This is a HUGE article about the Avian Flu, and its possible implications for the United States. Read it here, or go to the Big Medicine website to see the article with the USA maps showing effects of a plague running rampage.

How bad WILL it get?

Avian flu modeled on supercomputer, explores vaccine and isolation options for thwarting an epidemic
[Apr 4 Los Alamos NM USA]–Using supercomputers to respond to a potential national health emergency, scientists have developed a simulation model that makes stark predictions about the possible future course of an avian influenza pandemic, given today’s environment of world-wide connectivity.

The research, by a team of scientists from Los Alamos National Laboratory in New Mexico, the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle, is presented in the Proceedings of the National Academy of Science online the week of April 3-7, and in the print issue of April 11.

The large-scale, stochastic simulation model examines the nationwide spread of a pandemic influenza virus strain, such as an evolved avian H5N1 virus, should it become transmissible human-to-human. The simulation rolls out a city- and census-tract-level picture of the spread of infection through a synthetic population of 281 million people over the course of 180 days, and examines the impact of interventions, from antiviral therapy to school closures and travel restrictions, as the vaccine industry struggles to catch up with the evolving virus.

“Based on the present work . . . we believe that a large stockpile of avian influenza-based vaccine containing potential pandemic influenza antigens, coupled with the capacity to rapidly make a better-matched vaccine based on human strains, would be the best strategy to mitigate pandemic influenza,” say the authors, Timothy Germann, Kai Kadau, Ira Longini and Catherine Macken.

Longini is a biostatistician with the Fred Hutchinson Cancer Research Center and the University of Washington, while the rest of the team is at Los Alamos. Their collaboration is supported by grants from the Department of Homeland Security and the National Institute of General Medical Sciences MIDAS (Models of Infectious Disease Agent Study) program.

“It’s probably not going to be practical to contain a potential pandemic by merely trying to limit contact between people (such as by travel restrictions, quarantine or even closing schools), but we find that these measures are useful in buying time to produce and distribute sufficient quantities of vaccine and antiviral drugs,” said Germann of Los Alamos’ Applied Physics Division.

“Based on our results, combinations of mitigation strategies such as stockpiling vaccines or antiviral agents, along with social distancing measures could be particularly effective in slowing pandemic flu spread in the U.S.,” added Longini.

The results show that advance preparation of a modestly effective vaccine in large quantities appears to be preferable to waiting for the development of a well-matched vaccine that may not become available until a pandemic has already reached the United States.

“Because it is currently impossible to predict which of the diverging strains of avian H5N1 influenza virus is most likely to adapt to human transmission, studies of broadly cross-reactive avian-influenza based vaccines with even modest immunogenicity in humans are important,” said Macken, an influenza researcher in the Los Alamos Theoretical Division. Ideally, both vaccine strategies would be done in parallel: Stockpile a modestly effective vaccine to use while the better-matched one is being developed, the authors suggest.

How it all computes

The computer simulation models a synthetic population that matches U.S. census demographics and worker mobility data by randomly assigning the simulated individuals to households, workplaces, schools, and the like. Department of Transportation travel data is used to model long-distance trips during the course of the simulation, realistically capturing the spread of the pandemic virus by airplane and other passenger travel across the United States.

“In the highly mobile U.S. population, travel restrictions alone will not be enough to stop the spread; a mixture of many mitigation strategies is more likely to be effective than a few strictly enforced ones,” said Kadau, also of Los Alamos’ Theoretical Division.

The model of disease transmission involves probabilities that any two people in a community will meet on any given day in any one of a number of settings, such as home or workplace. Thus, simulated disease transmission is more likely for two people in the same household and less likely for two people who have less in common. “So we are only computing the probability of any person becoming infected on any given day, and a roll of the dice is needed to decide whether they are infected or not,” said Germann.

Other elements of randomness modify the simulated disease course. A significant fraction of infected people (33 percent in the present model) never develop clinical symptoms, although they are themselves infectious. In addition, the durations of the incubation and infectious periods can vary and are randomly chosen from distribution functions for each individual, involving more throws of the virtual dice.

“Computer models serve as virtual laboratories where researchers can study how infectious diseases might spread and what intervention strategies may lessen the impact of a real outbreak,” said Jeremy M. Berg, director of the National Institute of General Medical Sciences. “This new work exemplifies the power of such models and could aid policymakers and health officials as they plan for a possible future pandemic.”

The pandemic simulation model has been implemented in the Laboratory’s celebrated Scalable Parallel Short-range Molecular dynamics (SPaSM) large-scale simulation platform developed for the nuclear weapons program. It runs on the Los Alamos supercomputer known as Pink, a 1,024-node (2,048 processor) LinuxBIOS/BProc “Science Appliance” running Clustermatic 3, the largest single-system image Linux cluster in the world. Pink’s nodes have dual 2.4 GHz Intel Xeon processors (Pentium 4) with 2 gigabytes of memory per node. The purchase of the Science Appliance was funded by the National Nuclear Security Administration’s Advanced Simulation and Computing program.Pink is currently a system software research platform, a science appliance cluster concept invented at Los Alamos in the Computer and Computational Science Division. Los Alamos has four science appliance clusters in use at this time for a variety of projects across the full range of Laboratory mission areas.

Simulation of a pandemic flu outbreak in the continental United States, initially introduced by the arrival of 10 infected individuals in Los Angeles. The spatiotemporal dynamics of the prevalence (number of symptomatic cases at any point in time), is shown on a logarithmic color scale, from 1 or fewer (blue) to 100 or more (red) cases per 1,000 persons.

Without vaccination, antiviral drugs, or other mitigation strategies, the entire nation becomes infected within a few months. Depending on the reproductive number R0, effective intervention strategies including vaccination and targeted antiviral prophylaxis can be successful without resorting to economically damaging measures like school closure, quarantine, and work or travel restrictions.

This large-scale agent-based simulation involves 280 million people, and uses demographic and worker flow data at the Census tract level, as well as long-range travel statistics, to describe the geographic movement of people. In this simulation, long-range travel is assumed to occur at a lower-than-normal rate (10%) due to travel advisories, but with no other mitigation strategies the pandemic quickly spreads nationwide, peaking about 90 days after the initial introduction.

[Timothy C. Germann, Kai Kadau, Catherine A. Macken (Los Alamos National Laboratory); Ira M. Longini Jr. (Emory University)]

If pandemic flu were to emerge in the United States, what interventions might slow its spread and minimize the impact? With support from the National Institutes of Health (NIH), researchers from the Fred Hutchinson Cancer Research Center in Seattle, Wash., and the Los Alamos National Laboratory have used computer models to suggest possible answers. The findings appear in the April 11, 2006, issue of the Proceedings of the National Academy of Sciences and will be available in the online edition the week of April 3.

By developing a model that represents the U.S. population and tests different properties of a potential pandemic flu virus, the researchers evaluated the effectiveness of different intervention strategies. They found that, depending on the contagiousness of the virus, a variety of approaches could reduce the number of cases to less than that of an annual flu season.

“Preparing for a potential pandemic is tremendously challenging, given the potential scope and the large number of unknowns,” said NIH Director Elias A. Zerhouni, M.D. “The best approach is to use all of the tools available to us, including computer modeling. By predicting the impact of intervention strategies, these models can help health officials and policymakers plan for a real pandemic.”

The recent modeling work is part of an ongoing research program called the Models of Infectious Disease Agent Study (MIDAS), supported by NIH’s National Institute of General Medical Sciences (NIGMS). Researchers in the network develop computer models to better understand the spread of infectious diseases, whether they occur naturally or deliberately. With growing concerns that the H5N1 strain of the avian flu virus, initially found in birds throughout Southeast Asia, could eventually be transmitted easily between people, the research network has been modeling pandemic flu in different parts of the world.

“The MIDAS researchers previously developed models of a potential pandemic flu outbreak in Thailand and surrounding areas that showed containment at the source is feasible,” explained Jeremy M. Berg, Ph.D., NIGMS director. “But we need to consider the possibility that if the outbreak isn’t contained, it could quickly spread globally.”

Using data from the 2000 U.S. Census and the U.S. Department of Transportation, the researchers developed a model that represents the demographics and travel patterns of 281 million people living in the United States. They also incorporated information about the potential virus based on previous flu pandemics, including different assumptions about its possible contagiousness (but not its potential effects on mortality). The researchers then introduced a small number of hypothetical travelers, who are infected but not yet symptomatic, arriving daily at 14 major U.S. international airports. With these assumptions in place, the scientists simulated a virtual outbreak on high-performance computers at the Los Alamos National Laboratory.

“The goal for the U.S. modeling project was to determine how to slow spread long enough so that a well-matched vaccine could be developed and distributed,” said the research team’s leader, Ira M. Longini, Jr., Ph.D., a biostatistician at the Fred Hutchinson Cancer Research Center and the University of Washington School of Public Health and Community Medicine. An additional guideline was to reduce the number of overall cases to or below 10 percent of the population, the average percentage reported during an annual flu season.

To identify such measures, the researchers tested different interventions: distributing antiviral treatments to infected individuals and others near them to reduce symptoms and susceptibility; vaccinating people, possibly children first, with either one or two shots of a vaccine not well matched to the strain that may emerge; social distancing, such as restricting travel and quarantining households; and closing schools.

