Health posts

March 24, 2010
06:15 AM
540 views

Backpackers in Australia are a sexual health risk

by Helen Jaques in In Sickness and In Health

Young people, especially Brits, famously head to Australia in their droves in search of travel, adventure, and, crucially, some hot weather. In 2009-09, 560,105 international backpackers visited Australia, representing 10.9% of all international visitors.
It seems that backpackers in Oz aren’t just looking for fun and sun though – according to a new study they’re [...]... Read more »

McNulty, A., Egan, C., Wand, H., & Donovan, B. (2010) The behaviour and sexual health of young international travellers (backpackers) in Australia. Sexually Transmitted Infections. DOI: 10.1136/sti.2009.038737

Health

March 24, 2010
01:24 AM
1,132 views

Crohn’s Disease Treatment Also Helps Protect the Gut From Infection

by Walter Jessen in Highlight HEALTH

A recent report in Cell Host and Microbe reveals that in the gut, the gene Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) helps protect against infection by a bacterial pathogen.... Read more »

Hirata Y, Egea L, Dann SM, Eckmann L, & Kagnoff MF. (2010) GM-CSF-facilitated dendritic cell recruitment and survival govern the intestinal mucosal response to a mouse enteric bacterial pathogen. Cell host , 7(2), 151-63. PMID: 20159620

March 23, 2010
04:35 PM
981 views

Meth Babies—Fact or Fiction?

by Dirk Hanson in Addiction Inbox

Research team finds brain abnormalities.

When it came to babies born to crack-addicted mothers, the media went overboard, creating a crisis in the form of an epidemic that never quite was. By contrast, when it came to babies born to alcoholic mothers, Fetal Alcohol Syndrome went unrecognized in the science and medical community until 1968.

Now comes a study on prenatal methamphetamine exposure in The Journal of Neuroscience, headed up by Elizabeth Sowell of the University of California, Los Angeles, with support from both the National Institute on Drug Abuse (NIDA) and the National Institute of Alcoholism and Alcohol Abuse (NIAAA.) The report garnered considerable media attention. “We know that alcohol exposure is toxic to the developing fetus and can result in lifelong brain, cognitive and behavioral problems,” Sowell said in a press release. “In this study, we show that the effects of prenatal meth exposure, or the combination of meth and alcohol exposure, may actually be worse.”

It makes sense that meth might effect the health of unborn children. There is a modest body of research to support the notion. The Sowell study points a finger at the caudate nucleus, a brain region involved with learning and memory. The study showed that the caudate nucleus of the meth-using group was reduced in size. “Identifying vulnerable brain structures may help predict particular learning and behavioral problems in meth-exposed children,” the press release optimistically states. And the potential problem is real enough: More than 16 million Americans have used meth, according to government numbers. An estimated 19,000 of these users are pregnant women.

But is this particular study a definitive one? The icing on the cake? To begin with, the press release from The Journal of Neuroscience admits to a major problem right up front: “About half of women who say they used meth during pregnancy also used alcohol, so isolating the effects of meth on the developing brain is difficult.” Even in cases of meth exposure only, there are a host of negative behavioral factors that often accompany meth addiction (bad nutrition, minimal health care, poor health) that can significantly effect fetal development.

The study team compared the MRI brain scans of 61 children: “21 with prenatal MA (methamphetamine) exposure, 18 with concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but not MA exposure (ALC group), and 27 unexposed controls. While finding “striatal volume reductions,” as well as increases in the size of certain limbic structures in both groups with meth and/or alcohol exposure, the researchers conclude that striatal and limbic structures “may be more vulnerable to prenatal MA exposure than alcohol exposure.” However, that conclusion was apparently reached despite the fact that only 3 of the 61 children under study were born to mothers who did meth, and meth only, during pregnancy.

Furthermore, there is significant controversy over brain scan studies that measure gross anatomical changes in the size of specific brain regions, rather than brain region activity based on blood flow.

Is there other evidence for the danger of meth use during pregnancy? There is, but as is frequently the case, some of the best evidence comes from animal studies. A 2008 guinea pig study by Sanika Chirwa
showed neural damage to the hippocampus, another region involved in memory, in newborn animals with prenatal meth exposure. Furthermore, the newborn animals showed an impaired ability to distinguish novel objects from familiar ones.

