May 21, 2012
04:50 PM
9 views

Francis Collins wants to put you on a chip.

Well, ok, not quite yet. But he thinks it’s coming. Have a look (and hang on to the end for you on a chip): [YouTube TEDMED talk here].

At a recent TEDMED session, Francis Collins gave a short talk about some ways forward in drug development. It’s just taking too long, and there are many hazards that affect the process today. He had a nice illustration of the pipeline that takes us from a bucketload of promising compounds –pre-clinical testing – clinical trials – 1 FDA approval if you are lucky, and have a billion dollars to spend on this.... Read more »

Collins, F. (2011) Reengineering Translational Science: The Time Is Right. Science Translational Medicine, 3(90), 90-90. DOI: 10.1126/scitranslmed.3002747

May 21, 2012
03:36 PM
5 views

#Exergame Benefits Review & Improved Body Comp Studies (SciVee)

by Stephen Yang in ExerGame Lab

I just came across SciVee and thought it is a great way to make science and research understandable for the masses. Although the quality of the videos can really vary, it has great potential to...

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Maddison, R., Foley, L., Ni Mhurchu, C., Jiang, Y., Jull, A., Prapavessis, H., Hohepa, M., & Rodgers, A. (2011) Effects of active video games on body composition: a randomized controlled trial. American Journal of Clinical Nutrition, 94(1), 156-163. DOI: 10.3945/ajcn.110.009142

Primack, B., Carroll, M., McNamara, M., Klem, M., King, B., Rich, M., Chan, C., & Nayak, S. (2012) Role of Video Games in Improving Health-Related Outcomes : A Systematic Review. American Journal of Preventive Medicine , 42(6), 630-638. info:/10.1016/j.amepre.2012.02.023

May 21, 2012
03:32 PM
6 views

Communal mining bees

by Blackbird in BugBlog

A few years ago, a crack in the concrete path at the front of our house became busy with bees coming in and out. We assumed they were honeybees that had settled their hive there, but on closer inspection they turned out to be mining bees instead. Their cleptoparasite bees, Nomada, hung around the nest entrance awaiting an opportunity to get in and lay their eggs. There are many similar species of Andrena mining bees in the UK and several of them looked very similar to mine so I finally gave up with obtaining an ID and I didn't find much more about my front path bee. The bees are back again in the same spot, and a couple of days ago, thanks to tweep @DayMoonRoseDawn I finally knew the identity of these curious bees: they are Andrena carantonica, a large, furry mining bee. Although mining bees are solitary, a handful of species in the UK often nest communally. Communal bees have a simple form of social structure: they share a nest, but individual females will build their own cells, lay eggs and provision their own offspring: they do not have the complex social organisation with workers and division of labour of honeybees. Nesting aggregations of A. carantonica consist of hundreds of females (up to 600) females using the same nest entrance. In my street, cracks on concrete in front garden paths are favoured. Adults emerge in April, with the smaller males doing so just before females and awaiting them inside the nest. In a series of study on this species by Robert Paxton and collaborators reveaed fascinating details of the social structure of this species. In one of these studies they installed nets on nest entrances to be able to capture recently emerged bees: 75% of females were already inseminated when they left the nest for the first time, indicating that copulation happens most of the time inside the communal nests. Although the females in the nest are not highly related, there is a large amount of inbreeding in this species: genetic analysis suggests that 44% of females mate with their full brothers. Emerging females are much more numerous in a given nest (about 1 male to 3 females), although, as Rose Dawn pointed out, it is likely that many males never leave the nest and die inside after having mated, so emergence nets do not capture them. Females must by necessity swap nests after emergence so that the relatedness levels is still low within a given nest, and the bees show a high degree of tolerance to conspecifics, regardless of their nest of origin. If a high level of relatedness is not responsible for the evolution of communality, why do these bees nest communally? A potential benefit is improved nest defence. There are always bees going in or out, and in my own observations, a few bees often sit by the nest entrance (like as in the photo at the top), therefore opportunities for parasitism by cleptoparasites might be reduced. There are still many questions to answer, which probably will have to await to observations being carried out inside nests, but the study of these and other communal species might offer clues as to how and why complex social systems like those of honeybees evolved.A male Andrena carantonica near the nest entranceFemale Andrena carantonicaA cleptoparasite bee Nomada flava by mining bee nest entrance.Thanks to Rose Dawn for providing an ID and sharing lots of information on this bee, including results from her own researchMore informationPaxton, R., Thoren, P., Tengo, J., Estoup, A., & Pamilo, P. (1996). Mating structure and nestmate relatedness in a communal bee, Andrena jacobi (Hymenoptera, Andrenidae), using microsatellites Molecular Ecology, 5 (4), 511-519 DOI: 10.1046/j.1365-294X.1996.00117.xPAXTON, R., THOREN, P.A., & GYLLENSTRAND, N. (2000). Microsatellite DNA analysis reveals low diploid male production in a communal bee with inbreeding Biological Journal of the Linnean Society, 69 (4), 483-502 DOI: 10.1006/bijl.1999.0371... Read more »