The results showed that with no intervention a pandemic flu with low contagiousness could peak after 117 days and infect about 33 percent of the U.S. population. A highly contagious virus could peak after 64 days and infect about 54 percent of people.

The researchers then compared what might happen in scenarios involving the use of different interventions. When the simulated virus was less contagious, the three most effective single measures included distributing several million courses of antiviral treatment to targeted groups seven days after a pandemic alert, school closures, and vaccinating 10 million people per week with one dose of a poorly matched vaccine. The results also showed that vaccinating school children first is more effective than random vaccination when the vaccine supply is limited. Regardless of contagiousness, social distancing measures alone had little effect.

But when the virus was highly contagious, all single intervention strategies left nearly half the population infected. In this instance, the only measures that reduced the number of cases to below the annual flu rate involved a combination of at least three different interventions, including a minimum of 182 million courses of antiviral treatment.

While the results are specific to the United States, the researchers said the general findings can apply to other developed countries and could aid the drafting of preparedness plans both here and abroad. Because computer models can’t capture all the complexities of real communities and outbreaks, MIDAS scientists will continue to refine their models and test different scenarios as new information becomes available.

Other members of the Longini team who contributed to the recent findings include Los Alamos National Laboratory scientists Timothy C. Germann, Ph.D.; Kai Kadau, Ph.D.; and Catherine A. Macken, Ph.D.

Fears of death prompt similar response from students [Apr 5 Colorado Springs CO USA]–In both American and Iranian students, thoughts of death increase support for extreme actions ranging from suicide bombings to military raids where civilians are likely victims, according to the first study of the role fear plays in attitudes toward the conflict in the Middle East.

“Mortality Salience, Martyrdom, and Military Might: The Axis of Evil Versus the Great Satan” appears this month in the academic journal, Personality and Social Psychology Bulletin. The article was written by Tom Pyszczynski, professor, Psychology, University of Colorado at Colorado Springs, Abdolhossein Abdollahi, professor, Psychology, Islamic Azad University, Zarand, Iran, Sheldon Solomon, professor, Psychology, Skidmore College, Saratoga Springs, N.Y., and Jeff Greenberg, professor, Psychology, University of Arizona, Tuscon. The publication citation is “Personality and Social Psychology Bulletin” 2006 32: 525-537.

The work is believed to be the first analysis of Iranian student attitudes regarding suicide bombings and similar martyrdom attacks on Americans. The researchers also analyzed the attitudes of young Americans regarding extreme military interventions in the Middle East. The researchers found that although both groups showed little support for such extreme tactics under neutral control conditions, support for such tactics increased among students in both countries who were first asked a pair of simple questions that reminded them of the inevitability of death.

In Iran, 40 undergraduate students at two universities heard statements they were told were written by fellow students. One statement supported and one opposed martyrdom attacks on U.S. targets. Students who were asked questions such as “jot down what you think will happen to you as you physically die” showed a significant increase in favorable views toward the pro-martyrdom essay and increased willingness to consider joining such a cause.

“Thoughts of death led young people in the Middle East who ordinarily preferred a person who took a pacifist stance to switch their allegiance to a person who advocated suicide bombings,” the authors said. “These findings provide the first experimental evidence documenting the psychological determinants of the appeal of martyrdom.”

To gauge the attitudes of American college students, 127 students at Rutgers University, New Brunswick, N.J., were given a booklet that included questions designed to get them to think about their own death, the September 11, 2001 terrorist attacks or dental pain (an unpleasant anxiety-producing topic unrelated to death).

The students were then asked to respond to questions gauging their support for extreme military actions ranging from the use of nuclear and chemical weapons to pre-emptive strikes against countries that may pose a threat to the United States. Support for extreme measures increased when thoughts of either death or 9/11 were introduced prior to the survey, and this increase was most prominent among political conservatives.

The fact that thoughts of 9/11 and death produced identical results suggests that at least part of the reason that reminders of this tragic event increase support for aggressive military policies is that they remind people of their own mortality. Consistent with this idea, previous studies by this group have shown that presenting the numbers “911” or letters “WTC” so rapidly that people are not aware that they have seen them brings death related thoughts closer to consciousness.

The scientific findings demonstrate that thoughts of death increase people’s readiness to support extreme violent solutions to global conflicts. These findings are consistent with the authors’ Terror Management Theory, which proposes one reason people cling to cultural beliefs and values, and react negatively toward those who are different, is rooted in the protection from core human fears of death and vulnerability from which our cultural worldviews protect us. The same factors that increased Iranians’ support for martyrdom attacks against Americans increased Americans’ support for extreme military interventions in the Middle East, both of which could cause the loss of thousands of innocent lives, the authors concluded.

“Despite their differences, Americans and Iranians have something in common – thoughts of death increase the willingness of people from both nations to inflict harm on citizens of the other nation,” the authors wrote. “The same psychological inclinations that make them want to kill us make us want to kill them – regardless of which specific group is referred to by the words ‘us’ and ‘them.’

New approach to treating hepatitis C virus discussed [Apr 5 Stanford CA USA]–Last year Peter Sarnow, PhD, professor of microbiology and immunology at the Stanford University School of Medicine, identified a previously unknown mechanism that the hepatitis C virus uses to replicate, yielding a promising new approach to combating the disease-causing virus.

On April 5 at the Experimental Biology meeting in San Francisco, Sarnow will discuss recent developments in this work - including his partnership with two pharmaceutical companies that seeks to use the new understanding of the virus to develop treatments.

According to the World Health Organization, hepatitis C virus infects 170 million people worldwide. About 70 percent of those infected develop liver disease, including cirrhosis and liver cancer. In the United States, it is the most common blood-borne viral infection, killing more than 10,000 people each year. Currently available treatments are expensive and do not work in about half of the cases.

“Normally with an RNA virus like hepatitis C, resistance to antivirals very quickly emerges, so the drug is not effective any more,” said Sarnow, who has been studying the virus for years, sorting out how the viral RNA amplifies in cultured liver cells.

In the normal sequence of events, genetic information is stored in DNA and then is copied into RNA, which serves as a template to create proteins. With RNA viruses such as hepatitis C, the genetic information is stored in RNA instead of DNA.

RNA is genetically more unstable than DNA, resulting in the accumulation of many mutations. These mutations allow the virus to outwit the immune system and develop resistance to antiviral medication.

Sarnow’s group has shown that a small fragment of RNA found in the liver, known as a microRNA, is necessary for hepatitis C to grow and reproduce. Their work, published in September 2005 in the journal Science, is the first to link the presence of a specific microRNA with a major infectious disease.

When the researchers inactivated the microRNA, called miR-122, the amount of hepatitis C virus RNA was reduced by approximately 80 percent. “The cool thing is that here, an antiviral is encoded by a host function and not by the virus - so it cannot change,” said Sarnow. In other words, because the virus needs miR-122 to replicate, there is no way the virus could develop resistance to a strategy that inactivates miR-122.

A couple of years ago, Sarnow learned that other scientists had discovered miR-122, found only in the liver. He knew that there could be up to 65,000 copies of miR-122 per cell in the liver. “And we know that the virus can persist in the liver for as long as 30 years, so we made the hypothesis that the virus might interact with miR-122 in some way,” he said. “It turns out that yes, the virus grabs it for its own good.”

“This is a completely different way for microRNA to interact with its target from what is known and it brings up the idea that other microRNAs might work like that,” said Catherine Jopling, PhD, a postdoctoral researcher in Sarnow’s laboratory who spearheaded the work. “But nobody’s been looking for that.”

The researchers think that their findings may have therapeutic potential for a new antiviral target that does not attack the virus directly.

“If you can lower the amount of the microRNA in the liver without affecting liver function maybe this will help lower the viral load,” said Sarnow. Stanford has entered into a licensing agreement with Alnylam Pharmaceuticals and Isis Pharmaceuticals to explore the possibility of using miR-122 as a novel therapeutic against hepatitis C.

The big question is what this microRNA normally does in the liver. It is possible that lowering microRNA levels in the liver might produce an undesirable outcome, such as cancer, said Sarnow. However, recent promising reports from researchers at Rockefeller University, Alnylam and Isis have demonstrated that miR-122 can be inactivated in mouse liver for some time without impairing liver function.

Nurses and midwives come under microscope in unique e-cohort study [Apr 5 Brisbane QLD Australia]–University of Queensland (UQ) researchers are undertaking the largest and only longitudinal study of nurses and midwives ever attempted in the world.

Associate Professor Cathy Turner, Coordinator of Research & Higher Degrees at UQ’s School of Nursing, is leading the Nurses and Midwives e-cohort project, which will look into the work and health of those involved in these crucial health professions.

The study was launched by the Queensland Minister for Health, Stephen Robertson, today in Brisbane.

Despite being the largest single health professional group in Australia, Dr Turner said very little detailed research had been done on workforce trends over time within the nursing and midwifery professions and there are no previous longitudinal studies.

“There are about 270,000 nurses and midwives in Australia and yet we have little data about the factors affecting their work and health but have recently had to deal with severe workforce shortages,” Dr Turner said. “This study will provide important information to inform education and workforce policy for the nursing and midwifery professions and in addition, will have the capacity to examine a range of population health outcomes.

Dr Turner said the study also hoped to look at the issues associated with the short supply of nurses, not only in Australia but also in New Zealand where similar workforce problems existed.