In 2006, a study at Brown Medical School, published in Pediatrics , found that newborns exposed to meth during pregnancy were born “small for gestational age,” meaning they were born full-term, but smaller than babies not exposed to meth in utero. According to study author Barry Lester, “Children who are born underweight tend to have behavior problems, such as hyperactivity or short attention span, as well as learning difficulties.”

However, Lester added an important caveat in a Brown University press release : “I hope that the ‘crack baby’ hysteria does not get repeated. While these children may have some serious health and developmental challenges, there is no automatic need to label them as damaged and remove them from their biological mothers.”

Similar caution was urged by the authors of a 2009 report in the Journal of Developmental and Behavioral Pediatrics: “Efforts to understand specific effects of prenatal methamphetamine exposure on cognitive processing are hampered by high rates of concomitant alcohol use during pregnancy.”

In 2005, an open letter from the Center for Substance Abuse Research at the University of Maryland warned about the dangers of hyperbole, calling upon the media and public officials to “stop perpetuating ‘meth baby’ myths.” The Center argued that “The terms ‘ice babies’ and ‘meth babies’ lack medical and scientific validity and should not be used,” and requested that “policies addressing prenatal exposure to methamphetamines and media coverage of this issue be based on science, not presumption or prejudice.”

Sowell, E., Leow, A., Bookheimer, S., Smith, L., O'Connor, M., Kan, E., Rosso, C., Houston, S., Dinov, I., & Thompson, P. (2010). Differentiating Prenatal Exposure to Methamphetamine and Alcohol versus Alcohol and Not Methamphetamine using Tensor-Based Brain Morphometry and Discriminant Analysis Journal of Neuroscience, 30 (11), 3876-3885 DOI: 10.1523/JNEUROSCI.4967-09.2010

Smith, L., LaGasse, L., Derauf, C., Grant, P., Shah, R., Arria, A., Huestis, M., Haning, W., Strauss, ... Read more »

Sowell, E., Leow, A., Bookheimer, S., Smith, L., O'Connor, M., Kan, E., Rosso, C., Houston, S., Dinov, I., & Thompson, P. (2010) Differentiating Prenatal Exposure to Methamphetamine and Alcohol versus Alcohol and Not Methamphetamine using Tensor-Based Brain Morphometry and Discriminant Analysis. Journal of Neuroscience, 30(11), 3876-3885. DOI: 10.1523/JNEUROSCI.4967-09.2010

Smith, L., LaGasse, L., Derauf, C., Grant, P., Shah, R., Arria, A., Huestis, M., Haning, W., Strauss, A., Grotta, S.... (2006) The Infant Development, Environment, and Lifestyle Study: Effects of Prenatal Methamphetamine Exposure, Polydrug Exposure, and Poverty on Intrauterine Growth. PEDIATRICS, 118(3), 1149-1156. DOI: 10.1542/peds.2005-2564

March 23, 2010
04:25 PM
541 views

There are side effects, and there are real side effects

by Lorimer Moseley in BodyInMind

The NEJM just posted this entry that clearly shows that when clinicians report side effects of the drugs that their patient is taking, their reports don’t agree with what patients report. Interestingly, clinicians are doing the reporting of these side effects as part of their participation in clinical trials, and the clinical trials are almost [...]... Read more »

Basch, E. (2010) The Missing Voice of Patients in Drug-Safety Reporting. New England Journal of Medicine, 362(10), 865-869. DOI: 10.1056/NEJMp0911494

March 23, 2010
02:32 PM
923 views

Efficiency & pain management

by Adiemusfree in Healthskills: Skills for Healthy Living

I can’t remember a time when people working in health were told ‘Go and spend as much as you like to help people get well’ – in fact, in over 20 years I can only recall being told ‘there is less money in the kitty, we need to look for efficiencies, tighten your belts’!
So it’s [...]... Read more »

Lamb, S., Hansen, Z., Lall, R., Castelnuovo, E., Withers, E., Nichols, V., Potter, R., & Underwood, M. (2010) Group cognitive behavioural treatment for low-back pain in primary care: a randomised controlled trial and cost-effectiveness analysis. The Lancet, 375(9718), 916-923. DOI: 10.1016/s0140-6736(09)62164-4

