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Anti-Rejection Drug Can Prevent Pancreatic Inflammation Triggered by Common Procedure to Remove Gallstones

PrintPITTSBURGH, July 2, 2015 – Exposure to an X-ray dye during a common procedure to treat gallstones causes some patients to develop inflammation of the pancreas, according to researchers at the University of Pittsburgh School of Medicine and Children’s Hospital of Pittsburgh of UPMC. In a study published online in Gastroenterology, the team noted that a single dose of FK506, an anti-rejection drug typically used after organ transplantation, might be able to prevent the complication.

During the endoscopic retrograde cholangiopancreatography (ERCP) procedure, doctors insert a fiber-optic endoscope through the mouth, esophagus, stomach and duodenum to access the bile ducts, where a gallstone might be lodged. The X-ray dye, also known as radiocontrast, is infused through a catheter so doctors can visualize the bile ducts and anything obstructing them, explained senior author and principal investigator Sohail Z. Husain, M.D., associate professor of pediatrics at the Pitt School of Medicine and Children’s Hospital.

“Thousands of ERCP procedures are performed every year, particularly for the removal of gallstones,” Dr. Husain said. “But after the procedure, a fair number of patients develop acute pancreatitis, which is an exquisitely painful, life-threatening inflammation of the pancreas. Our findings provide the first explanation for why this complication occurs, namely through the signals that FK506 can block.”

The research team examined what happened to pancreatic cells in mice after they received infusions of two common radiocontrast agents. They found the agents elevated cellular calcium levels, in turn activating proteins, particularly calcineurin, involved in inflammatory pathways that cause tissue injury. Similar results were observed in experiments with human pancreatic cells. Also, mice that were genetically modified to lack calcineurin failed to develop pancreatitis after radiocontrast exposure.

Mice that were given the anti-rejection drug FK506, which is an inhibitor of calcineurin, before and after infusion of the X-ray dye also were protected from pancreatitis.

“In the future, we will test other radiocontrast agents to see if they, too, affect the same inflammatory pathways,” Dr. Husain said. “This study already sets the stage for a clinical trial to test whether calcineurin inhibitors alone or in combination with other drugs can prevent post-ERCP pancreatitis.”

The team included Shunqian Jin, Ph.D., Abrahim I. Orabi, B.S., Tianming Le, M.D., Tanveer A. Javed, B.S., Swati Sah, B.A., and John F. Eisses, M.D., Ph.D., all of the University of Pittsburgh; Rita Bottino, Ph.D., of Allegheny General Hospital; and Jeffery D. Molkentin, Ph.D., of the University of Cincinnati. The project was funded by National Institutes of Health grants DK083327, DK093491 and DK03002.

Children’s Hospital of Pittsburgh of UPMC Named a Center of Excellence by Food Allergy Research & Education

PrintPITTSBURGH, June 29, 2015Children’s Hospital of Pittsburgh of UPMC has been named a center of excellence by Food Allergy Research & Education, which has established the FARE Clinical Network, an initiative that aims to accelerate the development of drugs for patients with food allergies as well as improve the quality of care for this serious illness. Children’s Hospital is one of 21 centers named as inaugural members.

FARE Clinical Network members will serve as sites for clinical trials for the development of new therapeutics and will develop best practices for the care of patients with food allergies. The Network will serve as a powerful driver of collaboration to advance the field of food allergy, with member centers contributing to the development of a national food allergy patient registry and biorepositories.

“We were honored to be invited to apply for membership with the FARE Clinical Network and to receive designation as a FARE Clinical Network Center of Excellence,” said Todd D. Green, M.D., Division of Pulmonary Medicine, Allergy and Immunology, Children’s Hospital. “This will be a great opportunity for food-allergic patients and their families in our region and will allow us to collaborate with other top food allergy centers on maximizing the quality of care these patients receive, as well as to participate in more multicenter research studies.”

Participation in the FARE Clinical Network will ensure that Children’s remains on the forefront of efforts to improve the quality of life for food-allergic individuals as they work toward development of potential new treatments.

“We need to push for the development of drugs and other therapies to prevent life-threatening food allergy reactions, while ensuring that children and adults with food allergy receive the best care possible,” said James R. Baker, Jr., M.D., C.E.O. and chief medical officer of FARE. “To that end, FARE will direct the Clinical Network centers of excellence across the country to a common goal of ensuring that patients with food allergies have access to state-of-the-art diagnosis, treatments and research. We will continue to expand the number of centers to provide access to more patients. This effort is fundamental to our mission — to improve the quality of life and the health of individuals with food allergies while providing them hope through the promise of new treatments.”

