University of Southern California : Robot playmates may help children with autism

USC studies document that kids with ASD actively interact with robots; creation of therapy tools is next step

Feil-Seifer, Matarić and assistants: "a doorway into the attention " of ASD children.

Papers delivered at three conferences in the US and Europe this summer report on new research at the University of Southern California Viterbi School of Engineering studying interactions of children with Autism Spectrum Disorders (ASD) with bubble-blowing robots.

The preliminary studies, by Professor Maja Matarić and PhD student David Feil-Seifer of the USC Interaction Laboratory, confirm what has been widely reported anecdotally: that ASD children in many cases interact more easily with mechanical devices than with humans.

Matarić and Feil-Seifer, both specialists in Socially Assisted Robotics (SAR), are now engaged in further research to confirm their findings, and to develop a robot "control architecture" which will tailor robot interactions to the specific needs of ASD children to help therapists treating their condition.

The initial study, reported in the June Conference on Interaction Design for Children with Special Needs in Chicago, tested whether interaction as opposed to simple passive observation was going on between ASD children and a colorful bubble-blowing wheeled robot.

Bubblebot: When set in "contingent " behavior mode, children's actions can control its behavior. A video can be viewed at http://www.youtube.com/watch?v=VRNWRlSmiA0

The robot had two settings. In one, it carried on its rolling and bubble blowing on its own internal schedule, regardless of the behavior of the child. In the other, "when the child pushes a button, then the bubbles blow," in the words of the Chicago presentation.

The study watched the children and observed differences. "We found that the behavior of the robot affects the social behavior of a child (both human-human interaction and human-robot interaction): social behavior with a contingent robot was greater than with a random robot.

"Total speech went from 39.4 to 48.4 utterances, robot speech from 6.2 to 6.6 utterances, and parent speech from 17.8 to 33 utterances. Total robot interactions went from 43.42 to 55.31, with button pushes increasing from 14.69 to 21.87 and other robot interactions going from 24.11 to 28. Total directed interactions (interactions that were clearly directed at either the robot or the parent) went up from 62.75 to 89.47. Generally, when the robot was acting contingently, the child was more sociable."

While only four children were part of the initial study, Feil-Seifer and Matarić believe the work clearly demonstrates the ability of robots to actively engage with ASD children - "offer a doorway into their attention," Matarić says. A much more extensive follow-up with more subjects is already in progress, in collaboration with Los Angeles Childrens Hospital and the Autism Genetic Resource Exchange.

Two other presentations by Feil-Seifer and Matarić, at the 11th International Symposium on Experimental Robotics 2008 in Athens, Greece in July, 2008, and at the IEEE Proceedings of the International Workshop on Robot and Human Interactive Communication, discuss these results in more detail, particularly in regard to the "Behavior-Based Behavior Intervention Architecture" (B3IA) they have developed to make the robots flexible and useful tools help ASD children.

This architecture (the system, including robotic and non-robotic components, plus provisions for recording and analyzing the proceedings) is based on an ASD therapy format called DIR/Floortime, in which a therapist shares floor with various toys used to try to engage the child.

Matarić and Feil-Seifer, in collaboration with Dr. Marian Williams from Childrens Hospital Los Angeles and Shri Narayanan from Viterbi School's Department of Electrical Engineering, are replacing toys with robots, both the rolling robots with horns and bubble blowers used in the initial results, and humanoid robots capable of smiles and other expression.

Behind the scenes, the architecture also includes an overhead video view that analyzes, documents, and stores every interaction, and a control system for the therapist operator that allows for switching between scenarios for interaction with the child, to concentrate on what works, and change what works to make it work better -- while still retaining a standard record-keeping and monitoring system used in ASD therapy.

Matarić has for years been working in the field of socially assisted robots to help a variety of other user populations, including patients with Alzheimer's Disease and stroke victims receiving help in rehabilitation. She notes that ASD is now at "epidemic" proportions in the United States.

"I am gratified by these preliminary results," she said. "I believe that Socially Assistive Robotics has a part to play in helping families, both the affected children and their parents and siblings."

###

While not authors of the studies, Dr. Clara Lajonchere of Childrens Hospital of Los Angeles and Dr. Michele Kipke of the Autism Genetic Resource Exchange played key roles in the work and will be continuing to collaborate with the USC roboticists.

The research was funded by the USC Provost's Center for Interdisciplinary Research, the Okawa Foundation, and an NSF Computing Research Infrastructure Grant.

Copies of the conference presentations are available in PDF form here:

David J. Feil-Seifer and Maja J. Matarić, "Robot-assisted therapy for children with Autism Spectrum Disorders," Refereed Workshop Conference on Interaction Design for Children: Children with Special Needs, pp. 49-52, Chicago, Il, Jun 2008.
http://cres.usc.edu/pubdb_html/files_upload/588.pdf

David J. Feil-Seifer and Maja J. Matarić, "Toward Socially Assistive Robotics For Augmenting Interventions For Children With Autism Spectrum Disorders," 11th International Symposium on Experimental Robotics 2008, Athens, Greece, Jul 2008.
http://cres.usc.edu/pubdb_html/files_upload/589.pdf

David J. Feil-Seifer and Maja J. Matarić, "B3IA: An architecture for autonomous robot-assisted behavior intervention for children with Autism Spectrum Disorders," IEEE Proceedings of the International Workshop on Robot and Human Interactive Communication, Munich, Germany, Aug 2008.
http://cres.usc.edu/pubdb_html/files_upload/549.pdf

Project on Emerging Nanotechnologies : Local officials move toward monitoring nanotechnologies

Massachusetts city health officials urge adoption of unique voluntary program

Washington, DC — State and local officials have taken steps to begin monitoring the manufacture and storage of nanomaterials, a major step for a cutting-edge technology that has yet to be regulated by the federal government.

On July 28, the Cambridge (Mass.) Public Health Department recommended to the city manager that Cambridge take several steps to gain a better understanding of the nature and extent of nanotechnology-related activities now underway within the city. In addition, news outlets are reporting that a key member of California State Assembly Committee on Environmental Safety and Toxic Materials is holding meetings around the state in advance of introducing legislation next year that may grant state regulators landmark oversight of nanomaterials.

In 2006, Berkeley, Calif., passed the first local ordinance in the nation by requiring handlers of nanomaterials to submit toxicology reports on the materials to the city government.

The efforts by state and local officials come as the Project on Emerging Nanotechnologies (PEN) recently released a report that discusses possible options for state and local governments to follow for oversight of potential negative impacts of nanotechnology – including local air, waste and water regulations, as well as labeling and worker safety requirements.

"In the absence of action at the federal level, local and state governments may begin to explore their options for oversight of nanotechnologies," says Suellen Keiner, the author of Room at the Bottom? Potential State and Local Strategies for Managing the Risks and Benefits of Nanotechnology.

Another recent PEN report, Application of the Toxics Release Inventory To Nanomaterials, addresses the potential application of local "right-to-know" laws concerning nanotechnologies.

The Cambridge Public Health Department, in collaboration with the Cambridge Nanomaterials Advisory Committee, in its new report does not recommend the city manager enact a new ordinance regulating nanotechnology, but it does recommend that the city take the following steps:

• Establish an inventory of engineered nanoscale materials that are manufactured, handled, processed, or stored in the city, in cooperation with the Cambridge Fire Department and the Local Emergency Planning Committee.

• Offer technical assistance, in collaboration with academic and nanotech sector partners, to help firms and institutions evaluate their existing health and safety plans for limiting risk to workers involved in nanomaterials research and manufacturing.

• Offer up-to-date health information to residents on products containing nanomaterials and sponsor public outreach events.

• Track rapidly changing developments in research concerning possible health risks from various engineered nanoscale materials.

• Track the evolving status of regulations and best practices concerning engineered nanoscale materials among state and federal agencies, and international health and industry groups.

• Report to the city council every two years on the changing regulatory and safety landscape of the nanotechnology sector.

David Rejeski, the director of PEN and a member of an advisory committee that oversaw the public health department's document, says that while the recommendations are encouraging and important, there is still a need for federal oversight of nanotechnology and an increase in research concerning the risks posed by nanomaterials.

"Today, there are more than 600 manufacturer-identified consumer products available on the market that contain nanomaterials and countless other commercial and industrial applications the public and policymakers are not aware of," Rejeski says. Unfortunately, federal agencies currently have to draw on decades-old laws to ensure the safe development and use of these technologically advanced products -- many of which are woefully out of date. Federal officials need 21st century tools for cutting-edge technologies. Anything short of that is unacceptable."

Meanwhile, California Assemblyman Mike Feuer (D), a member of the Assembly's Committee on Environmental Safety and Toxic Materials, is holding meetings at major state universities and research centers with representatives from industry, government, environmental groups and others in an effort to craft legislation for introduction in 2009 that would establish a state nanotechnology regulatory program, according to an April article in Inside Cal/EPA.

###

The Cambridge recommendations are available here: http://www.cambridgepublichealth.org/policy-practice/nano_policy.php

Room at the Bottom? Potential State and Local Strategies for Managing the Risks and Benefits of Nanotechnology is available here: http://www.nanotechproject.org/publications/archive/room_at_bottom/

Application of the Toxics Release Inventory To Nanomaterials is available here: http://www.nanotechproject.org/publications/archive/toxics/

About Nanotechnology

Nanotechnology is the ability to measure, see, manipulate and manufacture things usually between 1 and 100 nanometers. A nanometer is one billionth of a meter; a human hair is roughly 100,000 nanometers wide. In 2007, the global market for nanotechnology-based products totaled $147 billion. Lux Research projects that figure will grow to $3.1 trillion by 2015.

