Apr 23 2014

Illustrating Commitment to Education, CHOP Research Honors Trainees

traineeThe Children’s Hospital of Philadelphia Research Institute has long been committed to education, offering programs at all levels, from those for undergraduates to opportunities for physician fellows. As part of its commitment to training the next generation of pediatric pioneers, every year CHOP Research takes time to honor its exceptional trainees, and recently announced the 2014 Distinguished Research Trainee Award winners.

Comprised of a physicist, a molecular biologist, and a cancer geneticist, the 2014 awardees’ expertise spans the research spectrum. Doctoral candidate Jennifer Lynch, as well as James Psathas, PhD, and Jennifer Kalish, MD, PhD, a postdoctoral fellow and a physician fellow, respectively, were recognized with this year’s Distinguished Trainee Awards.

After receiving her bachelor’s degree from Emory University, Jennifer Lynch came to the University of Pennsylvania to pursue a doctorate in Physics, with a concentration on biomedical optics. Since 2010 she has worked with CHOP’s Daniel J. Licht, MD, aiding in several congenital heart defect investigations as well as using optical spectroscopies to monitor cerebral hemodynamics.

Lynch was the winner of the “Outstanding Investigator” Award at Cardiac Center’s Cardiology 2014 conference in Orlando, Fla. in February. She has also been the lead author on a number of recent papers, including a recent Academic Radiology study on using near-infrared spectroscopy to measure cerebral venous oxygen saturation.

“Most physics graduate students would shy away from clinical studies,” but Lynch “wholeheartedly embraces” and relishes in the complexity of clinical physiology, Dr. Licht said, adding, “I see a very bright future for her at the interface of physics and clinical research.”

The second awardee, James Psathas, PhD, was nominated by Andrei Thomas-Tikhonenko, PhD. A molecular biologist and biochemist, Dr. Psathas studies the mechanisms of oncogenesis. In 2012 he contributed to a Journal of Clinical Investigation study of CD19, while in December 2013 Dr. Psathas was the first author of a Blood paper on B cell signaling. In both cases, it was Dr. Psathas’ “painstaking bioinformatics work” that led to successful publication, Dr. Thomas-Tikhonenko said.

And rounding out the 2014 award winners is geneticist Jennifer Kalish, MD, PhD, who was nominated by Matthew Deardorff, MD, PhD. Currently working in the laboratory of the University of Pennsylvania’s Marisa S. Bartolomei, PhD, Dr. Kalish is also an attending physician in the Division of Genetics as well as an instructor in Pediatrics at the University of Pennsylvania.

Much of her work has been focused on better understanding Beckwith-Wiedemann Syndrome (BWS), a rare genetic overgrowth disorder that is associated with an increased risk of childhood cancers, in particular kidney cancer and hepatoblastoma, a form of liver cancer. In late 2013 Dr. Kalish received a “Young Investigator” grant from Alex’s Lemonade Stand Foundation to further study the mechanisms of BWS.

“There’s such amazing research that goes on at CHOP, and it’s an honor to be recognized as part of that research,” Dr. Kalish said.

To read more about each of this year’s awardees, and to learn more about training opportunities at CHOP Research, see the Office of Postdoctoral Affairs Trainee Web Portal. And to learn more about CHOP Research’s educational programs, click here.

Permanent link to this article: http://www.research.chop.edu/blog/illustrating-commitment-education-chop-research-honors-trainees/

Apr 22 2014

Rare Disease Project Makes Progress, Empowers

rare disease

By using next-generation sequencing (NGS) technologies, researchers from CHOP and BGI are one-third of the way toward their goal of sequencing 1,000 rare diseases.

Imagine facing a devastating medical problem, but when you searched for a diagnosis, even the experts had no answers because your condition was so rare.

In the U.S., a disease is considered rare if it affects fewer than 200,000 people. Many rare diseases have genetic origins, and almost 70 percent of Americans affected by a rare disease are children, according to the National Organization for Rare Disorders (NORD).