In addition to Children’s, the inaugural members of the FARE Clinical Network are:

  • Ann & Robert H. Lurie Children’s Hospital of Chicago
  • Arkansas Children’s Hospital Research Institute
  • Boston Children’s Hospital
  • Children’s Hospital Colorado
  • Children’s Mercy Kansas City
  • Children’s National Health System
  • Cincinnati Children’s Hospital Medical Center
  • Joe DiMaggio Children’s Hospital – a facility of Memorial Healthcare System
  • MassGeneral Hospital for Children
  • National Jewish Health (Denver)
  • Rady Children’s Hospital/University of California, San Diego
  • Riley Hospital for Children at IU Health
  • Sean N. Parker Center for Allergy Research at Stanford University
  • Texas Children’s Hospital Food Allergy Program, Baylor College of Medicine
  • The Children’s Hospital of Philadelphia
  • The Northwest Asthma and Allergy Center (Seattle)
  • The University of Chicago Medicine
  • UNC Food Allergy Initiative at the University of North Carolina at Chapel Hill
  • University of Arizona College of Medicine – Tucson
  • UT Southwestern Medical Center and Children’s Medical Center Dallas

The centers of excellence selected as part of the FARE Clinical Network provide high-quality clinical and subspecialty food allergy expertise and services and are focused on applying new evidence-based knowledge to this important field. Additionally, these centers meet high standards for clinical care, teaching and clinical research.

Children’s Hospital of Pittsburgh of UPMC Named One of America’s Top 10 Children’s Hospitals for Sixth Consecutive Year

PrintPITTSBURGH, June 9, 2015 – Children’s Hospital of Pittsburgh of UPMC has once again been named one of America’s Best Children’s Hospitals by U.S. News & World Report, making this the sixth consecutive year the hospital has been listed on the Honor Roll.

Children’s Hospital ranks eighth on the magazine’s 2015-16 Honor Roll of America’s Best Children’s Hospitals, which was released today. Children’s also ranks in each of the 10 pediatrics specialties ranked by U.S. News.

The Best Children’s Hospitals rankings highlight the top 50 U.S. pediatric hospitals in each of 10 specialties: cancer; cardiology and heart surgery; diabetes and endocrinology; gastroenterology and GI surgery; neonatology; nephrology; neurology and neurosurgery; orthopedics; pulmonology; and urology.

The hospital ranked in the top 25 in nine of the specialties, including second in gastroenterology and GI surgery; third in diabetes and endocrinology; sixth in pulmonology; and 10th in three categories: cardiology and heart surgery, neonatology, and neurology and neurosurgery.

“This recognition speaks to the talent, passion, and dedication of our physicians, nurses, staff, and volunteers,” said Christopher Gessner, president, Children’s Hospital. “We are proud to have built a reputation of excellence over our 125-year history and we’re grateful to have those efforts recognized.”

The 2015-16 Best Children’s Hospitals rankings will be released online today and also will be published in the U.S. News “Best Hospitals 2016” guidebook, available in September.

U.S. News introduced the Best Children’s Hospitals rankings in 2007 to help families of children with rare or life-threatening illnesses find the best medical care available. The rankings open the door to an array of detailed information about each hospital’s performance.

In addition to Children’s Hospital of Pittsburgh of UPMC, the other hospitals named to U.S. News’ Honor Roll of Best Children’s Hospitals for 2015-16 are:

  • Boston Children’s Hospital
  • Children’s Hospital of Philadelphia
  • Cincinnati Children’s Hospital Medical Center
  • Texas Children’s Hospital, Houston
  • Children’s Hospital Colorado, Aurora
  • Seattle Children’s Hospital
  • Children’s Hospital Los Angeles
  • Nationwide Children’s Hospital, Columbus, Ohio
  • Children’s National Medical Center, Washington, D.C.
  • Ann and Robert H. Lurie Children’s Hospital of Chicago
  • Children’s Healthcare of Atlanta

Children’s Hospital of Pittsburgh of UPMC and Its Foundation Celebrate 125 Years of Caring

PrintPITTSBURGH, June 4, 2015 – Children’s Hospital of Pittsburgh of UPMC opened its doors on June 4, 1890, and today kicks off a yearlong celebration of 125 years of caring for kids.

