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October 15, 2009

Research Notes

Biofuels research funded

Civil and environmental engineering faculty member Amy Landis has been awarded a National Science Foundation (NSF) grant to investigate the environmental impacts of next-generation biofuels and to develop a more sustainable trajectory for biofuels development.

The goal of her research is to quantify the water quality degradation tradeoffs associated with second- (cellulosic ethanol) and third-generation (such as algae-produced) biofuels.

Trustworthy computing funding awarded

Computer science faculty member Adam Lee recently received his first NSF award. His three-year project “Towards a Dynamic and Composable Model of Trust” is a joint effort with Ting Yu of North Carolina State University.

The project is part of the NSF’s trustworthy computing program, which supports research and education activities that explore novel frameworks, theories and approaches toward secure and privacy-preserving systems, recognizing that many intertwined scientific, technological, economic and sociological challenges must be overcome in order to realize a trustworthy computing future.

According to Lee, everyday decisions rely on both vertical and horizontal trust. Vertical trust captures trust relationships between individuals and institutions, while horizontal trust represents the trust inferred from the observations and opinions of peers.

While the two mechanisms have evolved independently in computing systems, Lee’s project focuses on developing a composable trust model capable of tightly coupling vertical and horizontal trust in an efficiently deployable manner amenable to formal analysis.

Multi-organ transplant survival up

A study published in the October issue of Annals of Surgery finds that survival rates for adult and pediatric intestinal and multi-visceral transplant patients have improved with the advent of innovative surgical techniques, novel immunosuppressive protocols and better post-operative management.

The research, led by Kareem Abu-Elmagd, a faculty member  in the School of Medicine and director of the Intestinal Rehabilitation and Transplantation Center at the Thomas E. Starzl Transplantation Institute, assessed the evolution of intestinal and multi-visceral transplantation in the first 500 such transplants conducted at UPMC from 1990 to 2008, which represent more than 25 percent of the worldwide total.

Over nearly two decades divided into three eras, 453 patients received 215 intestine, 151 liver-intestine and 134 multi-visceral transplants.

Abu-Elmagd noted, “Our research found that survival rates for such transplant recipients greatly increased as treatment strategies evolved; this included the reduction in the use of immunosuppressive therapy.”

During what the researchers dubbed Era I (1990-94), transplant recipients were treated with the immunosuppressive drug tacrolimus and steroids. In 1994, this protocol was discontinued due to high mortality and morbidity rates. The five-year survival rate for these patients was 40 percent.

Era II (1995-2001) introduced the use of donor bone marrow to encourage organ acceptance. The five-year survival rate for these patients was 56 percent.

During Era III (2001-08), patients were given a pre-conditioning protocol with agents that depleted recipients’ own immune cells. Their post-transplant drug regimen was minimal and was initiated with tacrolimus, followed by steroids when necessary. Tacrolimus doses subsequently were spaced to a single dose two or three times per week with a weaning process that started three-six months after transplant.

Through the use of new immunosuppressive and management strategies, the five-year survival rate for these patients increased to 68 percent, which is similar to survival rates for any other abdominal and thoracic organ transplant procedure.

“We have learned that patients who are using multiple anti-rejection drugs over a period of several years may experience long-term detrimental effects, which erodes survival rates beyond 10 years post-transplant,” noted Abu-Elmagd. “With that in mind, we will strive to reduce use of these drugs as much as possible in our patients.”

Among the study co-authors were surgery faculty members Guilherme Costa, Ruy J. Cruz, Geoffrey J. Bond, Kyle Soltys, Noriko Murase, Rakesh Sindhi, Abhinav Humar and George Mazariegos; Laura Matarese of surgery, Adriana Zeevi of pathology and Maher O. Ayyash of psychiatry, all of the Starzl Transplantation Institute.

$1M from V Foundation funds trials for lung cancer patients

Jill M. Siegfried, co-director of the University of Pittsburgh Cancer Institute’s lung and thoracic malignancies program, has received a $1 million grant from the V Foundation for Cancer Research to help support new clinical trials for lung cancer patients at UPMC Cancer Centers.

The first clinical trial is based on Siegfried’s research, which found that estrogen acts as a proliferation agent in the lung, activating lung cancer development through pathways similar to those in breast cancer. According to Siegfried, it might be possible to inhibit lung cancer tumor growth in cancers that progress in response to estrogen.

“We learned that some very basic, biological functions put women at risk for developing lung cancer. Now we know estrogen plays a role in the growth of some lung cancers and that gives us something to target in the clinical setting.”