The Project on Emerging Nanotechnologies (www.nanotechproject.org) is an initiative launched by the Woodrow Wilson International Center for Scholars and The Pew Charitable Trusts in 2005. It is dedicated to helping business, government and the public anticipate and manage possible health and environmental implications of nanotechnology.

Soil Science Society of America : Soil’s Carbon Storage Capacity Investigated

Three studies demonstrate that C storage capacity of soils in different regions of the Western Hemisphere respond similarly to a diverse range of management practices to increase soil C input.

Madison, WI July 28, 2008--As atmospheric CO₂ levels rise, methods to mitigate these increases are becoming very important. Three studies published in the July-August 2008 issue of Soil Science Society of America Journal explore the potential roles of soils as a C sink in different regions in the Western Hemisphere. Scientists from Alberta Agriculture and Rural Development (Canada), the National Institute of Agricultural Technology, the University of Buenos Aires (Argentina), and University of California, Davis (USA) have investigated soil C balance in distinct agroecosystems under different management practices including soil tillage, N fertilization, elimination of fallow, and establishment of grass. In each case, C sequestration occurred in response to higher C input to soil; however, increase in SOC was confined to labile fractions such as the light fraction and larger soil aggregates.

Investigation: Canada
In southeastern Alberta, a long-term study showed previously that eliminating summer fallow or establishing grass significantly increased soil organic C after 6 yr. In the 12th year of the study, total organic C and light fraction C were determined in three rotations with summer fallow, two continuously cropped rotations and grass. All rotations had subtreatments with different levels of fertilization. The light fraction of soil C was obtained using density separation and consisted mostly of non-decomposed root and straw fragments.

Although soil organic C was increased by elimination of summer fallow, fertilization, and establishment of grass, gains in soil organic C between Years 6 and 12 were negligible in all treatments except the fertilized grass treatment. Most of the gains in total soil organic C were due to increased light fraction C. The results indicate that much of the gain in soil organic C in response to improved practices on semiarid prairie soils likely occurs within one decade.

The full article is available for no charge for 30 days following the date of this summary. View the abstract at:http://soil.scijournals.org/cgi/content/abstract/72/4/970

Investigation: Argentina
In the semiarid portion of the Pampas, scientist compared no-till management to a conventional tillage system (disk-tillage). Emissions of CO₂-C from the soil and crop C inputs were determined, estimating soil C balance under both tillage systems.

As a part of this study, a field experiment was performed during 6 yr on an Entic Haplustoll where no-till and disk-tillage was applied to a soil cropped under a common rotation in the region (oat + hairy vetch, corn, wheat, oat). From Year 3 to 6 in situ CO₂-C fluxes were measured and C inputs from above and below ground plant residues were estimated.

Results showed that in the semiarid environment of the study C sequestration occurred under no-till. The sequestration process was attributed to the effect of tillage systems on crop productivity rather than on the mineralization intensity of soil organic pools.

The full article is available for no charge for 30 days following the date of this summary. View the abstract at:http://soil.scijournals.org/cgi/content/abstract/72/4/1140


Investigation: United States
In Kentucky (USA) a study was conducted in a corn agroecosystem experiment to test the soil C saturation concept which postulates that there is an upper limit to the equilibrium soil C level of mineral soils even when soil C input is increased. In this experiment, a gradient of soil C input was produced with four N fertilizer application rates under two tillage systems, no-till and moldboard plowing. To investigate if physical protection of organic C leads to soil C saturation, C stabilization in soil fractions that differ in C stabilization potential was determined, and the relationship between soil C input and soil organic C was analyzed.

Total soil organic C was positively related to C input, and this was primarily due to C stabilization in larger soil aggregates. In both tillage systems, however, C in the two smallest soil size fractions did not increase with greater C input. Moreover, in three soil fractions further separated from larger soil aggregates, C associated with particulate organic matter and microaggregates increased with C input, but there was no increase in C associated with silt-plus-clay, which was the smallest soil size fraction.

Haegeun Chung at University of California, Davis, the first author of the study conducted in Kentucky (USA), stated “Our results indicate that soil fractions with low C stabilization potential show C saturation. Therefore, we need to consider soil C saturation levels to better predict the change in C sink capacity and fertility of soils when soil C input increases under higher plant production or organic amendment.”

The full article is available for no charge for 30 days following the date of this summary. View the abstract at http://soil.scijournals.org/cgi/content/abstract/72/4/1132.

Soil Science Society of America Journal, http://soil.scijournals.org, is a peer-reviewed international journal published six times a year by the Soil Science Society of America. Its contents focus on research relating to physics; chemistry; biology and biochemistry; fertility and plant nutrition; genesis, morphology, and classification; water management and conservation; forest, range, and wildland soils; nutrient management and soil and plant analysis; mineralogy; and wetland soils.

The Soil Science Society of America (SSSA) is a progressive, international scientific society that fosters the transfer of knowledge and practices to sustain global soils. Based in Madison, WI, and founded in 1936, SSSA is the professional home for 6,000+ members dedicated to advancing the field of soil science. It provides information about soils in relation to crop production, environmental quality, ecosystem sustainability, bioremediation, waste management, recycling, and wise land use.

SSSA supports its members by providing quality research-based publications, educational programs, certifications, and science policy initiatives via a Washington, DC, office. For more information, visit www.soils.org.

SSSA is the founding sponsor of an approximately 5,000-square foot exhibition, Dig It! The Secrets of Soil, opening July 19, 2008 at the Smithsonian's National Museum of Natural History in Washington, DC.

DOE/Oak Ridge National Laboratory: Revolutionary green technology bus has DOE roots

	Fisher Coachworks' lightweight hybrid bus, which achieves twice the fuel economy of current hybrid buses, has some Oak Ridge National Laboratory roots.

Insight from Oak Ridge National Laboratory, commitment from two Michigan companies and funding from the Department of Energy have led to the commercialization of a lightweight urban transit bus with double the fuel efficiency of conventional hybrid buses.

This new green technology 40-foot bus features a high-strength stainless steel body and chassis and a hybrid power system that drives the bus primarily with stored electrical energy. This approach reverses the paradigm of conventional parallel hybrid designs that use electric energy only to supplement the acceleration and torque requirements of a diesel engine.

At the heart of the bus is a chassis made of Nitronic 30, a nitrogen-strengthened stainless steel that is stronger and stiffer than conventional steel. These attributes translate into less material required for a chassis, resulting in reduced weight.

"Nitronic stainless steel is incredibly durable and enables our chassis designs to have significantly longer service life vs. ordinary steel vehicles," said Bruce Emmons, president of Autokinetics (http://www.autokinetics.com/) of Rochester, Mich., which developed the bus. "The fact that stainless is also 100 percent recyclable and more environmentally friendly to produce than aluminum makes this an ideal green raw material for vehicle structures."

Additional advantages of Nitronic 30 include excellent mechanical properties at sub-zero and elevated temperatures along with low-temperature impact resistance and superb resistance to high-temperature oxidation. While this material is more costly than conventional steel, Emmons noted that the additional cost is offset by design innovation, parts consolidation and streamlined manufacturing processes.

"The benefits of improved strength-to-weight performance quickly compound to all other vehicles systems such as smaller tires, lighter brakes, batteries, motors and so on," Emmons said. "By optimizing the total vehicle we have been able to cut the weight almost in half, which has led to performance improvements, most notably fuel economy gains."

In addition to its reduced weight and hybrid power system, the bus will incorporate a number of advanced design features and advantages, said Gregory Fisher, chief executive officer of Fisher Coachworks (http://www.fishercoachworks.com/), which licensed the technology, has produced a prototype and plans full commercialization. The bus made its debut today and deliveries of the bus are expected to begin in 2009.

Some of the advantages are improved vehicle safety for passengers, lower cost, reduced noise and improved ride dynamics. The major advantage, though, will be in cost to operate, according to Fisher.

Specific contributions from ORNL included computer crash studies and infrared thermal imaging to evaluate the quality of some of the initial laser welds in the structure. Early tests showed some problems with the laser welding technique, so Autokinetics chose to use resistance spot welding in most places and tungsten inert gas welding for the remainder of the joining needs.

But even before its technical contributions, Emmons said ORNL had a huge impact.

"ORNL was the first to suggest the possibility of applying Autokinetics' light-weighting ideas and technologies to the bus field," Emmons said. "Without that insight, this program would never have happened."

Phil Sklad of ORNL's Materials Science and Technology Division served as the program manager and technical monitor and noted that DOE's $2.5 million investment in this project is being rewarded with a revolutionary bus.

"This is a perfect example of how the Department of Energy, a national laboratory and the private sector can collaborate to produce something that is potentially of great value to society," Sklad said.

Fisher Coachworks, located in Troy, Mich., is planning to use this patented technology for transit buses and other commercial vehicle market segments that would benefit from vastly improved fuel economy in urban stop and start applications. Fisher Coachworks was formed in 2007 to focus on production of advanced hybrids using an ultra-lightweight stainless steel unibody construction.

Funding for this project was provided by DOE's Office of FreedomCAR and Vehicle Technologies Program. UT-Battelle manages Oak Ridge National Laboratory for the Department of Energy.