“The median age is 42 and we already have a critical shortage of nurses at the moment and it is only going to get worse with our ageing nursing and midwifery workforce, retention problems and our ageing population.”

Dr Turner said people studying undergraduate nursing programs would also be targeted in the study to try and quantify the attrition from those studying nursing at university and the retention of new graduates into the profession.

The Australian Research Council-funded study will invite all nurses and midwives in Australia and all nurses in New Zealand to take part during a 12-month recruitment process.

The Macquarie Bank Foundation is funding a post-doctoral research fellow to work on the study and Virgin Blue is sponsoring the study with the offer of free holiday flights to participants in the hope to entice a high recruitment rate.

Dr Turner said the project was also unique in that it would be one of the first to employ electronic research methods on such a large scale.

“Historically, studies of this nature are expensive as they are conducted in traditional paper-based mode and the studies are therefore confined to one country,” Dr Turner said. “Developing and employing e-research techniques will significantly reduce the costs and enable recruitment of multiple international cohorts.”

Dr Turner has also received a 2006 Fulbright Senior Scholar award to enable her to spend several months with researchers who have been conducting the Harvard Nurses’ Health Study, about to celebrate its 30th year, to learn about the challenges of longitudinal studies.

Nurses and midwives willing to take part in the research can visit the study website at www.e-cohort.net and register to be part of the study.

Parents need better education to reduce drug overdoses in feverish children [Apr 5 Brisbane QLD Australia]–More than 50 per cent of feverish children are given incorrect doses of medicine by parents and overdoses have almost trebled in the last two decades, according to a research review in the latest Journal of Advanced Nursing.

Health professionals are also concerned about the increasing number of parents who give their children alternate doses of paracetamol and ibuprofen without leaving sufficient gaps between them.

“Our review found that overdosing with ibuprofen is now a particular concern, both in terms of dosage and frequency” says nurse researcher Anne Walsh from Queensland University of Technology in Australia.

“We also discovered that some parents are giving their children one fever-reducing drug and then trying another type within a few hours if the first one doesn’t have the desired result.”

The Australian research team reviewed more than 70 studies published worldwide since 1980 to see how parental attitudes and practices had changed when it came to treating common childhood fevers.

They found that:

Latest figures show that the number of parents providing their children with overdoses has risen from 12 per cent in 1987 to 33 per cent. Meanwhile, correct doses have risen from a third to between 43 and 49 per cent.

Many parents administer fever-reducing drugs in doses that are too low, too high or too frequent.

Underdosing is more common in younger and low-weight children.

Up to 27 per cent of parents alternate fever reducing drugs.

The researchers also discovered that parents consistently treat childhood fevers based on inaccurate temperature readings and suggest that they would be better off focussing on their child’s general well-being rather than just how hot they are.

“Parents knowledge about normal body temperature and what constitutes a feverish temperature is poor” adds Anne Walsh, from the University’s Institute of Health and Biomedical Innovation. “They classify mild fever as high and actively reduce temperatures, sometime normal temperatures, with fever-reducing drugs such as paracetamol and ibuprofen.

“Overdoses have sharply increased over the last 20 years and recent studies have suggested that parents are giving children higher than recommended doses in about a third of cases. Other parents underdose their children and, when their temperature hasn’t reduced to a level they consider satisfactory, they seek professional assistance, placing burdens on already strained healthcare systems.”

Other key findings included:

Today’s parents have similar worries to their 1980’s counterparts - including brain damage, febrile convulsions and death – regardless of how well educated they are or their socio-economic status. Attitudes to fever seem to be similar in all countries.

The use of cold or iced water and aspirin to lower fever has reduced, especially after research showed links between Reye syndrome, a potentially fatal disease, and aspirin. But parents have increased their use of other fever-reducing drugs and often wake sleeping children to sponge them or give them medicine.

Education programmes run for parents in various countries have helped them to handle fever more effectively and reduced unnecessary use of healthcare services.

“Caring for a feverish child is emotionally challenging for parents and the limited improvements in knowledge, attitudes and practices highlighted by our research point to the need for a closer examination of the subject” says Anne Walsh.

“It is also very important that parents receive advice and guidance from healthcare professionals before their child experiences his or her first feverish episode. Fever management education needs to highlight the benefits of mild fever and equip parents with the knowledge and skills they need to manage mild to moderate fevers.”

However the authors stress that although effective parental education will improve knowledge and reduce unnecessary concerns, parents shouldn’t hesitate to ask for professional advice if they are worried about a child’s fever.

Aha! favors the prepared mind [Apr 5 Chicago IL USA]–If you’ve experienced the highs and lows of creative thinking, you know that sometimes the creative well is dry, while at other times creativity is free flowing. It is during the latter times that people often experience so-called “Aha!” moments – those moments of clarity when the solution to a vexing problem falls into place with a sudden insight and you see connections that previously eluded you.

But why do “Aha!” moments sometimes come easily and sometimes not at all? A new study reveals that patterns of brain activity before people even see a problem predict whether they will solve it with or without such an insight, and these brain activity patterns are likely linked to distinct types of mental preparation.

John Kounios of Drexel University, Mark Jung-Beeman of Northwestern University, and their research team report their findings in a new paper to appear in an upcoming issue of the journal Psychological Science.

Previous research by this team demonstrated that the brain functions differently when a person arrives at “Aha!” solutions, compared to methodical solutions. The current study reveals that the distinct patterns of brain activity leading to “Aha!” moments of insight begin much earlier than the time a problem is solved. The research suggests that people can mentally prepare to have an “Aha!” solution even before a problem is presented. Specifically, as people prepare for problems that they solve with insight, their pattern of brain activity suggests that they are focusing attention inwardly, are ready to switch to new trains of thought, and perhaps are actively silencing irrelevant thoughts. These findings are important because they show that people can mentally prepare to solve problems with different thinking styles and that these different forms of preparation can be identified with specific patterns of brain activity. This study may eventually lead to an understanding of how to put people in the optimal “frame of mind” to deal with particular types of problems.

This research team’s previous study revealed that just prior to an “Aha!” solution, after a person has been working on solving a problem, the brain momentarily reduces visual inputs, with an effect similar to a person shutting his or her eyes or looking away to facilitate the emergence into consciousness of the solution. The new study extends these findings by suggesting that mental preparation involving inward focus of attention promotes insight even prior to the presentation of a problem. Therefore, it may be that how a person is thinking before problem solving begins is just as important as the kind of thinking involved in reaching the solution, and perhaps even determines whether the solution will be derived with a sudden insight.

Participants in the new study were presented with a series of word puzzles. Each problem consisted of three words (for example, tank, hill, secret), and participants had to think of a single word that could form a compound or common phrase with each of the three words.

People sometimes solve such problems with a sudden flash of insight – the solution suddenly pops into their heads and seems obviously correct – and other times solve such problems more methodically, perhaps “trying out” possible solutions until they hit on the correct one (in this case, top: tank top, hilltop, top secret).

In two parallel experiments, participants solved these problems while brain activity was monitored either with electroencephalograms (EEG), which provide precise timing information and approximate anatomical information, or with functional magnetic resonance imaging (fMRI), which gives a more precise location of active brain areas, but with less precise timing. The researchers focused on neural activity that occurred during the period just before each problem was displayed.

The two brain imaging techniques yielded highly similar results and showed a different pattern of brain activity prior to problems that they subsequently solved with an “Aha!”, compared to the pattern of brain activity prior to problems they solved more methodically.

According to David E. Meyer, professor of psychology at the University of Michigan, who was not involved in the research, “It’s remarkable how similar the results were across the two experiments, using different methods, and these results nicely demonstrate that different types of mental preparation are conducive to different types of problem solving.”

Mental preparation that led to insight solutions was generally characterized by increased brain activity in temporal lobe areas associated with conceptual processing, and with frontal lobe areas associated with cognitive control or “top-down” processing. Jung-Beeman noted that “Problem solvers could use cognitive control to switch their train of thought when stuck on a problem, or possibly to suppress irrelevant thoughts, such as those related to the previous problem.” In contrast, preparation that led to more methodical solutions involved increased neural activity in the visual cortex at the back of the brain — suggesting that preparation for deliberate problem solving simply involved external focus of attention on the video monitor on which the problem would be displayed.

More than a century ago, the great scientist Louis Pasteur said “Chance favors only the prepared mind.” By this, he meant that sudden flashes of insight don’t just happen, but are the product of preparation. According to Kounios, “We have begun to understand how the brain prepares for creative insight. This will hopefully lead to techniques for facilitating it.”

Asteroids: treasures of the past and a threat to the future [Apr 3 Paris France]– If a large asteroid such as the recently identified 2004 VD17 – about 500 m in diameter with a mass of nearly 1000 million tonnes - collides with the Earth it could spell disaster for much of our planet. As part of ESA’s Near-Earth Object deflecting mission Don Quijote, three teams of European industries are now carrying out studies on how to prevent this.

ESA has been addressing the problem of how to prevent large Near-Earth Objects (NEOs) from colliding with the Earth for some time. In 1996 the Council of Europe called for the Agency to take action as part of a “long-term global strategy for remedies against possible impacts”. Recommendations from other international organisations, including the UN and the Organisation for Economic Cooperation and Development (OECD), soon followed.

In response to these and other calls, ESA commissioned a number of threat evaluation and mission studies through its General Studies Programme (GSP). In July 2004 the preliminary phase was completed when a panel of experts appointed by ESA recommended giving the Don Quijote asteroid-deflecting mission concept maximum priority for implementation.