Paxton, R., Thoren, P., Tengo, J., Estoup, A., & Pamilo, P. (1996) Mating structure and nestmate relatedness in a communal bee, Andrena jacobi (Hymenoptera, Andrenidae), using microsatellites. Molecular Ecology, 5(4), 511-519. DOI: 10.1046/j.1365-294X.1996.00117.x

PAXTON, R., THOREN, P.A., & GYLLENSTRAND, N. (2000) Microsatellite DNA analysis reveals low diploid male production in a communal bee with inbreeding. Biological Journal of the Linnean Society, 69(4), 483-502. DOI: 10.1006/bijl.1999.0371

May 21, 2012
03:09 PM
8 views

Having a Water Bottle for a Mom Not Ideal

by Elizabeth Preston in Inkfish

In the wild, young rhesus macaques can reasonably expect not to have their mothers replaced by kitchen props. The monkeys depend on their moms to nurse them and tote them through tree branches while they're small, just like other primates. But a laboratory experiment in Maryland took these babies from their mothers and had them raised alone or in groups of their peers. The monkeys' strange infancies had physical and mental effects that lasted into adulthood.

At the National Institute of Child Health and Human Development (part of the National Institutes of Health), rhesus macaques born between 2002 and 2007 were randomly assigned to one of three groups. The lucky first group got to stay with their mothers, who kept their young close by while living in a large cage with other monkeys.

The rest of the young monkeys were taken from their mothers and reared by humans in a nursery for their first five weeks of life. Then, if they were in the second experimental group, they were put into a cage with three other monkeys of the same age. The four peers were left to "raise" each other, Lord of the Flies style.

The final group of monkeys, after being nursed by humans for five weeks, spent two hours a day in these same peer cages. During the remaining 22 hours, they lived alone in a cage with a "surrogate mother." The name is a bit of an insult to primate intelligence, though, since researchers describe this object as "effectively a terry cloth-covered hot water bottle hanging from the top of the cage."

By the end of their first year of life, all the juvenile monkeys had been moved from their experimental cages into one social group. Now the researchers, led by Gabriella Conti at the University of Chicago, began to collect data on the monkeys' health. Over the years of the study, they watched 231 rhesus macaques grow up in this bizarre daycare system. Even though the monkeys all ended up living together, their disparate childhoods left a mark.

The first clear effect was illness. Male monkeys that had been raised by a "surrogate" got sick nearly twice as often as mother-raised or peer-raised monkeys, even though by this time in their lives they all shared the same living conditions. Nearly every surrogate-raised male monkey had an illness at some point during the study.

Female monkeys that had been raised by peers, rather than by a real or fake mother, were more likely to have wounds and bald patches once they were living in the large group. Since these females displayed more aggressive behavior, the researchers think they may have been starting fights with the other monkeys. Their aggression may have goaded other monkeys into biting them and pulling their hair out.

And across all the groups taken away from their mothers—male and female, peer-raised and surrogate-raised—monkeys were more likely to have repetitive habits called stereotypies. In the zoo, a stereotypy such as pacing or swimming in circles suggests that an animal is in distress. In humans, stereotypies can be a symptom of autism. Habits displayed by the rhesus monkeys in this study included "digit sucking (the most frequent behavior), pacing, head tossing, self-grasping, saluting, spinning, rocking, circling, and swinging."

Some of the difference between monkeys raised by their mothers and the rest could be due to breastfeeding, Conti points out. But the increased illness in male monkeys was limited to the surrogate-mom group; the peer-raised monkeys, despite also missing out on breastfeeding, didn't have extra illnesses. And although all motherless monkey groups showed an increase in stereotypy, the effect was greatest in surrogate-raised males. This suggests that even if formula feeding causes some of the health effects seen here, it can't account for all of them.

The not-shocking conclusion is that monkeys need their moms to develop normally. Being raised parentless seems to make them less able to cope with infections or social stressors later in life. It's something to consider for research centers or zoos raising animals without their mothers. Even if the young have been orphaned or abandoned, there may be ways for human keepers to mitigate the damage.

Conti is an economist, though, and she's more interested in another primate: humans. She compares the rhesus research to studies of human children raised without either of their parents. These studies have found mental and physical health effects in children in Romanian orphanages, for example, or Israeli kibbutzim (where kids were raised communally). As smart and independent as we are, we're still primates who need someone to haul us through the tree branches when we're young.

