This mini course will set the stage for several discussions of particular issues of major importance and interest. What is "preparedness" and what are the real risks of continuing terrorism in the United States? What is the current status of preparedness in the U.S. hospital and public health systems? How do children differ from adults in terms of response to weapons of mass destruction (chemical, biological and radiological)? How do these differences matter in disaster planning? Are the needs of children being incorporated in local, state and federal disaster plans? Smallpox, anthrax and other biological threats: Where do we stand? What do we do? Nuclear power plants, nuclear weapons, dirty bombs and potassium iodide: What do we know? The mental health consequences of terrorism: What have we learned since 9/11, how do we prepare children for an increasingly vulnerable world, building resiliency and sustaining a positive vision. The new pediatric agenda: What do we have to teach students, residents and pediatricians about the pediatric aspects of terrorism planning. Children and exposure to weapons of mass destruction: science and the essential research agenda.

Introduction
Paul H. Saenger, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY

Welcome and Context
Irwin Redlener, National Center for Disaster Preparedness, Columbia University Mailman School of Public Health, New York, NY

Pediatric Preparedness for Terrorism and Disasters
David S. Markenson, Columbia University Mailman School of Public Health, New York, NY

Biological Weapons of Terror: What Pediatricians Need to Know
Theodore J. Cieslak, U.S. Army Research Institute of Infectious Diseases, Ft. Detrick, MD

Helping Children and Families Cope with Terrorism
David J. Schonfeld, Yale University School of Medicine, New Haven, CT

Radiologic Terrorism, Children and the Question of Potassium Iodide
Thomas P. Foley, University of Pittsburgh, Children's Hospital of Pittsburgh, Pittsburgh, PA

Anorexia nervosa is an eating disorder characterized by a relentless and obsessive pursuit of thinness that most commonly develops in adolescent females. The severe restriction of calories and compulsive exercising that can occur in this chronic condition may result in life-threatening weight loss. In addition to the serious medical complications associated with semi-starvation and severe energy deficits, there are often significant psychological and social problems that may precede or follow, as well as complicate the treatment during, the active phase of the illness. Practitioners and researchers in pediatrics and adolescent medicine in the field of eating disorders have generally focused on the acute and the chronic medical complications associated with anorexia nervosa. Although no organ is spared the effects of chronic malnutrition that occur with this condition, two that have the potential of long-term biological morbidity are the skeletal and reproductive systems. The long-term clinical outcomes of continued morbidity in these organs are osteoporosis and amenorrhea with reproductive failure, respectively. The latest research findings and their clinical implications relative to these organ systems will be discussed, and future research directions will be explored. In addition to the biological effects of anorexia nervosa, we shall address the biological vulnerability to developing anorexia nervosa, based on genetic predisposition. Emerging data from research studies and their clinical implications will be presented.

Overview
Richard E. Kreipe, University of Rochester School of Medicine, Golisano Children's Hospital at Strong, Rochester, NY

Morbidity of the Skeletal System in Anorexia Nervosa
Neville H. Golden, Schneider Children's Hospital, New Hyde Park, NY

Morbidity of the Reproductive System in Anorexia Nervosa
S. Jean Emans, Harvard Medical School, Children's Hospital Boston, Boston, MA

Genetic Susceptibility to Anorexia Nervosa
Wade Berrettini, University of Pennsylvania, Institute of Neurological Sciences, Center for Neurobiology and Behavior, Philadelphia, PA

Discussion
 

Congenital heart defects are present in nearly 1% of all newborns and continue to be a significant cause of death in infancy. A major goal for clinicians and basic scientists has been to understand the sources of these relatively common developmental errors. With the completion of the sequencing of the human genome, molecular genetic efforts directed at finding genes for monogenetic traits have accelerated dramatically. This topic symposium is directed toward exploring the state of the art understanding of the molecular basis of certain syndromic forms of congenital heart defects as well as their implications for non-syndromic heart disease. The discussion will focus on four syndromes (Holt-Oram, heterotaxy, DiGeorge/velocardiofacial, and Noonan syndromes) for which disease genes have been discovered and insights into disease pathogenesis are available.

