by mrr in genome ecology evolution etc
This blog section concerns a trendy debate in science, the human population history, which has extensions into daily life, as it can constitutes a topic of general public curiosity. Therefore, let’s see what is contribution described herein.BackgroundModern human populations seems to be derived from a single African ancestral population, under the well supported “out of Africa” hypothesis (1). Particularly, for eastern Asian colonization a “single-dispersal” model have been hypothesized (2), which suggest the aboriginal australians are a lineage diversified recently within the Asian cluster. This hypothesis could be summarized in a topological representation, as drawn in figure 1A of the article (Africans,(Europeans,(Asians,Australians))). Recent studies dated the split between Europeans and Asians around 17K-43K years before the present (ybp). In addition, archaeological evidence supports modern humans in Australia back to ~50K ybp. Those inferences are incompatible with the above mentioned hypothesis, at least in a time framework. A second scenario could be hypothesized, with an early branching process and occupation of Australia, and probable later genetic exchange between Asians and Australians, described as (Africans, (Australians,(Asians, Europeans)). This possibility has been non tested so far. Using an ancient, free of current admixtures, aboriginal australian genome, and SNPs data from different human populations, as well as, a background in molecular evolution and population genetic theories, this paper aims to distinguish between competing hypotheses to tackle the human population relatedness and migrations history of ancient australian populations.The facts in briefA 100-year-old lock of hair from an aboriginal Australian male (from Museum of Archaeology and Ethnology, UK)31 Institutions implied in a worldwide scale58 Authors, with same geographical extentAn ancient genome sequenced by Illumina technology and SNP-chip on other human populationsComputational analyses (PCA, clustering methods, ABBA/BABA expectations)A Science podcast interview (http://www.sciencemag.org/content/334/6052/94/suppl/DC2)Discussion We found the paper quite convincing in testing the two possible scenarios for human colonization in the Australian area. Next paragraphs will describe and discuss the evidence and test they used.1. Testing the genetic clustering of Aboriginal Australian genome.The principal component analysis illustrated in figure 1B shows the clustering pattern from 1220 individuals SNP chip data (449k SNPs), covering 79 human populations. This figure revealed a close relationship between the Australian genome, Highland Papua New Guinea (PNG), Bougainville and Aeta samples, all of them from the australo-melanesian region. That pattern could exclude any European contamination of the sample, which is highly probable by his long handling by Europeans. We noted the geographical tendency of a “continuous” colonization for human populations outside of Africa. I quoted continuous to clarify we are not referring to a single wave of colonization, but to a geographical ordination of the populations. A confusing point was expressed for the PCA inset, which looks like a 3D-box, but it already corresponds just to a zoom-in on the same PCA graph. A further review of the next PCA axes on supplementary material evidenced a very clear differentiation of the australo-melanesian sequences in the axis4.We speculated about the amount of data explained in the first two PCA axes, which is not described. Contrary to our expectations, from experiences in other types of characters (as morphology and climatic variables), the proportion of variance explained on this plot seems to be very low, as usual for genomic studies. Then, we discussed a bit the idea of a checklist of requirements when a publication is being prepared: if you are planning to present an analysis, take at hand i, ii, iii and please do not forget to include them.2. Testing admixture between Aboriginal Australian genome and other populationsThe figure 1C describes the ancestry proportions of all individuals SNPs set, obtained by a maximum likelihood estimation in Admixture software. This clustering analysis resembles the Structure k-categories approach, in which each line in the plot correspond to an individual and the colors represent the ancestral populations identities. The number of k-categories is assigned a-priori, and can modify the ancestry proportions of certain individuals revealing admixture processes between populations. At