Stopping Heart Disease In Cancer Patients Before It Starts

Researchers in the Faculty of Medicine & Dentistry are trying to reverse a devastating trend: cancer survivors developing cardiovascular disease, one of the top two killers in Canada.

Ian Paterson, an assistant professor of cardiology at the University of Alberta and Edie Pituskin, a registered nurse and PhD candidate in the Faculty of Rehabilitation Medicine, are starting what is called the MANTICORE clinical trials. Women with breast cancer will be put on heart medication before their cancer treatment. "Our goal is to look at patients diagnosed with cancer and to detect heart disease and risk factors for heart disease sooner then they're being recognized and treat them aggressively," said Paterson. "We're hoping we can prevent heart disease not only during cancer treatment itself but after the cancer treatment is done."

All patients enrolled in this study must start on the heart disease medication with Paterson and Pituskin prior to treatment.

Paterson and Pituskin decided to start with breast cancer patients because it is the leading cancer in women and the leading cause of cancer deaths in women. Treatments have improved drastically over the years, in particular one pharmaceutical called Herceptin.

"The drug has been shown to really improve survival rates of some types of breast cancer," said Paterson. "Unfortunately it can also damage the heart in up to 20 per cent of women taking this drug.

"We're trying to detect signs of injury much more quickly using special blood tests and special imaging tests like an eco-cardiogram and MRI."

The pair will also try to detect if any of the women involved in the study have cardiac risk factors like high blood pressure and they'll try to treat those very aggressively.

MANTICORE looks to enrol 139 patients, so far 15 are involved in Edmonton and the study is now adding centres in Winnipeg and Toronto. The study is being funded by the Alberta Cancer Foundation and Canadian Institutes of Health Research.

Cardio-oncology is an emerging field of medicine and Paterson and Pituskin are leading the way.

"We're one of the first and we could serve as a blue print for other programs," said Paterson, who also added they want to get a number of sites nationally on board with the trials. "Then we'll be able to track outcomes for these patients and develop a registry where we can track how people are doing and have these clinics make a difference."

Source:
Quinn Phillips
University of Alberta Faculty of Medicine & Dentistry

As E Coli Outbreak In Germany Continues, Experts Are Concerned About Pressure On Health Facilities, Antibiotic Resistance And Preparedness Across EU

As the current virulent Shiga toxin-producing Escherichia coli (STEC) outbreak in Germany spreads, experts from The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) are concerned not only about the pressure health facilities are being put under, but also the use of antibiotics and broader implications for preparedness across Europe to cope, both now and in the future.

The current E coli outbreak is caused by a very rare strain. It has affected more than 1500 people, causing at least 17 deaths. Unlike previous STEC epidemics, the current outbreak is affecting mostly female adults. This infection is associated with a severe complication known as haemolytic-uremic syndrome (HUS) that leads to organ damage and often requires intensive care.

"This most recent E coli epidemic of a strain previously unseen in an outbreak shows us yet again that new bacteria and infections are just around the corner, and we are far from winning the fight against infectious diseases in Europe", said ESCMID President, Professor Giuseppe Cornaglia. "It reminds us that we continue to face new challenges, and must ensure we are vigilant in our preparedness, including monitoring, detection, and speedy and appropriate treatment."

Experts in Germany are concerned about public health facilities' capacity to cope with the outbreak. "The severity of this strain has resulted in great pressure on the health services, for example in the northern part of Germany, which has been experiencing a problem with availability of intensive care beds due to the high number of cases with life threatening complications," said Professor Winifred Kern, ESCMID Treasurer and Head of the Centre for Infectious Diseases and Travel Medicine at the University Hospital in Freiburg, Germany.

The use of antibiotics with this outbreak had previously been discouraged due to experience indicating there is a danger of aggravating the disease. But German infectious diseases experts have now issued a position paper stating that antibiotic therapy should not be withheld in certain clinical situations, and that carbapenem (a type of antibiotic) therapy can probably be used without putting the patient at an additional risk. Experiments with new therapies that neutralize the toxin are currently taking place.

Professor Kern also notes that, "Of particular concern to experts is the production of an antibiotic resistance mechanism called ESBL by this strain of E coli which highlights the risks of spread of resistance across human and animal microorganisms which could be linked to inappropriate antibiotic use."

Although focused largely in Germany, this outbreak has so far spread to Sweden, Denmark, The Netherlands, UK and Spain. "The pan-European nature of this E coli outbreak, and the multi-dimensional problems it presents, reinforce the need for concerted cooperation across borders to tackle not only this outbreak, but also future ones, "said Professor Cornaglia.

ESCMID experts stress the rapid identification of potential cases is vital to try and limit the development of severe disease, and that we have to avoid complacency about food and personal hygiene.

Source:
European Society of Clinical Microbiology and Infectious Diseases (ESCMID)

Fraunhofer USA CMB Announces Positive Phase 1 Interim Results For Its Plant-Produced H1N1 Influenza Vaccine

Fraunhofer USA Center for Molecular Biotechnology (CMB), a not-for-profit, Delaware-based organization focused on developing a proprietary plant-based protein production platform and its applications in vaccine and therapeutic fields, today announced positive interim results from the first human trial of plant-produced H1N1 influenza vaccine (HAC1) that began on September 13, 2010. This Phase 1, single-blind, placebo-controlled, dose-escalation study was conducted to assess the safety and reactogenicity and immunogenicity of CMB's HAC1. The trial was supported by funding from the Defense Advanced Research Projects Agency (DARPA) and was conducted at the Walter Reed Army Institute of Research Clinical Trials Center (WRAIR-CTC). Safety and reactogenicity assessments were completed at WRAIR-CTC, and immunogenicity evaluation was performed by the Influenza Division of the Centers for Disease Control and Prevention.

"Successful completion of this Phase 1 safety and immunogenicity trial is a significant milestone in advancement of our proprietary technology and its applications," said Dr. Yusibov, Executive Director of Fraunhofer USA CMB.

Eighty healthy adult volunteers between 18 and 50 years of age were enrolled in the study and received two intramuscular doses of either CMB's vaccine or placebo, three weeks apart. A reference vaccine group received a single dose of an approved, monovalent H1N1 vaccine. To date, the new HAC1 influenza vaccine was found to be safe and well tolerated at all dose levels, with or without adjuvant. Immunogenicity of the vaccine was assessed using hemagglutination inhibition and virus microneutralization antibody assays. Preliminary serologic results showed that CMB's vaccine performed better in the absence of adjuvant. The level of immune response correlated directly to the amount of antigen volunteers received in a dose.

Dr. James F. Cummings, Director, Division of Regulated Activities at WRAIR stated:"Preliminary results of the trial are quite promising and indicate that clinical products are possible".

Completion of this Phase 1 trial is expected in the 2nd quarter of 2011 with final results available by the end of the year. The preliminary positive results warrant further development of CMB's new H1N1 plant-produced influenza vaccine.

About Fraunhofer USA CMB's H1N1 influenza vaccine candidate

CMB's HAC1 is the recombinant HA derived from the A/California/04/09 strain of influenza virus and produced in Nicotiana benthamiana plants using the proprietary "iBioLaunch" system. CMB's expression system for recombinant protein production has been developed over the past decade as a safe, fast and cost-effective protein production system. The new platform technology has progressed from concept through technical innovations, process improvement, and large scale production. CMB produced the material for the clinical study in its recently completed pilot manufacturing facility in Newark, Delaware.

Source:
Fraunhofer USA CMB

Haiti: An Alarming Resurgence Of Cholera

The cholera epidemic in Haiti is far from over, with a sharp increase in cases seen in the capital, Port-au-Prince, and outbreaks reported elsewhere in the country, the international medical humanitarian organization Doctors Without Borders/Médecins Sans Frontières (MSF) said today.

Although the cholera epidemic began to decline in February, it has not yet ended. In MSF cholera treatment centers (CTCs) in Port-au-Prince, medical teams have witnessed an increase in cases since mid-May. MSF had to reopen emergency CTCs to prevent existing treatment centers in Carrefour, Delmas, Martissant, Cité Soleil, and Drouillard from being overwhelmed.

"Since May 29-in one week-MSF has treated almost 2,000 patients in the capital, and we have also been asked to intervene in other areas in the interior of the country," said MSF head of mission, Romain Gitenet. "Workload should be shared and coordinated in order to increase cholera treatment capacity in Haiti. Too many public facilities are still inadequate."

It is essential that Haitian authorities and their humanitarian partners mobilize to stop the spread of the disease by strengthening national surveillance systems and treatment facilities. Immediate improvements in hygiene, sanitation, and drinking water supplies should be a national priority, in order to protect the most vulnerable people.

"Vigilance is still the best protection," said Gitenet. "People must be strict about their hygiene and drink treated water. As soon as cholera symptoms appear, such as vomiting and diarrhea, it is vital that people go as quickly as possible to a treatment center. Cholera is treatable, but without medical care it kills quickly."

