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October 13, 2011

Research Notes

DOE grant awarded

A Pitt-Carnegie Mellon team of researchers has received a three-year, $1.7 million grant from the U.S. Department of Energy to develop new materials and processes for improving the efficiency of multi-core transformers for energy conversion systems. The work is expected to impact the economic success and global competitiveness of America’s manufacturing sector. The research could help reduce the size of a standard industrial grid transformer substantially and also improve efficiencies of power electronics conversion systems.

Gregory Reed, a faculty member in electrical and computer engineering and director of the Power and Energy Initiative in the Swanson School of Engineering, will assess complete systems engineering and turnkey installation aspects of the advanced converter technology for renewable energy applications, including economic impacts. “This grant is an important component of the continued growth of Pitt’s electric power and energy research for grid infrastructure efforts, and we are excited to be part of this talented team,” Reed said.

Lead researcher Michael McHenry, a faculty member in  materials science and engineering at Carnegie Mellon, said, “This research will ultimately help make power transformation in renewable energy conversion more economical and efficient in our complex energy grid system. Our work aims to bridge materials development, manufacturing, component design and economic analysis in one cohesive multidisciplinary team.”

Other team members include Joe Huth, head of research at Pittsburgh-based Spang, a producer of soft magnetic materials and cores for industrial control applications, and Michael Bland, an engineer from the Los Alamos National Lab.

Children’s joins ER research network

Children’s Hospital’s Division of Pediatric Emergency Medicine has received a grant to support its participation in the Pediatric Emergency Care Applied Research Network (PECARN). The division is one of 18 pediatric emergency departments to be selected to participate in PECARN, the nation’s first federally funded pediatric research network focused on emergency care for children.

PECARN is organized around six research “nodes,” each with three affiliated pediatric emergency departments. Children’s will lead the PRIDENET node partnered with Hasbro Children’s Hospital (Brown University) and A.I. duPont Hospital for Children (Jefferson University). The PRIDENET node will receive $630,000 in annual funding to support the hiring of a research administrator and one or more research nurses who will enroll patients in studies during emergency department visits.

The PRIDENET node will establish a regional research network to prevent and reduce child and youth morbidity and mortality.

Pediatrics faculty member Robert Hickey, the node’s principal investigator, said, “This is an exciting and important opportunity for our division to partner with nationally recognized researchers within a network delivering emergency care to 1.2 million children annually. The network includes many of the best children’s hospitals in the country, and we are proud to join this effort to improve pediatric emergency care.”

PECARN was founded in 2001 and is funded through grants from Emergency Medical Services for Children, a branch of the Health Resources Services Administration Maternal and Child Health Bureau.

Audits affect clinical pathways use

The implementation and auditing of clinical pathways in a cancer center network changed physician practice patterns, improved patient care and reduced health care costs, according to UPMC Cancer Centers research presented recently at the American Society for Radiation Oncology annual meeting.

Clinical pathways are evidence-based guidelines developed to treat a specific disease.

According to the researchers, the purpose of the study was to determine whether a clinical pathway that was implemented in 2004 for palliative radiation therapy for cancer that had spread to the bone changed practice patterns throughout more than 25 UPMC Cancer Centers in western Pennsylvania.

In 2009, physicians throughout the network were required to enter their patient management plans for that pathway into an online system for monitoring.

Study leader Sushil Beriwal, a UPMC Cancer Centers radiation oncologist, said, “Prior to the online auditing, we found community physicians were more likely than academic physicians to recommend longer courses of radiation therapy for palliative care, when shorter courses of treatment were effective.

“This difference remained despite the implementation of the clinical pathway, but it changed once we started the online auditing portion of the study. The auditing encouraged our academic and community physicians to favor a shorter course of treatment, which reduced the radiation levels that patients were exposed to while still managing their pain. It allowed us to establish a uniformity of care throughout the network and lowered costs as well.”

Pharmacy grants received

The School of Pharmacy recently announced the following grants:

Janice Pringle, a faculty member in pharmacy and therapeutics, received a $1.5 million grant from the Oregon Department of Justice for a three-year project to develop, implement nationally and evaluate a series of modules designed for family medicine trainees in pharmaceutical promotion and marketing practices, evidence-based prescribing and techniques for fostering clinical prescribing practices free from conflict of interest.