first, using a k=5, the aboriginal australian sample appears belonging to the same ancestral population than PNG and a higher proportion of the Bougainville individuals. Interestingly, south Asian population seems to share a small proportion of the SNPs with the ancestral aboriginal australian category. Once we moved in deep k-values, as far as k=20, the aboriginal australian genome appears more mixed with PNG, Bougainville, Aetas and South Asian populations.We debated the accuracy of use an individual genome to represent the admixture in the ancestral aboriginal australian population, and the unknown variability of the population at the ancient time, which is not being considered here. We formulated how could be affected the admixture patterns if this aboriginal Australian genome represents the most or the least mixed individual in the ancestral population? We wondered why there are not other recent Australian samples? Even if current aborigines inhabit in Australia. At this point in the discussion, we moved into more socio-political issues about the use of samples and information, as I stated at the beginning, this topic could be of general concern and discussion for several reasons.The evidence presented so far and an additional test below can help to distinguish between single vs. multiple dispersals “out of Africa” and likely the proportion of admixture between the first established populations and the second wave of migration. Furthermore, questions about how or why the second migration replaced almost in a complete way the first one, from my point of view, constitute statements largely "historical" and therefore difficult to draw and test from the evidence available. I consider is very difficult to go beyond of the patterns and processes we are able to model and test.3. D-test and ABBA/BABA hypothesis We tried to identify the goal and configuration of this test to discriminate between the competing hypotheses. Complete information of the test could be found in references 3 and 4. I will try to summarize it in a nutshell. The D-test is a four-taxon configuration (see figure) in which only biallelic sites are considered (A and B variants), two out of four taxa have fixed states, commonly on the outgroup sequence (here the Africans, but also the Europeans), and the other two sites differ between groups (here Aboriginals and Asians). This configuration produces either BABA or ABBA patterns. The next step is to count the number of sites supporting one or other patterns. The D test = ∑ (sites ABBA - sites BABA) / ∑ total sites. Usually, the test was defined to identify admixture between populations (with AB/BA sites), with the expectation of an equal number of the two types of sites. D test can be considered more robust to sequencing errors because it compares nucleotides in more than one sequence, which is less probable that have been taken place twice by error. The authors explicitly said the test do not allow to distinguish neither between the two models of origin, nor gene flow between Asians and Australian populations, however I consider the D-test performed here can support the multiple dispersal model, due to a statistically significant excess of sites grouping Africans and Australian Aboriginal genomes (sites with pattern 2 in figure). Expected vs. observed values of the D-test can facilitate the hypotheses discrimination (as they tried on the Table 2), however the expected values reported here for single and multiple dispersal models are so closer each other (~50%), with no credible intervals, that does difficult to support one or other hypothesis with the observed patterns. Finally, it is worthy of attention in the implementation of the D-test, consider that the patterns on current populations given the hypothetical past events, may have been altered by many other evolutionary processes as secondary gene flow, structure in the ancient population, incomplete lineage sorting, among others.Figure 1. Grouping site patterns 1 and 2 used in D-test. Note that African and European populations have fixed states, whereas that Aboriginal Australian and Asian populations vary. This figure is a modification of the figure 3 in reference 5. Even though it is not clear the ABBA/BABA patters, the different grouping patterns are based on the article text describing the two models of early dispersal hypotheses used to perform the test. ... Read more »
Rasmussen, M., Guo, X., Wang, Y., Lohmueller, K., Rasmussen, S., Albrechtsen, A., Skotte, L., Lindgreen, S., Metspalu, M., Jombart, T.... (2011) An Aboriginal Australian Genome Reveals Separate Human Dispersals into Asia. Science, 334(6052), 94-98. DOI: 10.1126/science.1211177