Allcock N, Elkan R, & Williams J. (2007) Patients referred to a pain management clinic: beliefs, expectations and priorities. Journal of advanced nursing, 60(3), 248-56. PMID: 17908123

March 23, 2010
11:00 AM
582 views

Super fruits, super marketing.

by Colby in nutsci.org

0Last year was the year of the acai berry. Mangosteen, noni, goji, and others also proliferate on the juice and supplement market. Some are predicting what will be next. Are these so called “superfruits” any better than “regular” fruit?
Let’s look at a few lines of evidence.
What makes a fruit “super”?
First of all, we have to [...]... Read more »

Pérez VI, Bokov A, Van Remmen H, Mele J, Ran Q, Ikeno Y, & Richardson A. (2009) Is the oxidative stress theory of aging dead?. Biochimica et biophysica acta, 1790(10), 1005-14. PMID: 19524016

Prior RL, & Cao G. (1999) In vivo total antioxidant capacity: comparison of different analytical methods. Free radical biology , 27(11-12), 1173-81. PMID: 10641708

Shukitt-Hale B, Lau FC, & Joseph JA. (2008) Berry fruit supplementation and the aging brain. Journal of agricultural and food chemistry, 56(3), 636-41. PMID: 18211020

Seeram NP, Aviram M, Zhang Y, Henning SM, Feng L, Dreher M, & Heber D. (2008) Comparison of antioxidant potency of commonly consumed polyphenol-rich beverages in the United States. Journal of agricultural and food chemistry, 56(4), 1415-22. PMID: 18220345

March 23, 2010
04:44 AM
273 views

Who isn't afraid of Alzheimer's?

by Diane Jacobs in Neurotonics

I have found microglia interesting to learn about in the past, and have written here, here, here, here, and here, about their proposed relationship to pain.Yesterday I saw a news story about researchers in Germany who carefully studied the relationship between microglia and neurons undergoing Alzheimer-like changes in mice, Dangerous custodians: Immune cells as possible nerve-cell killers in Alzheimer's disease, and was immediately intrigued.An advance online publication of the paper, Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease, is freely accessible, at least for now.That stressed neurons exude the chemokine, fractalkine, or that this substance attracts microglia, isn't fresh news. Like a bunch of little cellular opportunists, microglia catch the "scent" and begin moving toward it. Like any bunch of scavengers converging on a picnic, in this case, the amyloid-β forming and piling up, they also secrete/excrete (while gorging and multiplying, I suppose). What they signal/secrete/excrete isn't really explained, but what is news, is that it, or else just the sheer numbers of microglia converging, apparently sickens the affected neurons even more, kills them, according to this story.In the paper, the authors, Fuhrmann etal., state, "In Alzheimer's disease, microglia represent a double-edged sword. On the one hand, microglia can have a beneficial effect by secreting neurotrophic factors and phagocytosing amyloid beta (Aβ)2, the latter of which remains controversial3. On the other hand, microglia may also be neurotoxic4. Little is known about the neurotoxic role of microglia in Alzheimer's disease. Human peripheral blood monocytes that are stimulated with Aβ induce neuron loss in vitro5. Neurons cultured without microglia are resistant to Aβ-induced neurotoxicity6." The authors decided to interfere, genetically, with the receptors in the microglia that allow them to sense fractalkine; CX3CR1, "the unique receptor for fractalkine/CX3CL1, which is expressed in neurons and presumably acts as a membrane-bound adhesion molecule and/or cleaved chemoattractant and is important for recruiting CX3CR1-expressing microglia to injured neurons9, 10."They managed to show that it was definitely the microglia causing the neuron death, not any other factor. Furthermore, knocking out the ability of microglia to "smell" fractalkine didn't seem to interfere with their ability to clear the amyloid material associated with Alzheimer's. Moreover, the same treatment of the microglial receptor gives inconclusive results in other kinds of conditions - only in Alzheimer's does it seem to be a helpful intervention.Supplementary information for this paper.Fuhrmann, M., Bittner, T., Jung, C., Burgold, S., Page, R., Mitteregger, G., Haass, C., LaFerla, F., Kretzschmar, H., & Herms, J. (2010). Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease Nature Neuroscience DOI: 10.1038/nn.2511... Read more »

Fuhrmann, M., Bittner, T., Jung, C., Burgold, S., Page, R., Mitteregger, G., Haass, C., LaFerla, F., Kretzschmar, H., & Herms, J. (2010) Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease. Nature Neuroscience. DOI: 10.1038/nn.2511

March 22, 2010
10:22 PM
534 views

Wealth and Longevity

by Reason in Fight Aging!