From our beginning — a single cot endowed by Kirk LeMoyne, son of local pediatrician Frank LeMoyne, to be used for children and infants at a local hospital — to present day, Children’s Hospital has grown to become one of the world’s top pediatric hospitals with a reputation for innovation as well as superior care and successful treatment of kids with highly complex medical issues.

Children’s medical team treats rare diseases, defines new standards of care, pioneers research and treatment protocols, and provides patient- and family-centered services in a top-of-class environment. Every discovery, milestone and advancement is rooted in the same mission and supported by the same essence of community philanthropy established 125 years ago.

“Today, with 125 Years of Caring, we celebrate the tremendous work of our staff and physicians and all that they do for patients and families in the region,” said Christopher Gessner, president, Children’s Hospital. “We are extremely grateful for the generous community support that enables us to continue to provide the world-class care that has catapulted Children’s to the forefront of pediatric health care.”

Throughout the year, Children’s Hospital of Pittsburgh Foundation will carry on a campaign — “Give Kids a Chance to be Kids” — celebrating 125 years of caring and the important role of community support for the clinical and research advances at Children’s. The campaign will raise funds for patient care and research, attract a new generation of support from leading organizations and individuals throughout the region and beyond, and engage the community with a collective goal: Cures for childhood illness and diseases.

“The 125th anniversary will celebrate Children’s Hospital’s history and build momentum for what can be accomplished for our children’s children with continued community support and engagement,” said Greg Barrett, president, Children’s Hospital of Pittsburgh Foundation. “Every gift, large or small, directly impacts the lives of children. By giving to Children’s, we truly are giving kids a chance to be kids.”

Today, Children’s officially began the celebration with a 125th anniversary kickoff event in the Eat’n Park Atrium at Children’s main campus in Lawrenceville. During the event, the Foundation announced a $1.25 million partnership with PNC as the lead corporate sponsor for the 125th Anniversary campaign. In addition, Jay Costa, State Senate Minority Leader; Wayne D. Fontana, State Senator, Democratic Caucus Chair; Rich Fitzgerald, Allegheny County Executive; and Bill Peduto, Mayor of Pittsburgh, all read proclamations.

Children’s Hospital of Pittsburgh Foundation also unveiled the “Giving Booth,” an interactive video booth that will travel throughout the region to various events encouraging individuals to share a childhood memory or a Children’s Hospital memory. All videos will be uploaded to the Foundation’s 125th Anniversary webpage where participants will be able to watch and share videos and encourage their friends and family to do the same, as well as make a donation to support Children’s. The 125th Anniversary webpage also will feature memories shared by local and national celebrities.

For more information on the Foundation and the campaign, visit www.givetochildrens.org/125.

Fine Particulate Air Pollution Associated With Increased Risk of Childhood Autism

PITTSBURGH, May 21, 2015 – Exposure to fine particulate air pollution during pregnancy through the first two years of a child’s life may be associated with an increased risk of the child developing autism spectrum disorder (ASD), a condition that affects one in 68 children, according to a University of Pittsburgh Graduate School of Public Health investigation of children in southwestern Pennsylvania.

The research is funded by The Heinz Endowments and published in the July edition of Environmental Research.

“Autism spectrum disorders are lifelong conditions for which there is no cure and limited treatment options, so there is an urgent need to identify any risk factors that we could mitigate, such as pollution,” said lead author Evelyn Talbott, Dr.P.H., professor of epidemiology at Pitt Public Health. “Our findings reflect an association, but do not prove causality. Further investigation is needed to determine possible biological mechanisms for such an association.”

Dr. Talbott and her colleagues performed a population-based, case-control study of families with and without ASD living in six southwestern Pennsylvania counties. They obtained detailed information about where the mothers lived before, during and after pregnancy and, using a model developed by Pitt Public Health assistant professor and study co-author Jane Clougherty, Sc.D., were able to estimate individual exposure to a type of air pollution called PM2.5.

This type of pollution refers to particles found in the air that are less than 2.5 micrometers in diameter, or 1/30th the average width of a human hair. PM2.5 includes dust, dirt, soot and smoke. Because of its small size, PM2.5 can reach deeply into the lungs and get into the blood stream. Southwestern Pennsylvania has consistently ranked among the nation’s worst regions for PM2.5 levels, according to data collected by the American Lung Association.