By the end of May cholera had killed nearly 5,000 people from among the 300,000 cases reported in the country. Three percent of the country's population has contracted the disease.

MSF has treated 130,000 Haitians for cholera (43 percent of total cases). As soon as the first cases were confirmed in October 2010, MSF teams deployed to 9 of Haiti's 10 departments to support local health facilities.

Source:
Doctors Without Borders/Médecins Sans Frontières a

Antifungal Drug Delays Need For Chemo In Advanced Prostate Cancer

The oral antifungal drug itraconazole, most commonly used to treat nail fungus, may keep prostate cancer from worsening and delay the need for chemotherapy in men with advanced disease. Details of the finding, from a clinical trial led by Johns Hopkins experts, are scheduled for presentation on Saturday, June 4 at the 2011 American Society of Clinical Oncology (ASCO) annual meeting (abstract #4532). Currently, the drug is approved to treat fungal infections in nails and other organs. Serious side effects can include heart failure, and Johns Hopkins experts caution that itraconazole needs further study before it can be considered for prostate cancer treatment. Identified as a potential anticancer drug after Hopkins scientists scoured a database of more than 3,000 FDA-approved drugs, itraconazole appears to block tumor blood vessel growth -- the only drug in its class to do so -- much like the anticancer drug bevacizumab (Avastin). The antifungal also disrupts a key cancer-initiating biological pathway called Hedgehog. Laboratory testing by Johns Hopkins scientist Jun Liu, Ph.D., has shown that human prostate tumors implanted in mice shrink when treated with itraconazole. "The most effective therapy we have right now for metastatic prostate cancer is hormone therapy, and when it doesn't work, the next step is usually chemotherapy," says Emmanuel Antonarakis, M.D., assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center. In a search for compounds that could put off chemotherapy, the Johns Hopkins team turned to itraconazole. For the study, patients with prostate cancer that had spread to other organs and did not respond to hormone therapy were randomly assigned to receive low or high doses of itraconazole. Over 24 weeks of daily treatment with oral itraconazole, the investigators tracked the length of time for each patient's prostate cancer to worsen (called progression-free survival). Evidence of worsening disease was measured by a 25 percent increase in their blood level of prostate specific antigen (PSA), a marker for prostate cancer. Early in the trial, preliminary analysis of 17 men receiving low doses of itraconazole showed that only two of them (11.8 percent) had stable or declining PSA. Because of the limited response, no further men were given low doses of the drug. However, 11 of 24 (48.4 percent) men taking high doses of itraconazole had stable or declining PSA levels lasting at least 24 weeks. In addition, nearly a third of men taking the high dose had PSA reductions of 30 percent or more. Metastatic prostate cancer patients receiving no treatment typically would worsen in eight to 12 weeks, according to Antonarakis. The investigators also found that 12 of 14 men taking high doses of itraconazole had lower levels of circulating tumor cells present in their blood after therapy, compared with their baseline levels. Seven patients experienced side effects, including low potassium, hypertension and fluid retention, but the problems were resolved with potassium replacement pills, anti-hypertension drugs, and diuretics. "We also tested whether itraconazole acted as hormone therapy by tracking levels of testosterone and DHEA (a testosterone derivative) in the blood, and we found no reductions of either testosterone or DHEA," says Antonarakis. "This finding shows that itraconazole is not just another hormone therapy, and has a unique mechanism of action." Antonarakis and colleagues next plan to examine blood and skin samples taken from study participants specifically to look for levels of proteins linked to tumor blood vessel formation and the Hedgehog pathway. "With these results, we believe that high-dose itraconazole is worth studying in a larger group of men with advanced prostate cancer," adds Antonarakis. The clinical trial was funded by the Department of Defense (DoD) Prostate Cancer Research Program, the Commonwealth Foundation for Cancer Research, the David H. Koch Charitable Foundation, a 2009 American Society of Clinical Oncology (ASCO) Young Investigator Award granted to Antonarakis, and the National Institutes of Health/National Cancer Institute. In addition to Antonarakis, other investigators participating in the research on behalf of the Prostate Cancer Clinical Trials Consortium included Amanda Blackford, Serina King, Anja Frost, Seun Ajiboye, Sushant Kachhap, Michelle Rudek, and Michael Carducci from Johns Hopkins; Elisabeth Heath from the Karmanos Cancer Institute; David Smith from University of Michigan, Ann Arbor; and Dana Rathkopf and Daniel Danila from Memorial Sloan Kettering Cancer Center. Source: Johns Hopkins Kimmel Cancer Center

Understanding Cancer Energetics

It's long been known that cancer cells eat a lot of sugar to stay alive. In fact, where normal, noncancerous cells generate energy from using some sugar and a lot of oxygen, cancerous cells use virtually no oxygen and a lot of sugar. Many genes have been implicated in this process and now, reporting in the May 27 issue of Cell, researchers at the Johns Hopkins University School of Medicine have discovered that this so-called Warburg effect is controlled.

"It turns out to be a feed-forward mechanism, where protein A turns on B, which in turn goes back and helps A do more," says Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Medicine, director of the vascular program at Johns Hopkins' Institute for Cell Engineering and a member of the McKusick-Nathans Institute of Genetic Medicine. "PKM2 normally functions as an enzyme involved in the metabolism of glucose, but in this case we have demonstrated a novel role in the control of gene expression in cancer cells."

Nearly 20 years ago, Semenza's research team discovered that HIF-1 can turn on a number of genes that that help cells survive when oxygen levels fall too low. In addition to genes that contribute to building new blood vessels, HIF-1 also turns on genes involved in the metabolic process that turns glucose into energy. One of those genes, pyruvate kinase M2 or PKM2, catalyzes the first step of this metabolic process and is present only in cancer cells.

To figure out whether and if HIF-1 and PKM2 interact, the team first engineered cells to have or lack HIF-1. They kept them in high or low oxygen for 24 hours and found that cells starved of oxygen, but containing HIF-1, had more PKM2 than cells without HIF-1, suggesting that HIF-1 controls the production of PKM2.

The team then asked if HIF-1 and PKM2 physically interact with each other by isolating one of the two proteins from cells; they found that pulling one out also resulted in the other coming along for the ride, showing that the two proteins do in fact bind to each other.

Knowing that the primary function of HIF-1 is to bind DNA and turn on specific genes, Semenza's team next asked whether PKM2 somehow helped HIF-1 do that. They examined genes known to be activated by HIF-1 in low oxygen after the removal of PKM2 and found that without PKM2, less HIF-1 was bound to DNA.

Now armed with evidence that PKM2 helps HIF-1 turn on genes, the team looked at the activity of genes directly involved in the metabolic pathway that burns so much sugar in cancer cells and compared genes known to be activated by HIF-1 with those not affected by HIF-1. Removing PKM2 from cells had no effect on genes not controlled by HIF-1 but reduced the activity of HIF-1-controlled genes.

"These results were really astounding," says Semenza. "In addition to solving the long-standing mystery of the Warburg effect, we also discovered that PKM2 may play a far broader role in promoting cancer progression than has been appreciated before." This study was funded by the National Heart, Lung and Blood Institute.

Authors on the paper are Weibo Luo, Hongxia Hu, Ryan Chang, Jun Zhong, Matthew Knabel, Robert O'Meally, Robert Cole, Akhilesh Pandey and Gregg Semenza, all of Johns Hopkins.

Source:
Johns Hopkins Medicine

Examining The Brain As A Neural Information Super-Highway

The brain functions as a complex system of regions that must communicate with each other to enable everyday activities such as perception and cognition. This need for networked computation is a challenge common to multiple types of communication systems. Thus, important questions about how information is routed and emitted from individual brain regions may be addressed by drawing parallels with other well-known types of communication systems, such as the Internet.

The authors, from the Rotman Research Institute at Baycrest Centre, Toronto, Canada, showed that - similar to other communication networks - the timing pattern of information emission is highly indicative of information traffic flow through the network. In this study the output of information was sensitive to subtle differences between individual subjects, cognitive states and brain regions.

The researchers recorded electrical activity from the brain and used signal processing techniques to precisely determine exactly when units of information get emitted from different regions. They then showed that the times between successive departures are distributed according to a specific distribution. For instance, when research study participants were asked to open their eyes in order to allow visual input, emission times became significantly more variable in parts of the brain responsible for visual processing, reflecting and indicating increased neural "traffic" through the underlying brain regions.

This method can be broadly applied in neuroscience and may potentially be used to study the effects of neural development and aging, as well as neurodegenerative disease, where traffic flow would be compromised by the loss of certain nodes or disintegration of pathways.