History teaches us that the wealth of a region and the longevity of its inhabitants go hand in hand. The societal and economic changes wrought across the 17th century in England, for example, show us that increased longevity leads to increased wealth, through more foresighted allocation of capital resources and the compounded effect of small gains, year after year. The converse is also true: increased wealth leads to increased longevity, a fact well illustrated by the passage of many Asian countries from undeveloped to developed in a short span of decades. Let us take the economic history of South Korea, for example: South Korea is a developed country and had one of the world's fastest growing economies from the early 1960s to the late 1990s. Its rapid transformation into a wealthy and industrialized economy in this short time was termed the Miracle on the Han River. This growth surge was achieved through manufacturing oriented exports and a highly educated workforce. As of 2009, South Korea is the world's eighth largest exporter. Across this same period of time, life expectancy in South Korea rose dramatically: Objectives. We assessed life expectancy increases in the past several decades in South Korea by age...... Read more »

Yang S, Khang YH, Harper S, Davey Smith G, Leon DA, & Lynch J. (2010) Understanding the Rapid Increase in Life Expectancy in South Korea. American journal of public health. PMID: 20299661

March 22, 2010
08:00 PM
379 views

Cardiac Output Regulation Within the SCN

by Allison in Dormivigilia

Circadian researchers have preliminary evidence suggesting that normal circadian clock functioning is necessary for cardiac output regulation. Therefore, vast disturbances to the circadian timing system, whether genetically or environmentally induced, may be have a contributory role in cardiovascular disease. ... Read more »

Sara C. Mednick1, Nicholas A. Christakis, James H. Fowler. (2010) The Spread of Sleep Loss Influences Drug Use in Adolescent Social Networks. PLoS ONE, 5(3). info:/10.1371/journal.pone.0009775

W. John Sheward, Erik Naylor, Seymour Knowles-Barley, J. Douglas Armstrong, Gillian A. Brooker, Jonathan R. Seckl, Fred W. Turek, Megan C. Holmes, Phyllis C. Zee, Anthony J. Harmar. (2010) Circadian Control of Mouse Heart Rate and Blood Pressure by the Suprachiasmatic Nuclei: Behavioral Effects Are More Significant than Direct Outputs. PLoS ONE, 5(3). info:/10.1371/journal.pone.0009783

March 22, 2010
04:29 PM
1,099 views

Multidrug and extensively drug-resistant tuberculosis

by C. Julian in The Swarm

In memoriam of Sir John Crofton (1912–2009), The greatest disaster that can happen to a patient with tuberculosis is that his organisms become resistant to two or more of the standard drugs... The development of drug resistance may be a tragedy not only for the patient himself but for others. For he can infect other people with his drug-resistant organisms...

The World Health Organization (WHO)... Read more »

World Health Organization. (2010) Multidrug and extensively drug-resistant TB (M/XDR-TB): 2010 Global report on surveillance and response. WHO. info:other/978 92 4 159919 1

Gillespie, S. (2002) Evolution of Drug Resistance in Mycobacterium tuberculosis: Clinical and Molecular Perspective. Antimicrobial Agents and Chemotherapy, 46(2), 267-274. DOI: 10.1128/AAC.46.2.267-274.2002

March 22, 2010
08:30 AM
894 views

Responding to Anti-vaccine Misinformation: Understanding the Issues

by Scott in Science-Based Pharmacy

Pharmacists pride themselves as being the most accessible health professionals. In community pharmacy settings, pharmacists speak with hundred of patients per day, and are available (free, and without an appointment) for quick consultations. Building good relationships is a rewarding part of being a pharmacist, and the level of trust that can develop supports open dialogue [...]... Read more »

Kata, A. (2010) A postmodern Pandora's box: Anti-vaccination misinformation on the Internet. Vaccine, 28(7), 1709-1716. DOI: 10.1016/j.vaccine.2009.12.022