NORD recently hosted Rare Disease Day USA, when the U.S. joined more than 80 nations around the world to focus attention on rare diseases as an important global public health challenge. Rare Disease Day also presented the opportunity to recognize the important gains made through international cooperation in clinical and scientific research.

Under a collaboration announced in 2012, The Children’s Hospital of Philadelphia and BGI, the world’s largest genomics organization, initiated the 1,000 Rare Diseases Project to accelerate the discovery of genetic variants underlying rare diseases. By using next-generation sequencing (NGS) technologies, researchers from CHOP and BGI are one-third of the way toward their goal of sequencing 1,000 rare diseases.

“We have made major progress,” said Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics at CHOP who directs the project. “A number of our discoveries have exciting potential because there are existing drug therapies that could be repositioned or repurposed for some of these rare diseases we have now resolved. That will be a big impact.”

One of the project’s first success stories involved a family that had been coming to CHOP for almost 20 years. The parents wanted to track down the disease that caused their son and daughter to have progressive muscular weakness and also weakening of the heart muscle (cardiomyopathy) beginning at age 8.

Through whole-genome sequencing, the research team located RBCK1, a disease-predisposing gene for a novel and extremely rare single-gene disorder that had never been identified before. Genetic mutation shortens the protein that RBCK1 encodes, and then the modified protein accumulates in muscle fibers. Researchers confirmed that truncating mutations in RBCK1 were the culprit when they found the same exact gene to be mutated in a second family that had a comparable disease profile. Genome Medicine published their findings in 2013.

“It was very rewarding,” Dr. Hakonarson said. “The families have been fundraising for us so that we can gain a better understanding of the mechanism by which the gene mutation causes this devastating disease.”

Another study published in the American Journal of Human Genetics determined that mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis (AD IM). The disorder arises in infancy and childhood and is characterized by proliferative fibrous tumors affecting the skin, muscle, bone, and internal organs. Researchers performed whole-exome sequencing in members of nine unrelated families diagnosed with AD IM to identify the genetic origin of the disorder. In addition to pinpointing PDGFRB, they highlighted NOTCH3 as another disease-causing gene for IM.

“Both of these genes have been targeted by drugs that pharmaceutical companies have developed for totally different diseases,” Dr. Hakonarson said. “We have the opportunity to make a big shortcut here to develop new therapies to treat this disease.”

Other studies published by the investigators have shown:

  • mutation in ANKRD26 causes thrombocytopenia, a rare platelet disorder
  • mutation in ABCC6 causes generalized arterial calcification of infancy
  • a subset of mutations in DcR3 have a role in pediatric-onset inflammatory bowel disease
  • HK1 is a likely disease gene candidate for a novel congenital hyperinsulinism disorder.

Overall, the researchers have collectively identified between 40 and 50 new diseases so far, and they continue to make discoveries that elucidate rare diseases and resolve weighty questions for families.

“When we find these new mutations, the clinicians who treat these families have been able to validate these mutations by rigorous clinical testing and inform families that this is the disease-causing gene, and they have been immensely appreciative,” Dr. Hakonarson said. “They can go to other geneticists and clinicians and share these results. Now that they know what causes the disease, they can have other family members tested, and prenatal testing becomes an option for future pregnancies.”

Permanent link to this article: http://www.research.chop.edu/blog/rare-disease-project-makes-progress-empowers/

Apr 21 2014

Going With the Gut to Build Preterm Infants’ Immunity

infantsAt birth, infants move from a sterile environment to one full of microorganisms. They rapidly acquire alterations in their immune systems that help them to survive in this dirty world. Researchers at The Children’s Hospital of Philadelphia used mouse models to show that changes in microbial colonization of the gastrointestinal tract play a vital role in this transition.

Their findings published in Nature Medicine offer a possible explanation as to why human premature infants are more vulnerable to serious infections. Ultimately, this research may lead to potential treatments to restore critically ill newborns’ resistance to common pathogens, such as E. coli., in the neonatal intensive care unit. One out of every eight babies is born premature each year in the U.S., according to the Centers for Disease Control and Infection.