by erichorow in peer-reviewed by my neurons
It’s irritating that people talk about educational technology in terms of iPads in the classroom when the real impact will come from pinpoint differentiation, instant student assessment, and a third thing that nobody talks about – improved simulations in speciality learning. For example, medical students who use virtual patients — an “interactive computer simulation of real-life [...]... Read more »
Consorti, F., Mancuso, R., Nocioni, M., & Piccolo, A. (2012) Efficacy of virtual patients in medical education: A meta-analysis of randomized studies. Computers , 59(3), 1001-1008. DOI: 10.1016/j.compedu.2012.04.017
by Kyle Harris in Sports Medicine Research (SMR): In the Lab & In the Field
Anterior cruciate ligament (ACL) ruptures often coincide with meniscal and cartilaginous injuries. These ruptures are generally treated with surgical reconstruction or non-surgical treatment. Patients who chose to delay surgical treatment may be at greater risk for increasing the severity of the associated injuries; however, this has not been demonstrated in the literature. Therefore, Fok and Yau completed a retrospective, comparative study investigating (1) if delaying ACL reconstruction is associated with the number of meniscal and articular cartilage lesions, and (2) if ACL-deficient patients experiences greater frequency and magnitude of pain.... Read more »
Fok AW, & Yau WP. (2012) Delay in ACL reconstruction is associated with more severe and painful meniscal and chondral injuries. Knee Surgery, Sports Traumatology, Arthroscopy. PMID: 22552616
by Tetyana Pekar in Science of Eating Disorders
Given the popularity of my post on how the media portrays eating disorders, I thought I’d do a follow-up post about a more recent and comprehensive study on media reporting of eating disorders. Shepherd & Seale (2010) wanted to build up on the findings of O’Hara & Clegg-Smith, but focusing on UK newspapers.... Read more »
Shepherd, E., & Seale, C. (2010) Eating disorders in the media: The changing nature of UK newspaper reports. European Eating Disorders Review, 18(6), 486-495. DOI: 10.1002/erv.1006
by Patrick Mineault in xcorr
I was reading the Wikipedia article on tinnitus, and came across this pearl of a sentence: A common and often misdiagnosed condition that mimics tinnitus is Radio Frequency (RF) Hearing in which subjects have been tested and found to hear high-pitched transmission frequencies that sound similar to tinnitus. Hmm, what? Yes, humans, under special circumstances, [...]... Read more »
Elder, J., & Chou, C. (2003) Auditory response to pulsed radiofrequency energy. Bioelectromagnetics, 24(S6). DOI: 10.1002/bem.10163
by Rogue Medic in Rogue Medic
The current Annals of Emergency Medicine has a pair of editorials on the article I wrote about[1] in This is the Way to Bad Medicine back in January. Dr. Radecki also was critical of this paper.[2] There is another study that refers to the same question published in this issue, but I will write about that paper later.
"These data raise the real question, Do such findings matter? By admitting more patients and ordering more CTs, do we improve outcomes? Or do we simply find more things that have little clinical importance? Indeed, in Menditto’s sample,8 only 1 patient needed craniotomy. In Kaen’s,14 none did.[3]"... Read more »
Menditto, V., Lucci, M., Polonara, S., Pomponio, G., & Gabrielli, A. (2012) Management of Minor Head Injury in Patients Receiving Oral Anticoagulant Therapy: A Prospective Study of a 24-Hour Observation Protocol. Annals of Emergency Medicine. DOI: 10.1016/j.annemergmed.2011.12.003
by Cath in Basal Science (BS) Clarified
Summer time means BBQ season but it’s also the start of road construction. Road construction usually leads to traffic jams and slowdowns, so it makes sense to avoid construction in [...]... Read more »
You, Z., Mills-Beale, J., Foley, J., Roy, S., Odegard, G., Dai, Q., & Goh, S. (2011) Nanoclay-modified asphalt materials: Preparation and characterization. Construction and Building Materials, 25(2), 1072-1078. DOI: 10.1016/j.conbuildmat.2010.06.070
by Clay Clark in Biochem Blogs
What is referred to as “MudPit” here is not “a pit of mud” but a technique in the mass spectrometry field which stands for “multi-dimensional protein identification technology”, a very powerful approach that has been widely used since the … Continue reading →... Read more »