Funding: This research was funded by grants from the Canadian Institutes of Health Research (CIHR) and Santa Fe Institute Consortium to TP and a J.S. McDonnel Foundation grant to ARM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation:
"Extracting Message Inter-Departure Time Distributions from the Human Electroencephalogram"
Mišić B, Vakorin VA, Kovačević N, Paus T, McIntosh AR (2011)
PLoS Comput Biol 7(6): e1002065. doi:10.1371/journal.pcbi.1002065

Ahead Of Major UN Aids Meeting, New HIV Investment Model Is Proposed, Including Benefits Of Extension Of Antiretroviral Therapy For Prevention

It has been exactly 30 years since HIV/AIDS was identified, and 10 years since the UN General Assembly Special Session on HIV/AIDS convened. To review progress, world leaders and experts on HIV AIDS will take part in a high level UN meeting in New York from June 8-10.

Ahead of this meeting, in a Health Policy published Online First by The Lancet, a group of HIV experts propose a new investment model intended to support better management of national and international HIV/AIDS responses than exists with the present system. The new model proposes a paradigm shift in the way AIDS funding is approached, with a greater emphasis on priority setting and optimization of AIDS responses, a shift to community mobilization to deliver programmes and greater synergies between programme elements. Implementing the model would require 30 per cent more funding than currently available when expenditure would be projected to peak, in 2015. The Health Policy is by Dr Bernhard Schwartländer, Joint United Nations Programme on HIV/AIDS (UNAIDS) Geneva, Switzerland, and colleagues.

The authors say: "Substantial changes are needed to achieve a more targeted and strategic approach to investment in the response to the HIV/AIDS epidemic that will yield long-term dividends...We propose an investment framework to support management of national and international HIV/AIDS responses, encourage transparency in programme objectives and results, and enable decision makers and financiers to galvanise support for effective action."

They add that, until now, advocacy for resources has been done on the basis of a commodity approach that encouraged scaling up of numerous strategies in parallel, irrespective of their relative effects. But the authors propose a more targeted approach. Basic programme activities in the framework range in complexity and consisted of procurement, distribution, and marketing of male and female condoms; activities designed to prevent mother-to-child transmission; promotion of medical male circumcision; integration of activities addressing key populations, in particular sex workers, men who have sex with men, and harm reduction programmes for injecting drug users; behaviour change programmes that target reduction of the risk of HIV exposure through changing of people's behaviours and social norms; and antiretroviral therapy programmes.

The new framework also stresses the importance of so called 'critical enablers'. that fall into two categories, social enablers that make environments conducive for rational HIV/AIDS responses possible and programme enablers that create demand for and help improve the performance of key interventions. Social stigma, poor health literacy, and a punitive legal environment hinder implementation of basic HIV/AIDS programme activities and adversely affect programme priorities by stifling of adoption of evidence-based policies and best practices. Complementary 'critical enabler' strategies to increase the effect of basic programme activities are therefore crucial to the success of HIV/AIDS programmes.

The authors conclude: "The yearly cost of achievement of universal access to HIV prevention, treatment, care, and support by 2015 is estimated at no less than US$22 billion*. Implementation of the new investment framework would avert 12•2 million new HIV infections and 7•4 million deaths from AIDS between 2011 and 2020 compared with continuation of present approaches, and result in 29•4 million life-years gained. The framework is cost effective at $1060 per life-year gained, and the additional investment proposed would be largely offset from savings in treatment costs alone."

Dr Schwartländer** adds: "With a more focused upfront investment we could really turn the HIV epidemic around ... it's not a question of whether we pay now or later. It is rather a question of whether we pay now or forever."

*adding the US$500 million to ART cover treatment for prevention purposes in this framework takes the estimated cost to between $22 and $23 billion

**Quote direct from Dr Schwartländer, not found in Health Policy paper

Link to Abstract

Source
The Lancet

C-reactive Protein Levels Predict Breast Cancer Survival Rates

Levels of C-reactive protein (CRP) are increased in response to acute inflammation, infection and tissue damage. There are also reports that CRP levels are elevated because of cancer. New research published in BioMed Central's open access journal Breast Cancer Research shows that elevated CRP levels are predictive of a poor prognosis for breast cancer sufferers.

C-reactive protein is produced by the liver, in response to infection or injury, when stimulated by the cytokine IL-6. Tumor sites are often associated with inflammation and this inflammation contributes to tumor growth, invasion and metastasis. While elevated CRP has been found associated with a poor outcome for many solid tumors, including endometrial, cervical, prostate and colorectal cancer, there has been some discussion about whether this is true for breast cancer.

Researchers from Denmark looked at data from over 2000 breast cancer patients and followed their progress for up to seven years from diagnosis (average follow up was three years). The researchers found that regardless of lifestyle, menopause status and presence of cardiovascular disease, increasing levels of CRP resulted in increasingly poor prognosis. The five-year survival decreased from 90% for low CRP to 74% for high levels of CRP, disease-free survival reduced from 87% to 74%, and deaths from breast cancer increased from 11% to 20%.

Dr Kristine Allin, from Herlev Hospital, said, "Elevated CRP at time of diagnosis remained predictive of overall survival rates regardless of patient's age, tumor size, lymph node status, or presence of metastasis, and whether or not the patient was estrogen receptor positive. It was still true even when we excluded patients which we believed to have bacterial infections because of their very high CRP levels."

Dr Allin continued, "While measuring CRP levels gives a general indication of health and longevity, measuring CRP levels for breast cancer patients seems to be an easy way to predict the severity of the patient's disease. This may allow clinicians to alter their treatment tactics and improve cancer survival rates."

"Elevated pre-treatment levels of plasma C-reactive protein are associated with poor prognosis after breast cancer: a cohort study"
Kristine H Allin, B°rge G Nordestgaard, Henrik Flyger and Stig E Bojesen
Breast Cancer Research

Personal Experience Tilts Our Risky Decision Making

From high-stakes gambling in a casino to deciding whether or not to buy an airplane ticket today or wait for a possible seat sale, our processes for making decisions involving risk show distinct patterns.

A new study from the University of Alberta provides evidence that decisions involving risk depend on how we get the information about the potential risks and rewards.

The research team, led by Elliot Ludvig, gave people two kinds of choices. One choice was between a surefire win and a 50/50 chance at a double-or-nothing win. The other choice was between a surefire loss and a 50/50 chance at a double-or-nothing loss.

Decades of economic research have shown that people tend to take the safe option when the choice involves wins, but they tend to gamble when the choice involves losses. This aversion to risk for wins poses a puzzle: If people avoid gambling for wins, then why are casinos so popular, and why does problem-gambling affect so many people?

To answer these questions, the study compared people's decisions when choices were described to them versus when they experienced the wins and losses first hand.

The researchers put two games of chance on computers for a group of volunteer players. In one game, the choices were clearly described in text on a computer screen. This approach is the traditional way to study economic choice.

In the other game, the odds of winning and losing were exactly the same, but players were given no guidance whatsoever. Players were presented with doors and their choices revealed the wins or losses behind each door. The players had to learn about the odds through their own experience of trial and error. All players were put through both styles of games.

The researchers found that if people experienced the wins and losses first hand, as they would in a casino, they behaved completely differently than when they were told the odds. When they learned from experience, people were more likely to take the leap and gamble on the double-or-nothing wins. But with experience they become less likely to take the double-or-nothing gamble when the choice involved losses.

In other words, most people make the opposite choices if the odds are described to them than if they learn about the odds from their own experience.

"We are continuously confronted with risky decisions--be it shopping at the mall, picking a course of medical treatment, gambling at a casino, or deciding how to allocate assets in our retirement accounts," said Dr. Ludvig. "Our research suggests that people's propensity for risk in these situations may depend on how they learn about the odds."

Experiencing the odds causes people to behave differently than if the odds are presented to them verbally. The researchers suggest that part of this discrepancy may result from the influence of memory of winning, or possibly even by the wins they see other people experience.

"We think that people choose in fundamentally differently ways when they are remembering their past wins and losses than when they are thinking about abstract future possibilities", said Dr. Marcia Spetch, an author of the study. "When basing choices on memory, people may focus more on the bigger wins and the bigger losses."

The research was published in the journal PLoS ONE.

Citation: Ludvig EA, Spetch ML (2011) Of Black Swans and Tossed Coins: Is the Description-Experience Gap in Risky Choice Limited to Rare Events? PLoS ONE 6(6):e20262. doi:10.1371/journal.pone.0020262

Funding: This research was funded by Natural Sciences and Engineering Research Council of Canada Discovery Grant #38861 (MLS) and the Alberta Gaming Research Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Source:
PLoS ONE

World Wars Camouflage Technique Could Have Benefits In Modern Warfare

Painting army vehicles with high contrast geometric patterns - 'dazzle camouflage' - affects the perception of their speed and thus could make them less susceptible to rocket propelled grenade attacks, according to new research from the University of Bristol. Warships in both the First and Second World Wars were painted with dazzle camouflage: startling geometric patterns aimed at confusing the enemy rather than concealing the vessel.

It was thought that such patterning would disrupt the enemy's perception of a ship's range, heading, size, shape and speed, thus reducing losses from torpedo attacks by submarines. While there were good reasons to believe that these perceptual distortions occurred, the effectiveness of dazzle camouflage was never scientifically proven.