Gabriella Conti, Christopher Hansman, James J. Heckman, Matthew F. X. Novak, Angela Ruggiero, & Stephen J. Suomi (2012). Primate evidence on the late health effects of early-life adversity PNAS : 10.1073/pnas.1205340109

Image: Baby Japanese macaque by Nemo's great uncle/Flickr

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Gabriella Conti, Christopher Hansman, James J. Heckman, Matthew F. X. Novak, Angela Ruggiero, & Stephen J. Suomi. (2012) Primate evidence on the late health effects of early-life adversity. PNAS. info:/10.1073/pnas.1205340109

May 21, 2012
01:54 PM
15 views

Total recall: The man who can remember every day of his life in detail

by Christian Jarrett in BPS Research Digest

For most of us, it's tricky enough to remember what we were doing this time last week, let alone on some random day years ago. But for a blind 20-year-old man referred to by researchers as HK, every day of his life since the age of about eleven is recorded in his memory in detail. HK has a rare condition known as hypermnesia, like the opposite of amnesia, and his is only the second case ever documented in the scientific literature (the first, a woman known as AJ, was reported in 2006; pdf).

Brandon Ally and his team have completed comprehensive tests with HK and they've scanned his brain and compared its structure with 30 age-matched controls. They found that HK has normal intelligence, that he performs normally on standard desktop tests of short and long-term recall, and that he has normal verbal learning skills. It's specifically his autobiographical memory that's phenomenal.

The researchers assessed HK's autobiographical memory by choosing four dates from each year of his life since his first memory (that was from 1993 when he was aged three and half), making 80 dates in total. For each of these dates, they gathered at least three facts from HK's family, medical records and the historical records for his neighbourhood in Nashville. HK was then interviewed about each of these 80 dates - for example, he was asked "Can you tell me what happened during your day on January 2nd, 2001". His answers, often detailed, were transcribed and fact-checked.

HK's recollection of days from his life between the ages of 9 and 12 grew dramatically more accurate and detailed, reaching nearly 90 per cent accuracy for memories at age 11, rising to near perfect accuracy thereafter. For some dates, HK was quizzed again at a second session - the consistency of his answers was 100 per cent.

What's it like to have hypermnesia? HK told the researchers that his autobiographical memories are rich in sensory and emotional details and feel just as vivid regardless of whether they're from years ago or from yesterday. Ninety per cent of the time he experiences these memories in the first-person, compared with rates of approximately 66 per cent in the general population. HK said autobiographical memories frequently enter his consciousness, triggered by sights, sounds and emotions. Most days he wakes up thinking about what he's done on that day in previous years. Bad memories come to mind just as often as positive ones, but he is able to choose to focus more on the positive.

In terms of brain structure, overall HK's brain was smaller than average (likely related to his having been born prematurely at 27 weeks). By contrast, his right amygdala was larger, by about 20 per cent, than in the controls. He also has enhanced functional connectivity between his right amygdala and hippocampus and in other regions. The amygdala is a small subcortical structure and part of the limbic system, which is involved in emotional processing. The researchers think that HK's enlarged amygdala and its enhanced connectivity lends a deeper personal salience to his experiences than is normal, thus making them more memorable.

Ally and his team acknowledged that "unique case studies such as HK are not easily translated or generalisable to the normal population", and so should be interpreted with caution. That said, they argued their results provide further evidence for the role of the amygdala in autobiographical memory. "Further, perhaps the present findings can help help guide future regions of brain stimulation in memory-disordered populations, with the goal of improving memory function," they speculated. "Indeed, brain stimulation to deep, subcortical memory-related structures has shown very early promise in patients with Alzheimer's Disease."
_________________________________

Ally, B., Hussey, E., and Donahue, M. (2012). A case of hyperthymesia: rethinking the role of the amygdala in autobiographical memory. Neurocase, 1-16 DOI: 10.1080/13554794.2011.654225

Post written by Christian Jarrett for the BPS Research Digest.

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Ally, B., Hussey, E., & Donahue, M. (2012) A case of hyperthymesia: rethinking the role of the amygdala in autobiographical memory. Neurocase, 1-16. DOI: 10.1080/13554794.2011.654225

Psychology

May 21, 2012
01:47 PM
6 views

Children with CP Benefit from #exergames

by Stephen Yang in ExerGame Lab

#Exergaming can one way to incorporate more physical activity into the day and hopefully reduce the amount of sedentary time (The irony is not lost as I'm sitting down to write this). Seventeen...

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Howcroft J, Klejman S, Fehlings D, Wright V, Zabjek K, Andrysek J, & Biddiss E. (2012) Active Video Game Play in Children With Cerebral Palsy: Potential for Physical Activity Promotion and Rehabilitation Therapies. Archives of Physical Medicine and Rehabilitation. PMID: 22571917