“There is increasing and compelling evidence that points to associations between Pittsburgh’s poor air quality and health problems, especially those affecting our children and including issues such as autism spectrum disorder and asthma,” said Grant Oliphant, president of The Heinz Endowments. “While we recognize that further study is needed, we must remain vigilant about the need to improve our air quality and to protect the vulnerable. Our community deserves a healthy environment and clean air.”

Autism spectrum disorders are a range of conditions characterized by social deficits and communication difficulties that typically become apparent early in childhood. Reported cases of ASD have risen nearly eight-fold in the last two decades. While previous studies have shown the increase to be partially due to changes in diagnostic practices and greater public awareness of autism, this does not fully explain the increased prevalence. Both genetic and environmental factors are believed to be responsible.

Dr. Talbott and her team interviewed the families of 211 children with ASD and 219 children without ASD born between 2005 and 2009. The families lived in Allegheny, Armstrong, Beaver, Butler, Washington and Westmoreland counties. Estimated average exposure to PM2.5 before, during and after pregnancy was compared between children with and without ASD.

Based on the child’s exposure to concentrations of PM2.5 during the mother’s pregnancy and the first two years of life, the Pitt Public Health team found that children who fell into higher exposure groups were at an approximate 1.5-fold greater risk of ASD after accounting for other factors associated with the child’s risk for ASD – such as the mother’s age, education and smoking during pregnancy. This risk estimate is in agreement with several other recent investigations of PM2.5 and autism.

A previous Pitt Public Health analysis of the study population revealed an association between ASD and increased levels of air toxics, including chromium and styrene. Studies by other institutions using different populations also have associated pollutants with ASD.

“Air pollution levels have been declining since the 1990s; however, we know that pockets of increased levels of air pollution remain throughout our region and other areas,” said Dr. Talbott. “Our study builds on previous work in other regions showing that pollution exposures may be involved in ASD. Going forward, I would like to see studies that explore the biological mechanisms that may underlie this association.”

Additional co-authors of this study are Vincent C. Arena, Ph.D., Judith R. Rager, M.P.H., Drew R. Michanowicz, Dr.P.H., Ravi K. Sharma, Ph.D., and Shaina L. Stacy, Ph.D., all of Pitt Public Health.

Children’s Hospital of Pittsburgh of UPMC Lung Researcher Receives Prestigious Scientific Award

PrintPITTSBURGH, May 18, 2015John F. Alcorn, Ph.D., assistant professor of pediatrics in the Division of Pulmonology at Children’s Hospital of Pittsburgh of UPMC, has been selected as the 2015 recipient of the Parker B. Francis Jo Rae Wright Award for Scientific Excellence. The award has been established by the Parker B. Francis Fellowship Program and the Francis Family Foundation to honor Jo Rae Wright, Ph.D.

The award will be presented to Dr. Alcorn today at the Parker B. Francis Fellowship Reception at the American Thoracic Society meeting.

“The Parker B. Francis Fellowship Program and the Francis Family Foundation has been instrumental in my early career development to independence,” said Dr. Alcorn, also assistant professor of pediatrics, University of Pittsburgh School of Medicine. “Receiving this award is exceptionally meaningful to me as I previously completed my Ph.D. training under Jo Rae’s mentorship at Duke University. I am honored to be the recipient Jo Rae Wright Award and I hope to continue on the path toward becoming a leader in pulmonary research.”

Dr. Alcorn’s research focuses on T-cell mediated immunity during influenza infections and secondary bacterial pneumonia, as well as the role of T-cells in severe, steroid-insensitive asthma.

The Parker B. Francis Jo Rae Wright Award for Scientific Excellence is given annually to a recent graduate of the Fellowship Program whose research shows outstanding creativity and promise and who has demonstrated outstanding mentoring and professional leadership qualities. Dr. Alcorn will receive a one-time award of $5,000 to be used to support research costs.

Dr. Jo Rae Wright was a world-renowned scientist, devoted teacher and mentor, and a leader in academia and professional organizations. She served as dean of the Graduate School of Duke University and was president of the American Thoracic Society in 2008. She received the American Physiological Society’s Walter B. Cannon Award for lifetime achievements in research in 2005. She served as a member of the Parker B. Francis Fellowship Program Council of Scientific Advisors from 2004 through 2007 and was a mentor to Parker B. Francis Fellows.