The Bristol study, an interdisciplinary collaboration between the Schools of Experimental Psychology and Biological Sciences, led by Dr Nick Scott-Samuel, is the first to find evidence that dazzle camouflage can affect perception of speed - but only if the camouflaged object is moving quickly.

These findings suggest that, while it would probably not have successfully distorted ships' speeds in the two World Wars, dazzle camouflage could play a role in today's battlefields where fast-moving army vehicles frequently come under attack from shoulder-launched, rocket-propelled grenades.

Our perception of speed is affected by many disparate factors: for example larger objects appear to move more slowly than smaller objects, changes in contrast alter perceived speed, and differently oriented textures can be seen as moving at different speeds. Any of these effects could be elicited by dazzle patterning.

Dr Scott-Samuel and colleagues showed their experimental participants two moving patterns on a computer screen, and asked them to report which one moved faster. One pattern was always plain and the other was selected from a typical range of textures used in dazzle camouflage: stripes, zigzags and checks. The stimuli moved either slowly or quickly, and could be either low or high contrast.

When moving quickly, two of the high contrast patterns caused a significant reduction in perceived speed of around 7 per cent. These patterns - zigzags and checks - were two-dimensional, in contrast to the other, one-dimensional, patterns tested. Patterns which were less visible (low contrast) or slow moving had no effect on perceived speed; the former finding indicates that the effect is not simply due to texture per se, and implies that straightforward background-matching camouflage (which is generally lower contrast) would not produce a speed distortion. High contrast texture, as used for dazzle camouflage, is necessary.

Dr Scott-Samuel said: "The effect should obtain in predators launching ballistic attacks against rapidly moving prey,or on modern, low-tech battlefields where handheld weapons are fired from short ranges against moving vehicles. In the latter case, we show that in a typical situation involving an RPG7 attack on a Land Rover the reduction in perceived speed would be sufficient to make the grenade miss where it was aimed by about a metre, which could be the difference between survival or otherwise for the occupants of the vehicle."

Citation: Scott-Samuel NE, Baddeley R, Palmer CE, Cuthill IC (2011) Dazzle Camouflage Affects Speed Perception. PLoS ONE 6(6): e20233. doi:10.1371/journal.pone.0020233

Funding: These authors have no support or funding to report.

Competing Interests: The authors have declared that no competing interests exist.

Source:
PLoS ONE

New Antibiotics A Step Closer With Discovery Of Bacterial Protein Structure

Scientists have uncovered the structure of the protein complex that assembles the tiny hair-like strands that cover the outside of bacteria. Called pili, these 'hairs' allow bacteria to group together and stick to human cells to cause infection - and are therefore a key target for a new generation of antibiotics.

Published today in Nature, scientists at the Institute of Structural and Molecular Biology (a joint institute between University College London (UCL) and Birkbeck) have revealed the structure of a complex protein called FimD that acts as an assembly platform for the pili of cystitis bacteria. The structure of the FimD protein means scientists can see the process of pili assembly, from individual protein subunits to complete structures, for the first time.

Pili are tiny hair-like strands on the outside of bacteria that help them to link together in groups. In the case of cystitis, pili allow bacteria to attach themselves to the wall of the bladder, leading to bladder cells engulfing the bacterium. Once the bacteria have invaded the bladder cells, they escape traditional antibiotic treatment and lie dormant, making recurrent infections very common.

Scientists believe that antibiotics could be developed that disrupt the FimD protein, and therefore the production line of pili proteins. The UCL/Birkbeck group, together with collaborators in the USA, have already discovered small molecules able to interfere with pilus biogenesis. Without their pili, bacteria cannot attach to each other or the host, making infection much less likely.

Professor Gabriel Waksman from the UCL Research Department of Structural and Molecular Biology and the Birkbeck Department of Biological Sciences, who led the research, said: "Cystitis is one of the most common gram negative bacterial infections; it can also be extremely painful and surprisingly hard to treat - especially repeat infections."

"Pili are a prime target for a new breed of antibiotics to target cystitis and other conditions, as without pili bacteria are unable to attach themselves to each other or the walls of human cells, and therefore much less likely to cause serious infections."

Pili protein subunits are made inside bacteria and initially transported through the inner cell wall. Each subunit is then picked up by a 'chaperone' protein which takes it across to a protein in the outer cell wall called the 'usher'.

The usher protein coordinates the ordered assembly of pilus subunits, i.e. the growth of the pili. This research, funded by the Medical Research Council, has isolated and crystallised the usher protein in cystitis bacteria, FimD, while it's bound to the chaperone/subunit combination.

The structure of FimD provides insights into pilus biogenesis because it unravels the entire mechanism of subunit polymerization and transport across the outer wall of the bacteria. "Scientists have been working for a number of years to work out the how pili are assembled. This is the first view of the transportation and assembly of pili in action," said Professor Waksman.

Source
University College London

Fear Of Dying During A Heart Attack Is Linked To Increased Inflammation

Intense distress and fear of dying, which many people experience when suffering the symptoms of a heart attack, are not only fairly common emotional responses but are also linked to biological changes that occur during the event, according to new research published online today in the European Heart Journal [1]. These changes, in turn, are associated with other biological processes during the following weeks that can predict a worse outcome for patients.

Acute coronary syndrome (ACS) is a medical emergency arising from blockage of the coronary arteries, resulting either in a myocardial infarction (heart attack) or unstable angina. The symptoms are varied, but often include pain in the chest, shortness of breath, sweating, nausea and vomiting. ACS patients are at risk of further heart problems and a worse quality of life in the future.

Researchers in London (UK) set out to discover whether there was an association between the intense emotional responses of patients suffering ACS and levels of a cell-signalling molecule - tumour necrosis factor alpha (TNF alpha) - that is involved in inducing systemic inflammation. They also wanted to see whether the emotional response and TNF alpha correlated with indicators of worse biological function (and, therefore, worse prognosis) three weeks later.

A total of 208 patients admitted to St George's Hospital (London, UK) between June 2007 and October 2008, with a diagnosis of ACS were included in the study. The researchers assessed the patients' level of distress and fear of dying and measured levels of TNF alpha within two to three days of hospital admission. Around three to four weeks after the hospital admission researchers made a home visit to record heart rate variability (HRV) and the stress hormone cortisol. Low levels of cortisol may lead to a failure to control inflammation, while low HRV indicates that the heart is functioning poorly and is a predictor of future cardiac problems [2].

Professor Andrew Steptoe, Head of the Department of Epidemiology and Public Health and British Heart Foundation Professor of Psychology at University College London (UK), said: "We found that, first of all, fear of dying is quite common among patients suffering a heart attack; it was experienced by one in five patients. Although survival rates have improved tremendously over the last few decades, many patients remain quite frightened during the experience.

"Secondly, fear of dying is not just an emotional response, but is linked into the biological changes that go on during acute cardiac events. Large inflammatory responses are known to be damaging to the heart, and to increase the risk of longer-term cardiac problems such as having another heart attack. We found that, when compared with a low fear of dying, intense fear was associated with a four-fold increased risk of showing large inflammatory responses, measured by raised levels of TNF alpha. Interestingly, this was independent of demographic and clinical factors such as the severity of the cardiac event.
"Thirdly, fear of dying and inflammatory responses in turn predicted biological changes in the weeks following an acute cardiac event, namely reduced heart rate variability and alterations in the output of the hormone cortisol. These processes may contribute to poor outcomes in the longer term."

The level of distress was unrelated to any previous experience of having a heart attack, but the research suggested that intense distress might be stimulated by worse or more painful symptoms during ACS, and then accentuated in patients who are more socially isolated and economically deprived.

Prof Steptoe and his co-authors say that processes underlying the association between the intense emotional responses and higher levels of TNF alpha are not fully understood. However, they may be connected as manifestations of an integrated biological and emotional response to severe injury to the heart.

The findings could suggest new avenues of research to improve the management of ACS patients. "This is an observational study, so we do not know whether helping people overcome their fears would improve the clinical outlook, or whether reducing the levels of acute inflammation would have beneficial emotional effects, but these are possibilities," said Prof Steptoe. "At the immediate clinical level, we would recommend that doctors talk to patients more about their emotional experience when having a heart attack, rather than just concentrating on the physical outcomes. The two are closely linked, and better information and reassurance could be of great benefit.

"Care for patients with acute heart disease has improved greatly over recent decades, but we are still concerned about people who recover in the short-term, but remain at risk for repeat heart attacks or other cardiovascular problems. This research is an illustration of how closely emotional, behavioural and biological responses are integrated. Patients' emotional responses are relevant to how they react biologically, and vice versa."

In an accompanying editorial [3], Susanne Pedersen, Professor of Cardiac Psychology at the University of Tilburg (Tilburg, The Netherlands), and colleagues describe Prof Steptoe's findings as "seminal" and write that they "point towards an avenue worthwhile pursuing for the fields of translational cardiovascular medicine and behavioural cardiology".