Now it is time for industry to put forward their best design solutions for the mission. Following an invitation to tender and the subsequent evaluation process, three industrial teams have been awarded a contract to carry out the mission phase-A studies. :

a team with Alcatel Alenia Space as prime contractor includes subcontractors and consultants from across Europe and Canada; Alcatel Alenia Space developed the Huygens Titan probe and is currently working on the ExoMars mission

a consortium led by EADS Astrium, which includes Deimos Space from Spain and consultants from several European countries, brings their experience of working on the design of many successful ESA interplanetary missions such as Rosetta, Mars and Venus Express

a team led by QinetiQ (UK), which includes companies and partners in Sweden and Belgium, draws on their expertise in mini and micro satellites including ESA’s SMART-1 and Proba projects

This month the three teams began work and a critical milestone will take place in October when the studies will be reviewed by ESA with the support of an international panel of experts. The results of this phase will be available next year.

No reason for panic – yet

The risk is still small however, and may decrease even further when new observations are carried out. Still, if this or any other similar-sized object, such as 99942 Apophis, an asteroid that will come close enough to the Earth in 2029 to be visible to the naked eye, collided with our planet the energy released could be equivalent to a significant fraction of the world’s nuclear arsenal, resulting in devastation across national borders.

Luckily, impacts with very large asteroids are uncommon, although impacts with smaller asteroids are less unlikely and remote in time. In 1908 an asteroid that exploded over Siberia devastated an unpopulated forest area of more than 2000 km²; had it arrived just a few hours later, Saint Petersburg or London could have been hit instead.

Fossils of the Solar System

Asteroids are a part of our planet’s history. As anyone visiting the Barringer Meteor Crater in Arizona, USA or aiming a small telescope at the Moon can tell, there is plenty of evidence that the Earth and its cosmic neighbourhood passed through a period of heavy asteroid bombardment. On the Earth alone the remains of more than 160 impacts have been identified, some as notorious as the Chicxulub crater located in Mexico’s Yucatan peninsula, believed to be a trace of the asteroid that caused the extinction of the dinosaurs 65 million years ago.

Collisions have shaped the history of our Solar System. Because asteroids and comets are remnants of the turbulent period in which the planets were formed, they are in fact similar to ‘time capsules’ and carry a pristine record of those early days. By studying these objects it is possible to learn more about the evolution of our Solar System as well as ‘hints’ about the origins of life on Earth.

Comet 67P/Churyumov-Gerasimenko is one of these primitive building blocks and will be visited by ESA’s Rosetta spacecraft in 2014, as a part of a very ambitious mission - the first ever to land on a comet. Rosetta will also visit two main belt asteroids (Steins and Lutetia) on its way to comet 67P/Churyumov-Gerasimenko. The mission will help us to understand if life on Earth began with the help of materials such as water and organisms brought to our planet by ‘comet seeding’.

ESA’s Science programme is already looking at future challenges, and its Cosmic Vision 2015-2025 plan has identified an asteroid surface sample return as one of the key developments needed to further our understanding of the history and composition of our Solar System.

Work still in progress

Asteroids and comets are fascinating objects that can give or take life on a planetary scale. Experts around the world are putting all their energy and enthusiasm into deciphering the mysteries they carry within them.

With an early launch provisionally scheduled for 2011, Don Quijote will serve as a ‘technological scout’ not only to mitigate the chance of the Earth being hit by a large NEO but also for the ambitious journeys to explore our solar system that ESA will continue to embark upon. The studies now being carried out by European industry will bring the Don Quijote test mission one step nearer.

More black, Hispanic parents dissatisfied with health care for special needs children [Apr 3 Milwaukee WI USA]–Black and Hispanic parents of children with special heath care needs are twice as likely as white parents to be dissatisfied with their child’s care, according to a study appearing in the April issue of Pediatrics, the journal of the American Academy of Pediatrics.

Researchers in Milwaukee at the Medical College of Wisconsin and Children’s Hospital of Wisconsin Center for Advancement of Underserved Children studied outcomes data on 38,886 children with special healthcare needs (CSHCN) in the National Survey of CSHCN. They found that 13 percent of black parents and 17 percent of Hispanic parents were dissatisfied with their child’s care, in contrast to only seven percent of white parents. They also found that over one-third of black or Hispanic parents reported problems with ease of using health care services, compared to less than one-fourth of white parents.

The team identified parental interview language as the key factor in Hispanic parents’ dissatisfaction with care and ease of use of services. Hispanic/white disparities in both satisfaction with care and ease of use disappeared when a statistical adjustment was made for interview language. Similarly, they found inadequacy of family-centered care the key factor in Black /white disparities in satisfaction with care. However, black/white disparities in ease of use persisted.

“Our results underscore the importance of providing adequate medical interpreter services for Latino families of CSHCN, and the significance of providing adequate family-centered care and making services easier to use for black families,” says principal investigator principal investigator Emmanuel M. Ngui, Dr.PH.

Dr. Ngui is an assistant professor of pediatrics, epidemiology, and health policy in the Center. The Center’s director, Glenn Flores, M.D., FAAP, associate professor of pediatrics, co-authored the study.

“Previous studies have linked family-centered care factors such as adequate listening, respect, trust and participatory decision-making to greater satisfaction with care among black adults, compared to other racial/ethnic groups,” says Dr. Ngui “However, it is not clear why black/white disparities in ease of using healthcare services persist after adjusting for this and other factors studied, such as socio-demographics, insurance, the child’s condition severity/stability and having a personal doctor or nurse. It may be that other, unmeasured factors, such as attitudes, discrimination, transportation barriers, waiting times and limited availability of specialized providers or services in minority communities contribute to this disparity.”

For all parents, difficulty in using services was three times more likely to be associated with dissatisfaction with care, and lack of insurance coverage was associated with twice the odds of dissatisfaction with care. However, public insurance was the only factor that seemed to protect against reported difficulty in using health care services. Compared with parents of CSHCN with private insurance, parents of publicly-insured CSHCN had significantly lower odds of reporting problems in ease of use of services.

Just the expectation of a mirthful laughter experience boosts endorphins 27 percent, HGH 87 percent [Apr 3 San Francisco CA USA]–There’s no doubt that laughter feels good, but is there real neurophysiology behind it and what can you do about it?

In a paper being presented in an American Physiological Society session at Experimental Biology 2006, Lee S. Berk of Loma Linda University, reports that not only is there real science and psychophysiology, but just the anticipation of the “mirthful laughter” involved in watching your favorite funny movie has some very surprising and significant neuroendocrine/hormone effects.

According to Berk: “The blood drawn from experimental subjects just before they watched the video had 27% more beta-endorphins and 87% more human growth hormone, compared to blood from the control group, which didn’t anticipate the watching of a humorous video. Between blood pulls, the control group stayed in a waiting room and could choose from a wide variety of magazines,” he explained.

*Paper presentation: “Beta-Endorphin and HGH increase are associated with both the anticipation and experience of mirthful laughter,” 12:30 p.m.- 3 p.m. Sunday April 2, APS Behavioral neuroscience & drug abuse Section abstract 233.18/board #C706. Research was by Lee S. Berk, Department of Health Promotion and Education, School of Public Health and Department of Pathology, School of Medicine, Loma Linda University; Stanley A. Tan, Oakcrest Health Research Institute, Yucaipa; and James Westengard, Dept. of Pathology, School of Medicine; Berk is associated with all three institutions.

HGH, endorphin difference is long-lasting; setting the baseline and environment is key

Berk said that the strong difference between the two groups in terms of human growth hormone (HGH) and beta-endorphin blood levels was maintained from just prior to the beginning of video watching, throughout the hour of viewing and afterwards, also.

“We believe the results suggest that the anticipation of a humor/laughter eustress (positive stress) event initiates changes in neuroendocrine response prior to the onset of the event itself,” Berk said. “From our prior studies, this modulation appears to be concomitant with mood state changes, and taken together, these would appear to carry important, positive implications for wellness, disease-prevention and most certainly stress-reduction,” he noted.

In the current experiment, Berk and his colleagues studied 16 healthy and fasting males, who hadn’t exercised for at least a day and were not taking supplement medications. The test subjects had chosen a favorite video. Three days before the experiment, all the subjects were told which group they were randomly selected to be in, experimental (video watching) or control (no video watching). All subjects had blood drawn just before the video watching experiment began (baseline), four times during the hour-long experiment, and three times afterward.

“One of the keys in this kind of experiment is to set the baseline and control environment carefully,” Berk said. “In this case, the control group basically sits in a ‘neutral’ room waiting to have their blood drawn, and on the tables there is a wide variety of magazines that they can browse, because you don’t want to bias what they do or watch. Time and behavior have proved me right with this approach,” he added.

Earlier experiments showed stress reduction

Berk said the results of this “anticipatory mirthful laughter experience, which is a kind of eustress or ‘positive/good stress’ event, builds on our earlier work and may constitute a real construct for what is the ‘biology of hope.’” Earlier experiments showed that viewing a favorite funny video can offset symptoms of chronic stress, which can suppress various components of the immune responses, particularly those related to anti-viral and anti-tumor defenses. In addition, there appears to be a rebalancing of the Th1/Th2 immune response which suggestively could lead to reduction of autoimmune issues.

