Research Roundup	Print Issue
February 24, 2009, Volume 55, No. 23

Surviving Cardiac Arrest Depends On Where Treated

Efforts to fight the toll of cardiac arrest have typically focused on pre-hospital factors—bystander CPR education and improvement, public defibrillation programs, and quicker EMS response. But research from the School of Medicine reveals that the hospital where patients are cared for after being resuscitated plays a key role in their chances of survival following these incidents, which take the lives of more than 300,000 Americans each year.

Patients in large, urban, and teaching hospitals are more likely to survive compared to those in small, often rural, non-academic hospitals, according to a study published in the journal Intensive Care Medicine. A second study, published in Resuscitation, suggests that patients who are cared for in the highest volume intensive care units after cardiac arrest are also most apt to survive. The findings point to a need to explore the development of specialized, regional post-cardiac arrest care centers modeled after those that treat serious trauma patients, said lead author Dr. Brendan Carr, assistant professor of emergency medicine and epidemiology, and associate director of the Division of Emergency Care Policy & Research.

“We are describing the variability that exists in cardiac arrest outcomes—not at the level of the patient but at the level of the hospital. Hospitals with more resources and hospitals with higher volumes have better outcomes,” Dr. Carr says. “There are two possible implications: Either we need to get everyone up to speed on how to optimize survival, or we need to selectively transfer patients to hospitals that have expertise in the post-arrest period.”

The two studies, which examined a combined 115,000 cases in two different national datasets, also point to an overall improvement in cardiac arrest care of a small reduction in mortality that translates to about 11,000 additional lives saved per year—a significant decrease for a condition that is typically fatal. Better survival odds are multifactorial, but likely related to advances in critical care, the recognition of the role of therapeutic hypothermia, and the creation of national guidelines for post-cardiac arrest care.

“Among the patients that regain a pulse after cardiac arrest, only one out of three survive to hospital discharge, and there appears to be significant variability among hospitals. Further research is needed to determine if this variability in outcome is caused by the quality of post-cardiac arrest care. If it is, we need to identify best practices and develop mechanisms to deliver optimal care for all patients, ” said senior author Dr. Robert Neumar, associate professor of emergency medicine and associate director of Penn’s Center for Resuscitation Science, and chair of the Advanced Cardiac Life Support Subcommittee for the American Heart Association

Dr. Carr and his colleagues say further study of post-cardiac arrest care among these large, urban, and teaching hospitals will be crucial in mapping strategies that maximize a patient’s chances to be discharged without the neurological deficits that often plague cardiac arrest survivors. 

Serious Spread of the Vine by Ancient Wine Makers

Ancient civilizations responsible for the birth of grape cultivation and wine-making valued sweetness over any other wine characteristic. The finding proves more than the idea that times and tastes change. It also provides archaeologists with a marker as to when casual fermentation gave rise to serious, domesticated wine production in the Early Bronze Age.

Naomi F. Miller, a research specialist with the Penn Museum, considered evidence from pollen cores, residue from ancient wine jars, archaeological seeds, stems, ancient fruit and the charred wood of grape vines to explain her observation that, despite remarkably early residue evidence for wine in the Neolithic period, the mid-sixth millennium BC, other evidence for grape use does not become common in the archaeological record until 3,000 years later, during the Early Bronze Age. Presumably during that 3,000 year gap, wine-makers were content to use sour grapes; wine-making would be a way to make the genetically wild fruit edible and potable.

According to published studies, initial cultivation of wild grape vines was used primarily for wine production; however, according to Ms. Miller’s interpretation, grape and vine cultivation exploded during the Early Bronze Age, becoming more widespread due to civilization’s ability to exploit the vine and select for ideal traits in flavor and robustness, probably in pursuit of the rare, sweet flavor that existed at the time only in other natural products like honey.

The search for sweeter grapes, Ms. Miller said, required genetic changes made during farming and cultivation, and distinguishes the first era of wine making around 6000 BC from periods 3,000 years later when wine-makers began to cultivate domesticated grapes. Domesticated grapes are hermaphroditic, or self-fertilizing, a key component in cultivating for characteristics such as taste and for marking a leap in the sophistication of farming.