Overview
D. Woodrow Benson, Children's Hospital Medical Center, Cincinnati, OH

Holt-Oram Syndrome and TBX5
Craig Basson, Cornell University Medical College, New York, NY

Molecular Basis of Heterotaxy Syndromes
Martina Brueckner, Yale University School of Medicine, New Haven, CT

DiGeorge/Velocardiofacial Syndromes and 22q11
Elizabeth Goldmuntz, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA

Noonan and Related Syndromes and PTPN11
Bruce D. Gelb, Mt. Sinai School of Medicine, New York, NY

Discussion
 

Micronutrients are essential to normal growth and development in infancy. Preterm and small-for-gestational-age infants are especially vulnerable to deficiencies. This symposium will focus on two fundamental nutrients: zinc and iron. Michael Hambidge will discuss the physiologic and metabolic importance of zinc during the perinatal period and the methods that can be used to assess zinc requirements. Nancy Krebs will discuss recent information about zinc homeostasis and requirements in premature and small-for-gestational-age infants. Stanley Zlotkin will discuss the etiology of iron deficiency in preterm infants during the first year of life and interventions to prevent it.

The Importance of Zinc in the Perinatal Period: An Overview
Kenneth Michael Hambidge, University of Colorado Health Sciences Center, Denver, CO

Zinc Requirements in Premature and Small-for-Gestational-Age Infants
Nancy F. Krebs, University of Colorado Health Sciences Center, Denver, CO

Meeting the Iron Needs of the Preterm Infant Throughout the First Year of Life
Stanley H. Zlotkin, The Hospital for Sick Children, Toronto, Canada

TLRs (Toll-like receptors) are a family of transmembrane germ line coded pattern recognition receptors that bind structural motifs common to pathogenic organisms. These structural motifs include endotoxin, products of gram+ organisms, fungi and mycobacteria, as well as DNA and RNA structures common to bacteria and virus but not mammalian cells. The TLRs are expressed by diverse cell types. TLR signaling initiates the innate immune/inflammatory host response to pathogens and also initiates antigen processing for acquired immunity.

Moshe Arditi will review the recent progress in understanding how children respond to pathogens. Maria Abreau will explore how immune signaling is central to both the maintenance of normal gut function and how chronic GI disease may develop. Christopher Karp will then explore how immune signaling relates to the hygiene hypothesis regarding the striking increase in the prevalence of both allergic and autoimmune diseases in children in Westernized countries over recent decades. The goal is to provide an update about newly described mechanisms signaling inflammation/immunity that are central to multiple homeostatic and disease processes in children.

Toll Like Receptors—Bridging Innate and Adaptive Immunity
Moshe Arditi, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA

TLR Signaling in the Gut in Health and Disease
Maria Abreu, Cedars-Sinai Medical Center / UCLA School of Medicine, Los Angeles, CA

Signaling the Hygiene Hypothesis
Christopher Karp, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Children who are victims of violent behavior or merely observers of violence may learn destructive or self-destructive patterns of behavior. Violence is a major public health problem. This symposium will focus on breaking the cycle of violence and will showcase speakers who are working on violence prevention in the pediatric emergency department, school and community. The speakers will demonstrate what can be done by physicians who see the importance of this issue and the ways in which we can make a difference.

Violence Prevention in Primary Care: Moving from Public Health to Private Practice
Robert D. Sege, Tufts-New England Medical Center, Boston, MA

Beyond Treat and Street: Violence Prevention in the Emergency Department
Joel Fein, The Children’s Hospital of Philadelphia, PA

Efforts in the Community
Sheryl A. Ryan, University of Rochester School of Medicine, Rochester, NY

Blood vessels perfuse all tissues in the body and play a vital function in mediating the exchange of metabolites between the tissues and the blood. However, recent experimental evidence indicates that endothelial cells play an important signaling role during embryonic development and cell differentiation. Understanding the nature of the interaction between endothelial cells and the surrounding cells and tissues will provide valuable insight into normal developmental mechanisms and may lead to important therapeutic approaches for a variety of diseases. In this symposium, we will discuss endothelial signaling in early organ development with a particular focus on the interactions that occur between airway and vascular cells during lung organogenesis and how these interactions are perturbed in lung injury and repair. In addition, we will discuss the biology of a molecule critical to development, VEGF, and its role during angiogenesis.