They conclude: "In order to optimize the management and care of CHD [coronary heart disease] patients, we need to acknowledge that emotions carry independent additional risk, with particular subsets of patients dying prematurely due to their psychological vulnerability. Physiological mechanisms may provide part of the answer to the vicious cycle linking emotions to incident CHD and its progression. Behavioural mechanisms should not be forgotten, as there is an urgent need for more effective lifestyle management in these patients, due to increases in the prevalence of obesity and diabetes, and no change in the proportion of patients who smoke, despite an increase in the prescription of cardioprotective drugs. The issue of inadequate lifestyle management is unlikely to be resolved without attending to the emotions of our patients, as emotions such as depression play a pivotal role in compliance and adherence. This suggests that the 'one size fits all approach' to intervention in CHD patients is unlikely to work and that a personalized medicine approach is warranted."

[1] "Fear of dying and inflammation following acute coronary syndrome".
European Heart Journal. doi:10.1093/eurheartj/ehr132

[2] Heart rate variability (HRV): There are small variations in the time between each heart beat. The pace at which the heart beats is controlled by a branch of the nervous system called the autonomic nervous system. Heart rate variability is a measure of how effectively that system is operating. Low HRV is an indicator of poor functioning, and can predict future cardiac problems.

[3] "Heart and mind: are we closer to disentangling the relationship between emotions and poor prognosis in heart disease?".
European Heart Journal. doi:10.1093/eurheartj/ehr156

Mother's Body Size And Placental Size Predict Heart Disease In Men

Researchers investigating the foetal origins of chronic disease have discovered that combinations of a mother's body size and the shape and size of her baby's placenta can predict heart disease in men in later life. The research is published online today in the European Heart Journal[1].

Professor David Barker and colleagues studied 6975 men born in Helsinki (Finland) between 1934-1944 - a time when not only was the babies' size at birth recorded but also the size of the placental surface. Other available information included details of the mothers' height and weight in late pregnancy, age, parity, and date of last menstrual period.

They found that there were three combinations of mother's body size and placental shape and size that predicted coronary heart disease in boys when they reached late adulthood (from about aged 40 onwards):An oval-shaped placental surface in short mothers who had not been pregnant before - the narrower the placental surface in relation to its length, the more the risk of heart disease rose, increasing by 14% for each centimetre increase in the difference between the length and breadth of the surface. A small placental surface in tall, heavy women (those with a body mass index (BMI) over 26 kg/m2, the middle value for the women in the study); in these men their risk of heart disease rose by a quarter (25%) per 40cm2 decrease in the surface area. A large placental weight in relation to birthweight in babies born to tall mothers with a BMI below 26 kg/m2; these men had a seven percent increased risk for every one percent larger ratio of placental weight to birthweight. The associations were independent of the social class of the men or the family into which they were born.

Prof Barker, who is Professor of Clinical Epidemiology at the University of Southampton (UK) and Professor in Cardiovascular Medicine at Oregon Health and Science University (USA), has already discovered that there is a link between placental weight and heart disease in later live, but placental weight does not indicate the size of the surface that is available for absorbing and delivering nutrients for the growing baby. "Due to the fact that the shape and size as well as the weight of the placenta were routinely measured at the birth of this group of men, we have been able to show for the first time that a combination of the mother's body size and the shape and size of the placental surface predicts later heart disease," he said.

For each of the three combinations, the babies that developed heart disease in later life tended to be thinner than average, which indicated that they were undernourished at birth.

Prof Barker said that he thought the explanation for the first combination (oval placental surface in women who have not been pregnant before) is that "an oval placental surface is an indication that the implantation of the placenta was disrupted in early pregnancy, leading to foetal under-nutrition, which, in turn, programmes coronary heart disease in later life". The mechanisms that may play a role in disrupting the implantation of the placenta are not yet fully understood.
For the second combination (small placental surface in tall, heavy women), Prof Barker said: "Although the mother is tall and has a BMI of over 26 kg/m2, indicating that she was well-nourished at the time of her pregnancy, placental growth depends on the structure and function of the mother's uterine wall, which is established during her own foetal life. Therefore, her own foetal experience necessarily affects placentation in her offspring. Foetal growth depends on the availability of nutrients. Restricted placental growth may, paradoxically, have a greater effect in babies who are growing rapidly because their mothers are well-nourished. We think that these babies were able to grow rapidly at first, but the small placenta started to restrict their growth mid-gestation, so that by the time they were born, they were under-nourished."

For the third combination (large placental weight in relation to birthweight in babies born to tall women below the average weight), Prof Barker believes the explanation lies in what the mother ate during pregnancy. "Tallness indicates good nutrition before pregnancy, but their low body mass index indicates poor nutrition during pregnancy," he said.

Prof Barker says that this research is further evidence of the long-term effect of foetal development. "Chronic disease is the product of a mother's lifetime nutrition and the early growth of her child. It is not simply a consequence of poor lifestyles in later life. Rather it is a result of variations in the normal processes of human development."

Now the researchers plan to study the diets and body characteristics (body size and shape, fat and lean mass) of pregnant women, the growth patterns of their babies before birth using ultrasound, and the placentas of their offspring. They hope to discover the links between the mother, her baby's placenta and the development of the baby's cardiovascular system in ways that lead to poor liver and vascular function - two of the primary culprits for heart disease in later life.

"Mother's body size and placental size predict coronary heart disease in men"
European Heart Journal. doi:10.1093/eurheartj/ehr147

Sexual Health Of Men With Chronic Heart Failure Significantly Improves With CRT

A new study published in the journal Clinical Cardiology reveals that in men with chronic heart failure, cardiac resynchronization therapy (CRT) improves patients' libido, erectile dysfunction, and sexual performance.

Chronic heart failure (HF) is a common, complex clinical syndrome characterized by fatigue and exercise intolerance. HF patients experience decreased libido and erectile dysfunction (ED). CRT, which is a type of pacemaker that paces the right and left ventricle, is used to treat patients with HF.

Led by Ahmet Vural of Kocaeli University, researchers investigated the effects of CRT on libido and ED. 31 male patients with advanced HF, scheduled for implantation of a CRT device, were included in the study. They were assessed before and six months after CRT.

At the six-month follow-up after CRT, 23 patients reported no ED, and only two patients had moderate ED. Severe ED was not found in any patient. A significant increase in patients with normal libido was found, with 25 men reporting improvement compared to only three reporting normal libido prior to CRT.

The findings show that CRT results in significant improvement in libido, ED, and sexual performance as a consequence of the improvement in functional capacity and ejection fraction.

"Not only does CRT decrease mortality in heart failure patients, it also brings improvement in sexual health to the patient's life," Vural concludes.

Full citation:
"Effect of Cardiac Resynchronization Therapy on Libido and Erectile Dysfunction."
Vural et al.
Clinical Cardiology

THT Launches New Weekly HIV Testing Session In Telford, UK

HIV and sexual health charity Terrence Higgins Trust (THT) is to launch a mid-week rapid HIV testing session in Telford, to compliment the existing weekend service. Following a launch event on Friday 10th June, the service will run every Wednesday evening from THT's centre on Park Street.

The rapid testing service, which is called 'Fastest', is free and confidential. The clinic is open to everyone, providing an alternative testing environment for people who are not able to access services during the normal working day, or who may be put off by hospitals and traditional sexual health clinics.

Testing is done using a finger-prick blood test, with the results provided within one hour. Those who attend the clinic will be given information and support before and after the test, and those who test positive will be referred immediately to a specialist clinic. THT staff will also provide free condoms, and information and advice on safer sex.

The launch on Friday 10th June runs from midday until 6:00pm. During that time members of the public can come in and see for themselves what the service is like, as well as find out more about what THT is doing locally.

Lotte Hakeman, Senior Practitioner at THT in Telford, said: "With advances in HIV treatment, there are now far more reasons to know your HIV status than there are not to. However, some people might find it difficult taking time out from work to check-up on their sexual health. We're delighted to be expanding our Fastest service, and hope we can encourage more people to come forward for testing and reduce undiagnosed HIV locally. So, if you haven't had a test in a while, or you're worried you may have put yourself at risk, please come along and take advantage of our fast and friendly service."

From Wednesday 15th June, THT will run a weekly 'Fastest' clinic in Telford on Wednesday evenings from 5:00pm - 7:00pm; and a monthly Saturday clinic from 12:30pm - 2:30pm on the first Saturday of the month. Testing is also available at other times by appointment. All clinics take place at 4 Park Street, Wellington, Telford TF1 3AE. For further information or to make an appointment, please call (01952) 221410, or email info.shropshire@tht.org.uk.