March 22, 2010
06:00 AM
521 views

News reports on cancer don’t give the full story

by Helen Jaques in In Sickness and In Health

Cancer stories seem to make the news on a daily basis. For example, just today in the UK there are stories about a gene that could predispose non-smokers to lung cancer, how infertile men are at raised risk of prostate cancer, and how testing for the HPV virus during cervical screening doesn’t help pick up [...]... Read more »

Fishman, J., Ten Have, T., & Casarett, D. (2010) Cancer and the Media: How Does the News Report on Treatment and Outcomes?. Archives of Internal Medicine, 170(6), 515-518. DOI: 10.1001/archinternmed.2010.11

Health

March 21, 2010
05:12 PM
507 views

Cancer and the media

by Martin Fenner in Gobbledygook @ Nature Network

Last Tuesday the Archives of Internal Medicine released a study that anayzed the news reporting about cancer in 8 large-readership newspapers and 5 national magazines in the United States. The authors identified 2228 cancer-focused articles published between 2005-2007 and...... Read more »

Fishman J, Ten Have T, & Casarett D. (2010) Cancer and the Media: How Does the News Report on Treatment and Outcomes?. Archives of internal medicine. PMID: 20233800

March 21, 2010
02:21 PM
910 views

Accepting chronic pain

by Adiemusfree in Healthskills: Skills for Healthy Living

How willing are you to have persistent pain? Can you accept pain without fighting against it? If you were told your pain was going to be there forever, would you avoid important activities or would you start to get back into life again?
Recently I reviewed about 200 questionnaires completed by people attending the [...]... Read more »

Fish, R., McGuire, B., Hogan, M., Morrison, T., & Stewart, I. (2010) Validation of the Chronic Pain Acceptance Questionnaire (CPAQ) in an Internet sample and development and preliminary validation of the CPAQ-8. Pain. DOI: 10.1016/j.pain.2009.12.016

March 20, 2010
03:00 PM
734 views

Absinthe Fact and Fiction

by Neuroskeptic in Neuroskeptic

Absinthe is a spirit. It's very strong, and very green. But is it something more?I used to think so, until I came across this paper taking a skeptical look at the history and science of the drink, Padosch et al's Absinthism a fictitious 19th century syndrome with present impactAbsinthe is prepared by crushing and dissolving the herb wormwood in unflavoured neutral alcohol and then distilling the result; other herbs and spices are added later for taste and colour.It became extremely popular in the late 19th century, especially in France, but it developed a reputation as a dangerous and hallucinogenic drug. Overuse was said to cause insanity, "absinthism", much worse than regular alcoholism. Eventually, absinthe was banned in the USA and most but not all European countries.Much of the concern over absinthe came from animal experiments. Wormwood oil was found to cause hyperactivity and seizures in cats and rodents, whereas normal alcohol just made them drunk. But, Padosch et al explain, the relevance of these experiments to drinkers is unclear, because they involved high doses of pure wormwood extract, whereas absinthe is much more dilute. The fact that authors at the time used the word absinthe to refer to both the drink and the pure extract added to the confusion.It's now known that wormwood, or at least some varieties of it, contains thujone, which can indeed cause seizures, and death, due to being a GABA antagonist. Until a few years ago it was thought that old-style absinthe might have contained up to 260 mg of thujone per litre, a substantial dose.But that was based on the assumption that all of the thujone in the wormwood ended up in the drink prepared from it. Chemical analysis of actual absinthe has repeatedly found that it contains no more than about 6 mg/L thujone. The alcohol in absinthe would kill you long before you drank enough to get any other effects. As the saying goes, "the dose makes the poison", something that is easily forgotten.As Padosch et al point out, it's possible that there are other undiscovered psychoactive compounds in absinthe, or that long-term exposure to low doses of thujone does cause "absinthism". But there is no evidence for that so far. Rather, they say, absinthism was just chronic alcoholism, and absinthe was no more or less dangerous than any other spirit.I'm not sure why, but drinks seem to attract more than their fair share of urban myths. Amongst many others I've heard that the flakes of gold in Goldschläger cause cuts which let alcohol into your blood faster; Aftershock crystallizes in your stomach, so if you drink water the morning afterwards, you get drunk again; and that the little worm you get at the bottom of some tequilas apparently contains especially concentrated alcohol, or hallucinogens, or even cocaine maybe.Slightly more serious is the theory that drinking different kinds of drinks instead of sticking to just one gets you drunk faster, or gives you a worse hangover, or something, especially if you do it in a certain order. Almost everyone I know believes this, although in my drinking experience it's not true, but I'm not sure that it's completely bogus, as I have heard somewhat plausible explanations i.e. drinking spirits alongside beer leads to a concentration of alcohol in your stomach that's optimal for absorption into the bloodstream... maybe.Link: Not specifically related to this but The Poison Review is an excellent blog I've recently discovered all about poisons, toxins, drugs, and such fun stuff.Padosch SA, Lachenmeier DW, & Kröner LU (2006). Absinthism: a fictitious 19th century syndrome with present impact. Substance abuse treatment, prevention, and policy, 1 (1) PMID: 16722551... Read more »