“Babies who are born preterm, in addition to them having less ability to fight infection, are more likely to get infected, either as a consequence of being born premature or exposure to microbes from the mother’s womb,” said Hitesh Deshmukh, MD, PhD, of CHOP’s division of neonatology and department of pediatrics, who co-authored the study.

Human babies experience a burst of production of infection-fighting white blood cells within 12 to 24 hours after birth, a process known as granulocytosis. The investigators demonstrated that neonatal mice had the same spike in white blood cells; however, this acceleration was diminished in mice that had been exposed to antibiotics, which contributed to increased susceptibility to E. coli K1 sepsis, a severe blood infection.

“Usually a low white count is a harbinger of bad things,” Dr. Deshmukh said. “It means that your body does not have enough white cells to fight an infection, and you’re more likely to be sicker.”

Neonatologists frequently prescribe antibiotics in NICUs because signs of infection in preterm babies are difficult to decipher, Dr. Deshmukh said. Yet, counter intuitively, recent research shows that prolonged antibiotic use in preterm babies can give rise to late-onset sepsis.

The Nature Medicine study suggests a mechanism that explains why preterm babies exposed to antibiotics, either directly or through their mother, tend to get sicker. Perhaps antibiotics hamper their natural buildup of granulocytes, as described in the mice models, which makes the preterm babies more prone to infection and less able to resist sepsis.

Study senior author G. Scott Worthen, MD, professor of pediatrics in the division of neonatology at the Perelman School of Medicine at the University of Pennsylvania, emphasized that researchers do not know definitively how closely newborn mice resemble preterm human babies from an immunological perspective, so this study cannot be applied directly to humans. But the results point to a fascinating pathway for investigation that could offer new interventions.

The CHOP researchers found that regulation of postnatal granulocytosis likely lies within the gut microbiome. By adulthood, a community of a hundred trillion microbes form along a person’s gastrointestinal tract, but at birth, the gut is sterile. Microbial colonization of the gut starts upon an infant’s arrival into the world, initiating an immune response.

“When you interrupt this pattern of colonization, either by giving antibiotics or some other mechanism, you make the babies more susceptible to infection,” Dr. Deshmukh suggested.

A prevailing thought is that antibiotics act on the bone marrow and decrease its ability to produce white blood cells, but Dr. Deshmukh and his team showed that this is not the case. They demonstrated that germ-free mice, which are born in sterile environments and are not naturally colonized with microbiota, behaved similarly to the mice that were exposed to antibiotics.

“While some antibiotics may affect the bone marrow directly, we believe these effects are due to the influence of antibiotics on bacteria in the gut,” Dr. Deshmukh said. “If you were to replace some of those microbes, you might restore the resistance of the newborn to the infection.”

His research team proved this by taking normal intestinal microbiota from mice that were not exposed to antibiotics and transferring them to mice that had received antibiotics. In adult humans, this procedure is called a fecal transplant, which is highly effective at eradicating C. difficile infection.

“Fecal transplant could be one of the ways in which you could make sure that babies have more resistance or more power to fight infection,” Dr. Worthen said.

But he cautioned that substantial research and safety testing must be done to determine which groups of microbes potentially are beneficial for preterm infants. Once researchers pinpoint the good and bad bugs, they could isolate, purify, and manipulate certain bacterial components that could trigger postnatal granulocytosis.

“One of the things you could do with this mixture is to use it to rapidly reconstitute an infant after they’ve finished a course of antibiotics,” Dr. Worthen said. “We still have to give antibiotics, but what happens after you stop? The infants get colonized with the germs that are in the NICU. That’s a horrible combination of events.”

Dr. Deshmukh and his team will focus their future research on identifying bacterial components that could generate a new microbial community for preterm infants’ who needed antibiotics and subsequently preserve or restore their resistance to infection.