Johns Hopkins University Bloomberg School of Public Health Study Suggests 86 Percent of Americans Could be Overweight or Obese by 2030

Most adults in the U.S. will be overweight or obese by 2030, with related health care spending projected to be as much as $956.9 billion, according to researchers at the Johns Hopkins Bloomberg School of Public Health, the Agency for Healthcare Research and Quality and the University of Pennsylvania School of Medicine. Their results are published in the July 2008 online issue of Obesity.

“National survey data show that the prevalence of overweight and obese adults in the U.S. has increased steadily over the past three decades,” said Youfa Wang, MD, PhD, lead author of the study and associate professor with the Bloomberg School’s Center for Human Nutrition. “If these trends continue, more than 86 percent of adults will be overweight or obese by 2030 with approximately 96 percent of non-Hispanic black women and 91 percent of Mexican-American men affected. This would result in 1 of every 6 health care dollars spent in total direct health care costs paying for overweight and obesity-related costs.”

The researchers conducted projection analyses based on data collected over the past three decades from nationally representative surveys. Their projections illustrate the potential burden of the U.S. obesity epidemic if current trends continue.

“Our analysis also shows that over time heavy Americans become heavier,” says May A. Beydoun, a former postdoctoral research fellow at the Johns Hopkins Bloomberg School of Public Health.

“The health care costs attributable to obesity and overweight are expected to more than double every decade. This would account for 15 to 17 percent of total health care costs spent,” Wang says. “Due to the assumptions we made and the limitations of the available data, these figures are likely an underestimation of the true financial impact.”

Current standards define adults with a body mass index (BMI) between 25 and 29.9 as overweight and adults with a BMI of 30 or higher as obese. Both the overweight and obese are at an increased risk for developing a number of health conditions, including hypertension, type 2 diabetes, heart disease and stroke. Researchers estimate that children and young adults may have a shorter life expectancy than their parents if the obesity epidemic is left unaddressed.

The authors warned that obesity has become a public health crisis in the U.S. Timely, dramatic and effective development and implementation of corrective programs and policies are needed to avoid the otherwise inevitable health and societal consequences implied by their projections. If current trends continue, the researchers say that the U.S. Department of Health and Human Services will not meet its Healthy People 2010 initiative to increase the proportion of adults who are at a healthy weight and to reduce the proportion of adults who are obese.

Lan Liang, PhD; Benjamin Caballero, MD, PhD and Shiriki Kumanyika, PhD, MPH, co-authored the study “Will All Americans Become Overweight or Obese? Estimating the Progression and Cost of the U.S. Obesity Epidemic.”

The U.S. Department of Agriculture and the National Institutes of Health provided partial funding for the research.

Public Affairs media contact: Natalie Wood-Wright at 410-614-6029 or nwoodwri@jhsph.edu.

Public Library of Science : Sensitive testing reveals drug-resistant HIV with possible consequences for treatment

Drug-resistant HIV at levels too low to be detected by standard tests is not unusual and may contribute to treatment failure, according to research published in PLoS Medicine.

Mutations in the AIDS virus commonly occur during treatment, especially if HIV drugs are not taken consistently, and may cause treatments to fail. HIV treatment in developed countries normally includes testing for these mutations, both to select first-line drugs for a given patient and to choose second-line drugs if the virus rebounds from initial treatment. However, tests used by clinical laboratories cannot reliably detect mutant viruses that make up less than about 20% of the virus in a patient's blood.

To investigate the role of resistant virus present at lower levels, Jeffrey Johnson of the Division of HIV/AIDS Prevention Laboratory in the National Center for HIV, STD, and TB Prevention at the US Centers for Disease Control and Prevention and colleagues studied HIV from more than 500 recently infected patients in Canada and the US. Although these individuals had not received anti-HIV drugs, a highly sensitive test developed by the researchers showed that more than 10% carried HIV with common drug-resistance mutations that were not detected using usual tests.

The researchers then studied 316 samples from a separate study of about 1400 patients who were started on their first HIV treatment, which included the drug efavirenz. Before starting treatment, none of these patients had resistance to efavirenz according to standard tests. However, highly sensitive testing showed that 7 of the 95 patients who experienced treatment failure had low levels of HIV with resistance mutations to efavirenz prior to treatment. Of 211 patients whose treatment did not fail, only 2 showed low level resistance prior to treatment.

These data suggest that sensitive testing for resistance could avert failures in HIV treatment. However, given the small number of cases in this initial study, larger studies are needed to confirm the results.

In an accompanying Perspective, Steven Deeks of the University of California San Francisco, who was uninvolved with the research, discusses "whether assays for the detection of low level variants can or even should be developed for patient management." He notes that although "a sizable proportion of treatment naïve HIV infected individuals harbor a minority population of drug-resistant HIV," many patients with positive results on highly sensitive resistance testing might not go on to experience treatment failure.

###

Citation: Johnson JA, Li J-F, Wei X, Lipscomb J, Irlbeck D, et al. (2008) Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naïve populations and associate with reduced treatment efficacy. PLoS Med 5(7): e158. doi:10.1371/journal.pmed.0050158

University of Alabama at Birmingham: Anti-HIV Therapy Boosts Life Expectancy

• Improvements due to modern antiretroviral cocktails

• Study underscores HIV testing, treatment needs

BIRMINGHAM, Ala. - The life expectancy for patients with human immunodeficiency virus (HIV) has increased by more than 13 years since the late 1990s thanks to advancements in antiretroviral therapy, according to researchers at the University of Alabama at Birmingham (UAB) and Simon Fraser University in Vancouver, British Columbia.

Improved survival has led to a nearly 40 percent drop in AIDS deaths among 43,355 HIV-positive study participants in Europe and North America, bolstering the call for improved anti-HIV efforts worldwide, the study authors said.

The study is published in the British medical journal The Lancet. It was compiled by The Antiretroviral Therapy Cohort Collaboration, which includes UAB, Simon Fraser University and more than a dozen other research sites around the world.

COCKTAIL OF DRUGS

The authors looked at changes in life expectancy and mortality among the 43,355 HIV patients taking a cocktail of drugs called combination antiretroviral therapy (cART). Data was compiled from a total of 14 studies in Europe and North America.

"Since their introduction in 1996 cART regimens have become more effective, better tolerated and easier to follow," said Michael Mugavero, M.D., an assistant professor in UAB's Division of Infectious Diseases and a co-author on the study.

"We are now seeing the benefits of years of research, hard work and efforts to make these medications widely available. This has led to dramatic improvements in life expectancy, but patients who start cART with more advanced HIV infection do not have the same level of benefit," Mugavero said.

The new Lancet study found cART yielded a 13.8-year life-expectancy increase - from 36.1 years in study participants who began therapy during the 1996-1999 period to 49.9 years in participants who began therapy during the 2003-2005 period.

Despite the good results, the study found life expectancy for HIV patients is far lower on average than the general population, which includes all those with other chronic illnesses. For example, an HIV-positive patient starting cART at age 20 will live to 63, about 20 years shorter than the average life span of non-infected adults.

With nearly half of all patients diagnosed with advanced HIV infection, the life expectancy benefits of cART are not fully realized, said Mugavero and lead study author Robert Hogg, Ph.D., of Simon Fraser University. Improved AIDS testing and increased access to care is needed.

Funding from the study came from the UK Research Council and from GlaxoSmithKline.

Media Contact

Troy Goodman

(205) 934-8938

tdgoodman@uab.edu

Wake Forest University Baptist Medical Center Researchers disprove long-standing belief about HIV treatment

Researchers at Wake Forest University Baptist Medical Center have disproved a long-standing clinical belief that the hepatitis C virus slows or stunts the immune system's ability to restore itself after HIV patients are treated with a combination of drugs known as the "cocktail."

Hepatitis C (HCV) infection is more serious in HIV-infected people, leading to rapid liver damage, according to the Centers for Disease Control. Intravenous drug use is a main method of contraction for both HIV and HCV and 50 to 90 percent of HIV-infected drug users are also infected with HCV.

The Wake Forest Baptist study looked at whether having HCV co-infection impairs immune restoration in patients receiving highly active anti-retroviral therapy (HAART) to suppress their HIV infection. The results appear in the July issue of AIDS Research and Human Retroviruses.

The research focused on levels of CD4 cells, the specific type of immune cell that is attacked by the HIV virus, and their ability to rebuild after HIV is suppressed.

"We've been observing that in some patients that are co-infected with hepatitis C, we were treating their HIV with HAART but didn't always get very good restoration of CD4," said Marina Nunez, M.D., lead researcher and an assistant professor of infectious diseases. "Some studies suggested it was because of the hepatitis C. This study says it's not the presence of active hepatitis C replication."

Thus, said Nunez, genetic factors involved in the immune system regulation, confounding factors associated with HCV acquisition, or other unknown factors might explain the blunted immune restoration observed in some co-infected patients. "Research efforts should pursue the role of those other factors in the immune restoration," she said.

"From a clinical standpoint, although these findings will not alter the clinical management of HIV-HCV-co-infected patients, they make clear that even after successful treatment of the HCV infection, some patients may still not get an adequate CD4 recovery under HIV treatment."