This online program is a collaboration between the School of Pharmacy and the School of Medicine.

Maureen Reynolds, a faculty member in pharmaceutical sciences, under the guidance of Center for Education and Drug Abuse Research (CEDAR) director Ralph Tarter, will prepare CEDAR baseline data collected 1990-2003 to be archived in the National Addiction and HIV Data Archive Program system housed at the University of Michigan.

The project is funded under a one-year, $113,625 grant from the National Institutes of Health.

Unknown viruses call sewage home

Biologists have described only a few thousand different viruses so far, but a new study by researchers from the Department of Biological Sciences in conjunction with others from the University of Barcelona and the Washington University School of Medicine reveals a vast world of unseen viral diversity. A paper in the online journal mBio finds that ordinary raw sewage is home to thousands of novel, undiscovered viruses, some of which could relate to human health.

Viruses are everywhere — on surfaces, in foods and in water. However, knowledge of the viral universe is limited to a tiny fraction of the viruses that likely exist. While living organisms host untold numbers of unique viruses, only about 3,000 viruses have been identified.

The team, which included Paul G. Cantalupo, Michael Grabe, Roger W. Hendrix, Josh P. Katz, James M. Pipas and Adam D. Wier of biological sciences, looked for the genetic signatures of viruses present in raw sewage from North America, Europe and Africa.

They detected signatures from 234 known viruses that represent 26 different families of viruses. This makes raw sewage home to the most diverse array of viruses ever found.

Hendrix said, “What was surprising was that the vast majority of viruses we found were viruses that had not been detected or described before.” The viruses that already were known included human pathogens like human papillomavirus and norovirus, which causes diarrhea. Also present were several viruses belonging to rodents and cockroaches. Bacteria also are present in sewage, so it was not surprising that the viruses that prey on bacteria dominated the known genetic signatures. And a large number of the known viruses found in the raw sewage came from plants, probably owing to the fact that humans eat plants, and plant viruses outnumber other types of viruses in human stool.

“The big question we’re interested in is, ‘Where do emerging viruses come from?’” Hendrix said. The team hypothesized that new viruses emerge, in large part, through gene exchange. But before research on gene exchange can begin in earnest, large numbers of viruses must be studied, the researchers said.

Pipas said,  “First you have to see the forest before you can pick out a particular tree to work on. If gene exchange is occurring among viruses, then we want to know where those genes are coming from, and if we only know about a small percentage of the viruses that exist, then we’re missing most of the forest.”

Study editor Michael Imperiale of the University of Michigan said it was significant that the vast majority of viral genetic signatures the researchers found belong to unknown viruses, noting that such unknown viruses probably play many roles in human health and environmental processes that we simply do not appreciate yet.

Of the unknown sewage viruses that come from humans, some of them may be opportunists that lie in wait for the human host’s immune system to break down and provide an opening, he said.

Other viruses may be benign or even helpful. “There’s a theory out there that we may be infected with viruses that don’t cause any disease and may have beneficial effects,” said Imperiale. There are examples of animal viruses that bear this out, he said, including a herpes virus in mice that makes them somewhat resistant to bacterial infections.

The study’s authors plan to follow up their examination of sewage viruses with studies of other environments around the world where viruses are likely to thrive.

Imperiale expects more discoveries to come. “I think this is going to be the tip of the iceberg of how many viruses are out there,” he said. “I think the ocean is going to top raw sewage by orders of magnitude,” although they won’t be found in such densities as they are in sewage, he said.

Supply chain modeling benefits vaccine distribution

Proper planning before new vaccines are introduced in developing nations could prevent problems that can decrease availability of existing vaccines.

A Pitt study, which will appear in the November issue of the American Journal of Public Health, finds that computational models can assess the evolving needs of the vaccine supply chain, can forecast the impact of new vaccine introduction and can identify potential disruptions.