Permanent link to this article: http://www.research.chop.edu/blog/going-gut-build-preterm-infants-immunity/

Apr 17 2014

Studies Find Genes Linked to BMI, Cardiovascular Health

BMITwo recent studies expand the list of genes associated with body fat and body mass index (BMI), and their connection to heart disease, high blood pressure, and diabetes. One study showed higher BMI caused harmful effects on the risk of type 2 diabetes, high blood pressure, and inflammation, while a second investigation found gene signals linked to higher levels of body fat metrics.

According to the CDC, heart disease causes approximately 600,000 deaths each year in the United States, and 67 million adults have high blood pressure (which is associated with increased rates of heart attack, heart failure, and stroke). For its part, diabetes is the 7th most common cause of death, and nearly 12 percent of American adults over 20 years of age are living with diabetes.

“These findings are highly relevant to the obesity pandemic in the United States and many other countries,” said the Center for Applied GenomicsBrendan J. Keating, DPhil, who co-led both studies.

Lowering BMI Could Improve Cardiovascular Health

In the BMI investigation, published recently in the American Journal of Human Genetics, Dr. Keating collaborated with clinical epidemiologist Michael V. Holmes, MD, PhD, of the Perelman School of Medicine at the University of Pennsylvania. That study made use of a recently developed tool called Mendelian randomization (MR) that allows researchers to construct genetic risk scores for specific traits of interest.

The study team analyzed eight population cohorts including over 34,000 individuals of European descent, of whom over 4,400 had type 2 diabetes, over 6,000 had coronary heart disease and over 3,800 had a previous stroke.

“This study is the first to use this emerging MR technique with a combination of genetic markers known to impact BMI, to assess the causal relationship of BMI and a comprehensive repertoire of traits,” said Dr. Holmes.

The authors concluded that their analysis supports the importance of BMI in regulating cardiometabolic traits and the risk of type 2 diabetes. “Our findings suggest that lowering BMI is likely to result in multiple reductions of cardiovascular traits: in blood pressure, inflammation, fasting glucose and insulin, and in the risk of type 2 diabetes,” said Dr. Keating.

Body Fat Genetic Signals Discovered

Dr. Keating also co-led a second study, published in Human Molecular Genetics, that analyzed genes associated with central adiposity. Measures of central adiposity, or body fat, can be derived using waist circumference and waist-to-hip ratio.

Keating’s co-senior author was Kira C. Taylor, PhD, MS, of the University of Louisville. The study team performed a meta-analysis in over 57,000 subjects of European ancestry, then validated their results in even larger numbers from independent studies.

This study discovered three novel genetic signals associated with central adiposity, in the genes TMCC1, HOXC10, and PEMT. In addition, the team found two more novel genetic signals, in the SHC1 and ATBDB4 genes, which were only observed in women.

“Previous research has reported different gene variants operating between men and women related to adiposity,” said Dr. Keating. “This gives us initial clues of the genes involved with sex-specific body shapes. Future research using these findings may yield insight into the actual biological mechanisms that dictate why males and females have different body distributions of fat deposits.”

The adiposity study showed an association, not a causal role, for the genetic signals, with other signals yet to be discovered using even larger sample sizes. Several of the genes are in regulatory regions, Dr. Keating noted. While additional work is needed to tease out the biology of these signals, but the first steps of identifying genes underpinning these traits has been accomplished, Dr. Keating added.

For more information about both studies, see the full press release.

Permanent link to this article: http://www.research.chop.edu/blog/studies-find-genes-linked-bmi-cardiovascular-health/

Apr 16 2014

Investigating Breakthrough Cystic Fibrosis Drug’s Effect on Weight

cystic fibrosis

“What caught our eye with this is as they were doing the clinical trials there was a completely unexpected weight gain … almost every participant was gaining weight,” Dr. Stallings noted.

A new project at The Children’s Hospital of Philadephia seeks to gain a clearer idea of what effect the novel cystic fibrosis drug ivacaftor has on energy balance and weight gain. With the support of the drug’s manufacturer, Vertex Pharmaceuticals, CHOP’s Virginia A. Stallings, MD, will measure the degree to which patients with cystic fibrosis taking ivacaftor — which is sold under the name Kalydeco — experience improvements in nutritional status and growth.