Source:
Terrence Higgins Trust

Plasma Blood Resuscitation Protects Blood Vessel Walls

Using plasma rather than standard resuscitation fluids seems to improve survival in trauma patients with massive blood loss. Now a new study in animals suggests that this benefit may result from plasma's ability to restore the "endothelial glycocalyx," a special layer lining the blood vessels, reports the June issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

Dr. Rosemary A. Kozar of University of Texas Health Science Center at Houston conducted a study in rats to find out how plasma resuscitation affects the endothelial glycocalyx-a coating that lines and protects the integrity of endothelial cells and blood flow within blood vessels. Recent studies have found the glycocalyx performs a number of important functions, including protecting the blood vessel wall from inflammation-promoting factors in blood.

Plasma Infusion Restores Damage to Glycocalyx Caused by Hemorrhagic Shock

In the experiments, rats were subjected to hemorrhagic shock, then resuscitated with electrolyte solutions or with plasma-the liquid portion of blood (ie, with the blood cells removed). Consistent with recent epidemiologic studies in human trauma patients, plasma appeared more effective than standard fluid in resuscitating the rats from hemorrhagic shock, and helped to reverse evidence of lung damage that accompanies shock.

The researchers took a close look at how the endothelial glycocalyx was affected during the experiments. Electron microscope images showed that hemorrhagic shock caused a sharp reduction in the thickness of the glycocalyx-it was basically stripped away. This damage was little affected by resuscitation with standard fluids.

However, in animals receiving plasma resuscitation, the damage to the glycocalyx was largely restored within a few hours. The plasma-resuscitation group also showed higher levels of messenger RNA for syndecan-a protein that forms the "backbone" of the glycocalyx.

"Taken together, our findings support the protective effects of plasma seen clinically, which may be due in part to its ability to restore the endothelial glycocalyx and preserve syndecan-1 after hemorrhagic shock," Dr. Kozar and coauthors conclude. Although the results of animal studies may not directly apply to the human situation, they provide an important clue as to how plasma resuscitation works to improve outcomes in trauma patients.

An accompanying editorial by Dr. Marie Csete of iFluidics and the University of California, San Diego, sets the results in the context of the "Great Fluid Debate"- the ongoing controversy among anesthesiologists as to the best approach to fluid resuscitation in critically ill patients. While the study raises many new questions, "It does point to syndecan-1 and the glycocalyx as a whole as potential targets of therapies in shock patients," according to Dr. Csete.

"The rapid time course of reversal of the cellular pathologies by plasma resuscitation was particularly striking, but also may indicate a short therapeutic window for optimal resuscitation," Dr. Csete adds. She calls for further studies to see whether syndecan-1 (which coordinates signals from outside cells to the inside of cells) and other glycocalyx components could be used as markers of severity of injury, and potentially markers of the adequacy of resuscitation for patients with massive blood loss.

Source:
International Anesthesia Research Society (IARS)

Study Finds Very Low Risk Of Anesthesia-Related Death In Healthy Children

A large study at an Australian children's hospital suggests that there's little or no risk of death related to anesthesia in healthy children, reports the June issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

Although the study identified ten anesthesia-related deaths out of a series of nearly 102,000 anesthesia procedures in children, all of the children who died had heart disease or other serious medical conditions. The overall rate is actually higher than reported in some previous studies, raising questions about how "anesthesia-related deaths" should be defined. The lead author of the study was Dr. Benjamin F. van der Griend of Christchurch Hospital, New Zealand.

More Accurate Data on Anesthesia-Related Deaths in Children
The researchers analyzed 101,885 anesthesia procedures in 56,000 children undergoing surgery at Children's Hospital, Melbourne, Australia, from 2003 to 2008. Deaths within 24 hours and 30 days after the anesthesia were identified. A panel of expert anesthesiologists judged whether each death was related to the anesthesia in any way.

The overall rate of death from any cause within 24 hours was 13.4 per 10,000 anesthesia procedures, while the rate of death within 30 days was 34.5 per 10,000 procedures. The risk of death was higher among infants aged 30 days or younger and among infants and children undergoing heart surgery.

Overall, 10 deaths were considered to be related to anesthesia, or to factors under the control of the anesthesiologist-a rate of just under 1 out of 10,000 anesthesia procedures. "In all 10 cases, preexisting medical conditions were identified as being a significant factor in the patient's death," according to the authors. Five of the ten deaths occurred in children with pulmonary hypertension, or abnormally high blood pressure in the arteries of the lungs.
Especially in children, anesthesia-related death is a rare event-so rare that it's difficult to get reliable estimates of the risk. The rates reported in the new study are higher than in most previous studies. However, they're also based on patients seen at a national children's hospital, many with serious illnesses.

All of the deaths occurred in children with "significant life-threatening medical problems." Before recent medical advances, many of these children would likely have been considered "unfit for anesthesia," Dr. van der Griend and colleagues note. They highlight the need for careful planning and clear communication with families to provide "realistic pictures of the risks and benefits" of anesthesia for children with such complex medical conditions.

The study also suggests that, for healthy children, the risk of anesthesia-related death should be very low. Dr. van der Griend and colleagues even question whether it's appropriate to list death as a potential risk of anesthesia for children without significant medical problems.

In an accompanying editorial, Dr. Jayant K. Deshpande of Arkansas Children's Hospital and University of Arkansas for Medical Sciences emphasizes that the study used a new and not generally accepted definition of anesthesia-related deaths-which likely helps to explain why the reported rate is higher than in previous studies. Dr. Deshpande believes that establishing a "uniform, clinically useful definition" of anesthesia-related death would help in standardizing studies of anesthesia risks, and thus in clarifying the true risks-for healthy children as well as those with serious medical conditions.

Source:
International Anesthesia Research Society (IARS)

HbA1C Test For Glucose Monitoring Poorly Predictive In Dialysis Patients

The gold standard long-term glucose monitoring test for patients with diabetes proved to be of limited value in dialysis patients, according to a new study at Wake Forest Baptist Medical Center. The study appears online in the Clinical Journal of the American Society of Nephrology and is scheduled for the July print issue.

Blood sugar monitoring is a vital part of diabetes management. Patients and physicians rely on the hemoglobin A1c (HbA1c) test to measure an individual's average blood sugar level over the prior three months. It is the most commonly used long-term blood sugar test, and is widely trusted in the medical community. While the American Diabetes Association has deemed the HbA1c test an effective tool for diagnosing diabetes, kidney doctors recently determined that the HbA1c is not as useful for managing patients with diabetes and advanced kidney failure. Another test, the glycated albumin or GA assay, appears to be far more effective in this setting.

"Many organs don't function properly in severe kidney failure," explained Barry I. Freedman, M.D., John H. Felts III Professor and lead investigator. "For example, most dialysis patients have anemia with fewer red blood cells than they should, which has a dramatic impact on the accuracy of the HbA1c reading."

Hemoglobin inside red blood cells carries oxygen in the body. Blood sugar chemically interacts with the hemoglobin to identify a value for HbA1c. But HbA1c results are only accurate when red cells have a normal lifespan. Dialysis patients have shorter red cell survival, reducing the time that sugar in the bloodstream has to interact with hemoglobin, and causing lower HbA1c values.

"Doctors long thought the HbA1c predicted outcomes in diabetes," Freedman said. "This test is not predictive of outcomes in diabetes patients with kidney disease on dialysis. Dialysis patients and physicians get a false sense of security because their lower HbA1c actually relates to shorter red cell survival, yet suggests diabetes control is better than it really is."

Nearly 500,000 people are on dialysis in the Unites States and diabetes is the cause of kidney failure in nearly 50 percent of them. Diabetes is the most common cause of kidney failure worldwide and is associated with high mortality rates - more than 20 percent of dialysis patients die each year. As such, there is an urgent need for accurate blood sugar testing in diabetic dialysis patients.

Freedman and colleagues evaluated 444 patients with diabetes undergoing dialysis. Patients continued their normal treatment and HbA1c monitoring, but also agreed to have a GA test every three months for an average of more than 2.3 years.

The GA test, developed by Tokyo-based Asahi Kasei Pharma Corporation, measures blood sugars over the past 17 days, as opposed to the longer time frame for HbA1c. In situations where rapid changes occur in blood sugar, the GA gives a more accurate picture of diabetes control. The GA test used in this study is available in Japan, China and South Korea, but is not yet FDA approved in the United States.

Wake Forest Baptist researchers compared the patients' HbA1c and GA test results, assessing their ability to predict hospitalizations and survival. They found that the HbA1c failed to predict these important medical outcomes. In contrast, the GA was a strong predictor of patient survival and hospitalizations.

"This is the first study showing that a blood sugar test predicts risk of death in diabetic dialysis patients, as well as risk of hospitalization," Freedman said. "This test provides the missing link that will allow dialysis patients and physicians to accurately gauge risk. The association is clear: high GA readings predict higher risk."

Freedman suggests physicians not rely on the HbA1c in dialysis patients, instead suggesting that blood glucose levels be directly monitored with multiple daily readings until the GA test is available in the states.

