appendix 2 The eGVHD App 445Hélène Schoemans Index 448

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Book SynopsisThe fourth medical atlas in this new series on the human body and filled with detailed pictures, this atlas details the topographical and pathotopographical anatomy of the pelvis, spine, and limbs, a useful reference for medical professionals and students alike. Written by an experienced and well-respected physician and professor, this new volume, building on the previous volume, Ultrasonic Topographical and Pathotopographical Anatomy, and its sequels, also available from Wiley-Scrivener, presents the ultrasonic topographical and pathotopographical anatomy of the pelvis, spine, and limbs, offering further detail into these important areas for use by medical professionals. This series of atlases of topographic and pathotopographic human anatomy is a fundamental and practically important series designed for doctors of all specializations and students of medical schools. Here you can find almost everything that is connected with the topographic and pathotopoTable of ContentsIntroduction vii Part 1: The Pelvis 1 Part 2: The Spine 69 Part 3: The Limbs 91 Conclusion 185 About the Author 199

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Book SynopsisWritten by an experienced and well-respected physician and professor, this new volume combines the entire previous four books, Ultrasonic Topographical and Pathotopographical Anatomy, and its three sequels, also available from Wiley-Scrivener, presenings the ultrasonic topographical and pathotopographical anatomy of the entire body, offering further detail into these important areas for use by medical professionals. This comprehensive and exhaustive medical atlas of topographic and pathotopographic human anatomy is a fundamental and practically important book designed for doctors of all specializations and students of medical schools. Here you can find almost everything that is connected with the topographic and pathotopographic human anatomy, including original graphs of logical structures of topographic anatomy and development of congenital abnormalities, topography of different areas in layers, pathotopography, computer and magnetic resonance imaging (MRI) of topographic aTable of ContentsPreface ix Part 1: Ultrasonic Topographical and Pathotopographical Anatomy 1 Topography and Pathotopography of the Head 3 2 Topography and Pathotopography of the Neck 25 3 Topographical and Pathotopographical Anatomy of the Chest 43 4 Topographical and Pathotopographical Anatomy of the Abdomen 61 5 Topographical and Pathotopographical Anatomy of the Retroperitoneal Space 91 6 Topography and Pathotopography of the Pelvis 103 Topographical anatomy of the pelvic organs 103 Topography of the female pelvis 104 Topography of male pelvis 107 Ultrasonic topographical anatomy of male pelvis 108 7 Topography and Pathotopography of Lower Extremity 123 8 Conclusion 153 Part 2: Topographical and Pathotopographical Medical Atlas of the Head and Neck 9 Introduction 159 10 The Head 163 Topographic Anatomy of the Head 163 Cerebral Cranium 163 Basis Cranii Interna 177 The Brain 180 Surgical Anatomy of Congenital Disorders 203 Pathotopography of the Cerebral Part of the Head 204 Facial Head Region 209 Dentes-Teeth 226 The Lymphatic System of the Head 251 Congenital Face Disorders 254 Pathotopography of the Facial Part of the Head 256 Attachment 1: Neurocranial Part Topography 264 Attachment 2: Facial Part Topography 265 11 The Neck 267 Topographic Anatomy of the Neck 267 Fasciae, Superficial and Deep Cellular Spaces and their Relationship with Spaces Adjacent Regions 269 Triangles of the Neck 275 Organs of the Neck 297 Pathography of the Neck 306 Attachment 3: Topography of the Neck 317 Part 3: Topographical and Pathotopographical Medical Atlas of the Chest, Abdomen, Lumbar Region, and Retroperitoneal Space 12 The Chest 321 Topographic Anatomy of the Chest 321 Chest Cavity Organs Projection and Layers of Chest 322 Surgical Anatomy of Thoracic Wall Congenital Malformation 337 Thoracic Cavity 338 Mediastinum Topography 343 13 Abdomen 371 Topographic Anatomy of Anterolateral Abdomen Wall 371 Surgical Anatomy of Congenital Malformations of Anterior Lateral Abdominal Wall 384 Abdominal Region Topography 385 Peritoneum and Abdominal Cavity Levels 385 Abdominal Cavity Organs 392 14 Lumbar Region and Retroperitoneal Space 431 Topographic Anatomy of Lumbar Region and Retroperitoneal Space 431 Topographic Anatomy of Lumbar Region 431 Topographical anatomy of retroperitoneal space 437 Organs of Retroperitoneal Space 440 Surgical Anatomy of Congenital Malformations 450 15 Pathotography of the Chest 459 Abdominal Cavity 467 Retroperitoneal Space 487 Part 4: Topographical and Pathotopographical Medical Atlas of the Pelvis, Spine, and Limbs 16 Introduction 501 17 The Pelvis 503 Topographic Anatomy of the Pelvis 503 Individual, Gender and Age Differences 503 The Organs of the Male Pelvis 512 The Topography of the Vas Deferens 520 The Organs of the Female Pelvis 523 Defects of the Genitourinary System in Children 530 Perineum Topography 531 Pudendal Region in Men 533 Pudendal Region in Women 538 The Topography of the External Female Genitalia 538 Surgical Anatomy of Congenital Pelvic and Perineum 542 Anus. Ischiorectal Fossa. Perineal Rectum 546 Surgical Anatomy of Congenital Malformations of the External Genitalia 551 Pathotophography of the Peivis 553 18 The Spine 571 Topographic Anatomy of the Spine 571 Individual and Age Differences of the Spine 573 The Spinal Cord and Nerve Roots 573 Surgical Anatomy of the Malformations of the Spine and Spinal Cord 581 Pathotopography of the Spine 583 19 The Limbs 593 Topographic Anatomy of the Upper Limb 593 Supra Brachium – Shoulder Girdle 593 Shoulder 598 Forearm 603 Hand 612 Surgical Anatomy of Congenital Malformations of the Upper Limb 618 Pathotopography of the Upper Limbs 621 Topographic Anatomy of Lower Limbs 634 Gluteal Region 635 Femur 636 Canals of Thigh 648 Shin 652 Foot 664 Pathotopography of the Lower Limbs 671 Conclusion 687 Appendix A 701 Appendix B 709

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