“Mirthful laughter diminishes the secretion of cortisol and epinephrine, while enhancing immune reactivity. In addition, mirthful laughter boosts secretion of growth hormone, an enhancer of these same key immune responses. The physiological effects of a single one-hour session viewing a humorous video has appeared to last up to 12 to 24 hours in some individuals,” Berk noted, ” while other studies of daily 30-minute exposure produces profound and long-lasting changes in these measures.

Next steps to seek physiological linkage mechanisms

In addition, Berk noted: “An area we will pursue is the modulation and change in Th1 and Th2 cytokine and inflammatory immune responses to the anticipation and experience of the positive mood state changes associated with mirthful laughter.”

Future research in this area with more subjects “needs to elaborate these findings in psychoneuroimmunology understanding and the mechanism linkage modulation between anticipatory positive behaviors and neuroendocrine and immune responses,” Berk said. “It may sound corny but we in the health care medical sciences need to ‘get serious about happiness’ and the lifestyle that produces it, relative to mind, body and spirit and its biotranslation,” he added.

“Why do you think Reader’s Digest has claimed that ‘Laughter is the Best Medicine’ for so many years?” Berk concludes.

Special education data provide misleading trends of changing autism prevalence [Apr 3 Madison WI USA]–If statistics compiled by the U.S. Department of Education are to be believed, in 1992 the state of Illinois had only 322 diagnosed cases of autism among school children. In 2003, according to the same statistical source, Illinois had more than 6,000 children diagnosed as autistic.

National special education statistics, which showed a 657 percent increase in autism over the decade from 1993 to 2003, are routinely used to suggest the country is experiencing an epidemic of autism, a developmental disorder of children characterized by impaired social and communication skills as well as repetitive behaviors and obsessive interests.

But inconsistencies in how the condition is diagnosed throughout the nation’s schools, and the fact that the increasing trend for autism coincides with a corresponding slump in the reporting of mental retardation and learning disabilities, challenges the use of special education data to portray a national epidemic of autism, according to a new study published in the current issue of a leading medical journal (April 3, 2006).

Paul Shattuck, a researcher at the University of Wisconsin-Madison’s Waisman Center, writing in Pediatrics, says special education data cannot be used to claim there is an autism epidemic because the figures are “hopelessly confounded” by changing and uneven identification and reporting practices among schools and states.

At issue, says Shattuck, is the practice of “diagnostic substitution,” where educators, over time, have increasingly applied the autism label to children who, in the past, would have been labeled differently.

“My research indicates that the increase in the number of kids with an autism label in special education is strongly associated with a declining usage of the mental retardation and learning disabilities labels in special education during the same period,” Shattuck says. “Many of the children now being counted in the autism category would probably have been counted in the mental retardation or learning disabilities categories if they were being labeled 10 years ago instead of today.”

The point, says Shattuck, is that identification and diagnostic practices change over time and can lead to a misperception that a condition is more prevalent than it has been in the past.

“Each year since 1994, the probability of using the autism label has increased while there has been a corresponding decrease in the likelihood of educators using the mental retardation and learning disabilities categories.”

In contrast to the dominant pattern, California was found to be one of only a handful of states where there was no decrease in the number of children labeled mentally retarded corresponding with an upward trend in identification of autism. This undermines the use of data coming out of California as a representative indicator of what is happening in the rest of the country, as has been suggested in recent press accounts and official reports, Shattuck argues.

In the U.S., federal law mandates the provision of special education in the nation’s schools. Schools are required to provide specialized services to children identified as having special needs and they must classify individuals according to 13 specified categories for the sake of annual enrollment reports. Autism was only added to the list in the early 1990s, and the federal statute’s definition of the condition, amounting to just a few sentences, is vague, Shattuck says.

What’s more, there are no uniform diagnostic practices or guidelines among states or school districts, meaning that how children are diagnosed and sorted in special education settings can vary dramatically from school to school.

“Schools nationwide don’t adhere to any common diagnostic guidelines when they’re sorting kids into these categories,” Shattuck explains. “States and individual schools are left to devise criteria. Everyone is using a different yardstick to measure the same thing.”

Shattuck notes that the diagnostic methods employed by schools in special education settings are distinct from medical and psychological diagnoses of autism, which entail a more precise definition of the condition and uniform diagnostic methodologies.

Catherine Lord, an expert on autism at the University of Michigan, noted that the new study has important implications for understanding the link between the everyday lives of children with autism and the ways the condition is identified and labeled in schools. “Shattuck’s work has both theoretical and practical importance. It highlights the need to consider the immediate implications for children’s lives of the lag between scientific findings regarding the diagnosis and prevalence of autism, and state and school system policies,” Lord says.

Shattuck emphasized that his study does not show, one way or another, whether there is an epidemic of autism. His study, he says, only shows that trends from special education data are insufficient to make such a determination, as is commonly done.

“The upshot is that it is not valid to conclude there is an epidemic of autism by looking to special education data, because the special education data is plagued with this diagnostic substitution phenomenon and the lack of nationally uniform diagnostic procedures.”

Shattuck says his study reveals, among other things, a national inability to accurately measure the scope of developmental disability among Americans.

“In fact, we simply do not have an adequate infrastructure of public health data in this country to say one way or another whether the true prevalence of autism has changed in the general population since the early 1990s. And this study emphasizes why it is so important to continue funding the longitudinal study of prevalence in several states, funded by the Centers for Disease Control, that began recently,” he says.

“It is in the absence of good quality information that people understandably make the mistake of looking to the special education data to draw conclusions. And I think parents and advocates have every right to be angry at our collective inability to answer such consequential questions as, ‘Do more of our children have autism than in the past? If yes, then why?’ ”

Shattuck’s research was supported by a grant from the National Institute of Child Health and Human Development.

Patient safety study shows increase in hospital incidents, gaps among state, hospitals [Apr 3 Golden CO USA]–Incidents cost medicare $9.3 billion over 3 years; patients at top-performing hospitals have 43 percent lower incidence of medical errors compared to worst; Minnesota, ranked #1, is success story

Patient safety incidents in American hospitals grew from 1.18 million to 1.24 million among the 40 million hospitalizations covered under the Medicare program, and incidents varied widely from state to state, and among the best and worst hospitals, according to a study released today by HealthGrades, the leading healthcare ratings company.

“Overall we see the number of patient safety incidents in American hospitals continuing to increase, at an enormous cost, and we still see a large gap between the incidence rates at the nation’s top-performing and worst-performing hospitals,” said Dr. Samantha Collier, HealthGrades vice president of medical affairs. “But we do find the results of serious attempts to grapple with this issue in the success of top-performing hospitals and in progressive states like Minnesota.”

The third HealthGrades Patient Safety in American Hospitals study, the largest annual study of its kind, also finds:

Differences Among Hospitals

Medicare patients going to hospitals ranked among the top 15 percent in terms of patient safety incidents had, on average, 43 percent lower incidence of patient safety incidents compared to bottom-ranked hospitals

If all hospitals performed at the level of the top 15 percent, 280,134 fewer patient safety incidents and 44,153 fewer deaths among Medicare patients would have occurred, saving $2.45 billion during the years 2002 through 2004

Of the 304,702 deaths that occurred among patients who developed one or more patient safety incidents, 250,246 were potentially preventable

Medicare beneficiaries experiencing one or more patient safety incidents had a one-in-four chance of dying during their hospitalization, a rate that is unchanged since HealthGrades’ first study

Number and Cost of Patient Safety Incidents

Approximately 1.24 million total patient safety incidents occurred among the nearly 40 million hospitals under the Medicare program over the years 2002, 2003 and 2004. That compares with 1.18 million over the previous three-year period, and 1.14 million over the years 2000, 2001 and 2002.

These patient safety incidents were associated with $9.3 billion in excess costs during the years 2002 to 2004
State Rankings and Differences

Wide and highly significant gaps in patient safety incidence levels were discovered between the top-performing states and those at the bottom over the years 2002, 2003 and 2004. Minnesota, Wisconsin, Iowa, Michigan and Kansas ranked as the top states for hospital patient safety. New Jersey, New York, Nevada, Tennessee and the District of Columbia ranked last.

Medicare patients in the best state, Minnesota, had an almost 30 percent overall lower relative risk of developing one or more of the patient safety incidents, compared with the worst state, New Jersey .

Trends in Patient Safety Incidents

The patient safety incidents with the highest prevalence continue to be failure to rescue, decubitus ulcer and post-operative sepsis. Failure to rescue improved over the study period, while post-operative sepsis worsened by almost 25 percent.