May 21, 2012
11:52 AM
11 views

First Panic Attack and Agoraphobia

by William Yates, M.D. in Brain Posts

Panic disorder commonly presents acutely with a first severe panic attack. Many patients can distinctly remember their first attack even years after the onset of the disorder.Agoraphobia may complicate panic disorder. The word agoraphobia stems from the Greek word "agora" meaning gathering place. The Greek agora was the common area for public assembly. People with agoraphobia commonly fear situations where they may be in a crowd of people. They often fear that in such situations a panic attack may occur and they will be unable to escape. In the modern world, common settings for agoraphobia are crowded buses, airplanes or motor vehicles.Not all individuals with panic disorder develop agoraphobia. It is unclear why this pattern exists. Agoraphobia does tend to occur with more severe and chronic panic disorder. Individuals with relative few and mild panic attacks are less likely to develop agoraphobia.A recent clinical research study from Japan suggests that the place where the first panic attack occurs may play a role in the risk of developing panic disorder. Hara and colleagues studied a large group (n=830) of individuals with panic disorder and classified them into 5 groups based on the site of their first panic attack. These five sites were:homeschool or officedriving a carpublic transportationoutside of homeIndividuals experiencing their first panic attack while driving or using public transportation had higher rates of agoraphobia. The rank order for agoraphobia rates by site of first panic attack were: public transportation (61%), driving a car (56%), outside of home (49%), school or office (41%) and home (37%).Although individuals experiencing their first panic attack at home had lower rates of agoraphobia they exhibited other markers of severity. They had higher rates of endorsement of the symptom of "fear of dying". Additionally, individuals experiencing their first panic attack at home rated the severity of their first panic attack higher than the other 4 groups.This study supports exploration of the setting and severity of the first panic attack in the assessment of panic disorder. First panic attack setting may contribute to the pattern clinical symptoms and risk of agoraphobia.Photo of black bear and yearling cub from Itasca State Park from the author's files.Hara N, Nishimura Y, Yokoyama C, Inoue K, Nishida A, Tanii H, Okada M, Kaiya H, & Okazaki Y (2012). The development of agoraphobia is associated with the symptoms and location of a patient's first panic attack. BioPsychoSocial medicine, 6 (1) PMID: 22494552... Read more »

Hara N, Nishimura Y, Yokoyama C, Inoue K, Nishida A, Tanii H, Okada M, Kaiya H, & Okazaki Y. (2012) The development of agoraphobia is associated with the symptoms and location of a patient's first panic attack. BioPsychoSocial medicine, 6(1), 12. PMID: 22494552

May 21, 2012
10:49 AM
10 views

FROM SOIL TO HUMAN: EVOLUTION OF BACTERIAL IMMUNE EVASION MECHANISMS

by Brooke N in Smaller Questions

Most, if not all, pathogenic bacteria did not get their start infecting humans, no, most of them started off as meager soil or water bacteria, just hoping to catch a rock to colonize. A lot of biologists have dedicated their lives to understanding the genetics or mechanisms behind harmless soil/water bacteria evolving into lean-mean human killing machines.... Read more »

Li Y, Powell DA, Shaffer SA, Rasko DA, Pelletier MR, Leszyk JD, Scott AJ, Masoudi A, Goodlett DR, Wang X.... (2012) LPS remodeling is an evolved survival strategy for bacteria. Proceedings of the National Academy of Sciences of the United States of America. PMID: 22586119

May 21, 2012
08:08 AM
10 views

Repetitive brain injury from high impact sports generates similar pathophysiology to traumatic brain injury in soldiers blown up by IEDs

by Pieter Droppert in Biotech Strategy Blog

Several retired American Football stars have ended up with chronic traumatic encephalophy (CTE), previously known as dementia pugilistica. It’s similar to Alzheimer’s disease in that the brain ends up with neurofibrillary tangles. CTE has also been seen in soldiers who … Continue reading →

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Goldstein, L., Fisher, A., Tagge, C., Zhang, X., Velisek, L., Sullivan, J., Upreti, C., Kracht, J., Ericsson, M., Wojnarowicz, M.... (2012) Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model. Science Translational Medicine, 4(134), 134-134. DOI: 10.1126/scitranslmed.3003716

May 21, 2012
07:53 AM
16 views

Patterns of RNA methylation

by Habib Maroon in Biobabel

A new paper in Cell provides a transcriptome-wide survey of the methylation of adenosine residues in RNAs. Meyer et al find that this epitranscriptomic post-transcriptional modification is widespread and dynamically regulated, and likely to play important roles in cellular regulation. … Continue reading →... Read more »

Meyer, K., Saletore, Y., Zumbo, P., Elemento, O., Mason, C., & Jaffrey, S. (2012) Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3′ UTRs and near Stop Codons. Cell. DOI: 10.1016/j.cell.2012.05.003

May 21, 2012
07:02 AM
17 views

No one knows you’re a dog on the internet (actually, they do!)

by Rita Handrich in The Jury Room

Contrary to the now famous New Yorker cartoon, people on the internet do know you’re a dog. Sort of. We’ve all heard of undercover police officers pretending to be children in online chat rooms as they attempt to identify pedophiles. The assumption behind this strategy is that an adult can successfully manipulate perceptions of their gender [...]
No related posts.... Read more »

Lincoln, R., & Coyle, IR. (2012) No-one knows you’re a dog on the internet: Implications for proactive police investigation of sexual offenders. Psychiatry, Psychology and Law. info:/