For the retrospective study, researchers examined existing medical records of 322 patients from two separate databases – one from Madrid, Spain, and the other from Wake Forest University Baptist Medical Center. Patients were separated into two groups – those co-infected with hepatitis C and HIV and those infected only with HIV. Researchers reviewed CD4 levels at baseline (before beginning HIV suppression) and every year after for up to three years, while the patients continuously received HAART, an HIV treatment consisting of three different types of medicines used by many patients, and formerly referred to as the HIV "cocktail."

Years of clinical experience have shown that, with HAART treatment suppressing the HIV, CD4 levels are typically able to restore themselves, Nunez said.

However, in some patients, it has been observed that the immune restoration is poorer after HAART. Therefore, Nunez said, it has been a common practice for doctors to attribute less than desirable CD4 restoration after HAART in co-infected patients to the hepatitis C virus.

Studies to date have found evidence both in support of and against this belief, Nunez said. But a limitation in previous studies has been that co-infected patients have been identified by the presence of HIV and the hepatitis C antibody. Since many patients with hepatitis C clear the active virus but continue to carry the antibody, there hasn't been a pure sample of patients truly co-infected with both active viruses to analyze. In this study, only patients with HIV and active hepatitis C cell replication, therefore active virus, were classified as "co-infected."

The study found that there is no difference in the CD4 restoration of co-infected patients and mono-infected patients. However, it did show some differences that seem to be associated with age, gender or past intravenous drug use.

"The purpose of this study was to find out if hepatitis C was impeding the CD4 restoration in co-infected patients," Nunez said. "And it does not. There are other factors doing it. This study says that you can look into those other factors, but we cannot blame the hepatitis C anymore."

###

Media Relations Contacts: Jessica Guenzel, jguenzel@wfubmc.edu, (336) 716-3487; Bonnie Davis, bdavis@wfubmc.edu or Shannon Koontz, shkoontz@wfubmc.edu, (336) 716-4587

Wake Forest University Baptist Medical Center (www.wfubmc.edu) is an academic health system comprised of North Carolina Baptist Hospital, Brenner Children's Hospital, Wake Forest University Physicians, and Wake Forest University Health Sciences, which operates the university's School of Medicine and Piedmont Triad Research Park. The system comprises 1,154 acute care, rehabilitation and long-term care beds and has been ranked as one of "America's Best Hospitals" by U.S. News & World Report since 1993. Wake Forest Baptist is ranked 32nd in the nation by America's Top Doctors for the number of its doctors considered best by their peers. The institution ranks in the top third in funding by the National Institutes of Health and fourth in the Southeast in revenues from its licensed intellectual property.

New York- Presbyterian Hospital/Columbia University Medical Center research into robotic surgery for kidney cancer

New research helps optimize benefits of robotic approach

NEW YORK (July 28, 2008) -- Clinical research at NewYork-Presbyterian Hospital/Columbia University Medical Center is helping bring the advantages of robotic surgery, including reduced pain and quicker recovery, to kidney cancer patients.

Using the latest-generation da Vinci® S Surgical System by Intuitive Surgical, surgeons operate through several small incisions in the abdomen. Surgeons then remove only the cancerous tissue from the kidney, and repair the remaining normal kidney tissue, all using robotic arms guided by video taken by a camera controlled by a separate robotic arm.

The stereoscopic view provides enhanced visibility, and the nimble robotic mechanism makes for easy cutting and suturing, according to Drs. Ketan Badani and Jaime Landman, who make up the robotic kidney surgery team at NewYork-Presbyterian/Columbia.

"With robotics, there is a much greater opportunity for complex reconstruction of the kidney than can typically be achieved with a standard laparoscopic approach," notes Dr. Badani, director of robotic urologic surgery at NewYork-Presbyterian Hospital/Columbia University Medical Center and assistant professor of urology at Columbia University College of Physicians and Surgeons.

"This means that, hopefully, we will have an opportunity not only to reduce the need for kidney cancer patients to require a kidney transplant, but also reduce their need for dialysis later in life," adds Dr. Landman, director of minimally invasive urologic surgery at NewYork-Presbyterian Hospital/Columbia University Medical Center and associate professor of urology at Columbia University College of Physicians and Surgeons.

In a recent issue of the Journal of Endourology, Dr. Badani described a new technique for port placement -- the location of the small incision through which the robot operates -- that maximizes range of motion for the robot's camera arm and working arm. The approach was shown to be successful in more than 50 cases, and has been adopted for use by medical centers worldwide.

Robotic surgery, most widely used for prostate cancer surgery, is beginning to be more widely available for other conditions. In addition to kidney cancer, Dr. Badani and Dr. Mitchell Benson (George F. Cahill Professor and Chairman of the Department of Urology at Columbia University College of Physicians and Surgeons and urologist-in-chief at NewYork-Presbyterian Hospital/Columbia University Medical Center), have established robotic surgery for bladder cancer, and they cite work being undertaken in pelvic floor reconstruction and repair of vaginal wall prolapse.

###

Columbia University Medical Center

Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians & Surgeons was the first institution in the country to grant the M.D. degree and is now among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and state and one of the largest in the United States. For more information, please visit www.cumc.columbia.edu.

NewYork-Presbyterian Hospital

NewYork-Presbyterian Hospital, based in New York City, is the nation's largest not-for-profit, non-sectarian hospital, with 2,242 beds. The Hospital has nearly 2 million patient visits in a year, including more than 230,000 visits to its emergency departments -- more than any other area hospital. NewYork-Presbyterian provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine at five major centers: NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children's Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Allen Pavilion and NewYork-Presbyterian Hospital/Westchester Division. One of the largest and most comprehensive health-care institutions in the world, the Hospital is committed to excellence in patient care, research, education and community service. It ranks sixth in U.S.News & World Report's guide to "America's Best Hospitals," ranks first on New York magazine's "Best Hospitals" survey, has the greatest number of physicians listed in New York magazine's "Best Doctors" issue, and is included among Solucient's top 15 major teaching hospitals. The Hospital's mortality rates are among the lowest for heart attack and heart failure in the country, according to a 2007 U.S. Department of Health and Human Services (HHS) report card. The Hospital has academic affiliations with two of the nation's leading medical colleges: Weill Cornell Medical College and Columbia University College of Physicians and Surgeons. For more information, visit www.nyp.org.

Blackwell Publishing : Prostate Cancer Patients Undergoing Hormone Therapy May Experience Cognitive Effects

A recent review of the literature has found that hormone deprivation therapy, a commonly used treatment for prostate cancer, may have subtle adverse effects on cognition in patients--such as in the ability to recall and concentrate. Published in the September 1, 2008 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the study indicates that clinicians and patients should be aware of these potential effects and watch closely for their appearance.

For years, hormone deprivation therapy, also known as androgen depletion therapy, has been used as an effective treatment for prostate cancer because hormones such as testosterone drive the growth of prostate cancer cells. The most common way to achieve androgen depletion is through chemical castration with drugs such as leuprolide and goserelin. Androgen depletion therapy has traditionally been reserved for advanced cases of prostate cancer, but increasing numbers of men with earlier stages of the disease are also undergoing the treatment.

Prostate cancer patients who are prescribed these drugs often stay on them for the duration of their life, and researchers have been documenting the potential adverse effects associated with their use. Men may experience hot flashes, osteoporosis, anemia, fatigue, loss of libido, erectile dysfunction, risk of diabetes, risk of cardiovascular disease, emotional distress and other effects. Research also indicates that androgen depletion may impact cognitive functioning, which can affect a patient’s decision-making skills and quality of life.

Unfortunately, only a handful of relatively small studies have investigated the impact of androgen depletion on cognitive functioning, and some of these studies have reported contradictory results. Dr. Christian Nelson, a psychologist at Memorial Sloan-Kettering Cancer Center in New York City and his colleagues recently conducted the first review of these studies and summarized their overall results.

After performing a systematic literature search of studies in animals and humans, Dr. Nelson’s team found that testosterone and its derivatives may impact cognition via several mechanisms in the brain. For example, testosterone can modulate brain chemicals called neurotransmitters and stimulate the connections between neurons. Also, studies that have examined the impact of androgen depletion therapy in prostate cancer patients indicate that between 47 percent and 69 percent of men being treated decline in at least one cognitive area, most commonly in processes dependent on spatial ability and in high-order capacities such as the ability to multi-task.

The findings indicate that larger, more thorough studies that include brain imaging techniques are needed to better understand the nature and extent of the cognitive effects of androgen depletion.

In addition, researchers are exploring the effectiveness of using androgen depletion therapy in men with rising levels of prostate specific antigen, a potential precursor to prostate cancer. The authors concluded that “as the use of androgen depletion therapy increases, clinicians should become aware of this relationship [with cognitive decline], and inform and monitor patients for this possible side effect of treatment.”

Article: “The cognitive effects of hormone therapy in men with prostate cancer: a review.” Christian J. Nelson, Jennifer S. Lee, Maria C. Gamboa, and Andrew J. Roth. CANCER; Published Online: July 28, 2008 (DOI: 10.1002/cncr.23658); Print Issue Date: September 1, 2008.

Contact: Esther Napolitano, Media Relations Manager at Memorial Sloan-Kettering Cancer Center’s Department of Public Affairs. 212-639-3573, napolite@mskcc.org.