Washburn, M., Wolters, D., & Yates, J. (2001) Large-scale analysis of the yeast proteome via multidimensional protein identification technology. Nature Biotechnology, 19(3), 242-247. DOI: 10.1038/85686
Yang, F., Shen, Y., Camp, D., & Smith, R. (2012) High-pH reversed-phase chromatography with fraction concatenation for 2D proteomic analysis. Expert Review of Proteomics, 9(2), 129-134. DOI: 10.1586/epr.12.15
Tran, J., Zamdborg, L., Ahlf, D., Lee, J., Catherman, A., Durbin, K., Tipton, J., Vellaichamy, A., Kellie, J., Li, M.... (2011) Mapping intact protein isoforms in discovery mode using top-down proteomics. Nature, 480(7376), 254-258. DOI: 10.1038/nature10575
by Carian Thus in United Academics
Imagine how horrific life would be when you are convinced to be dead, while you are still alive. This delusional belief of non-existence characterizes sufferers of the rare mental disorder Cotard Delusion. Slight variations include those that believe they are rotting or have lost their blood or internal organs.... Read more »
Debruyne H, Portzky M, Van den Eynde F, & Audenaert K. (2009) Cotard's syndrome: a review. Current psychiatry reports, 11(3), 197-202. PMID: 19470281
by xylph in xylem || phloem
In this installment, I will discuss why it is difficult to discover, design and develop a drug, in view of our current knowledge of physiology.With numerous, intertwined reactions happening, our body is a complex clockwork of biomachinery gears. What do you do, then, if some gears fail—that is, if you got sick? On one hand, it is a consolation that many gears are what biologists call 'redundant', which means that it's alright that a certain gear fails, because there are other gears that can take over its function. On the other hand, due to the intricacy of the gears, it is hard to pinpoint which gear is the problem, let alone fixing it. And the sheer number of gears: ICD-10 classifies tens of thousands diagnoses — tens of thousands ways the gears can fail — and those are only the ones we know; how about those we don't? Granted, some are not caused by our own gears failing, but by interferences of other, pesky gear systems: viruses, bacteria, misfolded proteins, errant microbiome, etc.; but the sense of magnitude is there.So we take drugs. In the past, the way we administer drugs is the equivalent of throwing various types of wrenches to the clockwork and then observe whether the gears are working again. Today we know more about the gears and the various shapes and teeth so that we are able to design a more sophisticated and targeted wrench, but we still don’t know enough.Our current thinking is that the machinery gears, mostly proteins, are of distinct shapes, or perhaps more fittingly, different tooth shapes. A drug has gotta fit into these various shapes. We think that if we can find 'keys' that fit to these 'locks' we can modulate that particular gear's activity: turn it up or down, switch it on or off. The key would fit into the lock, the lock would be induced to change shape / dissociate / do other curious stuff; which triggers happenings in the next gear in line. Like the dominoes falling off in line. Only that ‘the curious stuff’ may be more than a domino keeling over or a gear turning, but something that is more wackily messy, something like a Rube Goldberg contraption than a precise-looking clockwork, in this respect.How should we shape the serrated key? The first problem is scale. These gears are small — not microscopically, but nanoscopically so: To design the keys, we need the moulds, and so these very gears are the moulds. Structural biology to the rescue — X-rays crystallography/multidimensional NMR/cryo-electron microscopy can characterise the gears with varying resolutions.However, structural determination techniques face a big challenge: the interconnectedness of the system. You can't take out a gear out of context of the surrounding gears, examine it, hoping that your examinations will be valid and/or useful. Well, you sort of can. Sure, systems biology is important to gain a bird's-eye view of the whole shebang, but structural biologists routinely single out a gear and determine its structure to make it crystal-clear (heh heh) what its possible activation mechanism is, how it interacts with its activator/inhibitor, how it transduces signal to the next gear, and so on.The structural data, then, has to be taken with a grain of sodium chloride because essentially it is performed—in the physics equivalent of—in vacuo. That said, the gleaned information can be incredibly useful. Case in point: enfuvirtide. This anti-HIV-1 drug mimics a region—C-heptad repeats (CHR)—of the viral envelope