May 21, 2012
07:00 AM
9 views

May 21, 2012

by Erin Campbell in HighMag Blog

Whenever we go on a trip, my long-suffering husband quietly puts our luggage next the car and slinks away, trembling and twitching. He knows a mad-woman is ready to pack the trunk, playing luggage-Tetris until it all fits and speaking in tongues. Seriously, though, I’m freaking awesome. That said, I don’t envy the insane packing that a cell must accomplish to jam all of that DNA into neat little chromosomes ready for their own cell division road trip. A recent paper helps us understand how that happens at the centromere.Centromeres are the regions on chromosomes that bind sister chromatids together and serve as the sites of kinetochore assembly during mitosis. The presence of the protein CENP-A is a hallmark of centromere location, as it is a histone H3 variant that helps package and compact centromeric DNA. It was previously presumed that CENP-A was passed down to daughter cells epigenetically, inherited from previous cell divisions, but a recent paper shows that this is not the case in the nematode worm C. elegans. According to Gassmann and colleagues, pre-existing CENP-A is not required for CENP-A localization to centromeres in subsequent divisions. In fact, CENP-A is unloaded from centromeres at one point in oogenesis, the production of eggs, and later reloaded onto centromeres. By mapping the location of CENP-A in the genome, Gassmann and colleagues found that regions of transcribed genes are regions where CENP-A is excluded, a pattern that changes when germline gene transcription switches to embryonic gene transcription. In the images above, the C. elegans germline is labeled to show chromosomes (top image) and the location of CENP-A (bottom). CENP-A is lost from chromosomes during the pachytene stage of meiosis and later reloaded onto chromosomes during diplotene, and is not found in sperm. Gassmann, R., Rechtsteiner, A., Yuen, K., Muroyama, A., Egelhofer, T., Gaydos, L., Barron, F., Maddox, P., Essex, A., Monen, J., Ercan, S., Lieb, J., Oegema, K., Strome, S., & Desai, A. (2012). An inverse relationship to germline transcription defines centromeric chromatin in C. elegans Nature, 484 (7395), 534-537 DOI: 10.1038/nature10973Adapted by permission from Macmillan Publishers Ltd, copyright ©2012... Read more »

Gassmann, R., Rechtsteiner, A., Yuen, K., Muroyama, A., Egelhofer, T., Gaydos, L., Barron, F., Maddox, P., Essex, A., Monen, J.... (2012) An inverse relationship to germline transcription defines centromeric chromatin in C. elegans. Nature, 484(7395), 534-537. DOI: 10.1038/nature10973

May 21, 2012
06:33 AM
12 views

Is the ability to distinguish 'speech sound contrasts' strictly human?

by Henkjan Honing in Music Matters

For various reasons the song of songbirds are currently considered to be the closest animal analogue to language. This raises questions about to what extent particular perceptual and cognitive abilities that are considered to be closely linked to the production, perception and learning of language are present in songbirds. In an upcoming SMART-Talk at the University of Amsterdam on Friday 25 May 2012, Prof. dr Carel ten Cate (Leiden University) will address two of such abilities.... Read more »

ten Cate, C., Verzijden, M., & Etman, E. (2006) Sexual Imprinting Can Induce Sexual Preferences for Exaggerated Parental Traits. Current Biology, 16(11), 1128-1132. DOI: 10.1016/j.cub.2006.03.068

May 21, 2012
04:12 AM
25 views

Individualized medicine, ignorant medics and an invitation to lose weight.

by Lutz Kraushaar in Chronic Health

Why individualized medicine will not be a reality anytime soon, how physicians often misinterpret published studies, and how individualized prevention is a clear and present benefit.

In my previous post I promised to talk about your
individualized way to achieving optimal health. If that made you think
about personalized medicine, you were right. Almost. Because personalized
medicine is still light-years away from us. That's the bad news. The good news,
personalized prevention is an emerging reality. At least in my lab. Which is
why I would like to invite you to become a part of it. No strings attached. But
before we get to this let's first get on the same page about the
personalization of medicine.

Two questions we need to ask ourselves: What is personalized
medicine and why would we want it?

Professor Jeremy K Nicholson of the Imperial College,
London, defined personalized medicine as "effective therapies that are
tailored to the exact biology or biological state of an individual" [1]. Such tailoring of a
treatment, say for your high blood pressure, would require your doctor to evaluate
your biochemical and metabolic profile in order to prescribe you the most
effective drug or treatment at the most effective dose, with the least possibility
of side effects.

Now, why would we want this?
Simply because we don't have it. Because our current drugs do not work optimally in most people [2]. But don't just take my word for it. Take that of Dr. Allen D. Roses, head of the Drug Discovery Institute at Duke University School of Medicine. In an interview he told a UK newspaper, The Independent, that more than 90% of
modern drugs work, at best, in 30-50% of the people. He said that in 2003. At the time,
Roses was also senior vice president for genetics research and pharmacogenetics
at GlaxoSmithKline.