Ms. Miller’s study, performed at Penn Museum’s Applied Science Center for Archaeology (MASCA), was published in the journal Antiquity.

Studying the fertile region of Western Asia bordered by the Caspian and Black Sea forests and the Mediterranean coastal woodland in what is now Syria, Israel, Jordan, Iraq, Turkey, Iran and Cyprus, where wine-making was born, Ms. Miller investigated a variety of sources to conduct an anthropological study of the earliest exploitation, cultivation, selection and spread of grapes.

“People learned how sweet fruits could be produced consistently by using hermaphroditic vines,” Ms. Miller said. “They probably had perfected much of their techniques by the middle of the third millennium, which explains the rapid spread of wine to all of western Asia and, ultimately, to the world.”

Consensus Building Influenced By Network Structure

A team of Penn computer scientists investigating the political, social and economic struggle between individual self-interest and the need to build a consensus have learned that, depending only on the structure of the network of participants, they can engineer surprising experimental results. The study, conducted by Dr. Michael Kearns, professor of computer and information science, is published online in Proceedings of the National Academy of Science.

For example, depending solely on the ability of individuals to interact in a network, as well as the number of connections they have to other participants and other structural properties, there are networks that generate the global adoption of minority viewpoints. In addition, the team demonstrated, individuals with extreme behaviors, or a greater awareness of the incentives of others, may actually improve the collective performance of the group.

In Dr. Kearns’ experiment, 36 human subjects were arranged in a variety of virtual networks, with each experiment differing in the number of neighbors each participant had and could see, but none having a global view of the overall network. Participants were financially motivated to build a global consensus to one of two opposing choices, in this case the color red or blue. If a consensus wasn’t reached in 60 seconds, no money was awarded any participant; however, some participants were rewarded greater amounts depending on the color that won the day, which created tensions between private incentives, global unity and the structure of the network. Of 81 experiments, 55 ended in a payout for reaching a global consensus.
The study revealed that not only could minority groups override the majority but could in fact facilitate global unity easier than a network that was evenly divided among red or blue. Dr. Kearns also found that the wealthiest players at the end of the experiments were those stubborn or stable players whose reluctance to change set the tone for the experiment. In addition, the more aware participants were of the opposing preferences held by their neighbors, the more likely they were to reach a global consensus.

Dr. Kearns previous study was inspired by the 2008 Democratic national primary. In that political contest, the network of American voters held opposing preference for a single candidate, either Barack Obama or Hilary Clinton; however, once Obama won the nomination, the urge to build consensus and unify the party became strong.

The study was performed by Dr. Kearns, Dr. Stephen Judd, and PhD candidates Jinsong Tan and Jennifer Wortman of the department of computer and information science at the School of Engineering and Applied Science.

Brain Structure Assists in Immune Response

For the first time, a team of researchers at Penn’s School of Veterinary Medicine have imaged in real time the body’s immune response to a parasitic infection in the brain.

The complete findings, published in the journal Immunity, provide unexpected insights into how immune cells are regulated in the brain and have implications for treatment of any inflammatory condition that affects the brain.

Toxoplasma, a common parasite of humans, is found in the brains of approximately 30 percent of the population. Yet, because the brain lacks its own lymphatic system for localized immune response and the blood brain barrier limits antibody entry, researchers have found it provides unique challenges for the immune system to control local infection. Therefore, little is known about the processes by which T cells access the central nervous system during toxoplasma infection or how the immune system keeps this parasite in check.

In this study, researchers aimed to better understand how the immune system is able to control infection in the brain. Using recent advances in two-photon microscopy that allow the visualization of T-cell populations in the brain, Dr. Hunter, professor and chair of the department of pathobiology at Penn Vet focused in his lab on the visualization of effector CD8+ T cells during toxoplasmic encephalitis.

“We found, quite unexpectedly, that the movement of infiltrating T cells was closely associated with an infection-induced reticular system of fibers in the brain,” said lead author Emma Wilson, now at the at the University of California, Riverside. “These structures were not present in normal brain tissue.”

“This observation suggests that in the brain, specialized structures are induced by inflammation that guide migration of T cells in this immune-privileged environment and allow them to perform a search-and-destroy type of mission required to find abnormal cells or microbes with the brain,” Dr. Hunter said.