State Rankings The study ranked the nation’s states in terms of the prevalence of patient safety incidents in each states’ hospitals and are grouped as performing better, as expected, or worse than expected to a statistically significant degree:

Performed Better Than Expected
1. Minnesota
2. Wisconsin
3. Iowa
4. Michigan
5. Kansas
6. Indiana
7. Ohio
8. Pennsylvania
9. South Dakota
10. North Dakota
11. Montana
12. Utah
13. Florida
14. Washington
15. Connecticut
16. Arizona

Performed As Expected
17. West Virginia
18. Idaho
19. Georgia
20. Maine
21. Illinois
22. Massachusetts
23. Colorado
24. Oklahoma
25. Wyoming
26. Oregon
27. Rhode Island
28. Louisiana
29. North Carolina
30. Missouri
31. Alabama
32. South Carolina
33. Delaware
34. Mississippi
35. Vermont
36. Alaska
37. New Hampshire
38. Texas
39. Virginia
40. Kentucky
41. Nebraska

Performed Worse Than Expected
42. California
43. Hawaii
44. Arkansas
45. Maryland
46. New Mexico
47. District of Columbia
48. Tennessee
49. Nevada
50. New York
51. New Jersey

Minnesota ranked first overall in this year’s state ranking by HealthGrades, and in this state are progressive efforts to improve patient safety. While twenty-five states now have some form of mandatory reporting of medical errors, Minnesota was the first state, in 2003, to legislate mandatory public reporting, using guidelines from the National Quality Forum. Minnesota’s Safest in America program allows competitive hospitals to work together to share data, highlight best practices and implement evidence-based, community-tested solutions. Of the eight non-children’s hospital systems participating in the Safest in America collaborative, four have hospitals that ranked in the top 15 percent in the national according to this study.

“Two of the patient-safety incidents found in the study to be among the most prevalent are failure to rescue and post-operative sepsis,” continued Dr. Collier. “Failure to rescue is the inability to save a hospitalized patient’s life when that patient has acquired in the hospital a complication, such as when a patient admitted for a total knee replacement develops pneumonia and dies. An example of post-operative sepsis is when an otherwise previously healthy patient is admitted for a total knee replacement and develops an overwhelming bacterial bloodstream infection requiring potent antibiotics and other treatment resulting in a longer hospital stay and possibly death. Both of these are areas of focus for the most progressive hospitals, who have developed successful ways of minimizing or eliminating deaths from these incidents.”

Distinguished Hospital Awards and Findings: Based on the study, HealthGrades identified 238 hospitals reaching the top 15 percent in the nation in terms of patient safety, qualifying them to receive the HealthGrades Distinguished Hospital Award for Patient Safety. The award was designed to highlight hospitals with the best records of patient safety in the nation and to encourage consumers to research their local hospitals’ patient safety records before undergoing a procedure. As a category, Medicare patients at Distinguished Hospitals experienced patient safety incidents, on average, 43.27 percent less often than patients at the bottom 15 percent of all hospitals.

Methodology: The study is based on 13 patient safety indicators developed by the Agency for Healthcare Research and Quality (AHRQ), and applied to the most recent MedPar file of Medicare admissions at nearly 5,000 hospitals covering 2002, 2003 and 2004. Teaching hospitals and non-teaching hospitals were evaluated separately, based on a recommendation from AHRQ that hospitals be compared to their peer group. All data was risk adjusted, so that hospitals with sicker patient populations could be compared equally with others.

The 13 AHRQ indicators are:

Death in low mortality Diagnostic Related Groupings (DRGs)
Decubitus ulcer
Failure to rescue
Foreign body left during procedure
Iatrogenic pneumothorax
Selected infections due to medical care
Post-operative hip fracture
Post-operative hemorrhage or hematoma
Post-operative physiologic and metabolic derangements
Post-operative respiratory failure
Post-operative pulmonary embolism or deep vein thrombosis
Post-operative sepsis
Post-operative wound dehiscence

The complete study and methodology can be found at http://www.healthgrades.com.

Increased health problems for Pakistani population living near the Tasman Spirit oil spill [Apr 3 Karachi Pakistan]–People living on the coast of Pakistan affected by the Tasman Spirit oil spill, in August 2003, experience more health problems than individuals living inland.

A study published today in the open access journal BMC Public Health reveals that individuals living on the coast of Karachi, near the oil spill, report an average of 14 different health symptoms. This is more than three times the number reported by populations living two or 20 kilometres away from the coast.

In the first study of its kind coming from a less developed country affected by an oil spill, Naveed Janjua and colleagues from Aga Khan University in Karachi, the Sindh Environmental Protection Agency in Karachi and the University of Alabama at Birmingham, USA, studied a group of 216 individuals living on the coast of Karachi.

The study period started in September 2003, 3 weeks after the Tasman Spirit spilled its oil off the coast of Karachi. Janjua et al. also studied a group of 83 individuals living two kilometres from the coast and a group of 101 individuals living 20 kilometres from the coast. The authors asked participants to fill in a questionnaire about their living conditions and their health - in particular about a list of 48 symptoms including eye, skin, respiratory, gastrointestinal and general symptoms.

Janjua et al.’s results show that the group living on the coast near the oil spill reported having more multiple health problems than the other two groups. Out of the list of 48 symptoms investigated, the group living on the coast reported having a mean symptom score of 14.1, compared with a score of 4.4 for the group living two kilometres away and 3.8 for the group living 20 kilometres inland. The authors conclude that the long-term effects of crude oil spills on the health of local populations should be further investigated.

Scent of fear impacts cognitive performance [Apr 1 Houston TX USA]–The chemical warning signals produced by fear improve cognitive performance, according to a study at Rice University in Houston.

Women who were exposed to chemicals from fear-induced sweat performed more accurately on word-association tasks than did women exposed to chemicals from other types of sweat or no sweat at all. The study was published this month in the journal Chemical Senses.

“It is well-documented in the research literature that animals experiencing stress and fear produce chemical warning signals that can lead to behavioral, endocrinological and immunological changes in their fellow animals of the same species, but we wanted to see if this applies to humans as well,” said principal investigator Denise Chen, assistant professor of psychology at Rice.

For the study, Chen collected samples of sweat from research volunteers who kept gauze pads in their armpits while they watched videos of horror movies and non-threatening documentaries. The sweat samples were then stored in a freezer until needed for the study.

Next, Chen had 75 female students between the ages of 18 and 22 respond to 320 pairs of words that flashed for three seconds each on a computer screen. For each pair, the participants had to press a key to indicate whether the words were associated with each other (for example, arms and legs) or not (arms and wind). Some of the words were associated with threatening or fear-related topics, like weapons.

Each participant had a piece of gauze attached above their lips so that they were exposed to either chemicals from sweat or none at all during the tests. Chen compared how the chemicals from sweat impacted the speed and accuracy of participants’ results on the word-association tests.

When processing meaningfully related word pairs, the participants exposed to the fear chemicals were 85 percent accurate, and those in either the neutral sweat or the control (no-sweat) condition were 80 percent accurate. “The subjects in the fear condition were six percent more accurate, which is a statistically significant difference,” Chen said.

When processing word pairs that were ambiguous in threat content, such as one neutral word paired with a threatening word or a pair of neutral words, subjects in the fear condition were 15 to 16 percent slower in responding than those in the neutral sweat condition, and this difference was statistically significant. Chen’s theory is that the chemicals from fear-induced sweat prompted subjects to be more cautious.

The research participants were not aware of the nature of the smells, and the smells did not differ on the intensity or pleasantness ratings.

“We demonstrated that in humans, chemical signals from fear facilitated overall accuracy in identifying word relatedness independent of the perceived qualities of the smells,” Chen said. “The effect may arise from a learned association, including greater cautiousness and changes in cognitive strategies.”

“Human olfaction is a young, vibrant field,” Chen said, noting that the behavioral study of this subject is still in the early stage. “Olfactory receptors were discovered in the early 1990s. We now know that olfaction involves hundreds of receptors.”

Results like these from Chen’s behavioral research and studies from other labs form an integral part of a multipronged approach to the understanding of human olfaction.

Coauthors of Chen’s study included former Rice undergraduate students Ameeta Katdare and Nadia Lucas, a Rice Century Scholar. Chen’s research was funded by the National Institutes of Health.

H5N1 vax induces immune responses in healthy adults [Mar 31 Washington DC USA]–Results from a clinical trial demonstrate that high doses of an experimental H5N1 avian influenza vaccine can induce immune responses in healthy adults.

Approximately half of those volunteers who received an initial and a booster dose of the highest dosage of the vaccine tested in the trial developed levels of infection-fighting antibodies that current tests predict would neutralize the virus.

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, funded the study, published in the current issue of The New England Journal of Medicine. Preliminary results from this trial were first disclosed late last summer.

“These findings represent an important step forward in the nation’s efforts to prepare for the possible emergence of a human pandemic of H5N1 avian influenza,” notes NIH Director Elias A. Zerhouni, M.D.

“We are working hard to address the many challenges that remain with regard to the development of an H5N1 vaccine,” adds NIAID Director Anthony S. Fauci, M.D. “For example, potentially protective immune responses were seen most frequently at the highest dose of this vaccine. We are investigating other options that may allow us to reduce the dosage — for example, adding an immune booster, or adjuvant, to the vaccine — so we can achieve a more practical immunization strategy.” In addition, the U.S. Department of Health and Human Services is pursuing other approaches to an H5N1 vaccine, including vaccines made in cell cultures rather than grown in eggs.

H5N1 avian influenza viruses are of enormous concern to public health officials worldwide. The potential for a human avian flu pandemic looms large, say experts, as daily reports indicate an increasing spread of infection in bird populations in Southeast Asia, Europe, the Middle East and Africa. According to the World Health Organization, as of March 24, 2006, 186 people had been infected with avian flu viruses, and more than half of them had died.

Generally, flu viruses are easily transmitted from person to person, but so far, the H5N1 avian influenza viruses have not demonstrated this characteristic. In the worst-case scenario, if an avian flu virus became easily transmissible from person to person, it could trigger an influenza pandemic because humans have no pre-existing immunity to these viruses.