Wake Forest Baptist is the largest academic provider of outpatient dialysis services in the country, with 17 freestanding facilities treating more than 1,550 patients. Co-authors on the study, sponsored by Asahi Kasei Pharma Corporation, are: Lilian Andries, M.D., Zak K. Shihabi, Ph.D., Michael V. Rocco, M.D., Gregory B. Russell, M.S., Cesar Y. Cardona, M.D., and Anthony J. Bleyer, M.D., all of Wake Forest Baptist. Additional support and testing was provided by Meridian Laboratories in Charlotte, NC, as well as the outpatient dialysis services of Wake Forest Baptist.

Source:
Wake Forest Baptist Medical Center

Global CO2 Emissions Reach Record High

Energy-related CO2 emissions reached a record high in 2010, raising doubts that agreed limits on global warming will be achieved by 2020, according to the Paris-based international energy watchdog, the IEA.

In a statement issued on Monday, the International Energy Agency (IEA), an intergovernmental organization set up by wealthy OECD nations following the 1973 oil crisis, said the "prospect of limiting the global increase in temperature to 2ºC is getting bleaker".

According to their latest estimates, 80% of the emissions anticipated from the power sector between now and 2020 are already "locked in" as they will come from power plants already in use or under construction.

Although there was a dip in 2009, caused by the global financial crisis, the IEA estimates that global CO2 emissions for 2010 rose to a record 30.5 Gigatonnes (Gt), the highest ever, and 5% higher than the 2008 figure of 29.3 Gt.

Broken down by fuel type, 44% of the the estimated CO2 emissions in 2010 came from coal, 36% from oil, and 20% from natural gas.

IEA's Chief Economist, Dr Fatih Birol, who oversees the IEA's annual flagship publication the World Energy Outlook, told the press that:

"This significant increase in CO2 emissions and the locking in of future emissions due to infrastructure investments represent a serious setback to our hopes of limiting the global rise in temperature to no more than 2ºC."

2ºC is the target limit that world leaders agreed to at the United Nations climate change conference in Cancún, Mexico, in November and December 2010.

The agreement recognizes that this will require deep cuts in global greenhouse gas emissions.

This means that the long-term atmospheric concentration of greenhouse gases must not exceed 450 parts per million of CO2-equivalent. This is only 5% higher than the estimated 430 ppm level of 2000.

In the 2010 issue of the World Energy Outlook, the IEA set out the energy pathway that would be consistent with staying inside this limit, called the "450 Scenario".

Essentially this shows that in order to achieve the 2ºC target limit, the global energy-related emissions must not exceed 32 Gt, which means that the rise in total emissions for the next ten years must be smaller than it was for the period 2009-2010.

Birol said the latest estimates are "another wake up call", and warn that we are "incredibly close" to the 2020 level already.

"Given the shrinking room for manoeuvre in 2020, unless bold and decisive decisions are made very soon, it will be extremely challenging to succeed in achieving this global goal agreed in Cancún," she added.

The IEA statement recognizes that the challenge of improving and maintaining people's quality of life while at the same time limiting CO2 emissions "has never been greater".

The agency estimates that while in 2010 about 40% of global CO2 emissions came from OECD countries, they only accounted for 29% of emissions growth. This contrasts with non-OECD countries, led by China and India, who saw much greater increases in emissions, due to the accelerated growth of their economies. But if you compare on a per head basis, the OECD countries emitted about 10 tonnes per person in 2009-2010, compared with only 5.8 tonnes in China and an even smaller 1.5 tonnes in India.

It doesn't take much brainpower to work out that it will take an enormous "paradigm shift" to put the world on a different path to reach the 2020 target.

Lord Stern, author of the 2006 Stern Review on the Economics of Climate Change, told BBC Radio 4's Today program, that the 2020 target is "not impossible" but the "window for action is closing".

If the global leaders who met in Cancún were to attain their promised goals, then in 2020, in ten years time, we would be at the same levels that we are now, he added. He agreed that the IEA estimates were a "wake up call" and they show we are already slipping behind on the promises made in Cancún.

Sources: International Energy Agency, World Energy Outlook, BBC.

Allergies Worst In Years This Spring, Including Hearing Problems, Chicago

Local hearing clinics in Chicago say this is the worst spring in several years for allergy-related hearing problems. Dr. Michael Jones, of the Hearing Health Center (HHC) said he is seeing a large number of patients each week with hearing problems caused by seasonal allergies.

Experts say this season is especially bad for allergies because late snowfalls, plus the particularly wet months of April and May have brought about excess moisture.
High pollen levels do not only cause problems in the nose and eyes, but also commonly trigger an accumulation of fluid and wax in the middle ear, which also swells, blocking off the Eustachian tubes, resulting in poor hearing.

Dr. Jones said:

"Typically, allergic patients have complained of a symmetrical hearing loss and a sense of fullness or pressure. In most cases the hearing test shows a slight hearing loss and a tympanogram shows reduced mobility of the tympanic membrane. That means the middle ear has become inflamed."

As allergies subside so do hearing problems, Dr. Jones explained. In most cases, if the audiologist cannot identify any other underlying problem, the patient is advised to check with an ENT (ear, nose and throat) specialist to make sure. OTC (over-the-counter) antihistamines and decongestants may provide some temporary relief.

Seasonal hearing problems caused by allergies have become so common that some doctors are treating patients with immunotherapy, which was shown in one 1992 study to improve the hearing of 60% of patients with Meniere's Disease (a condition with vertigo, tinnitus and progressive deafness).

Individuals who experience hearing loss, even if they believe it is caused by a seasonal allergy, should get it checked by a doctor. The doctor can than rule out any other serious problem, and help alleviate the symptoms. Continuous pressure in the middle ear can cause permanent hearing loss. If you experience ringing in the ears (tinnitus) or vertigo (dizziness, or a feeling that things are dizzily turning around you), see your doctor.
A significant proportion of Dr. Jones' current visitors are baby boomers with borderline hearing problems. They complain they cannot clearly hear what people are saying. In some cases, new invisible long-term hearing devices can help. 50% of the US population is affected by some kind of allergy, according to the Hearing Health Center, and at least 12% are affected by hearing loss.

Founder of the Hearing Health Center, Dr. Ronna Fisher Au.D., FAAA, said:

"People take it for granted that allergies cause sneezing in the nose and itching in the eyes. Yet they seem surprised to learn allergies inevitably affect their ears as well."

Source: Hearing Health Center

European Survey Show Significant Impact Of ADHD At School And Home, Yet Parents Wait Over Two Years For An ADHD Diagnosis

Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, today announced the results of a new European survey that found children with ADHD have statistically significant impairments in all aspects of life investigated vs. children without ADHD. Yet, parents take an average of 26.8 months to achieve a diagnosis for their child.


"These data fill a gap in ADHD understanding we have been trying to address for some time on the true impact of, and impairment caused by the disorder for children both at home and at school across European countries" said Dr Caci, Chair of the Survey Steering Committee, Hôpitaux Pédiatriques de Nice. "The survey results hint at the depth of the problem we see in these countries in trying to manage the condition optimally and highlight the pressing need for more work in this area to try and address the significant imbalance in all aspects of life between children affected by ADHD and their non-ADHD classmates and siblings."

Further data from the survey presented today showed teenagers with ADHD were significantly more likely to have conduct problems like excessive alcohol consumption and getting into fights than those without ADHD, as reported by their parents or caregivers. Frustration with either the number of visits or the number of doctors needed to be seen before a formal diagnosis of ADHD was given was reported by over half of respondents (54%). Over one third (38%) of parents/caregivers needed to see three or more doctors before receiving a diagnosis. However, almost half (46%) of children with ADHD were currently receiving medication with 73% of parents satisfied with that medication - most commonly feeling the medication provided sufficient control of symptoms during the school day but not beyond.

"It is worrying that parents still have to battle so hard to achieve the diagnosis that may enable them to begin to address some of the problems their children have, and access treatment that could make a real difference to their future. We all know that for a child's healthy development every year counts, so to see diagnosis take over two years on average highlights the need for better access to ADHD services to get the best package of care for every child and help avoid some of these consequences," said Myriam Menter, ADHD Europe.

These findings are further supported by a new review of ADHD studies. In 281 reviewed scientific papers, ADHD is shown to negatively impact major areas of life, including academic and professional achievement, health, and social behaviour, and is a significant cost to society. Recent research also demonstrates that ADHD has related problems such as low self-esteem, anger outbursts, mood swings, cognitive problems and social and family function and is associated with increased delinquency/criminality, criminal acts, and arrests/incarceration.

ADHD also carries an economic burden. Preliminary findings based on 13 US studies calculates that ADHD costs approximately 31.5 billion Euros in childhood and adolescence annually.

Source: Porter Novelli

Super-Sticky 'Ultra-Bad' Cholesterol Revealed In People At High Risk Of Heart Disease

Scientists from the University of Warwick have discovered why a newly found form of cholesterol seems to be 'ultra-bad', leading to increased risk of heart disease. The discovery could lead to new treatments to prevent heart disease particularly in people with type 2 diabetes and the elderly.