For more information on Dr. Alcorn, visit www.chp.edu.

Children’s Pulmonologist Honored By Association of American Physicians and American Thoracic Society

PrintPITTSBURGH, May 6, 2015 – Juan Celedón, MD, DrPH, Chief of Service in the Division of Pediatric Pulmonology, Allergy, and Immunology at Children’s Hospital of Pittsburgh of UPMC recently was elected to the Association of American Physicians. Dr. Celedón also was chosen for the Innovations in Health Equality — Lifetime Achievement Award from the American Thoracic Society’s Clinicians Advisory Committee and its Health Equality Subcommittee.

Dr. Celedón’s research is focused on the genetics and epidemiology of asthma in Puerto Rican and black children. He also is leading a study of chronic obstructive pulmonary disease (COPD) genetics in Costa Rica.

For more information on Dr. Celedón’s work, please visit the Division of Pulmonary, Allergy, and Critical Care Medicine page.

Pitt, Children’s Research Papers Receive Top 10 Awards from Clinical Research Forum

PrintPITTSBURGH, April 20, 2015 – Three scientific papers published in 2014 by research teams from the University of Pittsburgh School of Medicine and Children’s Hospital of Pittsburgh of UPMC have each been selected to receive a Clinical Research Forum Annual Top 10 Clinical Research Achievement Award. The awards were announced last night at the Forum’s annual meeting in Washington, D.C. The winning papers from Pitt and UPMC were chosen based on their degree of innovation from a pool of more than 50 nominations from 30 research and academic health centers nationwide. The Forum and its supporters believe these and other top ten papers represent the best and brightest work in the field, and will lead to advancements in medicine that will change lives and patient outcomes worldwide. “It is extraordinary to have three University of Pittsburgh projects in a variety of disciplines recognized by the Forum for their clinical impact and rigorous science,” said Arthur S. Levine, M.D., Pitt’s senior vice chancellor for the health sciences and the John and Gertrude Petersen Dean of Medicine. “This impressive showing reflects the commitment and caliber of the researchers on our campus, and is a tribute to the University’s Clinical and Translational Science Institute, which facilitates and supports these endeavors.” The three winners are:

  • “Upper-Airway Stimulation for Obstructive Sleep Apnea,” published Jan. 9, 2014, in the New England Journal of Medicine, showed implanting a device called Inspire® Upper Airway Stimulation led to a 70 percent reduction of severe obstructive sleep apnea symptoms. Project investigators included lead author Patrick Strollo, M.D., professor of medicine and clinical and translational science, Pitt School of Medicine, and medical director of the UPMC Sleep Medicine Center, and Ryan Soose, MD.
  • A Randomized Trial of Protocol-Based Care for Early Septic Shock,” published May 1, 2014, in the New England Journal of Medicine, showed that a structured, standardized approach to diagnose and treat sepsis in its early stages did not change patient survival rates. Project investigators included Derek Angus, M.D., M.P.H., distinguished professor and Mitchell P. Fink Chair, Department of Critical Care Medicine, Pitt School of Medicine, and Donald M. Yealy, M.D., professor and chair of Pitt’s Department of Emergency Medicine.
  • Antimicrobial Prophylaxis for Children with Vesicoureteral Reflux,” published June 19, 2014, in the New England Journal of Medicine, showed that children with abnormal flow of urine from the bladder to the upper urinary tract, called vesicoureteral reflux (VUR), can avoid recurrent urinary tract infections by taking daily low-dose antibiotics. Project investigators included senior author Alejandro Hoberman, M.D., chief, Division of General Academic Pediatrics at Children’s Hospital, and professor of pediatrics, Pitt School of Medicine.

“I applaud the researchers recognized for their groundbreaking clinical research that will advance new treatments to reduce suffering and bring hope to millions of people,” said National Institutes of Health director, Francis S. Collins, M.D., Ph.D. “And I’m especially proud that NIH funding makes these advances possible.” Other awardees include scientists from Harvard Medical School, Yale University, the University of Pennsylvania, UCLA and other leading institutions. The Clinical Research Forum was formed in 1996 to discuss the unique and complex challenges to clinical research in academic health centers. The mission of the Forum is to provide leadership to the national clinical and translational research enterprise and promote understanding and support for clinical research and its impact on health and health care.