Endothelial Signaling During Embryonic Development
Ondine Cleaver, Harvard University, Cambridge, MA

Impaired Vascular and Alveolar Interactions in the Pathogenesis of Bronchopulmonary Dysplasia
Steven H. Abman, The Children's Hospital, Denver, CO

Extracellular Matrix Imbalance and Abnormal Lung Morphogenesis
Mala Chinoy, Penn State University College of Medicine, Penn State Hershey Medical Center, Hershey, PA

New Insights in the Regulation of Angiogenesis by VEGF and Other Mediators
Napoleone Ferrara, Genentech, Inc., San Francisco, CA
 

The National Children’s Study is a national prospective, longitudinal study of environmental effects, including physical, chemical, biological and psychosocial effects, on child health and development. The goal of the study is to improve the health and well-being of children. The study will examine these environmental effects on the health and development of more than 100,000 children across the United States, following them from before birth until age 21. The study is led by a consortium of federal agency partners: the U.S. Department of Health and Human Services, including the National Institute of Child Health and Human Development (NICHD); the National Institute of Environmental Health Sciences (NIEHS); the Centers for Disease Control and Prevention (CDC); and the U.S. Environmental Protection Agency (EPA). For additional information, visit the website at http://www.nationalchildrensstudy.gov/.

The National Children’s Study—An Overview
Duane Alexander, NICHD, National Institutes of Health, Bethesda, MD

The National Children’s Study—Methods
Peter C. Scheidt, National Institutes of Health, Bethesda, MD

Children’s Health and Environmental Exposures: The Most Important Unanswered but Answerable Questions
Michael Weitzman, The AAP Center for Child Health Research at the University of Rochester, Rochester, NY

The neuroendocrine and genetic control of puberty remains one of the fundamental mysteries in human biology. Recent advances derived from sequencing the human genome have enabled the identification of novel genes affecting human puberty via clinical investigations of single patients or families with human disorders that were simply not possible even three years ago. Using these techniques, clinical investigators have been able to identify and chart several genetic defects affecting reproductive development and translate these insights into an improved understanding of how the brain controls puberty in the human. The lecture will focus upon several of these major advances and describe a new gene recently discovered that controls puberty.

William F. Crowley, Harvard Medical School, Massachusetts General Hospital, Boston, MA

The application of imaging technologies to solving questions in biology and medicine is revolutionizing medicine by accelerating analyses in situ and in vivo and providing new perspectives on biological processes as diverse as development, neoplasia and injury repair. In this plenary session, three internationally recognized speakers will focus on developmental processes and discuss how these new imaging technologies are providing dynamic insights into the genetic and epigenetic mechanisms that underpin hematopoiesis and vascular development.

Introduction
Lisa M. Guay-Woodford, University of Alabama at Birmingham, Birmingham, AL

Dynamic Imaging of Fluid Forces in Developing Mouse Vasculature
Mary Dickinson, Beckman Institute–Caltech, Pasadena, CA

Microscopic Imaging of Angiogenesis
Donald M. McDonald, University of California, San Francisco, CA

Watching Hematopoietic Stem Cell Engraftment and Hematopoiesis in Living Animals
Christopher H. Contag, Stanford University School of Medicine, Stanford, CA

Questions from the audience
 

This session will provide insight into the epigenetic mechanisms responsible for gene expression and its impact during development resulting in programming. These mechanisms may underlie interactions between different nutritional and environmental influences on gene expression. Various examples will be discussed, and the life-long impact of these processes on the phenotype described. This session will provide insight into the relationship between fetal/neonatal events and long-term effects that manifest as chronic adulthood diseases. The speakers will present various aspects of this phenomenon and its physiological outcome.