Contrary to what you might think, Roses did not reveal any nasty industry secret. What he said is plainly visible for everyone who can read the results of clinical trials through the lens of statistics. I simply quote Roses for effect. After all, he knows what he is talking about. Contrary to
many medical doctors, who have an amusingly limited grasp of the basic
statistics used to interpret and present the results of clinical trials. Just how
limited, that has been recently demonstrated for the case of cancer screening in
a mock-up trial investigating the understanding of practicing physicians [3].

Before I tell you the results of this trial, let me make you
understand what it was about. One big question in cancer screening is whether
screening helps to reduce the number of people dying from cancer. Let's
take a hypothetical example, and here I reuse the one which the study's authors
used to explain statistical outcomes. Let's say, cancer was detected in a group
of people at age 67. All of them died of their cancer at age 70. The 5-year
survival rate from diagnosis would stand at 0% (they all died before 5 years were over). Now imagine that all those
cancer cases would have been detected at age 60 with a screening test. And also imagine that all of them still died at age 70. In this case the 5-year survival rate
would have been 100% (they were all still alive at 65). You see the issue: the survival rate was better with screening, but the rate of dying remained the same. In epidemiology we call
this sort of thing lead-time bias. That is, simply detecting a disease earlier
might lead to an improved survival rate which has, in fact, nothing to do with
improved survival. Such lead time bias is rarely an all-or-nothing thing as in
this hypothetical case. Most of the time it comes in degrees. But in any case,
it would help you as a patient, if your doctor was able to see through the
reporting, and to question the clinical relevance of the results so presented. Your
doctor should look for the mortality rate, the rate of dying, not the survival
rate.

Back to the results of the mock-up trial about physicians' interpretive skills of clinical research publications. If the results of this mock-up trial are representative of
the population of your doctors, then you should be worried. Of the over 200
practicing physicians enrolled in this trial, fully 76% would recommend you
this useless screening test. They considered an improved 5-year survival rate as prove
for the test's efficacy! These were not undereducated physicians of a third
world country, mind you. They were randomly selected from the Harris
Interactive Physician Panel, which is representative of the general U.S.
physician population.

OK, you may say that this was a test related to cancer
screening. What has it got to do with understanding the efficiency of a drug,
which your doctor prescribes you? Well, maybe your doctor aces the statistics
test on drug trials after he has flunked the one on cancer screening. If you believe that, you probably also believe in the tooth fairy and in Santa Claus. But you may have another question: Can trial results be
presented in such misleading ways? Aren't researchers supposed to report their
results honestly and correctly? And what use is the peer-review process which
every published paper has to go through?

With 70% of all medical research being financed by the
private sector, data are a commodity. So, whether you develop a screening test,
a drug or a treatment, you will want to dress it up as a magic bullet. Because
when you have the magic bullet for, say high blood pressure or high
cholesterol, it will make it into every physician's armory. That's where the
money is. It's certainly not in personalized medicine, which may find your
competitors' drugs as more suitable solutions for a variety of cases.

Which
brings us back to personalized medicine. I have told you in my previous post
how much it costs to develop a drug. Which is why Big Pharma would love to
concentrate its research on the areas where the probability of success is high
and the potential risk of failure is low. That's the area of follow-up drugs, drugs of the same class as established drugs, but with incremental
improvements over the older version. Ironically, our health care system discourages
this type of pharmacological research. Incrementally improved drugs are
typically reimbursed at the same rate as older drugs. Not much profit potential
there. Particularly when competition is fierce.

Which is why Big Pharma looks for new grounds, that is new
therapeutic classes, for which, of course, there need to exist a large market [4]. Again, individualization is
certainly not desirable, as it would fragment any market. There is another
draw-back: when you break new grounds, it takes a lot longer to get off that
ground with some new product. Which is what we see in the FDA's records of drug
approvals over the past 10-15 years [5]. Ten years... Read more »

Nicholson, J. (2006) Global systems biology, personalized medicine and molecular epidemiology. Molecular Systems Biology. DOI: 10.1038/msb4100095

Wegwarth O, Schwartz LM, Woloshin S, Gaissmaier W, & Gigerenzer G. (2012) Do physicians understand cancer screening statistics? A national survey of primary care physicians in the United States. Annals of internal medicine, 156(5), 340-9. PMID: 22393129

Pammolli, F., Magazzini, L., & Riccaboni, M. (2011) The productivity crisis in pharmaceutical R. Nature Reviews Drug Discovery, 10(6), 428-438. DOI: 10.1038/nrd3405

Loscalzo, J. (2012) Personalized Cardiovascular Medicine and Drug Development: Time for a New Paradigm. Circulation, 125(4), 638-645. DOI: 10.1161/CIRCULATIONAHA.111.089243

Yang, Q. (2012) Trends in Cardiovascular Health Metrics and Associations With All-Cause and CVD Mortality Among US Adults. JAMA: The Journal of the American Medical Association, 307(12), 1273. DOI: 10.1001/jama.2012.339

