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March 22, 2007


Report reviews role of intelligence in national security surprises

Casting blame solely on U.S. intelligence agencies for strategic security mishaps may be misguided, according to a report recently released by Georgetown University’s Institute for the Study of Diplomacy (ISD).

The culmination of a two-year study co-chaired by ISD project directors Janne E. Nolan, professor in Pitt’s Graduate School of Public and International Affairs, and Georgetown research associate Douglas MacEachin, “Discourse, Dissent, and Strategic Surprise: Formulating U.S. Security Policy in an Age of Uncertainty” argues that the role of intelligence in assessing strategic surprises is more complex than traditionally assumed, particularly due to recent claims blaming the U.S. intelligence community for failing to avoid catastrophic events such as 9/11.

With support from the John D. and Catherine T. MacArthur Foundation, Nolan and MacEachin co-chaired a working group comprised of senior experts and practitioners drawn from the executive branch, Congress, think tanks, scholarly institutions and the media. The group held five meetings from November 2004 through the spring of 2006 to study the role of intelligence and policy failures in undermining the pursuit of U.S. strategic interests.

The report includes five case studies of “strategic surprises” since the late 1970s: 1) the evolution of U.S. policy toward Iran before the fall of the shah in 1979; 2) the threat of transnational, anti-Western Islamic terrorists who masterminded attacks on U.S. embassies in East Africa in 1998; 3) Soviet military preparations leading to the invasion of Afghanistan in 1979; 4) the rise of the Afghani mujaheddin after the Soviet occupation of 1989-91, and 5) the Asian financial crisis of 1998.

The study found that “the impulse to protect the policy consensus favored in Washington seems to impede the ability of policy makers (and senior intelligence officials who support the consensus) to accept the potential negative consequences of evolving conditions ‘on the ground’ and the need to adapt policy responses accordingly,” wrote ISD director Casimir Yost in the report’s foreword.

Nolan said, “Since 9/11, some Americans have worked hard at assigning blame — first for 9/11 and more recently for Iraq. The first target of this blame game was the intelligence community and when this effort largely ran its course, blame for mistakes of judgment was heaped on policy makers. More recently, some generals have been criticized for errors of policy in Iraq. In a democracy, it is not surprising that efforts to hold decision-makers accountable for mistakes and failures should emerge. What these case studies suggest is that, with respect to the debacle in Iraq, there has been a government-wide failure. Ultimately the president must be held accountable, but the true tragedy is that ‘government’ writ large — including most certainly the Congress — has not performed well for the American people.”


High autoantibodies, preeclampsia linked

Women who develop preeclampsia during pregnancy are more likely to develop certain dangerous autoantibodies than women with normal pregnancies, and these autoantibodies still are present two years after childbirth in about 20 percent of women who had the disorder, Pitt scientists report in the March issue of Hypertension, the journal of the American Heart Association.

Also known as toxemia, preeclampsia affects some 5 percent of pregnancies and is a leading cause of maternal and fetal illness and death, particularly in developing nations. Signs include high blood pressure, swelling of the ankles and the presence of protein in the urine. The condition typically appears after the mid-point of pregnancy. The only effective treatment is immediate delivery, which can be dangerous for the baby if it is too early. Untreated, the condition can lead to organ failure, coma and death. Preeclampsia also has been linked to an increased lifetime risk for heart disease.

“Further study is required to determine whether the presence of these autoantibodies could be an early marker for preeclampsia risk, but early data are promising,” said Carl A. Hubel, the study’s lead author and assistant professor of obstetrics, gynecology and reproductive sciences at the School of Medicine. “Learning more about these autoantibodies also might enable us to identify a subset of women who are at greater risk for heart disease later in life, and give us a closer understanding of what causes preeclampsia.”

For most women, the autoantibodies eventually go away after pregnancy. “But in some, they persist or reappear, consistent with other data showing that many of the risk factors for preeclampsia are the same as those for cardiovascular disease,” added Hubel, who also is an associate investigator at Magee-Womens Research Institute.

Autoantibodies are immune system proteins that attack the body’s own cells instead of microorganisms that represent a real threat, such as viruses, bacteria or other toxins.

Hubel and his colleagues studied the development of autoantibodies capable of activating the angiotensin II type 1 receptor (AT1-AA). The AT1 receptor is part of an amino acid group that works within cells to maintain healthy blood vessels and manage inflammation. Too much AT1 receptor activation, such as takes place when the autoantibodies are present, can lead to high blood pressure and inflammation.

“These antibodies are similar to antibodies in other conditions, such as those related to the autoimmune thyroid disorder, Grave’s disease,” said Hubel. “These kinds of antibodies also are related to high blood pressure, which is one of the signs of preeclampsia. Women with a history of preeclampsia have a substantially higher cardiovascular risk later in life, compared to women who experienced normal pregnancies.”