An inherited disease that is chronic, progressive, and often fatal, according to the Cystic Fibrosis Foundation cystic fibrosis affects approximately 30,000 adults and children in the United States and 70,000 worldwide. The disease is characterized by thick mucus that causes respiratory and digestive issues, and is associated with poor growth and weight gain, among other complications. There is currently no cure for cystic fibrosis, and until recently most treatments have focused on alleviating the disease’s symptoms.

Kalydeco is approved to treat CF in patients 6 years of age and older who have specific mutations in their cystic fibrosis gene. Kalydeco was first approved in 2012 on the strength of trials that showed it improved lung function “and other aspects of cystic fibrosis such as increasing weight gain,” according to the FDA. Though the FDA recently expanded the number of mutations for which Kalydeco is approved, because its approval is restricted to particular mutations it can currently only treat a small segment of the overall cystic fibrosis population. Nonetheless, Kalydeco is a “breakthrough” drug, said CHOP’s Dr. Stallings.

With this project, Dr. Stallings will examine Kalydeco’s effect on cystic fibrosis patients’ energy balance and weight gain. Dr. Stallings and her team proposed the study to Vertex after noting the unexpected weight gain observed during Kalydeco’s clinical trials.

Much of Dr. Stallings’ career has been spent working on ways to improve cystic fibrosis patients’ weight and growth, so the approval of Kalydeco — which treats the “primary cellular defect” — was “was a major, exciting, proof-of-principle,” she said.

“What caught our eye with this is as they were doing the clinical trials there was a completely unexpected weight gain … almost every participant was gaining weight,” Dr. Stallings noted.

She proposed a comprehensive study that will investigate what effect Kalydeco has on pancreatic function, how well patients are able to absorb food, and whether taking the drug has any effect on the patients’ appetite and food intake. Over the next 18 months, Dr. Stallings and her team will enroll patients who are about to go on the drug, to measure the effect Kalydeco has on their weight, appetite, and energy intake and needs before, during, and after treatment. The study will make use of innovative “SmartPills” that can measure changes in pH and gastrointestinal motility, Dr. Stallings said.

In a related project supported by the Cystic Fibrosis Foundation, Andrea Kelly, MD, from the Division of Endocrinology and Diabetes, has been working on an investigation of Kalydeco’s effect on insulin and insulin secretion. If the investigators were able to compare findings (not to mention share study participants), “we would have a spectacular look at the whole metabolic change,” said Dr. Stallings.

Saying she was excited about the study, and the promise of novel therapies like Kalydeco, Dr. Stallings said, “we’ve never had a time in CF when we could almost guarantee weight gain … so here we have an experimental design where almost everybody is going to gain weight.”

To learn more about cystic fibrosis, and cystic fibrosis research at The Children’s Hospital of Philadelphia, see the Cystic Fibrosis Center website.

Permanent link to this article: http://www.research.chop.edu/blog/investigating-breakthrough-cystic-fibrosis-drugs-effect-weight/

Apr 15 2014

Study Identifies Risk Factors for Obstructive Sleep Apnea

sleep apneaWhile obstructive sleep apnea syndrome (OSAS) is a relatively common condition, affecting about 2 percent to 4 percent of young children, the scientific community is just opening its eyes to pediatric sleep disorders. Little is known, for example, about the characteristics that increase OSAS severity in children.

OSAS occurs when a child stops breathing during sleep, usually because there is a blockage from enlarged tonsils or adenoids. Many of the pauses, called apneas and hypopneas, cause a brief arousal that increases muscle tone, opens the airway, and allows the child to resume breathing. These repeated disruptions result in restless sleep. Recurrent nightly episodes of obstructive apnea are associated with adverse behavioral, cognitive, quality of life, and health outcomes in children.