Blackwell Publishing : Hip Bone Density Helps Predict Breast Cancer Risk

Measuring a woman’s bone mineral density can provide additional information that may help more accurately determine a woman’s risk of developing breast cancer. That is the conclusion of a new study published in the September 1, 2008 issue of CANCER, a peer-reviewed journal of the American Cancer Society. The study’s results suggest that incorporating bone mineral density tests with current risk assessments might significantly improve physicians’ ability to predict breast cancer risk in older, postmenopausal women.

Bone mineral density testing is done to diagnose osteoporosis and help assess the risk of fractures. Low bone mineral density is linked to higher risk of fractures, while normal density is linked to lower risk of fractures. It is possible that over a woman’s lifetime, hormonal and other factors that lead to higher bone mineral density can also lead to higher risk of breast cancer. Studies have found an association between higher bone mineral density and higher breast cancer risk, and bone mineral density tests have been proposed as a potential addition to breast cancer risk models. This study, supported by Eli Lilly & Company, is the first to investigate the relationships among bone mineral density, traditional breast cancer risk assessment tool results, and breast cancer incidence among the same group of postmenopausal women.

To investigate these relationships, Dr. Zhao Chen of the University of Arizona Mel and Enid Zuckerman College of Public Health and her colleagues studied approximately 10,000 post-menopausal women (average age 63) taking part in the Women’s Health Initiative, a study conducted in 40 clinical centers throughout the United States and supported by the National Heart, Lung and Blood Institute of the National Institutes of Health. The researchers assessed the women’s initial bone mineral density level as well as their score on the Gail risk model, a well known and commonly used tool that estimates five year and lifetime risk of invasive breast cancer for women 35 years of age or older. They then followed the women for an average of approximately 8 years, noting which women developed breast cancer.

As expected, the study found that women with a high Gail score had a 35 percent increased risk of developing breast cancer compared to women with a lower Gail score. But the study also found a 25 percent increase in the risk of developing the disease with each unit increase in total hip bone mineral density t-score. While the two scores were independent of each other, women who had the highest scores on both assessments had a much higher risk in breast cancer.

The findings suggest that adding bone mineral density to currently used risk assessment tools may significantly improve the prediction of breast cancer risk. “Future studies should investigate whether incorporating bone mineral density and Gail score with other risk factors, such as breast density, can further improve the identification of women at high risk for developing breast cancer,” the authors wrote. This study also suggests that bone mineral density is a potential alternative for predicting breast cancer risk in postmenopausal women if Gail score is not available. Additional studies are needed to determine if the results from this investigation are applicable to a broader group of women, including minorities. The findings do not change the use of bone mineral density testing to diagnose osteoporosis or the need to treat osteoporosis in order to reduce the risk of fractures.

Article: “Hip bone density predicts breast cancer risk independently of Gail score - results from the Women’s Health Initiative.” Zhao Chen, Leslie Arendell, Mikel Aickin, Jane Cauley, Cora E. Lewis, and Rowan Chlebowski. CANCER; Published Online: July 28, 2008 (DOI: 10.1002/cncr.23674); Print Issue Date: September 1, 2008.

Contact: Lorraine Varela - University of Arizona Mel and Enid Zuckerman College of Public Health. (520) 626-7083, varelal@coph.arizona.edu.

Cedars-Sinai Medical Center : Erectile dysfunction drugs allowed more chemotherapy to reach brain tumors in laboratory study

The drugs blocked an enzyme and opened blood vessels to tumors but not normal brain

LOS ANGELES (July 28, 2008) – In a study using laboratory animals, researchers found that medications commonly prescribed for erectile dysfunction opened a mechanism called the blood-brain tumor barrier and increased delivery of cancer-fighting drugs to malignant brain tumors.

The experiments were conducted at Cedars-Sinai Medical Center's Maxine Dunitz Neurosurgical Institute and published in Brain Research.

Viagra (sildenafil) and Levitra (vardenafil) are known as PDE5 inhibitors because they block an enzyme, phosphodiesterase5, which interrupts a series of biochemical events that cause the decreased blood flow of erectile dysfunction. This laboratory rat study, published online ahead of print in the journal, found that similar biochemical interactions in the small vessels of the brain play a major role in the blood-brain tumor barrier, which impedes delivery of anti-tumor drugs into brain tumors. PDE5 inhibitors were found to open the barrier and increase drug transport in this early animal study.

Although the normal blood-brain barrier, which regulates access to the brain from the bloodstream, shares many characteristics with the blood-brain tumor barrier, the signaling mechanism blocked by PDE5 inhibitors is unique to the blood-brain tumor barrier. This allows the PDE5 inhibitors to selectively increase drug transport to malignant brain tumors without affecting normal brain tissue.

According to the researchers, these findings may have significant implications in improving drug delivery to brain tumors in patients.

"This is the first study to show that oral administration of PDE5 inhibitors increases the rate of transport of compounds across the blood-brain tumor barrier and improves the effectiveness of the anti-tumor drug adriamycin in the treatment of brain tumors in a rat model. We chose adriamycin for this study because it is one of the most effective drugs against brain tumor cell lines in the laboratory but it has very little effect in animals and humans because it is unable to cross the blood-brain tumor barrier. The combination of vardenafil and adriamycin resulted in longer survival and smaller tumor size," said neurosurgeon Keith L. Black, M.D., chairman of the Department of Neurosurgery at Cedars-Sinai Medical Center and director of the Maxine Dunitz Neurosurgical Institute.

Black, the article's first and corresponding author, has been recognized for his earlier groundbreaking work to break through the blood-brain tumor barrier with natural and synthetic bradykinin, a peptide that temporarily opens the barrier and increases anti-cancer drug delivery into certain tumors by more than 1,000 percent. In 2000, he received the Javits Neuroscience Investigator Award from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, for his blood-brain barrier research.

In the current studies, the blood-brain tumor barrier-opening effects of PDE5 lasted considerably longer than those of bradykinin and allowed greater transport across the barrier into tumor tissues. Because vardenafil was found to be more effective than sildenafil in increasing blood-brain tumor barrier permeability and transport, vardenafil was used in a survival study of 29 tumor-bearing rats. Those treated with saline (control) survived 32 days on average while those treated with vardenafil alone survived about 35 days and those treated with adriamycin alone survived about 42 days. When vardenafil was combined with adriamycin, rats survived an average 53 days.

Although the researchers exposed the laboratory animals to doses of sildenafil and vardenafil that are comparable to the dose range approved for erectile dysfunction in humans, there were no detectable side effects in the rats, and neither drug increased transport of tracers into normal brain tissue.

###

Funding for the studies was provided by the National Institute of Neurological Disorders and Stroke (the Javits Award), the Maxine Dunitz Neurosurgical Institute and the Ruth and Lawrence Harvey Chair in Neuroscience, held by Black.

Citation: Brain Research, "PDE5 Inhibitors Enhance Tumor Permeability and Efficacy of Chemotherapy in a Rat Brain Tumor Model," available online ahead of print.

American Cancer Society : Prostate cancer patients undergoing hormone therapy may experience cognitive effects

A recent review of the literature has found that hormone deprivation therapy, a commonly used treatment for prostate cancer, may have subtle adverse effects on cognition in patients-- such as in the ability to recall and concentrate. Published in the September 1, 2008 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the study indicates that clinicians and patients should be aware of these potential effects and watch closely for their appearance.

For years, hormone deprivation therapy, also known as androgen depletion therapy, has been used as an effective treatment for prostate cancer because hormones such as testosterone drive the growth of prostate cancer cells. The most common way to achieve androgen depletion is through chemical castration with drugs such as leuprolide and goserelin. Androgen depletion therapy has traditionally been reserved for advanced cases of prostate cancer, but increasing numbers of men with earlier stages of the disease are also undergoing the treatment.

Prostate cancer patients who are prescribed these drugs often stay on them for the duration of their life, and researchers have been documenting the potential adverse effects associated with their use. Men may experience hot flashes, osteoporosis, anemia, fatigue, loss of libido, erectile dysfunction, risk of diabetes, risk of cardiovascular disease, emotional distress, and other effects. Research also indicates that androgen depletion may impact cognitive functioning, which can affect a patient's decision-making skills and quality of life.

Unfortunately, only a handful of relatively small studies have investigated the impact of androgen depletion on cognitive functioning, and some of these studies have reported contradictory results. Dr. Christian Nelson, a psychologist at Memorial Sloan-Kettering Cancer Center in New York City and his colleagues recently conducted the first review of these studies and summarized their overall results.

After performing a systematic literature search of studies in animals and humans, Dr. Nelson's team found that testosterone and its derivatives may impact cognition via several mechanisms in the brain. For example, testosterone can modulate brain chemicals called neurotransmitters and stimulate the connections between neurons. Also, studies that have examined the impact of androgen depletion therapy in prostate cancer patients indicate that between 47% and 69% of men being treated decline in at least one cognitive area, most commonly in processes dependent on spatial ability and in high-order capacities such as the ability to multi-task.

The findings indicate that larger, more thorough studies that include brain imaging techniques are needed to better understand the nature and extent of the cognitive effects of androgen depletion.

In addition, researchers are exploring the effectiveness of using androgen depletion therapy in men with rising levels of prostate specific antigen, a potential precursor to prostate cancer. The authors concluded that "as the use of androgen depletion therapy increases, clinicians should become aware of this relationship [with cognitive decline], and inform and monitor patients for this possible side effect of treatment."

###

Article: "The cognitive effects of hormone therapy in men with prostate cancer: a review." Christian J. Nelson, Jennifer S. Lee, Maria C. Gamboa, and Andrew J. Roth. CANCER; Published Online: July 28, 2008 (DOI: 10.1002/cncr.23658); Print Issue Date: September 1, 2008.