“Our study highlights the importance of prior planning when introducing new vaccines to avoid last-minute temporary fixes,” said the study’s lead author, Bruce Y. Lee, a faculty member in medicine, epidemiology and biomedical informatics. “New vaccines may not fit smoothly into supply chains and therefore fail to reach their target populations easily. These problems may prevent other vaccines from reaching clinics as well. Manufacturers and policymakers should consider vaccine quantity and packaging before designing vaccines and introducing them in unfamiliar areas with limited resources.”

The Pitt scientists, who are part of the Vaccine Modeling Initiative (VMI), developed a computational model to determine the impact of introducing rotavirus vaccine and the 7-valent pneumococcal conjugate vaccine to Niger’s expanded program on immunization (EPI) vaccine supply chain.

The scientists estimated that  introducing these vaccine inventories to the supply chain could decrease vaccine availability by 24-69 percent.

Introducing the vaccines could displace other EPI vaccines from already limited storage and transport space, thus preventing EPI vaccines from reaching patients.

The study’s predictions are similar to what happened when officials introduced rotavirus vaccine to a Latin American program in 2006 and 2007, the researchers noted. In that case, bulky vaccines displaced existing EPI vaccines in already limited refrigerator space and forced overburdened health care workers to carry additional coolers to transport the new vaccines. As a result of these unforeseen problems, large stocks of vaccine expired.

Computational models can help decision makers plan and understand complex systems, Lee said. “Although computational models have been widely used in similar logistics planning in many other industries, such as transportation, manufacturing, the military and aerospace, their use in public health has been comparatively limited,” he said. “These models could be a very helpful tool for health workers to plan vaccine supply chains.”

The study was supported by VMI, which is funded by the Bill and Melinda Gates Foundation, and the National Institute of General Medical Sciences models of infectious disease agent study.

Co-authors included Tina-Marie Assi, Willem G. Van Panhuis and Ann E. Wiringa of epidemiology; Sheng-I Chen, Bryan A. Norman and Jayant Rajgopal of industrial engineering; Shawn T. Brown of biostatistics; Diana L. Connor and Angela R. Wateska of medicine, and Graduate School of Public Health Dean Donald S. Burke.

Glucose regulating protein identified

Researchers from the School of Medicine and Children’s Hospital at the John G. Rangos Sr. Research Center have identified a molecular pathway that regulates the way the liver manages insulin and new glucose production. The findings were published online in Diabetes, a journal of the American Diabetes Association.

Usually, the liver stores excess blood sugar as glycogen, which it releases during sleep and other periods of fasting to keep glucose levels within a normal physiological range. In diabetes, the liver continues to pump out glucose, explained Pitt pediatrics faculty member H. Henry Dong.

“Scientists have been trying to find the factors that contribute to this liver overproduction of glucose for decades,” Dong said. “If we can control that pathway, we should be able to help reduce the abnormally high blood sugar levels seen in patients with diabetes.”

The researchers, who have been studying a family of proteins called Forkhead box (FOX), focused on one called FOX06 for this project.

They found that mice engineered to make too much FOX06 developed signs of metabolic syndrome, the precursor to diabetes, including high blood sugar and high insulin levels during fasting as well as impaired glucose tolerance, while mice that made too little FOX06 had abnormally low blood sugars during fasting.

“In a normal animal, a glucose injection causes blood sugar level to rise initially and then it goes back to normal range within two hours,” Dong said.

“In animals that made too much FOX06, blood sugar after a glucose injection doesn’t normalize within two hours. They have lost the ability to regulate the level while the liver keeps making unneeded glucose.”

Other experiments showed that diabetic mice have abnormally high levels of FOX06 in the liver, he added. Blocking the protein markedly reduced liver production of glucose, although blood sugar did not normalize completely. Within two weeks of treatment, there was significant improvement in blood sugar and glucose metabolism in diabetic mice.

Tests with human liver cells echoed the importance of FOX06’s role in glucose production. “These findings strongly suggest that FOX06 has potential to be developed as a therapeutic target,” Dong said. “If we can inhibit its activity, we can possibly slow the liver’s production of glucose in patients with diabetes and better control blood sugar levels.”

Among the Pitt co-authors were Yong Fan and Steven Ringquist of pediatrics and Nick Giannoukakis, Roberto Gramignoli and Stephen Strom of pathology.

The study was funded by the National Institutes of Health.


The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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