Researchers from the Sleep Center at The Children’s Hospital of Philadelphia were involved with a large, multicenter study called the Childhood Adenotonsillectomy Study for Children With OSAS (CHAT), and recently they used the study’s baseline data to perform a cross-sectional screening to analyze which factors predict OSAS severity. They examined data from 421 children ages 5 to 9 years who had undergone sleep testing, known as polysomnography, and evaluated the relationship between their levels of OSAS to sex, race, body mass index, environmental tobacco smoke (ETS), prematurity, socioeconomic variables, and comorbidities.

“If presumably you know some of the risk factors, you might be able to address some of those risk factors and preempt the sleep apnea or at least diagnosis it earlier,” said Carole L. Marcus, MBBCh, director of CHOP’s Sleep Center, who was first author for the CHAT study and also participated in the auxiliary study that appeared in SLEEP in February.

The auxiliary study found that African American race predicted OSAS severity, which supports previous research. This is especially interesting, Dr. Marcus said, because the CHAT study results showed that African American children had less improvement postoperatively, both in terms of polysomnographic changes and behavioral changes. Much debate exists about why African American race would be associated with higher OSAS severity and poorer outcomes after surgery, but some research suggests genetic, craniofacial, and environmental components play a role.

“They have worse disease, but they don’t respond as well to the therapy and possibly have more complications from the treatment,” Dr. Marcus said. “That definitely deserves further research. We also found in another related study that looked at continuous positive airway pressure, which is an alternative therapy for kids who don’t improve following surgical therapy, that they had poor adherence to CPAP. So they’re definitely a more difficult group to treat.”

Study participants’ exposure to secondhand smoke was another significant risk factor for increased OSAS severity that researchers identified.  ETS already has been connected to snoring in children, so this novel finding advances pediatric sleep research by demonstrating its effect on OSAS.

African American race and exposure to ETS were each associated with an approximately 20 percent increase in apnea-hypopnea index. More research is needed, Dr. Marcus said, to define these specific factors and suggest better OSAS screening strategies that focus on African American children and children exposed to ETS.

In the meantime, pediatricians can use this study’s findings to promote awareness of OSAS by asking parents about snoring at their children’s regular healthcare maintenance visits, Dr. Marcus said. It also provides an ideal opportunity to encourage families with smokers to quit and protect their children from secondhand smoke.

Permanent link to this article: http://www.research.chop.edu/blog/study-identifies-risk-factors-obstructive-sleep-apnea/

Apr 14 2014

Forbes Article Features CHOP Gene Therapy Expert

gene therapy

Dr. High is an internationally recognized hematologist and molecular researcher.

A recent Forbes article on the resurrection of the gene therapy business featured The Children’s Hospital of Philadelphia gene therapy expert Katherine A. High, MD. Dr. High is cited as one of a small group of scientists who “kept the field alive” after business interest in gene therapy “dried up” when companies ran into issues bringing gene therapy from the bench to the bedside.

Dr. High felt “gene therapy researchers had been making two mistakes: using a virus that might make the patient very sick (the adenovirus) and not carefully picking the diseases they would treat,” the Forbes article says. “People were choosing targets based on high unmet medical need and the size of the market, not based on the scientific evidence that gene therapy would impact the disease,” Dr. High said.

An internationally recognized hematologist and molecular researcher, Dr. High is a professor of Pediatrics at the University of Pennsylvania, and a Howard Hughes Medical Institute investigator. She has led translational studies in hemophilia, including reporting on the first cure of hemophilia B in a canine model of the disease using gene therapy.

Pointing out that “High’s approach yielded amazing results,” the Forbes article cites Dr. High’s pioneering use of adeno-associated virus as a gene therapy delivery vector and her contribution to a study of RPE65-related inherited retinal dystrophy, a rare retinal disease that progresses to total blindness by adulthood. “In one trial 12 patients, 5 of them kids, had dramatic improvements in their sight. The children were able to move from Braille classrooms to sighted ones. A late-stage study that could result in the treatment’s approval is ongoing,” the Forbes article notes.