UPMC Inpatient Child and Adolescent Bipolar Services (In-CABS) Program Receives National Honor for Technological Initiatives

PITTSBURGH, April 6, 2015 – The Inpatient Child and Adolescent Bipolar Services (In-CABS) program at Western Psychiatric Institute and Clinic of UPMC has received a first prize National Council for Community Behavioral Healthcare 2015 Impact Award of Excellence in Health Information Technology. The award, which will be announced on April 21 at the Excellence Awards Dinner in conjunction with the National Council Conference in Orlando, recognizes In-CABS’ use of health IT interventions, comprehensive diagnostic assessments, state-of-the-art pharmacological treatment, and psychosocial interventions. The program also trains students and professionals from a broad range of disciplines in health IT.

Each year, the National Council’s Awards of Excellence honor individuals and organizations that are making large strides in fighting mental illness and addiction. Specifically, the awards celebrate the achievements of individuals who dedicate themselves to improving the lives of those with serious mental illnesses, and the accomplishments and efforts of those living with schizophrenia or bipolar disorder in improving their own lives and the lives of their peers.

“This award is important for In-CABS because it acknowledges our high-tech, innovative initiatives in our daily morning report and triage,” says Rasim Somer Diler, MD, assistant professor of psychiatry at the University of Pittsburgh School of Medicine and medical director of Inpatient Child and Adolescent Bipolar Services. “We’ve also implemented the Philips® Actiwatch to objectively measure sleep and arousal using neurocognitive measures, and we set up daily electronic mood and energy monitoring with an interactive projector through the Beckwith Institute’s Clinical Transformation Program.”

To learn more about In-CABS, please download the program brochure.

A Strategy for Stimulating Heart Muscle Regeneration in Infants, Study Finds

PrintPITTSBURGH, April 1, 2015 – Surgery often is life-saving for many infants born with heart defects, but one thing that doctors cannot do yet is replace heart muscle that is scarred and dysfunctional. Researchers from the Heart Institute at Children’s Hospital of Pittsburgh of UPMC and Boston Children’s Hospital hope to overcome the challenge by stimulating regeneration of heart tissue. The findings were described today in Science Translational Medicine.

Children born with congenital heart disease are at greater risk of developing heart failure even after surgical correction of the problem.

“It is not surprising that survivors often develop heart failure later on,” said lead author, Bernhard Kühn, M.D., director of research for the Division of Cardiology at Children’s Hospital, and associate professor of pediatrics at the University of Pittsburgh School of Medicine. “But when these patients were given adult medicines in clinical trials, it turned out that they were not effective. The need for pediatric-specific heart failure therapies is increasingly recognized.”

For the study, the research team examined the potential of recombinant growth factor neuregulin-1 (rNRG1), which stimulates heart regeneration by driving proliferation of heart muscle cells, called cardiomyocytes.

They treated newborn mice with injections of rNRG1 at various times after heart injury and found that early treatment starting the first day after birth boosted cardiomyocyte cell division and heart function, and reduced scarring to a significantly greater degree compared to treatment that began at five days after birth. The growth factor also drove cardiomyocyte proliferation in lab tests of heart muscle samples obtained during surgery from human infants with congenital heart disease.

“These findings suggest that rNRG1 administration in infants with these birth defects might be a new therapeutic strategy for pediatric heart disease,” Dr. Kühn said. “Delivering agents early on that encourage the heart to make new cardiomyocytes could help the heart perform normally and reduce the risk of developing heart failure later in life.”

More research needs to be done before clinical testing of this strategy, the research team says. Dr. Kühn began the research while a member of the faculty at Boston Children’s Hospital.

Collaborators on the study were Balakrishnan Ganapathy, M.S., and Niyatie Ammanamanchi, M.S., both of Children’s Hospital of Pittsburgh of UPMC; Brian Polizzotti, Ph.D., Stuart Walsh, Ph.D., Sangita Choudhury, Ph.D., all of Boston Children’s Hospital; David Bennett, Ph.D., Beth Israel Deaconess Medical Center; Cristobal G. dos Remedios, Ph.D., Bosch Institute; Bernhard J. Haubner, M.D., and Josef M. Penninger, M.D., both with Institute of Molecular Biotechnology of the Austrian Academy of Sciences.

The research was supported by National Institutes of Health grants R01HL106302, K08HL085143, T32HL007572, and RR028792; Boston Children’s Hospital; and the Richard King Mellon Foundation Institute for Pediatric Research at Children’s Hospital of Pittsburgh of UPMC.

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