The trial, conducted between March and July 2005, was carried out at three NIAID-supported Vaccine and Treatment Evaluation Units located at the University of Rochester Medical Center in Rochester, NY; the University of Maryland School of Medicine Center for Vaccine Development in Baltimore; and the Los Angeles Biomedical Research Institute at Harbor–University of California Los Angeles Medical Center. John Treanor, M.D., of the University of Rochester, led the group.

The study was conducted in two stages. In the first stage, the research team enrolled 118 healthy adults ages 18 to 64 years old. Each participant was assigned at random to one of five groups. Volunteers in each group received an initial dose of vaccine (7.5 micrograms [mcg], 15 mcg, 45 mcg or 90 mcg) or saline placebo into the upper arm muscle; about one month later, they received a booster shot of the same vaccine dosage or the placebo. The research team collected blood samples before each vaccination and one month after the second vaccination.

Before the study could be expanded, an independent Data and Safety Monitoring Board assessed the vaccine’s safety by reviewing data collected through day 7 after the second vaccination; no safety concerns were found. The investigators then began stage two of the study, eventually enrolling an additional 333 healthy adult volunteers into the trial according to the same protocol design as in stage one.

The NEJM article describes an analysis of data on the safety and immune responses to the vaccine. In general, the higher the dosage of vaccine, the greater the antibody response produced. Of the 99 people evaluated in the 90-mcg, high-dose group, 54 percent achieved a neutralizing antibody response to the vaccine at serum dilutions of 1:40 or greater, whereas only 22 percent of the 100 people evaluated who received the 15-mcg dose developed a similar response to the vaccine.

Generally, all dosages of the vaccine appeared to be well tolerated:

Almost all reported side effects were mild
The second dose of vaccine did not cause more local or systemic symptoms than the first
Systemic complaints of fever, malaise, muscle aches, headaches and nausea occurred with the same frequency in all dosage groups as in the placebo group
Lab tests did not reveal any clinically significant abnormalities

The vaccine, made from an inactivated H5N1 virus isolated in Southeast Asia in 2004, was manufactured by sanofi pasteur, Swiftwater, PA, under contract to NIAID. Because there are no manufacturers licensed in the United States to use adjuvants in inactivated influenza vaccines, NIAID’s first step was to test an H5N1 influenza vaccine made in a way that mimics the process used to make conventional flu vaccines. The clinical data collected in this study are now available to support the potential use of this vaccine should it be needed for an emerging pandemic.

Simple idea to dramatically improve dengue vaccinations [Mar 31 Houston TX USA]–An innovative new study explains, for the first time, the failure of previous attempts to vaccinate against the four known Dengue viruses, and it suggests a very simple solution – injecting the four vaccines simultaneously at different locations on the body.

A mosquito-born disease, Dengue kills tens of thousands of people per year and sickens 100 million more. Known as “bone-break disease,” Dengue is characterized by excruciating pain and was “the most important mosquito-borne viral disease affecting humans” in 2005 according to the U.S. Centers for Disease Control.

The study, from bioengineers and physicists at Rice University, appears in the March 24 issue of the journal Vaccine. The study suggests that the multi-site vaccination strategy, termed polytopic vaccination, may be effective against other diseases as well, including HIV and cancer.

Dengue infection occurs from one of four closely related viruses. Previous exposure to one of the four – either by prior infection or by vaccination – makes people significantly more likely to develop a potentially lethal hemorrhagic infection if they are later infected by one of the other three viruses.

“This is a classic case of something called ‘original antigenic sin,’ which happens when our immune system becomes overly reliant upon memory when recognizing diseases similar to those that it has seen before,” said lead researcher Michael Deem, the John W. Cox Professor in Biochemical and Genetic Engineering and professor of physics and astronomy. “With diseases like HIV, influenza and Dengue, our acquired immune system’s tendency to go-with-what-it-knows can leave us more vulnerable to infection from a mutant strain or a related virus. The immune system may respond less favorably in these cases than if it had never been exposed to the disease in the first place.”

Original antigenic sin, or immunodominance, arises out of the procedure the immune system uses to target infection. This starts when the immune system identifies infected cells and brings pieces of them into the lymph node for targeting. Within a few days of infection, the immune system completes a massive scan of the 100 million available T-cells in its arsenal. Through a complex trial-and-error process, it identifies three to five T-cells that best recognize and attack the components of the sickened cells. Once the cells are selected, they are produced by the millions and sent out to clear the infection. After the infection is gone, thousands of these pre-programmed T-cells remain in the body, lying in wait should the disease return.

In recent years, public health officials have documented the disturbing co-existence of two or more Dengue viruses in Brazil, Cuba, Thailand, and other tropical and subtropical countries. Because sequential infection by multiple Dengue viruses can lead to increased likelihood of deadly infections, public health officials have attempted to counter the threat of co-existent versions of Dengue by developing a vaccine against all four versions simultaneously. Doctors found that patients who got a four-component vaccine wound up only being protected against one or two versions at most, due to immunodominance.

Intrigued by these results, Deem and graduate student Hao Zhou developed a precise computer model of the immune system’s biochemical scanning process to see if they could recreate the effect and find out what caused it. Their program conducts statistical calculations about the likelihood of specific interactions at the atomic level. They conducted trillions of calculations and gradually built up a bigger picture of what occurs in Dengue immunodominance.

“When faced with more than one version of the virus, the immune system may respond preferentially against the version for which it has T-cells with the strongest affinity, which is immunodominance,” Deem said.

He said polytopic vaccination – giving different vaccines simultaneously at different locations on the body – could help overcome immunodominance by taking advantage of the relative isolation of lymph nodes throughout the body. Each person has hundreds of lymph nodes. Deem believes vaccinations at four different sites, served by four different lymph nodes, could allow the body to simultaneously develop immune responses against all four versions of Dengue.

“The literature about immunodominance is new and growing,” Deem said. “Ours is the first model that can predict immunodominance, and when we compare our results with experimental data from Dengue vaccination trials, they match quite closely. There may be other factors at work, but we appear to be explaining a significant portion of the effect that occurs in Dengue immunodominance.”

Immunodominance is also a problem for researchers working on vaccines for both the AIDS virus and cancer, each of which mutate quickly and occur in multiple strains.

The research is supported by the National Institutes of Health and the National Science Foundation.

New evidence questions the simple link between prion proteins and vCJD [Mar 31 London UK]–While newly published research confirms that under laboratory circumstances prion-protein can be absorbed across the gut, it also shows that this is unlikely to occur in real life.

In addition, the results show that the places in the gut that do take up these disease-associated proteins are different from the locations where infectivity is known to be amplified. The findings will be published in the Journal of Pathology.

Since the outbreak of BSE in cattle and vCJD in humans, scientists have struggled to make sense of how an abnormal variation of a normal protein can trigger an infectious disease. Some are questioning whether this simple relationship exists at all. This paper adds new evidence that can inform the debate.

Firstly, it is known that individual people and animals have different levels of genetic susceptibility to this group of diseases, but no one knows how this resistance is achieved. One option is that resistant people do not absorb the disease-associated prion protein (PrP) from their guts.

To test this, the researchers worked with 50 sheep, with different degrees of genetic resistance to scrapie – the sheep form of the disease. When they injected material containing abnormal prion protein (PrP) into the sheep’s gut, it was equally absorbed by all sheep.

“This clearly shows that resistance is not achieved by blocking uptake of abnormal proteins from the gut – it must be achieved by some other mechanism,” says lead author Dr Martin Jeffrey.

Secondly, they looked in more detail at the route of absorption in the gut. Using surgically modified sheep, they loaded a small area of the gut with a fluid mixture containing 0.5 grams of scrapie infected brain containing a large amount of the disease specific variant of the PrP protein and watched how it was taken up. They saw the abnormal PrP was rapidly taken up by finger-like projections called villi and passed in to the lymph. It was not, however, taken up by structures called Peyer’s nodules, that are believed to be the places where animals amplify the infective agent.

“The fact the PrP isn’t taken up by the Peyer’s nodules questions whether PrP is really infectious, or whether PrP is really just a secondary marker of the presence of the scrapie agent,” says Jeffrey.

His belief in this need to reappraise the fundamental understanding of prion diseases is enhanced by one more observation published in this same paper. The team pre-digested a mixture containing disease specific PrP with standard stomach contents, and then injected the resulting mixture into the gut. No PrP transferred into the villi. When they used a highly sensitive version of Western Blot analysis to examine the contents of this pre-digested mixture, they found only the faintest suggestion that some of the PrP had survived. This was despite the fact that the original mixture had a contained a high level of PrP.

“Think about it – a sheep grazing in a field is not naturally exposed to highly infected brain and could only pick up a tiny amount of PrP from other tissues. This will then be exposed to 48 hours or more digestion before it arrives in the gut, and our experiments show that after this, the chance of there being more than an unmeasurably small amount of PrP left to absorb is very small,” says Jeffrey.

“As sheep can become infected, the theoretical probability of this being due to an invisible sub-fraction of digestion resistant PrP molecules is unlikely. The possibility of there being infectious molecules other than PrP must therefore be seriously considered,” says Jeffrey.

“A lot of people are completely wedded to the prion hypothesis of diseases like vCJD, but the more you deal with whole animals as opposed to relying purely on in vitro studies, the more cautious you are about saying that prion proteins alone cause the disease,” says Martin Jeffrey.