The article also mentions the gene therapy company Spark Therapeutics. Based in part on Dr. High’s work, Spark was launched in October 2013 with a $50 million capital commitment from Children’s Hospital. In addition to building on Dr. High’s RPE65-related work, Spark — which received the “Deal of the Year” award at the 2014 Pennsylvania Bio Annual Dinner & Awards Celebration — is also working toward on hemophilia B treatments and neurodegenerative disease programs.

To read more, see the Forbes article, “Gene Therapy’s Big Comeback.”

Permanent link to this article: http://www.research.chop.edu/blog/forbes-article-features-chop-gene-therapy-expert/

Apr 11 2014

New iPad® App Helps Construct Genetic Pedigrees

geneticHuman pedigrees are diagrams similar to a family tree that make it easier to visualize genetic relationships within families and to record how diseases may recur across generations. Genetic counselors use pedigree analysis to study the inheritance of genes and apply this knowledge to patient-care decision making.

Families who have children with developmental delay or mental retardation, birth defects, multisystem medical problems, unusual facial features, or failure to thrive may benefit from genetic counseling to get clues to inheritance patterns.

Traditionally, genetic counselors interview parents and hand-draw pedigrees, but they now have a new app to create those diagrams digitally on an iPad® screen with a few finger taps. The Center for Biomedical Informatics (CBMi) at The Children’s Hospital of Philadelphia created the Proband app as an efficient data collection tool that enables genetic counselors, geneticists, and researchers to construct even the most complex family pedigrees simply and flexibly. It is based on standard pedigree nomenclature and symbols, and users can make edits seamlessly as they gather new information.

“We designed this app for ease of use with options appearing as you need them,” said Jeff Miller, lead analyst at the CBMi. “Our goal is to make those features contextually relevant, and not to overwhelm the user.”

The CBMi development team solicited critiques and feedback from clinical genetics specialists at CHOP. Mindy Li, MD, a clinical genetics and metabolism fellow, tested the app and compared it to reviewing traditional hand-drawn pedigrees. One advantage to the app is that she did not have to decipher someone else’s handwriting or idiosyncratic abbreviations. She also enjoyed the convenience of being able to set the iPad on her lap while conducting an interview.

“It’s a better interaction than if I had to turn toward a computer screen and input the information,” Dr. Li said.

The app can capture any level of detail, without the space limitations of paper. And instead of opening up a file cabinet, users can store the pedigrees in a standardized format and export the diagrams to other applications such as electronic medical records.

“As health technology in general is moving toward electronic data, it’s important to have pedigrees easy to read and easy to integrate,” Dr. Li said.

This application is one example of the many ways in which CBMi helps transform clinical care and research at CHOP and across the industry. Miller and other team members presented Proband at the annual meeting of the American College of Medical Genetics and Genomics, March 28 in Nashville. The National Human Genome Research Institute’s Clinical Sequencing Exploratory Research (CSER) Program grant 5U01HG006546-03 funded this work.

Genetic counselors, clinical genetics specialists, and others can download the app from the iTunes App Store. iPad is a trademark of Apple Inc. App Store is a service mark of Apple Inc.

For more information, read the press release.

Permanent link to this article: http://www.research.chop.edu/blog/new-ipad-app-helps-construct-genetic-pedigrees/

Apr 09 2014

Evaluating How Peer Passengers Affect Teen Drivers

teen driversThe work of Children’s Hospital’s Dennis Durbin, MD, MSCE, scientific director of CHOP’s Center for Injury Research and Prevention (CIRP), figured prominently in a recently published Atlantic article on teen drivers and distracted driving. The article, “How Gender Affects the Behavior of Teen Drivers,” in part reports on the recent Engaged Driving Symposium, held March 31 in Washington, D.C., and sponsored by State Farm and the Association for the Advancement of Automotive Medicine (AAAM).

The Atlantic article is focused on the “surprising differences” between how teen male and female drivers drive, and particularly on how boys’ and girls’ driving is affected by having passengers in the car. For example, boys are “three times more likely to drive recklessly when there was a girl in the car than when they were driving alone, and slightly more likely than with a boy in the car.”