glycoprotein, gp41, which is a crucial part of viral:cell membrane fusion machinery [1]. CHR is supposed to fold back to NHR like a hairpin (they are connected) and then Stuff happens, with gory details I will spare you from (Oh, fine: a channel is opened between HIV-1 membrane and that of your soon-to-be-infected T-cell; viral particles are pumped through and soon hijack your T-cell to become baby-virus-producing zombie until it bursts releasing said baby virions. Happy?) Now, the 'folding back' part is a mechanism that was uncovered through cleverly-devised experiments founded in structural studies. Thanks to this, we can deduce that if we somehow have a fake CHR, this 'folding back' can be circumvented. And that's exactly what enfuvirtide is: a dummy gear that connects to NHR gear, but not connected to the gears down the road, thus—hip hip hurray—no zombie outbreak.This is kinda cheating though. Enfuvirtide is essentially free-roaming CHR region of gp41 and no rational design work was done. For example, peptidomimetic strategy could have been used to find something similar to enfuvirtide but is able to survive the gut—since a peptidic drugs like enfuvirtide won’t, so they have to be taken intravenously. But of course, HIV-1-infected individuals don’t have the luxury of time to wait for further work on enfuvirtide optimisation.Back to the 3D protein mould model built by structural determination techniques. Ideally, we can start building up the drug à la Lego bricks, fitting the chimaera into the protein-shape mould, right, right? Couldn't be more wrong. Enter multidimensional fitting. You see, a protein ain't like your Mom's muffin pan. Besides topology, there are other dimensions to fit—electrostatic charges, hydrophilicity/hydrophobicity, to name a few. The topology is not necessarily fixedly rigid either — playing with those poppin’ stick-and-ball molecular models may give us the illusion that proteins are rigid, but protein electron clouds are more like wobbly pudding (Mmmm, pudding...); plus, different environments (pH, oxidising level) may give rise to largely different topologies (e.g. due to different protonation states, broken disulphide bridge(s), etc.).One aspect of nanoscopic scale that is somewhat entangled with multiparameter fitting is that at this scale, there is evidence that quantum effects play an important role. Several examples of such systems have been studied like photosystems and birds’ navigation, but of more interest to a medicinal chemist would be tunnelling effect in certain enzymatic reactions. Who knows if quantum effects are more routinely utilised? Our view of physiology is biasedly mechanical—even my clockwork allegory evokes the mechanistic, so a paradigm shift may well be in order as more is known about the inner workings of such systems. If you blindly design a drug that target such systems, well, you will get an entangled mess—hopefully not the quantum kind. Moving on to pharmacokinetic restrictions: the human body imposes further restrictions from the non-negotiables (e.g. a drug cannot be too insoluble otherwise how can it dissolve in the bloodstream; a drug cannot have side effects outweighing its efficacy), to convenience (e.g. a drug is preferable to be ingested rather than injected). Our own physiology thus severely restricts the chemical space of entities that make up our drug candidate pool. As I mentioned earlier, enfuvirtide is a peptide, so it won’t survive stomach acidity and peptidases in the gut. Even with intravenous administration, it would have a short half-life due to blood proteases. All peptidic drugs—insulin is one—suffer from these problems. And for drugs targeting the central nervous system (CNS), they have to overcome another obstacle, the blood brain barrier.There seems to be some sort of patterns to the drug chemical space. To wit, some have observed that certain chemical scaffolds occur more frequently than others; they are so-called privileged scaffolds (e.g. benzodiazepines) [2] and an experienced medical chemist would be able to take a look at a chemical structure and decide whether it's 'drug-like' (while an inexperienced chemist like me would only know that a drug-like molecule can't be too small and simplistic, possesses some heteroatoms, usually has an aromatic ring or two—that's about it). Problem being, at its current state, drug-likeness is an empirical measure. No one has formulated a set of rules or equations to produce a predictive model. Lipinski's Rule of Five, for example, surveys already-existing drugs and look at the prevalent drug-like characteristics. Useful as rule of thumb; hardly predictive.Next is the issue of specificity. If you choose to take a drug topically, that’s fine and dandy because you can apply the drug locally to the area in need of treatment. But if you take a drug via oral/intravenous/other numerous administration routes, the drug is going to circulate in your bloodstream. How would you ensure that your wrench would reach, and affect only, the faulty gear? You can’t—not with certainty, at least—the wrench is going to wreck another gear, and that’s why you always ha... Read more »