In a commentary published in the same edition of the journal Dr Nicole Sales of the Department of Infectology, at the Scripps Research Institute Jupiter, Florida, suggests that one possible explanation that keeps with the prion hypothesis is that infection occurs as PrPs are absorbed in the mouth, rather than in the gut.

Dr Jeffrey, however, is not convinced by this argument. “Were infection to be acquired from the mouth then the first tissues to accumulate infectivity would be lymph nodes in the throat or the tonsils. But we don’t tend to see this in animals, and have no reason to believe it would be different in humans,” comments Jeffrey.

Duke to test bird flu vax dosing [Mar 31 Durham NC USA]–A clinical trial to test different strengths of a vaccine designed to fight avian influenza will begin this month at Duke University Medical Center.

The Duke study is part of a multicenter trial that will test a modified form of an investigational bird flu vaccine to determine whether the vaccine still triggers a strong immune response at lower doses.

The seven-month trial is sponsored by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Also participating in the study are the University of Maryland, the University of Rochester and Baylor College of Medicine.

“We hope that by adding a compound called an adjuvant to the vaccine, we can create a stronger immune response to smaller doses of the vaccine,” said Emmanuel Walter, M.D., associate director of the Duke Clinical Research Institute’s Primary Care Research Consortium and leader of the Duke study. “If the smaller dose stimulates immunity against the virus, then more people could be immunized with existing supplies if a pandemic occurs,” he said.

The study will use an inactivated flu virus vaccine based on a strain taken from a Vietnamese patient in 2004. “There is no live flu virus in the vaccine, and there is no risk of volunteers contracting bird flu or spreading it to others,” Walter said.

The vaccine is designed to protect against the H5N1 strain of bird flu that has infected poultry in Asia, Europe and Africa and killed 101 humans. Initial trials in healthy adults showed the vaccine was safe and produced an immune response but required high doses and at least two injections to initiate a strong response, Walter said.

Trial participants will receive varying strengths of the H5N1 vaccine, either with or without an aluminum hydroxide adjuvant. An adjuvant works by increasing the body’s immune response to a vaccine, Walter said. Aluminum hydroxide is commonly used in pediatric and adult vaccines, including those for whooping cough, hepatitis A and hepatitis B.

As with current flu vaccines given yearly in the U.S., the H5N1 vaccine causes the body’s immune system to make antibodies to fight infection. In previous studies with this vaccine, two doses were necessary to stimulate antibodies. The doses needed to trigger antibodies were also much higher than necessary for other types of flu, Walter said.

The Duke researchers will recruit approximately 150 volunteers between the ages of 18 and 49 years. The volunteers will have a medical screening, have their blood drawn several times and receive two injections. Volunteers will be randomly assigned to two different groups – one receiving the vaccine with adjuvant and one receiving the vaccine alone. Several different doses will be tested to help determine the right dose to stimulate antibodies. Participants will keep a journal to record any side effects and will receive checkups to monitor their health. Compensation will be provided.

Duke will begin screening potential study volunteers this month. People interested in participating in the study should call (919) 620-5354.

Quantum dot method rapidly identifies bacteria [Mar 31 Gaithersburg MD USA]–A rapid method for detecting and identifying very small numbers of diverse bacteria, from anthrax to E. coli, has been developed by scientists from the National Cancer Institute (NCI) and National Institute of Standards and Technology (NIST).

Described in the March 28 issue of Proceedings of the National Academy of Sciences,* the work could lead to the development of handheld devices for accelerated identification of biological weapons and antibiotic-resistant or virulent strains of bacteria–situations where speed is essential.

Traditional ways of identifying infectious bacteria and their possible treatments can be time consuming and laborious, requiring the isolation and growth of the bacteria over many hours or even days. The new method speeds up the process by using fast-replicating viruses (called bacteriophages or phages) that infect specific bacteria of interest and are genetically engineered to bind to “quantum dots.”

Quantum dots are nanoscale semiconductor particles that give off stronger and more intense signals than conventional fluorescent tags and also are more stable when exposed to light. The method detects and identifies 10, or fewer, target bacterial cells per milliliter of sample in only about an hour.

The phages were genetically engineered to produce a specific protein on their surface. When these phages infect bacteria and reproduce, the bacteria burst and release many phage progeny attached to biotin (vitamin H), which is present in all living cells. The biotin-capped phages selectively attract specially treated quantum dots, which absorb light efficiently over a wide frequency range and re-emit it in a single color that depends on particle size.

The resulting phage-quantum dot complexes can be detected and counted using microscopy, spectroscopy or flow cytometry, and the results used to identify the bacteria. The new method could be extended to identify multiple bacterial strains simultaneously by pairing different phages with quantum dots that have different emission colors.

The new method is more sensitive than conventional optical methods. It can count how many viruses are infecting a single bacteria cell and how many quantum dots are attached to a single virus. A provisional patent application was filed originally through NIST, and a non-provisional patent application was filed more recently through the National Institutes of Health, the parent agency of NCI. The NIST contributions to the work include experimental design and fluorescence imaging. Other authors are from NCI, NIH, SAIC-Frederick Inc. and the National Cancer Institute at Frederick.

The work was funded by NIH, NCI, NIST, and the Center for Cancer Research.

RFID tags to assist in tracking first responders [Mar 31 Gaithersburg MD USA]–Radio Frequency Identification (RFID) technology has been around for many years and is widely used to identify, track, and communicate information about items, products and even animals.

An interdisciplinary team of researchers at the National Institute of Standards and Technology (NIST) is studying whether RFID technology can be used as a low cost, reliable means to track firefighters and other first responders inside buildings and help them navigate under hazardous conditions.

Typical RFID systems consist of tags, tag readers and application software. As the tagged products pass by a fixed reader they transmit data about the product and its location. The NIST researchers are looking at the “flip side.” They want to know whether inexpensive RFID tags placed inside buildings can help pinpoint the location of a first responder and provide local information to a small handheld device that includes an RFID reader and a navigation unit.

In place of GPS (Global Positioning System), which is unreliable inside most buildings, the researchers are evaluating whether inertial sensors such as accelerometers and gyroscopes can be used as part of the navigation system to help guide the first responder through the building. Navigation systems tend to “drift” over time and become increasingly inaccurate. When a first responder carrying the device encounters a tag, the system will make corrections by correlating the tag with its location. The reader’s interaction with a tag would be similar to using a “you are here” map in a shopping mall.

The research team’s plans over the next several years include defining the parameters needed to determine how many tags are needed and where they should be placed, developing a prototype RFID reader, integrating the reader and navigation hardware and software into a wireless network that can relay position information to others such as an incident commander, and testing a prototype system in a smoke-filled environment.

Young patients more likely to die in countries where health care is funded by private insurance [Mar 31 London UK]–Countries that have national health services easily accessible to people of all ages are more likely to have better survival rates for their teenagers and young adults (TYAs) with cancer, than are countries where individuals have to pay for their own medical insurance.

This is the suggestion that arises from new research presented at the 4th International Conference on Teenage and Young Adult Cancer Medicine today (Friday 31 March 2006), in which the health care systems of the United States of America and Australia were compared.

Professor Archie Bleyer told the conference, organised by Teenage Cancer Trust, that Australia’s system of health insurance for all, regardless of age, meant that TYAs were more likely to survive cancer in Australia than they were in the USA.

Prof Bleyer, who is medical advisor at the Cancer Treatment Center, St Charles Medical Center, Bend, Oregon, said: “However, both countries have a lower survival rate for their TYAs than for their younger and older patients, proving that TYAs remain the most neglected group of cancer patients across the globe.

“Our previous research has shown that the survival of older teenagers and young adults with cancer in the United States has lagged behind progress in younger and older patients. We found that diagnosis was delayed in TYAs who either lacked health insurance or had inadequate insurance, and therefore this lack of progress might be due to the USA health care system and less expected in countries with national health insurance.

“During the past year we have compared survival of TYAs in the USA with those in Australia, a country similar in many demographics to the USA, but with health insurance provided to all citizens regardless of age.

“From 1982 to 1998, the rate of improvement in the five-year survival from invasive cancer in Australia exceeded that which occurred in the USA, such that by the late 1990s, TYAs in Australia had an overall five-year cancer survival that was higher than in the USA. The deficit begins at 16 and ends at 55, the same years that national health insurance is not available in the USA. It ranges from 5% for 18 to 25 year-olds to 12% for those aged 30 to 35. This difference suggests that the health care system in Australia, with universal health insurance, was able to provide better cancer care to its TYAs.

“The advantage for Australian TYAs was not apparent in their children or older adults with cancer. This suggests that the need for private health insurance in the USA is responsible for the worse survival of TYAs, in that children and older adults in the USA are more adequately insured than TYAs.”

In the USA the greatest improvement in survival occurred amongst patients aged over 65 for whom national health insurance is provided. Prof Bleyer said: “Both countries, however, had a lower rate of improvement in the five-year cancer survival rate among TYAs than in either younger or older patients, albeit the relative deficit was greater in the USA than in Australia.

“These comparisons indicate that the relative lack of progress in cancer outcome among TYAs in the USA is due, at least in part to the lack of health insurance,” he said.

However, he warned that even in countries where there was national health insurance for all, this didn’t necessarily guarantee access to good diagnosis and treatment for cancer patients, and particularly n