Yang Q, Cogswell ME, Flanders WD, Hong Y, Zhang Z, Loustalot F, Gillespie C, Merritt R, & Hu FB. (2012) Trends in cardiovascular health metrics and associations with all-cause and CVD mortality among US adults. JAMA : the journal of the American Medical Association, 307(12), 1273-83. PMID: 22427615

May 21, 2012
12:57 AM
18 views

Inequality Aversion Is For Real

by erichorow in peer-reviewed by my neurons

A number of studies have found support for the idea that children as young as 4 or 5 dislike inequality. However, the studies generally don’t do a good job isolating the desire to curb inequality from concerns about social welfare or social comparisons. For example, if Billy is unhappy that Steve receives more candy than [...]... Read more »

Shaw, A., & Olson, K. (2012) Children discard a resource to avoid inequity. Journal of Experimental Psychology: General, 141(2), 382-395. DOI: 10.1037/a0025907

May 21, 2012
12:06 AM
14 views

Predictors of Failure After ACL Reconstructions

by Andrew Lynch in Sports Medicine Research (SMR): In the Lab & In the Field

Re-injury rates after ACL reconstruction (ACLR) are shockingly high, with up to 25% of patients suffering a re-injury. Surgical advancements abound in attempting to decrease re-injury rates and the development of osteoarthritis after ACL injury, but highly structured prospective analysis of re-injury rates for each type of ACLR are not currently available. Therefore, the purpose of this investigation was to systematically analyze the re-injury rate of patients undergoing an anatomic ACLR with allograft tissue, as well as to identify predictors of re-injury.... Read more »

van Eck CF, Schkrohowsky JG, Working ZM, Irrgang JJ, & Fu FH. (2012) Prospective analysis of failure rate and predictors of failure after anatomic anterior cruciate ligament reconstruction with allograft. The American Journal of Sports Medicine, 40(4), 800-7. PMID: 22238055

May 20, 2012
11:01 PM
21 views

Researchers Demonstrate The First Brain Controlled Robotic Arm

by Neurobonkers in Neurobonkers

esearchers have demonstrated the first 3D control of a robotic arm from electrodes implanted directly in the brain. This technology has been tested before in monkeys but this is the first time the technology has been successfully trialled in humans. Until now, human brain computer interfaces (BCI) have been limited to two dimensions. ... Read more »

Hochberg, L., Bacher, D., Jarosiewicz, B., Masse, N., Simeral, J., Vogel, J., Haddadin, S., Liu, J., Cash, S., van der Smagt, P.... (2012) Reach and grasp by people with tetraplegia using a neurally controlled robotic arm. Nature, 485(7398), 372-375. DOI: 10.1038/nature11076

May 20, 2012
10:32 PM
32 views

Phosphorus, detergent, and Canada's Experimental Lakes

by Patrick in Evidence and Error

“I'm angry at the people who decided that phosphate was growing algae. I'm not sure that I believe that.” –Sue Wright, Texas

Sue Wright, quoted above, was upset because in 2010, sixteen American states banned the sale of dishwashing detergent containing high levels of phosphorous, an aquatic pollutant that sometimes causes eutrophication (algal blooms). Unfortunately, phosphorous is a rather effective component of detergent, so phosphorous-free dishwashing detergents did not immediately perform quite as well as their predecessors. This led some consumers (like our pal Sue) to complain to detergent manufacturers, state governments, consumer protection agencies, and the media.

What I like most about Sue’s complaint is that her anger was directed toward “the people who decided that phosphate was growing algae” rather than the policymakers who drafted and enacted the legislation. Her implied logic is exquisite – a factual claim has resulted in legislation that negatively affects some aspect of my life, therefore I don’t believe this factual claim and furthermore am angry at those who made it!

So, who specifically should Sue have directed her anger toward? Which jackass scientist “decided that phosphate was growing algae”?

The answer, unsurprisingly, is that many independent studies (involving various research groups) have demonstrated that phosphorous pollution, under some conditions, will stimulate algal growth and lead to eutrophication (see Schindler 2006 for a review). Here, I will focus on just one of these studies, perhaps the most influential.

My real motivation for discussing this particular paper is the recent announcement that the Canadian Government is discontinuing its operation of the Experimental Lakes Area (ELA), a collection of 58 pristine lakes that for over 40 years have been set aside for long-term ecosystem monitoring and ecosystem-scale experiments (more on the ELA later).

Green sludge

In the 1960s and 70s, many North American rivers and lakes, especially the Great Lakes, were experiencing rapid declines in water quality (see here and here). Industrial and municipal effluents were stimulating the growth of algae and other aquatic plants (termed ‘eutrophication’) leading to unsightly mats of green sludge, oxygen depletion, massive die-offs of fish and other aquatic life, and problems with the taste and odour of municipal drinking water.