Evolution of Imprinted Disease Susceptibility Genes
Randy L. Jirtle, Duke University Medical Center, Durham, NC

The Contribution of Genomic Imprinting and Epigenetics to Phenotype
Arthur L. Beaudet, Baylor College of Medicine, Houston, TX

Maternal Care, DNA Methylation and the Development of Individual Differences in Stress Reactivity
Michael Meaney, McGill University, Montreal, Canada
 

Worldwide, more than 1,500 children per day become infected with HIV through mother-to-child transmission. Currently there are 2.7 million children living with HIV infection across the globe, >90% of whom reside in developing countries. While there have been enormous successes in the prevention and treatment of pediatric AIDS in the United States and Europe, it remains an open question as to how effectively these public health gains can be replicated in the poor countries of the world, which bear the greatest burden of disease. Efforts to develop an HIV vaccine appropriate for preventing infection among the world's children and adolescents are finally under way on a global scale. We will discuss these issues and accompanying controversies as they apply to the children of the developing world.

AIDS in Children—A Global Public Health Crisis
David L. Pugatch, Hasbro Children's Hospital and Brown Medical School, Providence, RI

Preventing Mother-to-Child Transmission of HIV in Developing Countries—Successes, Failures and Challenges
Catherine M. Wilfert, Elizabeth Glaser Pediatric AIDS Foundation, Santa Monica, CA and Washington, DC

HIV Treatment for Children—Can the Successes of Rich Countries Be Duplicated in Resource-Poor Settings?
Mark W. Kline, Baylor College of Medicine, Houston, TX

Finding an AIDS Vaccine That Works for the World's Children
Richard A. Koup, Vaccine Research Center, National Institutes of Health, Bethesda, MD

Despite continuing advances in neonatal care, bronchopulmonary dysplasia remains a vexing problem for neonatologists, other pediatric subspecialists, and general pediatricians. As our understanding of BPD improves, our expectation is that new targets for combating this condition will emerge. Today’s session is designed to explore new findings of biological importance relevant to the pathogenesis of BPD and to stimulate discussion about possible hypotheses for its treatment.

Cellular and Molecular Targets in Bronchopulmonary Dysplasia
Steven R. Seidner, University of Texas Health Sciences Center, San Antonio, TX

Sublethal Oxygen Exposure and Mechanisms of Lung injury
A. Keith Tanswell, The Hospital for Sick Children, Toronto, Canada

Neuropeptides, Immunity and BPD
Mary Sunday, Children's Hospital Boston, Boston, MA

TGF-ß and the Regulation of Lung Remodeling
David Warburton, Children's Hospital, Los Angeles Research Institute, Los Angeles, CA
 

The potential applications for using regenerated cells and tissues to treat injury and disease are unlimited. Early stem research concentrated on the hematopoietic stem cells of the bone marrow, but stem cells are now known to exist in most organs of the body. Furthermore, it may be possible to return mature, differentiated cells to a undifferentiated, stem-like state. This symposium will first provide an overview of non-hematopoietic stem cells, then focus on two rapidly-progressing areas of research—those of regenerating nervous tissue and liver.

Neural Stem Cells: Developmental Insights May Suggest Therapeutic Options
Evan Y. Snyder,

Hepatic Stem Cells and the Potential of Liver Repopulation for Cell Therapy
Sanjeev Gupta, Albert Einstein College of Medicine, Bronx, NY

Currently, there is debate regarding the optimal strategy for initial and ongoing respiratory support in preterm infants (e.g., nasal CPAP, nasal non-invasive ventilation, endotracheal mechanical ventilation) with a particular focus on reducing later bronchopulmonary dysplasia (BPD). This session will explore the pathophysiology behind the strategies involved, how to "fine-tune" those strategies and will provide in-depth analysis of current data examining various modes of respiratory support for the premature infant.

Introduction
Rita M. Ryan, State University of New York at Buffalo, Women & Children’s Hospital of Buffalo, Buffalo, NY

Delivery Room and Early Respiratory Support of the Premature Infant: To Intubate or Not To Intubate?
Neil N. Finer, University of California, San Diego, CA

How Can We Optimize Conventional Ventilation in Preterm Neonates?
Steven M. Donn, University of Michigan Health System, Ann Arbor, MI

Discussion/Questions

Has High-Frequency Ventilation Fulfilled the Promise To Reduce BPD?
David Henderson-Smart, Centre for Perinatal Health Services Research, University of Sydney, Sydney, Australia

Noninvasive Ventilation in the Neonate: Will This Decrease BPD?
Keith J. Barrington, Royal Victoria Hospital, Montreal, Canada

Discussion/Questions