American Cancer Society : Hip bone density helps predict breast cancer risk

Measuring a woman's bone mineral density can provide additional information that may help more accurately determine a woman's risk of developing breast cancer. That is the conclusion of a new study published in the September 1, 2008 issue of CANCER, a peer-reviewed journal of the American Cancer Society. The study's results suggest that incorporating bone mineral density tests with current risk assessments might significantly improve physicians' ability to predict breast cancer risk in older, postmenopausal women.

Bone mineral density testing is done to diagnose osteoporosis and help assess the risk of fractures. Low bone mineral density is linked to higher risk of fractures, while normal density is linked to lower risk of fractures. It is possible that over a woman's lifetime, hormonal and other factors that lead to higher bone mineral density (and lower risk of fractures) can also lead to higher risk of breast cancer. Studies have found an association between higher bone mineral density and higher breast cancer risk, and bone mineral density tests have been proposed as a potential addition to breast cancer risk models. This study, supported by Eli Lilly & Company, is the first to investigate the relationships among bone mineral density, traditional breast cancer risk assessment tool results, and breast cancer incidence among the same group of postmenopausal women.

To investigate these relationships, Dr. Zhao Chen of the University of Arizona Mel and Enid Zuckerman College of Public Health and her colleagues studied approximately 10,000 post-menopausal women (average age 63) taking part in the Women's Health Initiative, a study conducted in 40 clinical centers throughout the United States and supported by the National Heart, Lung and Blood Institute of the National Institutes of Health. The researchers assessed the women's initial bone mineral density level as well as their score on the Gail risk model, a well known and commonly used tool that estimates five year and lifetime risk of invasive breast cancer for women 35 years of age or older. They then followed the women for an average of approximately 8 years, noting which women developed breast cancer.

As expected, the study found that women with a high Gail score had a 35 percent increased risk of developing breast cancer compared to women with a lower Gail score. But the study also found a 25 percent increase in the risk of developing the disease with each unit increase in total hip bone mineral density t-score. While the two scores were independent of each other, women who had the highest scores on both assessments had a much higher risk in breast cancer.

The findings suggest that adding bone mineral density to currently used risk assessment tools may significantly improve the prediction of breast cancer risk. "Future studies should investigate whether incorporating bone mineral density and Gail score with other risk factors, such as breast density, can further improve the identification of women at high risk for developing breast cancer," the authors wrote. This study also suggests that bone mineral density is a potential alternative for predicting breast cancer risk in postmenopausal women if Gail score is not available. Additional studies are needed to determine if the results from this investigation are applicable to a broader group of women, including minorities. The findings do not change the use of bone mineral density testing to diagnose osteoporosis or the need to treat osteoporosis in order to reduce the risk of fractures.

###

Article: "Hip bone density predicts breast cancer risk independently of Gail score - results from the Women's Health Initiative." Zhao Chen, Leslie Arendell, Mikel Aickin, Jane Cauley, Cora E. Lewis, and Rowan Chlebowski. CANCER; Published Online: July 28, 2008 (DOI:10.1002/cncr.23674); Print Issue Date: September 1, 2008.

Harvard Medical School Being a control freak aids dividing cells

Micromanagers may generate resentment in an office setting, but they get results in your body. New data indicate that a dividing cell takes micromanagement to the extreme, tagging more than 14,000 different sites on its proteins with phosphate, a molecule that typically serves as a signal for a variety of biological processes.

This preponderance of signals suggests that the cell may become a control freak during the division process, regulating each of its parts, no matter how obscure. It may take extreme measures to ensure that each "daughter" receives a full complement of cellular material. The new data—published online the week of July 28 in PNAS—open unexplored frontiers to developmental biologists, cancer researchers, and others who study cell growth and proliferation.

"There's a massive wave of phosphorylation in dividing cells, much bigger than anyone expected," says HMS associate professor of cell biology Steven Gygi, who is corresponding author on the study. "This discovery implies that we've severely underestimated the scope of regulation in cell division for decades, which has implications for our understanding of a wide-range of diseases and developmental defects linked to the cell cycle, from cancer to holes in the heart."

Traditionally, researchers probed cell division by zooming in on a particular gene or protein and tracing its interactions. But Gygi took a different approach. A leader in the emerging field of "proteomics," which involves looking at thousands of proteins at once, his team used an instrument called a mass spectrometer to essentially take a wide-angle shot of dividing cells, capturing information that narrow studies missed. The panoramic view revealed a surprising level of signaling activity throughout the cell.

"An enormous number of proteins—more than 1,000—became highly phosphorylated during cell division, some more than 10 times," says postdoctoral researcher Noah Dephoure, who ran the experiment.

In collaboration with Chunshui Zhou, a researcher in HMS professor of genetics Stephen Elledge's lab, Dephoure worked with human cells, dividing them into two dishes. (The cells used are HeLa cells, which, while derived from a tumor, are used for many experiments because they thrive in culture. It's possible that some of the signaling events reported here are unique to these cells.) The first dish received nutrients with "heavy" carbon atoms—more massive than their "light" counterparts, which are abundant in nature. The second dish received normal nutrients, plus a toxic chemical to freeze the cells mid-division.

Dephoure and Zhou mixed all the cells together, killed them, chopped their constituent proteins—which were preserved—into small pieces called peptides, and fed these into a mass spectrometer. The instrument distinguished between otherwise identical peptides, based on the presence of "heavy" or "light" atoms, generating a ratio for each peptide. Dephoure paid particular attention to the ratios for peptides containing phosphate groups and uncovered major differences between the two populations of cells.

The dividing cells harbored a staggering number of regulated phosphate groups in unexpected places.

Gygi hypothesizes that the cell uses phosphorylation to break down every last protein complex before dividing. "Maybe the cell does something akin to putting Humpty Dumpty back together again at the end," he says.

"The massive number of phosphorylation changes in cell division strongly suggests that it involves a massive reorganization of the cell," adds HMS Department of Systems Biology chair Marc Kirschner, who was not involved in the study.

"Or the cell might phosphorylate everything to ensure that it hits a few key targets critical for proper division," says Dephoure. Under this scenario, extraneous phosphorylation may cloud the picture.

Armed with the team's list of proteins and phosphorylation sites, labs can conduct additional experiments to resolve this debate. They can investigate particular phosphorylation events and determine which ones contribute to successful regulation of cell division. Some may present therapeutic targets for patients with cell cycle diseases such as cancer.

"This study demonstrates how much a broad systematic approach to protein modification can facilitate experiments in the cell cycle field," says Kirschner. "We will be reaping results from this study for years ahead."

###

This research is funded by the National Institutes of Health, the Spanish Ministry of Education and Science, and Howard Hughes Medical Institute.

Fred Hutchinson Cancer Research Center : A new biomarker for early cancer detection? Research reveals that 'microRNA' may fit the bill

Scientists at Fred Hutchinson Cancer Research Center have discovered that microRNAs – molecular workhorses that regulate gene expression – are released by cancer cells and circulate in the blood, which gives them the potential to become a new class of biomarkers to detect cancer at its earliest stages. Muneesh Tewari, M.D., Ph.D., and colleagues describe their findings in the July 28 issue of the Proceedings of the National Academy of Sciences.

MicroRNAs, which act as brakes on different parts of a cell, keeping genes in check, have some advantages over protein-based early-detection systems, including that they can be detected potentially in smaller quantities and that the technology exists to rapidly develop microRNA-based early-detection tests, said Tewari, an assistant member in the Hutchinson Center's Human Biology and Clinical Research divisions. His work is focused on understanding why the brakes fail – allowing unchecked cell growth – in prostate and ovarian cancer.

"Current technology for developing tests to measure microRNAs in clinical samples is quite advanced, whereas the bottleneck for developing protein-based biomarkers is the slow process of generating assays for measuring specific proteins," he said.

The next steps, now that a proof of principle has been established, are to identify specific microRNAs that can signal the presence of a variety of solid-tumor cancers at an early stage, and to further develop the technology to detect the microRNAs in minute quantities.

For the study, Tewari and colleagues tested blood from mice and humans with advanced prostate cancers, as well as that from healthy controls. They measured microRNAs made by the tumors in both cases and controls, and they could distinguish which individuals had cancer based on blood microRNA measurement.

"This research shows that microRNAs, which weren't previously thought of as markers of cancer in the blood, are a worthwhile class of molecules to study for the purpose of early cancer detection," Tewari said.

The research that led to the surprising finding of microRNAs in plasma and serum resulted from a combination of observations and a hunch, he said.

MicroRNAs play a key role in a wide range of normal cell processes, including embryonic development and cell differentiation. The tiny regulatory molecules modulate the activity of specific messenger-RNA targets, which in turn give rise to proteins. Humans have 30,000 genes that can make messenger RNAs. There are more than 500 known microRNAs encoded by the human genome and each is thought to target up to hundreds of messenger RNAs.

That microRNAs existed in humans is in itself a recent discovery. Tewari's group initially was studying their role in cancer development and maintenance because microRNAs are often dysregulated in cancer. During the course of those experiments, the scientists found that microRNAs circulate outside of cells and are remarkably stable.