The research, funded by the British Heart Foundation (BHF), found that 'ultrabad' cholesterol, called MGmin-low-density lipoprotein (LDL), which is more common in people with type 2 diabetes and the elderly, appears to be 'stickier' than normal LDL. This makes it more likely to attach to the walls of arteries. When LDL attaches to artery walls it helps form the dangerous 'fatty' plaques' that cause coronary heart disease (CHD).

CHD is the condition behind heart attacks, claiming 88,000 lives in the UK every year (1).

The researchers made the discovery by creating human MGmin-LDL in the laboratory, then studying its characteristics and interactions with other important molecules in the body.

They found that MGmin-LDL is created by the addition of sugar groups to 'normal' LDL - a process called glycation - making LDL smaller and denser. By changing its shape, the sugar groups expose new regions on the surface of the LDL. These exposed regions are more likely to stick to artery walls, helping to build fatty plaques. As fatty plaques grow they narrow arteries - reducing blood flow - and they can eventually rupture, triggering a blood clot that causes a heart attack or stroke.

The discovery might also explain why metformin, a widely prescribed type 2 diabetes drug, seems to lead to reduced heart disease risk. Metformin is known to lower blood sugar levels, and this new research shows it may reduce the risk of CHD by blocking the transformation of normal LDL to the more 'sticky' MGmin-LDL.

Dr Naila Rabbani, Associate Professor of Experimental Systems Biology at Warwick Medical School, who led the study, said:

"We're excited to see our research leading to a greater understanding of this type of cholesterol, which seems to contribute to heart disease in diabetics and elderly people. Type 2 diabetes is a big issue - of the 2.6 million diabetics in the UK, around 90 per cent have type 2. It's also particularly common in lower income groups and South Asian communities. (2, 3)

"The next challenge is to tackle this more dangerous type of cholesterol with treatments that could help neutralise its harmful effects on patients' arteries."

Dr Shannon Amoils, Research Advisor at the BHF, which funded the study, said:

"We've known for a long time that people with diabetes are at greater risk of heart attack and stroke. There is still more work to be done to untangle why this is the case, but this study is an important step in the right direction.

"This study shows how the make-up and the shape of a type of LDL cholesterol found in diabetics could make it more harmful than other types of LDL. The findings provide one possible explanation for the increased risk of coronary heart disease in people with diabetes.

"Understanding exactly how 'ultrabad' LDL damages arteries is crucial, as this knowledge could help develop new anti-cholesterol treatments for patients."

The research was published in the journal Diabetes.

Notes:

1. Scarborough P et al (2010). Coronary heart disease statistics 2010 edition. British Heart Foundation: London.


2 Diabetes UK (2010). Diabetes in the UK: Key statistics on diabetes online.

3. Department of Health (2007). About diabetes online.

4. Research published in Diabetes online 27/05/11: 'Glycation of low density lipoprotein by methylglyoxal increases atherogenicity - a possible contributor to increased risk of cardiovascular disease in diabetes'. DOI 10.2337/db11-0085

Source:
Kate Cox
University of Warwick

Inattentional Deafness: How Our Focus Can Silence The Noisy World Around Us

How can someone with perfectly normal hearing become deaf to the world around them when their mind is on something else? New research funded by the Wellcome Trust suggests that focusing heavily on a task results in the experience of deafness to perfectly audible sounds.

In a study published in the journal Attention, Perception, & Psychophysics, researchers at UCL (University College London) demonstrate for the first time this phenomenon, which they term 'inattentional deafness'.

"Inattentional deafness is a common everyday experience," explains Professor Nilli Lavie from the Institute of Cognitive Neuroscience at UCL. "For example, when engrossed in a good book or even a captivating newspaper article we may fail to hear the train driver's announcement and miss our stop, or if we're texting whilst walking, we may fail to hear a car approaching and attempt to cross the road without looking."

Professor Lavie and her PhD student James Macdonald devised a series of experiments designed to test for inattentional deafness. In these experiments, over a hundred participants performed tasks on a computer involving a series of cross shapes. Some tasks were easy, asking the participants to distinguish a clear colour difference between the cross arms. Others were much more difficult, involving distinguishing subtle length differences between the cross arms.

Participants wore headphones whilst carrying out the tasks and were told these were to aid their concentration. At some point during task performance a tone was played unexpectedly through the headphones. At this point, immediately after the sound was played, the experiment was stopped and the participants asked if they had heard this sound.

When judging the respective colours of the arms - an easy task that takes relatively little concentration - around two in ten participants missed the tone. However, when focusing on the more difficult task - identifying which of the two arms was the longest - eight out of ten participants failed to notice the tone.

The researchers believe this deafness when attention is fully taken by a purely visual task is the result of our senses of seeing and hearing sharing a limited processing capacity. It is already known that people similarly experience 'inattentional blindness' when engrossed in a task that takes up all of their attentional capacity - for example, the famous Invisible Gorilla Test, where observers engrossed in a basketball game fail to observe a man in a gorilla suit walk past. The new research now shows that being engrossed in a difficult task makes us blind and deaf to other sources of information.

"Hearing is often thought to have evolved as an early warning system that does not depend on attention, yet our work shows that if our attention is taken elsewhere, we can be effectively deaf to the world around us," explains Professor Lavie. "In our task, most people noticed the sound if the task being performed was easy and did not demand their full concentration. However, when the task was harder they experienced deafness to the very same sound."

Other examples or real world situations include inattentional deafness whilst driving. It is well documented that a large number of accidents are caused by a driver's inattention and this new research suggests inattentional deafness is yet another contributing factor. For example, although emergency vehicle sirens are designed to be too loud to ignore, other sounds - such as a lorry beeping while reversing, a cyclist's bell or a scooter horn - may be missed by a driver focusing intently on some interesting visual information such as a roadside billboard, the advert content on the back of the bus in front or the map on a sat nav.

Source:
Craig Brierley
Wellcome Trust

Experts Would Like Specialized Teaching For Dyscalculia Introduced In Schools

Specialised teaching for individuals with dyscalculia, the mathematical equivalent of dyslexia, should be made widely available in mainstream education, according to a review of current research published in the journal Science.

Although just as common as dyslexia, with an estimated prevalence of up to 7% of the population, dyscalculia has been neglected as a disorder of cognitive development. However, a world-wide effort by scientists and educators has established the essential neural network that supports arithmetic, and revealed abnormalities in this network in the brains of dyscalulic learners.

Neuroscience research shows what kind of help is most needed - strengthening simple number concepts. This can be achieved with appropriate specially-designed teaching schemes, which can be supported by game-like software that adapts to the learner's current level of competence.

Professor Brian Butterworth, co-author of the paper and a member of the Centre for Educational Neuroscience (CEN) from the UCL Institute of Cognitive Neuroscience, said: "Dyscalculia is at least as much of a handicap for individuals as dyslexia and a very heavy burden on the state, with the estimated cost to the UK of low numeracy standing at £2.4 billion."

"Nevertheless, there are only cursory references to the disorder on the Department of Education website - no indications are offered for help either for learners, teachers or parents. It's as if the government does not want to acknowledge its existence."

Like dyslexia, dyscalculia is a condition we are born with, and may be heritable in many or most cases. Research from twins and special populations suggests that an arithmetical disability has a large genetic component, but the genes responsible have not yet been located.

Professor Diana Laurillard, another co-author and a member of CEN from the Institute of Education (IOE), University of London, said: "Just because dyscalculia is inherited it does not mean that there is nothing that can be done about it. As with dyslexia, specialized teaching can help. At the IOE we have developed software resources specifically to help children with dyscalculia, based on brain research showing exactly what problems the brain is having."

One of the main challenges of the effort to understand dyscalculia, is for scientists from these very different disciplines to understand each others' methods and results. The creation of interdisciplinary and inter-institutional centres to promote joint work, such as the Centre for Educational Neuroscience established by UCL (University College London); the Institute of Education, University of London and Birkbeck University of London, aims to address this challenge.

Professor Laurillard added: "Results from neuroscience and developmental psychology tell us that dyscalculic learners need to practice far more number manipulation tasks than mainstream learners. Adaptive, game-like programs that focus on making numbers meaningful, emulating what skilled SEN teachers do, can help learners practice beyond the classroom and build the basic understanding they need to tackle arithmetic."

What is dyscalculia?

Examples of common indicators of dyscalculia are (i) carrying out simple number comparison and addition tasks by counting, often using fingers, well beyond the age when it is normal, and (ii) finding approximate estimation tasks difficult. Individuals identified as dyscalculic behave differently from their mainstream peers, for example: To say which is the larger of two playing cards showing 5 and 8, they count all the symbols on each card. To place a playing card of 8 in sequence between a 3 and a 9 they count up spaces between the two to identify where the 8 should be placed. To count down from 10 they count up from 1 to 10, then 1 to 9, etc. To count up from 70 in tens, they say '70, 80, 90, 100, 200, 300...' They estimate the height of a normal room as '200 feet?' Source:
Clare Ryan
University College London