There has been remarkable progress in our understanding of the development and function of the immune system in health and disease. The regulation of immunity impacts profoundly on many of the conditions that pediatricians treat. The objective of this program is to enable PAS attendees coming from diverse disciplines to understand the language of modern immunology and the translation of recent advances in basic science to the diagnosis and treatment of diseases of children. This course will address three areas: immunology of infectious diseases, immunology of auto-immunity and tumor immunology.

Opening remarks
E. Richard Stiehm, UCLA Children's Hospital, Los Angeles, CA

Opening remarks
Beverly J. Lange, Children's Hospital of Philadelphia, Philadelphia, PA

Immunology of Infectious Disease
Katherine F. Luzuriaga, University of Massachusetts Medical School, Worcester, MA

Immunology of Autoimmunity
Betty Diamond, Albert Einstein College of Medicine, Bronx, NY

Tumor Immunology
Robert H. Vonderheide, University of Pennsylvania, Philadelphia, PA

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

The program will highlight new developments in clinical management of patients with chronic granulomatous disease as well as an update on the progress of gene therapy of CDG stem cells. There will also be an update on the management and diagnosis of patients with the Shwachman-Diamond syndrome, and, finally, there will be an update on diagnosis, treatment and pathophysiology of severe chronic neutropenias.

Overview
Laurence A. Boxer, Mott Children's Hospital, University of Michigan, Ann Arbor, MI

Severe Chronic Neutropenia Pathogenesis and Treatment
David Dale, University of Washington, Seattle, WA

Shwachman-Diamond Syndrome Pathogenesis and Treatment
Melvin H. Freedman, Hospital for Sick Children, Toronto, Canada

Chronic Granuloma Disease, Pathogenesis, Management
Harry Malech, National Institutes of Health, Bethesda, MD

Pain that is recurrent or persistent can create difficulties in diagnosis and treatment. Since research in pediatric pain is relatively recent but expanding, physicians may not have sufficient state of the art knowledge upon which to evaluate and treat their patients with chronic pain. There have been significant advances in the neurobiology of pain and the many factors that magnify and maintain the pain experience, pain behaviors and pain pathophysiology. The interface between mind, body and the environment, as well as new diagnostic tools, is creating new paradigms in our understanding of pain. For example, barostat and imaging studies have revealed new models for thinking about irritable bowel syndrome (IBS) as a condition of neuroenteric dysfunction. Other conditions, such as juvenile fibromyalgia and myofascial syndromes, are thought to be caused by central neurodysregulation. Many of these conditions are magnified and confounded by co-morbid anxiety disorders, learning disabilities and family system issues, among other factors. Why do some children with chronic pain develop a downward spiral of decreasing function and develop PADS? These conditions are not as difficult to evaluate and treat once they are understood from a biopsychosocial perspective. We will discuss the neurobiology, clinical assessment and approach to treatment of chronic pain and PADS, using IBS, juvenile fibromyalgia and myofascial pain as examples.

Overview of Pain Systems: A Mind–Body Perspective
Lonnie K. Zeltzer, David Geffen School of Medicine at UCLA, Mattel Children's Hospital, Los Angeles, CA

Neurobiology of Chronic Pain: Irritable Bowel Syndrome as a Model
Carlo Di Lorenzo, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA

How Do We Understand Disorders Such as Fibromyalgia and Myofascial Pain?
David D. Sherry, University of Pennsylvania School of Medicine, Children's Hospital of Philadelphia, Philadelphia, PA

Pain-Associated Disability Syndrome (PADS): What Is It and How To Evaluate and Treat It
Brenda Bursch, David Geffen School of Medicine at UCLA, UCLA Neuropsychiatric Institute & Hospital, Los Angeles, CA

Discussion
 

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

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 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 program will focus on emerging trends in hematopoietic stem cell transplantation for children with primary immunodeficiencies. Topics to be covered will include the use of alternative donor sources such as unrelated cord blood, new approaches with lower intensity pre-transplant conditioning regimens and an update on transplant outcomes for some of the more common primary immunodeficiencies such as SCID, WAS and HLH.

Hematopoietic Stem Cell Transplant for Primary Immunodeficiency Disorders: Update of Outcomes and Unrelated Cord Blood
Alexandra H. Filipovich, Children's Hospital Medical Center, Cincinnati, OH

Nonmyeloablative Stem Cell Transplant for Congenital Immunodeficiencies
Kanchana Rao, Great Ormand Street Hospital for Children, London, United Kingdom

Hematopoietic Stem Cell Transplant for Hemophagocytic Lymphohistiocytosis: Results from the Multi-institutional National Marrow Donor Program HLH Protocol
K. Scott Baker, University of Minnesota, Minneapolis, MN

Vaccines have an important function in preventing birth defects. The most obvious one is rubella vaccine and its application for the purpose of preventing congenital rubella syndrome (CRS) will be discussed. In addition, prospects of the development of other relevant vaccines will be presented. These will include: cytomegalovirus, parvovirus, herpes simplex and malaria. The first three, because they affect the fetus directly; the last, because of its adverse effect on pregnancy that results in small-for-gestational-age newborns.

Elimination of Rubella from the Americas by the Year 2010
Mirta Roses Periago, Director of PAHO, Panamerican Health Organization (PAHO), Washington, DC

Prevention of CRS by Universal Application of the Rubella Vaccine
Susan E. Reef, Center for Disease Control, Atlanta, GA

Prospects for a Vaccine Against Cytomegalovirus
Stanley A. Plotkin, Aventis Pasteur and the University of Pennsylvania, Doylestown, PA

Prospects for a Vaccine Against Herpes Simplex
Richard J. Whitley, University of Alabama at Birmingham, Children's Hospital, Birmingham, AL

Prospects for a Vaccine Against Parvovirus B-19
Neal S. Young, National Institutes of Health, Bethesda, MD

Prospects for a Vaccine Against Malaria
N. Regina Rabinovich, Bill & Melinda Gates Foundation, Seattle, WA

Discussion

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, 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 Six Revolutions in Vaccinology

The Pediatric Infectious Diseases Society (PIDS) has established the Stanley A. Plotkin Lecture in Vaccinology to honor Dr. Plotkin, the Society’s "Founding Father." The lecture, which will take place at the annual PIDS meeting, is sponsored by Aventis’ vaccines business, Aventis Pasteur. Dr. Plotkin was medical director at Aventis Pasteur and remains a medical and scientific advisor.