The August 1969 issue of Time Magazine describes the then deteriorating state of Lake Erie:

"Each day, Detroit, Cleveland and 120 other municipalities fill Erie with 1.5 billion gallons of inadequately treated wastes, including nitrates and phosphates. These chemicals act as fertilizer for growths of algae that suck oxygen from the lower depths and rise to the surface as odoriferous green scum. Commercial and game fish … have nearly vanished ... Weeds proliferate, turning water frontage into swamp. In short, Lake Erie is in danger of dying by suffocation."

The public, industry, and all levels of government agreed that something had to be done to curb the declining state of North American waterways. However, there was disagreement over the most effective course of regulatory action because at the time, scientists and policymakers were still debating which nutrients were responsible for eutrophication. Was algal growth primarily limited by carbon, nitrogen, or phosphorous?

Schindler 1974

Experiments are the best way to establish causation, but are not always feasible. For example, the best way to test the anthropogenic climate change hypothesis would be to release copious quantities of greenhouse gas into the atmospheres of a random sample of earth-like planets, leave another randomly-chosen bunch of planets untouched, and then compare change in climate across the two groups of planets. Clearly this is not feasible, and clearly we can’t experimentally pollute a bunch of lakes just for the sake of science. Right? Wrong. Well, wrong to the second assertion at least.

The aforementioned Experimental Lakes Area is (was) a wonderful place where scientists could manipulate whole lakes to test hypotheses on the scale of entire ecosystems. In the late 1960s and early 70s, David Schindler – a Canadian limnologist who at the time was director of the ELA – oversaw a number of whole-lake experiments designed to determine which nutrient (out of carbon, nitrogen, and phosphorous) was primarily responsible for eutrophication.

In an initial experiment, Schindler et al. added copious amounts of nitrogen and phosphorous to Lake 227 which naturally had an extremely low concentration of dissolved carbon. If algal growth was primarily limited by carbon (and not nitrogen or phosphorous), then the N P treatment should not stimulate the growth of algae. However, this was not the case. Within weeks of the treatment, Schindler et al. observed that Lake 227 “was transformed into a teeming, green soup” with algal concentrations up to two orders of magnitude higher than nearby untreated lakes. Clearly, low levels of carbon had not been limiting the growth of algae.

In a second experiment, Schindler et al. divided another lake, Lake 226, into two equal halves using a large vinyl curtain that was sealed into the sediment and surrounding bedrock. The team added an equivalent amount of carbon and nitrogen to both halves of the lake, but added phosphorous to only one side. This manipulation resulted in what James Elser at Arizona State University has called “the single most powerful image in the history of limnology”.

Figure 1. Lake 226 following fertilization with carbon, nitrogen, and phosphorous (below divider) versus carbon and nitrogen only (above divider).

Just a few months after the nutrient additions began, the side of the lake receiving C N P was completely covered by a bloom of blue-green algae whereas algae levels on the C N side were essentially unchanged from when the nutrient additions began. It was abundantly clear that phosphorous had been limiting the growth of algae in Lake 226.

In a final experiment, Schindler et al. manipulated a third lake, Lake 304, to test whether, and how quickly, a lake could recover from phosphorous-induced eutrophication. The team measured the concentration of algae in Lake 304 at approximately monthly intervals over the course of five years, between 1969 and 1973. For three of those years, 1971–1973, the lake received additions of carbon and nitrogen, and for two years, 1971–1972, also received phosphorous. The experiment therefore mimicked what might happen if governments took steps to limit the amount of phosphorous entering a polluted water body. The general finding was that summertime algal concentrations increased dramatically in 1971 and 1972 when the lake was being fertilized with C N P, but returned to near baseline levels in 1973 after phosphorous fertilization was discontinued.... Read more »

Schindler, D. (1974) Eutrophication and Recovery in Experimental Lakes: Implications for Lake Management. Science, 184(4139), 897-899. DOI: 10.1126/science.184.4139.897

May 20, 2012
07:15 PM
25 views

More Authors or Less Authors?

by Psych Your Mind in Psych Your Mind

source

In my brief time in research I have written journal articles authored by as few as two people and as many as six people. Many of those authors have been faculty members (senior researchers who provided me with valuable mentoring), colleagues (graduate students with similar experience and training), and trainees (early researchers learning the research process from me and others). This experience has got me wondering: What is the best combination of authors for writing a research paper? Is it better to have more authors or less authors? I consider these questions in today's post!

I should note that many of these challenges apply to any form of collaborative work, and not just research.
Read More->... Read more »

Ross, M., & Sicoly, F. (1979) Egocentric biases in availability and attribution. Journal of Personality and Social Psychology, 37(3), 322-336. DOI: 10.1037//0022-3514.37.3.322

Sapolsky, R. (2005) The Influence of Social Hierarchy on Primate Health. Science, 308(5722), 648-652. DOI: 10.1126/science.1106477

Latane, B., Williams, K., & Harkins, S. (1979) Many hands make light the work: The causes and consequences of social loafing. Journal of Personality and Social Psychology, 37(6), 822-832. DOI: 10.1037//0022-3514.37.6.822

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