The clinical trial at UPMC will be led by Athanassios (Ethan) Argiris, faculty member in medicine and clinical associate director of UPCI’s SPORE in lung cancer. SPORE is a federal grant awarded by the National Cancer Institute to assist researchers in examining innovative detection and treatment strategies designed to improve survival outcomes and quality of life for patients with early to late-stage lung cancer.

According to Argiris, the phase II trial will study the use of an aromatase inhibitor, a class of drugs designed specifically to counteractestrogen production, in postmenopausal women with advanced non-small cell lung cancer.

“We hope that by targeting estrogen we will be able to extend the lives of women with lung cancer. Moreover, we will have an opportunity to understand which womenrespond best to this treatment by examining the estrogen receptors found in their tumors,” Argiris said.

In addition, the V Foundation will support a phase I trial translated from previous SPORE-funded research conducted by Olivera Finn, chair of the Department of Immunology.

Lung cancer patients who enroll in the trial will receive a vaccine based on the protein cyclin B1. Finn discovered that this protein is expressed inappropriately by many lung tumors and causes a strong immune response. She hopes to boost the ability of the immune system to reject lung cancer by vaccination with portions of the purified cyclin B1 protein.

The V Foundation was founded by ESPN and the late Jim Valvano, former North Carolina State University basketball coach who died of cancer.

Study says most would refuse to get emergency flu vaccine

A study by the Graduate School of Public Health and the University of Georgia has found that a majority of Americans would not take an H1N1 flu vaccine or drug additive not officially approved but authorized for emergency use by the Food and Drug Administration. The study, which was published online in Biosecurity and Bioterrorism: Biodefense Strategy, Practice and Science, found that fewer than 10 percent of those surveyed said they would be willing to take such a vaccine or drug and nearly 30 percent remained undecided.research notes

The passage of the Project Bioshield Act in 2004 created the emergency use authorization (EUA) giving the FDA the ability to use experimental or “off-label” drugs in the event of an actual or potential emergency.

To date, four vaccines against H1N1 virus have been approved under the same process used by the FDA for the seasonal flu vaccine. Also, several drug additives, or adjuvants — sometimes added to vaccines to strengthen the immune response and stretch the quantity of available vaccines in the event of a pandemic — have been ordered and stockpiled by the federal government in case they are needed. But adding them to H1N1 vaccines would trigger the need for an EUA, which is one of the reasons the federal government has chosen not to use them.

Study author Sandra Quinn, associate dean for student affairs and education in GSPH, said, “Although the U.S government has held off on including an adjuvant in H1N1 vaccines for now, American officials may need to reconsider this decision as the pandemic unfolds. There also remains a significant shortage of the vaccines in many countries around the world. Given this, our finding that few people would accept a new but not yet fully approved H1N1 vaccine or drug is very worrisome,” she said.

The study was based on a survey that focused on attitudes toward H1N1 and willingness to accept flu vaccines and drugs not officially approved by the FDA, but authorized for emergency use. Of the 1,543 adults questioned in June 2009, 46 percent said they were concerned about getting swine flu. However, nearly 86 percent said they thought it was unlikely or very unlikely that they themselves would become ill.

Researchers also report that 63 percent of people surveyed said they would not be willing to take “a new, but not yet approved vaccine” and 50 percent said they would be very or extremely worried about taking it. Of those who reported they would be moderately to extremely worried, 70 percent said they would refuse the vaccine outright. Only 4 percent of the most worried said they would take the vaccine, compared to 23 percent of those who were not at all or slightly worried.

Race also was associated with refusal to take the vaccine: 66 percent of whites and 60 percent of blacks reported they would refuse the vaccine, compared to 47 percent of Hispanics. Blacks reported they were the most worried (62 percent), followed by Hispanics (52 percent) and whites (46 percent).

According to Quinn, these results differ from some current opinion polls on public acceptance of an H1N1 vaccine because the researchers explicitly asked about vaccines approved under the EUA designation. “Communication about the H1N1 vaccine is enormously challenging,” said Quinn. “The additional issue of emergency use designation would further complicate challenges to clear communication. In the event an emergency-use adjuvant is required to stem the H1N1 pandemic, public health professionals will need to articulate a strong case for the vaccine and aggressively address myths and misinformation to increase understanding and acceptance.”

The potential challenge in communicating with the public about emergency use authorization is relevant beyond the question of the H1N1 vaccine, added Quinn. “EUAs are an important tool for the protection of the public’s health in an emergency. It would behoove public health agencies to begin now to think about communication and education of the public on this issue.”

Pitt co-authors of the study were GSPH graduate students Supriya Kumar and Kelley Kidwell and University Center for Social and Urban Research postdoc Donald Musa.


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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