Padosch SA, Lachenmeier DW, & Kröner LU. (2006) Absinthism: a fictitious 19th century syndrome with present impact. Substance abuse treatment, prevention, and policy, 1(1), 14. PMID: 16722551

March 20, 2010
10:19 AM
554 views

Neury Thursday: Additive Teratogenic Effects of Alcohol and Metamphetamines in Utero and Neurodegeneration

by Allison in Dormivigilia

Researchers at UCLA have identified extensive neurodegeneration, particularly in the limbic and striatal areas, of infants whose mothers had used/abused alcohol and/or metamphetamines during pregnancy. The magnitude of reduced cortical volume was additive in that it was greatest for abuse of both alcohol and metamphetamines, which is common in drug abusers. ... Read more »

Sowell ER, Leow AD, Bookheimer SY, Smith LM, O'Connor MJ, Kan E, Rosso C, Houston S, Dinov ID, & Thompson PM. (2010) Differentiating Prenatal Exposure to Methamphetamine and Alcohol versus Alcohol and Not Methamphetamine using Tensor-Based Brain Morphometry and Discriminant Analysis. The Journal of neuroscience : the official journal of the Society for Neuroscience, 30(11), 3876-85. PMID: 20237258

March 19, 2010
07:08 PM
638 views

Calorie Restriction Reduces Lipofuscin Buildup, is Good for Nerves

by Reason in Fight Aging!

The long-term practice of calorie restriction has been demonstrated to slow almost every aspect of age-related change and degeneration in those mammals most exhaustively tested (i.e. mice and rats). So far the primate and human studies are producing the same sorts of result, but it will be another decade or more before the present research community has covered all the bases in humans. Still, the evidence to date is very compelling: regular exercise and calorie restriction kept up over the years have a far more powerful positive effect on general health and longevity than any medical technology presently available. I noticed a paper today that demonstrates another benefit of calorie restriction in rats: it reduces lipofuscin buildup and the consequent damage to lysosomes, the cell's recycling units. This buildup of unwanted biochemicals that the body cannot break down is one of the fundamental contributions to age-related degeneration of the body, and less of it is better for you. Lifelong calorie restriction alleviates age-related oxidative damage in peripheral nerves Aging is associated with protein damage and imbalance in redox status in a variety of cells and tissues, yet little is known about the extent of age-related oxidative stress in the peripheral...... Read more »

Opalach K, Rangaraju S, Madorsky I, Leeuwenburgh C, & Notterpek L. (2010) Lifelong calorie restriction alleviates age-related oxidative damage in peripheral nerves. Rejuvenation research, 13(1), 65-74. PMID: 20230280

March 19, 2010
03:00 PM
449 views

Winter getting you down? It might also be making you unhealthy

by Helen Jaques in In Sickness and In Health

Do the long nights and shoddy weather over the winter months make you feel low? If so, you could also be at raised risk of cardiovascular disease and being overweight, according to new research in PLoS ONE.

This study of 11,545 Norwegian adults found that people who were classified as having considerable variations in mood [...]... Read more »

Øyane, N., Ursin, R., Pallesen, S., Holsten, F., & Bjorvatn, B. (2010) Increased Health Risk in Subjects with High Self-Reported Seasonality. PLoS ONE, 5(3). DOI: 10.1371/journal.pone.0009498