"We were surprised to discover that there are microRNAs in plasma and serum that are not associated with cells and that are not being degraded by enzymes in the blood that would degrade regular RNA," Tewari said. It isn't fully known how the microRNAs are protected from degradation or how they get into the blood.

This in turn led the researchers into a new direction of determining whether cancer-associated microRNAs could be found. Earlier studies in model organisms such as worms and flies showed that some microRNAs have specific expression in certain kinds of cells and not anywhere else.

The paper details the step-by-step approach that led to discovering microRNAs in plasma and serum components of blood, that microRNAs remain stable even after incubation at room temperature for 24 hours and after eight freeze/thaw cycles, and finally that tumor-derived microRNAs enter the circulation at levels sufficient to be measured as biomarkers for cancer.

"The results presented here establish the foundation and rationale to motivate future global investigations of microRNAs as circulating cancer biomarkers for a variety of common cancers," the authors wrote.

The availability of existing, powerful tools to characterize and measure microRNAs, such as polymerase-chain reaction technology for DNA amplification, "suggests that the discovery-validation pipeline for microRNA biomarkers will be more efficient than traditional proteomic biomarker discovery-validation pipelines, which typically encounter bottlenecks at the point of antibody and quantitative assay development for validation of biomarker candidates," the authors wrote.

###

In addition to those from the Hutchinson Center, scientists from the Institute for Systems Biology in Seattle, the Department of Urology at the University of Washington School of Medicine and the Department of Veterans Affairs Puget Sound Health Care System contributed to the research. The National Cancer Institute, the Pacific Ovarian Cancer Research Consortium Specialized Program of Research Excellence, the Pacific Northwest Prostate Specialized Program of Research Excellence, the Core Center of Excellence in Hematology and the Paul Allen Foundation for Medical Research funded the research.

Note to editors/reporters: Contact Dean Forbes at Fred Hutchinson Cancer Research Center to schedule interviews with Dr. Tewari and to obtain an embargoed proof copy of the paper "Circulating microRNAs as stable blood-based markers for cancer detection."

At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit fhcrc.org.

Journal of Experimental Medicine Researchers tap into a new and potentially better source of platelets for transfusion

Clot-forming blood cells, or platelets, can drop to dangerously low levels in diseases such as anemia and in patients undergoing chemotherapy. To replace these critical cells, doctors filter platelets from donated blood, but this approach can increase the risk of transmitting blood infections and cause other side effects in patients who need frequent transfusions.

To get around these problems, scientists have been trying to generate platelets from embryonic stem cell lines. But stem cells also give rise to other types of cells, which tend to quickly outnumber the platelets. The Japanese group solved this problem with a simple refinement—they started with a stem cell population that was already committed to becoming platelets.

Another problem with making platelets from stem cells is that the resulting platelets often fail to form clots properly. This defect can be caused by the presence of enzymes that shear adhesive proteins from the cells' surface, preventing them from sticking to one another or to blood vessel walls. The researchers found these enzymes in their laboratory cultures and showed that blocking them restored platelet function when the cells were infused into injured mice. The scientists now plan to test whether the same approach will work in humans.

###

University of North Carolina School of Medicine Study provides clues to preventing and treating cancer spread

Isn't it odd that cancer cells from one organ, such as the skin, can travel and take root in a totally different organ, like the lung?

What's more, why is it that certain cancers prefer to spread, or metastasize, to certain places? Prostate cancer usually moves to bone; colon cancer, to the liver.

To answer these questions, Dr. Hendrik van Deventer, assistant professor of medicine at the University of North Carolina at Chapel Hill and a member of the UNC Lineberger Comprehensive Cancer Center, turned to a century-old idea of cancer spread: English surgeon Stephen Paget's "seed and soil."

The idea is that the spread of cancer isn't just about the tumor itself (the seed), but also the environment where it grows (the soil). Other scientists have shown that cells from bone marrow can migrate and change the environment so that it is receptive to incoming cancer cells. These cells do so by forming small neighborhoods or niches within distant organs. Thus, biologists refer to these areas as "premetastic niches."

Van Deventer and his colleagues wanted to know what mysterious non-tumor cell could change a normal organ so cancer cells would invade. If scientists could discover the identity of that normal cell, maybe they could devise treatments to stop metastases.

In a study published in the July issue of The American Journal of Pathology, van Deventer showed for the first time that that cell could be a fibrocyte – cells that travel around the body, rushing to the site of an injury to aid in healing when needed. The study also suggests ways to develop treatments to prevent metastases using already available medications.

"This study shows it's possible for fibrocytes to form the premetastatic niche. But it stops short of proving they positively are the cells," van Deventer said.

The UNC researcher's work with fibrocytes began when he wanted to figure out why "knockout mice" that are missing the cell receptor CCR5 get fewer cancer metastases than normal mice. CCR5 helps control the migration of cells through the body. He injected these knockout mice with all types of cells from normal mice, to try to make the mice form more metastases of melanoma (skin cancer).

The only cells that did it were those that appeared to be fibrocytes.

When van Deventer injected the mice with just 60,000 of these cells, the rate of metastases nearly doubled. "That's a big effect for a relatively small number of cells," he said.

Though cancer researchers don't usually study fibrocytes, it makes sense to van Deventer that fibrocytes could form the premetastatic niche. In healthy humans, fibrocytes travel through the bloodstream to areas of injury. Once there, they produce changes that are good for wounds. Unfortunately, these same changes can help cancers grow. It is not yet clear if fibrocytes are causing these problems in cancer patients. However, "there is some clinical data that suggests that these cells are increased in patients with metastatic cancer," he said.

The experiment also showed that injection of these cells induced MMP9, an enzyme that is known to promote cancer. The researchers considered this good news, since drugs are available that block MMP enzymes and have proven beneficial in treating cancer.

Still, many basic questions remain to be answered. How do cancers promote the formation of the premetastatic niche? Do they change the behavior of these circulating cells or simply increase their number? Are some patients at higher risk for metastasis because their environment changes their fibrocytes? Is some of the benefit of our cancer treatments lost because of inadvertent changes to these cells?

"These are daunting questions, but ones that would have pleased Dr. Paget," van Deventer said. "This paper gives us a place to start looking for the answers."

###

Other authors of the study, all from UNC Lineberger, are research specialist Qing Ping Wu; professional fellow Daniel T. Bergstralh, Ph.D.; research associate Beckley K. Davis, Ph.D.; postdoctoral fellow Brian P. O'Connor, Ph.D., distinguished professor of microbiology and immunology Jenny P. Y. Ting, Ph.D.; and distinguished associate professor of medicine and of microbiology and immunology, Jonathan S. Serody, M.D., Ph.D.

The study was funded by the National Cancer Institute, part of the National Institutes of Health.

Van Deventer can be reached at (919) 966-3835 or hvand@med.unc.edu.

School of Medicine contact: Leslie Lang, (919) 966-9366, llang@med.unc.edu
Lineberger Center contact: Dianne Shaw, (919) 966-7834, dgs@med.unc.edu
News Services contact: Patric Lane, (919) 962-8596, patric_lane@unc.edu

HealthGrades study Find Bariatric patients have 65% lower chance of complications at top hospitals

Better-performing hospitals have much higher volumes

Golden, CO (July, 29 2008) – Bariatric surgery patients treated at highly rated hospitals have, on average, a 65 percent lower chance of experiencing serious complications compared to patients who undergo surgery at poorly rated hospitals according to a study released today by HealthGrades, the nations leading independent healthcare ratings organization. As part of the study, the quality ratings of hospitals performing bariatric surgery in 17 states became available today at www.healthgrades.com.

HealthGrades' third annual Bariatric Surgery Trends in American Hospitals study, which evaluated bariatric surgical outcomes at every hospital that performed them in 17 states, also found that the complication rate for these surgeries continues to rise, increasing six percent from 2004 to 2006. One possible reason: lower volume facilities have higher complication rates.

Bariatric surgery is a general term describing several types of weight loss procedures. HealthGrades study analyzed the outcomes of the most common, including traditional open surgical gastric bypass procedures as well as newer, less invasive procedures such as "lap-banding" and laparoscopic gastric bypass.

Complications associated with gastric bypass surgery accounted for the highest rise in complications, increasing 17 percent. Comparatively, complications from less invasive laparoscopic surgery increased by just more than one percent. Complications associated with bariatric surgery include heart attack, kidney failure, stroke and post-surgical infections.

The HealthGrades study found a significant shift toward laparoscopic bariatric procedures. From 2004 through 2006, open gastric bypass procedures declined by 81.82 percent while during the same time period laparoscopic procedures increased 418.86 percent.

Meanwhile, the total volume of bariatric surgical procedures in the U.S. continues to grow rapidly. The American Society for Bariatric Surgery estimates that such surgeries have increased 1,431 percent in the last decade to more than 250,000 annually.

"The tremendous variation we are seeing in quality among bariatric surgery providers underscores the importance of readily available quality data to help consumers make a truly informed decision about where to seek care," said Rick May, MD, a senior physician advisor with HealthGrades and an author of the study.