While the cause of preeclampsia remains unknown, evidence is mounting that the disorder relates to poor formation and placement of the placenta combined with underlying maternal factors including insulin resistance, obesity and inflammation that are magnified during the physiological stress of pregnancy.

Elevated levels of AT1-AA are evident in nearly all women with preeclampsia, the researchers report.

“AT1-AA were detected in 17.2 percent of postpartum women who had developed preeclampsia, as opposed to 2.9 percent of postpartum women whose pregnancies were uncomplicated,” said Hubel.

Other Pitt researchers involved in the study were Augustine Rajakumar, research assistant professor in the Department of Obstetrics, Gynecology and Reproductive Sciences and an assistant investigator at MWRI; James M. Roberts, professor and vice chair for research in the Department of Obstetrics, Gynecology and Reproductive Sciences and professor of epidemiology who is vice president of research at Magee-Womens Hospital and senior scientist and director of MWRI, and Nina Markovic of the School of Dental Medicine and Graduate School of Public Health.

Funding for the study was provided by the Massachusetts Institute of Technology, Magee-Womens Hospital, the National Institutes of Health and the American Heart Association.


Pitt, PennDOT to partner

Pitt has entered into a five-year agreement with the Pennsylvania Department of Transportation that will fund up to $5 million per year in University research, education or technology transfer projects addressing transportation issues.

The contract is administered by Pitt’s civil and environmental engineering department, but department chair Radisav D. Vidic hopes to pool faculty experts from other Pitt schools and departments to handle any project PennDOT might propose, including land-use planning and the effects of urban sprawl.

“PennDOT issues are not only in the area of civil and environmental engineering, and we want other departments involved so we can be prepared for whatever PennDOT might require,” said Vidic.

In 2004, PennDOT worked with Pitt on a three-year, $2.1 million project to examine the environmental impact of Interstate 99 construction activities that will connect I-70 and I-80. Led by engineering professor Raphael G. Quimpo, the project studies ways to preserve surrounding wildlife during and after construction, divert road runoff from spilling into nearby waterways and minimize the environmental factors that would cause the road to deteriorate.

In another project, pavement engineer Julie M. Vandenbossche, associate professor and head of Pitt’s pavement mechanics and materials laboratory, is working on “smart pavement” that contains sensors that monitor surrounding environmental conditions as well as the deformation of the roadway over time. Her research aims to develop tools that will assist PennDOT in the design and construction of more cost-effective pavements. Vandenbossche published an initial report on smart pavement in 2005 and a project update in 2006. PennDOT officials would like to continue the project under this new agreement, said Michael Bonini, PennDOT’s program manager for the project.


NIH names HIV study sites

Pitt is among a dozen institutions named by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), as HIV/AIDS clinical trial units for the Microbicide Trials Network, a new HIV/AIDS clinical trials network established last year. The clinical trial units, located in Africa, India and the United States, will engage in multi-center studies spanning 17 locations in seven countries that seek to determine if topical microbicides can help prevent the sexual transmission of HIV in women.

Nearly half of the 39.5 million people living with HIV/AIDS are women, and in Africa, women account for 59 percent of all infected adults. Young women especially are vulnerable. For instance, in sub-Saharan Africa, those aged 15-24 with HIV outnumber men of the same age by three to one.

In developing countries, HIV most often is spread through unprotected heterosexual intercourse, and educational efforts promoting abstinence, monogamy and condoms have not been completely effective. Through its clinical trial units, the Microbicide Trials Network is evaluating the potential that microbicide gels or creams can reduce or prevent the sexual transmission of HIV and other sexually transmitted diseases when applied topically to the surface of the vagina.

In addition to Pitt, U.S.-based clinical trial units are Case Western Reserve University, Columbia University and the University of Pennsylvania.

The University of Alabama-Birmingham was granted two clinical trial unit awards — one for its international site in Zambia and the second for its U.S. site.

American schools named as clinical trial units that will be conducting Microbicide Trials Network trials exclusively at the international sites with whom they collaborate are the University of California-San Francisco, which operates in Zimbabwe, and Johns Hopkins Bloomberg School of Public Health and Johns Hopkins School of Medicine, with affiliations in Malawi and Uganda, respectively.

Other clinical trial units are the National AIDS Research Institute in Pune, India; the Medical Research Council in Durban, South Africa, and the University of Cape Town, South Africa.

Sharon Hillier, professor of obstetrics, gynecology and reproductive sciences and of molecular genetics and biochemistry at the School of Medicine and director of reproductive infectious disease research at the Magee-Womens Research Institute, is principal investigator of the Microbicide Trials Network. “The scope of the crisis requires an aggressive agenda in which the clinical trial units and clinical research sites play an essential role,” she said. “By virtue of being selected by NIH, our CTUs have proved themselves as the most qualified and the most committed to take part in an endeavor of such great global importance.”