“In the presence of peers, teens will overvalue the short-term rewards of their decisions rather than the long-term consequences,” the article quotes Dr. Durbin as saying at the conference.

Underscoring this, in a paper published in the Annals of Advances in Automotive Medicine to coincide with the Engaged Driving Symposium, citing a recent study the authors (led by Dr. Durbin) note “the rate of crashes and near crashes was nearly twice as high when teens drove with more risk-taking friends.”

Peer passengers “may serve as a source of driver diverted attention, either by diverting the driver’s eyes from the roadway or by engaging the driver in conversation to the extent that a cognitive distraction is created,” the authors write.

And in a recent post on the Center for Injury Research and Prevention blog, Dr. Durbin notes that he prefers the term “engaged driving” to “distracted driving” as “it better describes what we want drivers to do to be safe.”

“Research into how young drivers make decisions about how often and under what circumstances they’re likely to “disengage” from the driving task will help us understand how best to motivate teens to remain fully engaged and prevent crashing, especially in higher risk situations,” Dr. Durbin writes.

To read more, see the Atlantic article and Dr. Durbin’s CIRP blog post. To learn about the pioneering traffic injury prevention research being performed at the Center for Injury Research and Prevention, see the CIRP website.


Permanent link to this article: http://www.research.chop.edu/blog/evaluating-peer-passengers-affect-teen-drivers/

Apr 07 2014

Congress Passes Legislation to Train Pediatric Providers

pediatricLegislation that reauthorizes an important program to ensure that the U.S. has enough doctors trained to treat children cleared final passage in the House and now awaits President Obama’s signature.

The Children’s Hospital GME Support Reauthorization Act of 2013 reauthorizes federal funding to support graduate medical education for freestanding children’s hospitals. Rep. Joseph Pitts (R-PA) and Sen. Robert Casey Jr. (D-PA) sponsored the bill, which will invest $300 million annually in children’s hospitals over the next five years.

“CHOP is grateful for the bipartisan leadership that Sen. Casey and Rep. Pitts provided on this legislation,” said The Children’s Hospital of Philadelphia’s CEO Steven Altschuler, MD. “They recognize the importance of pediatric healthcare and ensuring it is accessible in communities throughout Pennsylvania and beyond. By enabling children’s hospitals to train pediatricians, we can meet the specialized needs of our patients and provide appropriate healthcare for children.”

By 2025, the U.S. will face a shortage of physicians to meet the needs of our U.S. population, according to the American Medical Association. Pediatric subspecialists who train at children’s hospitals are among the more than 20 specialty groups already experiencing severe shortages.  Close to 4 million babies are born annually in the U.S., so it is vital for the nation to maintain a robust pediatric workforce.

First enacted by Congress in 1999, the Children’s Hospital Graduate Medical Education program encourages more young doctors to pursue pediatrics. CHGME provides funding to about 55 freestanding children’s hospitals in 30 states to support the training of more than 6,000 pediatricians and other residents.

“Reauthorizing this program will help some of our country’s best medical centers train physicians and enable families and children to receive better care,” Casey said. “Pennsylvania’s children’s hospitals are some of the best in the country. Passing this bill will allow these hospitals to continue their lifesaving work and remain a driver of our economy.”

In his remarks on the House floor before the vote on the bill April 1, Pitts said, “I am glad that today we will pass a bill that will help keep American children healthy. … Locally in my area of Pennsylvania, the Children’s Hospital of Philadelphia participates in the program. I’ve had the privilege of visiting the hospital a number of times and meeting with the young patients and the doctors learning how to treat them.”

The CHGME program has a proven track record of success. Although they represent 1 percent of all hospitals, freestanding children’s hospitals train more than 45 percent of general pediatricians, 51 percent of all pediatric specialists, and the majority of pediatric researchers.

Permanent link to this article: http://www.research.chop.edu/blog/congress-passes-legislation-train-pediatric-providers/

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