Additionally, the third annual HealthGrades Bariatric Surgery Trends in American Hospitals study found that:

• A typical patient having a bariatric surgical procedure at a five-star rated hospital in one of the 17 states studied has on average, a 65 percent lower chance of experiencing one or more inhospital complications than at a one-star rated hospital and a 41 percent lower chance than at a three-star rated hospital during 2004- 2006.
• Five-star (top rated) hospitals performed almost twice the volume of procedures compared to 1-star and 3-star facilities–an average of 526 procedures from 2004 through 2006 compared with 266 and 283 respectively.
• Higher volume was associated with fewer risk-adjusted complications. Facilities with an annual case volume of 125 procedures had the lowest risk-adjusted complications. Facilities performing less than 25 cases per year had the highest rate of risk-adjusted complications.
• If all patients had received their bariatric surgery procedure at 5-star hospitals (from 2004 through 2006), 5,125 inhospital complications could have been potentially avoided in the 17 states studied.

HealthGrades Bariatric Surgery Ratings

HealthGrades' quality ratings for bariatric surgery at individual hospitals in 17 states were posted today to www.healthgrades.com as a free resource for consumers. Each hospital receives a star rating based on their patient outcomes for bariatric surgery. Hospitals with above-average outcomes receive a five-star rating. Hospitals with average outcomes receive a three-star rating, and hospitals with outcomes that are below average receive a one-star rating.

The study included a total of 154,451 bariatric inpatient surgery procedures performed in 680 hospitals in 17 states from 2004 through 2006. The majority of procedures were performed in four states: New York, Texas, Pennsylvania, and California.

• 93 hospitals stand out as "best" performers (5-star rated)
• 263 hospitals were rated as "as expected" performers (3-star rated)
• 99 hospitals were rated as "poor" performers (1-star rated)

Individuals contemplating bariatric surgery will find both quality and cost information at www.healthgrades.com. In addition to the free hospital-quality ratings, Web site visitors can also research surgeons who perform bariatric surgery as well as medical-cost reports that detail all of the costs, including out-of-pocket expenses, for the procedure.

Methodology

For this study, HealthGrades analyzed 154,451 bariatric procedures performed in the years 2004, 2005 and 2006. The states included in the study are: Arizona, California, Florida, Iowa, Maine, Maryland, Massachusetts, Nevada, New Jersey, New York, Oregon, Pennsylvania, Texas, Utah, Virginia, Washington, Wisconsin

To make accurate and valid comparisons of clinical outcomes at different hospitals with different patient characteristics, HealthGrades risk adjusted the data using multivariate logistic regression to account for age, gender and underlying medical conditions that could increase the patient's risk of mortality or complication. The full study and individual hospital ratings for bariatric surgery and other procedures can be found at www.healthgrades.com.

###

About HealthGrades

Health Grades, Inc. (Nasdaq: HGRD) is the leading healthcare ratings organization, providing ratings and profiles of hospitals, nursing homes and physicians. Millions of consumers and many of the nation's largest employers, health plans and hospitals rely on HealthGrades' independent ratings, advisory services and decision-support resources to make healthcare decisions based on the quality and cost of care. More information on the company can be found at http://www.healthgrades.com.

http://www.eurekalert.org/images/release_graphics/pdf/HealthGradesBaratricSurgeryTrendsStudy2008_Embargoed.pdf

UT Southwestern Medical Center digestive specialists freeze out esophagus cancer with new therapy

Dr. Jayaprakash Sreenarasimhaiah, and other gastroenterologists at UT Southwestern are using a novel procedure to freeze damaged cells in the esophagus, preventing them from turning cancerous.

UT Southwestern Medical Center gastroenterologists are using a new method to freeze damaged cells in the esophagus, preventing them from turning cancerous.

The Food and Drug Administration-approved cryoablation therapy helps Barrett's esophagus patients with dysplasia, a condition in which normal cells are transformed into potentially cancerous ones.

"Due to damage from chronic stomach acid, they are people who have a higher risk of developing esophagus cancer," said Dr. Jayaprakash Sreenarasimhaiah, assistant professor of internal medicine in the division of digestive and liver disease at UT Southwestern. "The goal of this therapy is to literally freeze the damage in its tracks and stop it before it turns to cancer."

Gastroenterologists, using a special catheter, spray liquid nitrogen on the damaged tissue to freeze the superficial lining of the esophagus, the long tube that carries food from the throat to the stomach. The treated tissue eventually falls off, allowing normal cells to grow and replace the damaged cells in about six to eight weeks.

"Repeated treatments can actually help get rid of Barrett's esophagus with dysplasia and prevent the progression to cancer," said Dr. Sreenarasimhaiah, a gastroenterologist who specializes in endoscopic technology.

The minimally invasive cryoablation therapy has recently been approved by the FDA for treating Barrett's, but it requires special training and equipment available in only a handful of centers in Texas and a few dozen nationally.

Barrett's esophagus can result from ongoing heartburn, which allows a constant splashing of acid from the stomach into the esophagus. Untreated, it can become Barrett's with dysplasia, in which cells start to transform.

Typical treatment includes endoscopic mucosal resection (EMR), in which the damaged lining is scraped away, a procedure that takes hours and can have side effects such as bleeding or narrowing of the esophagus. The most aggressive approach includes surgery to remove damaged portions of the tube.

Some patients, however, are too sick or elderly to be candidates for surgery. Others simply want another option.

"This is a disease we see in a lot of older patients with other illnesses, so the decision to send them to surgery requires careful consideration," Dr. Sreenarasimhaiah said. "Cryoablation therapy is particularly attractive for older patients who may have complications or other medical issues – such as accompanying heart or lung diseases – that make traditional surgeries for Barrett's with dysplasia too risky."

Cryoablation therapy takes about 30 to 40 minutes and requires sedation. As with an endoscopy, a tube down the patient's throat is used to insert a tiny camera and instruments. No incisions are required.

Early results from studies show the therapy – similar to that used by dermatologists to freeze off warts – works well inside the esophagus, though further study is needed, Dr. Sreenarasimhaiah said.

"Patients may feel a little pain in the first couple of days, like a heartburn-type pain, but that starts to improve after a few days and after that they usually don't feel anything," he said. "They can eat immediately after they wake. They are not on a special diet, but they do continue their anti-reflux medications."

###

Visit http://www.utsouthwestern.org/digestive to learn more about UT Southwestern's clinical services in digestive disorders.

This news release is available on our World Wide Web home page at http://www.utsouthwestern.edu/home/news/index.html

To automatically receive news releases from UT Southwestern via e-mail, subscribe at http://www.utsouthwestern.edu/receivenews

Dr. Jayaprakash Sreenarasimhaiah -- http://www.utsouthwestern.edu/findfac/professional/0,2356,55659,00.html

Elsevier Health Sciences New study finds smoking predicts increased stroke risk for your spouse

Risk declines if spouse stops smoking

San Diego, July 29, 2008 – Although Second Hand Smoke (SHS) is widely accepted as a risk factor for coronary heart disease, there have been few studies investigating the association of SHS and stroke risk. In a new study, published in the September 2008 issue of the American Journal of Preventive Medicine, researchers report on evidence of increased risk of stroke for spouses of smokers.

For those who never smoked, being married to a current smoker was associated with a 42% increase in risk of stroke compared to being married to a never-smoker. For former smokers, being married to a current smoker was associated with a 72% increase in risk compared to being married to a never-smoker. Being married to a former smoker was not associated with any increase in risk compared to being married to a never-smoker. This suggests that although stroke risk is elevated if your spouse smokes, that risk is eliminated if your spouse stops smoking. For example, never-smokers married to former smokers had nearly the same stroke risk as never-smokers married to never-smokers. Current smokers had significantly elevated stroke rates compared to never-smokers, and spousal smoking status did not affect this risk among current smokers.

The data were drawn from the Health and Retirement Study (HRS), a National Institute on Aging sponsored longitudinal survey of U.S. adults nationwide aged ≥50 years and their spouses. Enrollments occurred in 1992, 1993, 1998 and 2004 and final analyses included 16,225 respondents. Spousal smoking status was assessed at the time of enrollment and participants were followed an average of 9.1 years after enrollment for the incidence of stroke. All models were adjusted for age; race; Hispanic ethnicity; Southern birthstate; parental education; paternal occupation class; years of education; baseline income; baseline wealth; obesity; overweight; alcohol use; and diagnosed hypertension, diabetes or heart disease.

Recent National Health and Nutrition Examination Survey (NHANES) findings for women also suggested that a husband's smoking increased the wife's risk of stroke, but in NHANES this applied only among smoking women and not among nonsmoking women. The current study found that never-smoking women married to currently smoking husbands had an increased stroke risk, compared to never-smoking women married to never-smoking husbands. This apparent discrepancy may arise from sampling differences, where NHANES participants are younger and stroke rates are lower than in HRS. Because nonsmokers have lower overall stroke risks, spousal smoking may increase stroke risk for current smokers at younger ages but emerge as a detectable risk factor for nonsmokers only at older ages.

Writing in the article, M. Maria Glymour, ScD, Harvard School of Public Health, states, "These findings indicate that spousal smoking increases stroke risk among nonsmokers and former smokers. The health benefits of quitting smoking likely extend beyond individual smokers to affect their spouses, potentially multiplying the benefits of smoking cessation."

###

The article is "Spousal Smoking and Incidence of First Stroke: The Health and Retirement Study" by M. Maria Glymour, ScD; Triveni DeFries; Ichiro Kawachi, MD, PhD; and Mauricio Avendano, PhD. The authors are grateful to the National Institute on Aging and the Robert Wood Johnson Foundation Health and Society Scholars Program for financial support of this research. It appears in the American Journal of Preventive Medicine, Volume 35 Issue 3 (September 2008) published by Elsevier.