Based at Pitt and MWRI, MTN’s core operations are supported by a central laboratory at Pitt, a statistical and data management center housed within the Statistical Center for HIV/AIDS Research & Prevention at the Fred Hutchinson Cancer Research Center, and Family Health International, a global organization with expertise conducting clinical protocols.

It receives funding from three NIH institutes: NIAID, the National Institute of Mental Health and the National Institute of Child Health and Human Development.


Psychiatry research presented

Pitt researchers from the Department of Psychiatry’s cardiovascular behavioral medicine program recently presented their work at a meeting of the American Psychosomatic Society.

* Omega-3s linked to grey matter volume

Omega-3 fatty acids, found in fatty fish like salmon, are associated with increased grey matter volume in areas of the brain commonly linked to mood and behavior, a recent Pitt study found.

The research was presented by Sarah M. Conklin, a postdoctoral scholar in the cardiovascular behavioral medicine program in psychiatry.

Prior animal research has shown that raising omega-3 intake leads to structural brain changes. In a separate study Conklin presented at the society’s meeting last year, Pitt researchers reported that people who had lower blood levels of omega-3 fatty acids were more likely to have a negative outlook and be more impulsive while those with higher levels were more agreeable and less likely to report mild or moderate symptoms of depression.

In the current study, researchers sought to investigate whether grey matter volume was proportionally related to long-chain omega-3 intake in humans, especially in areas of the brain related to mood, helping them try to explain the improvement in mood often associated with long-chain omega-3 intake.

They interviewed 55 healthy adult participants to determine their average intake of long-chain omega-3 fatty acids, then calculated their grey matter volume using high-resolution structural MRI.

The researchers discovered that participants who had high levels of long-chain omega-3 fatty acid intake had higher volumes of grey matter in areas of the brain associated with emotional arousal and regulation — the bilateral anterior cingulate cortex, the right amygdala and the right hippocampus.

While this finding suggests that omega-3s may promote structural improvement in areas of the brain related to mood and emotion regulation — the same areas where grey matter is reduced in people who have mood disorders such as major depressive disorder — investigators note that more research is needed to determine whether fish consumption actually causes changes in the brain.

*Women’s aggression, anger may be genetic

Pitt researchers have found that behaviors such as anger, hostility and aggression may be rooted in genetic variations in a serotonin receptor gene. Indrani Halder, a postdoctoral scholar in Pitt’s cardiovascular behavioral medicine program, presented the research.

Previous studies have associated the hormone serotonin with anger and aggression in both humans and animals and have shown that increased serotonin activity is related to a decrease in angry and aggressive behaviors. In this study, researchers sought to learn if this relationship was genetically determined. The study is the first to look at the relationship between variations in the serotonin receptor 2C gene and anger and hostility.

Researchers studied 550 unrelated women of European descent. In order to find normal variations in genes and behavior, the women were not prescreened for behavioral type. It was found that those who had one or both of two alterations in the promoter region of the serotonin receptor 2C gene were more likely to score lower on two common tests for anger, hostility and aggression.

These findings may aid in establishing a potential marker for certain conditions associated with aggression and anger.

“Aggression and hostility are predictors of hypertension, glucose metabolism and heart diseases,” said Halder. “The genetic marker we found for hostility also may be useful for predicting a person’s predisposition to such diseases.”


Grant aims to preserve young cancer patients’ fertility

To protect the future fertility of boys diagnosed with cancer, University of Pittsburgh Cancer Institute researchers have received $120,000 from the Lance Armstrong Foundation. The Pitt research team was awarded a grant of $110,000 over the next two years and the J. Lee Walker Imagination Award of $10,000.

Treatment for childhood cancers often includes high doses of chemotherapy and radiation that can harm a child’s reproductive organs. In boys, cancer therapy can irreversibly destroy stem cells in the testes, leading to their inability to produce sperm in adulthood. In children treated repeatedly for cancer relapses or certain high-risk leukemias, adult infertility can be as high as 70 percent.

One way researchers have sought to protect the fertility of these patients is by preserving a biopsy of tissue from the testicles that contains stems cells before they begin cancer therapy.

The Pitt research group already has shown in pre-clinical studies involving non-human primates that it is possible to retrieve sperm from testicular biopsies after maturing them for a few months by grafting the tissue into immunodeficient mice. They will use the current funding to expand these studies to pre-pubertal human testicular tissue, which will be grafted into mice for 3-5 months, followed by the attempt to retrieve sperm from the matured tissue. The sperm then will be frozen and evaluated.

“As treatment for childhood cancer has become more successful in saving lives, there are more and more survivors seeking help from fertility clinics because of irreversible damage to their reproductive organs from high-dose treatment,” said Jens Ehmcke, principal investigator of the project and a research assistant professor in the School of Medicine. “This project could have an extremely beneficial impact on general quality of life for survivors by giving them the option to start their own families in the future. If this method is successful, we will be one step closer to offering a simple solution to boys with cancer that may give them the ability to make their own choices about reproduction later in life.”


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