Eckert, D., & Kim, P. (2001) Mechanisms of Viral Membrane Fusion and Its Inhibition. Annual Review of Biochemistry, 70(1), 777-810. DOI: 10.1146/annurev.biochem.70.1.777
Welsch, M., Snyder, S., & Stockwell, B. (2010) Privileged scaffolds for library design and drug discovery. Current Opinion in Chemical Biology, 14(3), 347-361. DOI: 10.1016/j.cbpa.2010.02.018
Marusyk A, Almendro V, & Polyak K. (2012) Intra-tumour heterogeneity: a looking glass for cancer?. Nature reviews. Cancer, 12(5), 323-34. PMID: 22513401
by Jason Carr in Wired Cosmos
As people continue to struggle with problems involving organ donation, a few robotic engineers continue to push the boundaries between humanity and machinery. A recent report in Nature (cited below) showed that two patients were able to overcome some aspects of their paralysis by way of an implant. Reaching and grabbing motions were possible by way [...]... 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
by Mostly Open Ocean in Mostly Open Ocean
A paper published a few months ago in Current Biology serves to highlight just how amazing cephalopods (squid, cuttlefish, octopus and their kin) are. The paper concerns how two species of cephalopods (Japetella heathi an octopus and Onychoteuthis banksii a squid) have evolved to avoid predators in the dynamic light environment of the mesopelagic layer of the open ocean.The mesopelagic layer of the ocean extends from 200 meters to 1000 meters deep. Sunlight in this zone transitions from present, but too dim for photosynthesis at the top, to totally absent at the bottom. This light transition poses a tricky problem for animals living there that want to avoid being eaten.In the shallower parts of the mesopelagic, predators are able to detect the shadows of prey swimming overhead. Here, the best strategy for small animals to reduce the risk of being eaten is for them to be translucent. Tissues that allow light to pass through cast a weaker shadow, which means that predators have to get closer to their prey in order to see them.In the deep dark depths, translucence is not such a good strategy. There's not enough sunlight for predators to hunt for shadows. Some predators, though, bring their own light in the form of light organs near their eyes. In the directed light of bioluminescence small imperfections in light transmission cause the light to be scattered making translucent animals much brighter than the background and easy prey.Where some predators, like the headlight fish (Diaphus effulgens), hunt by producing their own light, it pays to be a colour that absorbs light at the same wavelengths. The vast majority of bioluminescent organisms produce light in the blue wavelengths, which is best absorbed by reds and blacks. Unsurprisingly then, most animals that occur where sunlight is absent are red or black to reduce the risk that predators will find them using biologically produced light.But, some animals, like our two species of cephalopod, range over most of the mesopelagic and encounter a wide variety of light environments. High on the wish list for such animals would be the ability to become translucent in diffuse sunlight and red in directed bioluminescent light. And it turns out that this is exactly what J. heathi and O. banksii can do.Like most cephalopods, J. heathi and O. banksii have pigment containing cells in their epidermis, known as chromatophores. Cephalopods are able to rapidly change colour by expanding the size of the chromatophores. When muscles attached to a chromatophore contract, the pigment containing sac inside stretches out into a flat disc, which increases the visible area of pigment by about 50 times.A diagram showing the structure of a cephalopod chromatophore and the arrangement of the associated muscle and nerve cells (image: Richard Young)Most of the time J. heathi and O. banksii are translucent, but when they are exposed to blue light, like that produced by bioluminescent organs, they rapidly change colour to red. Neither strategy is complete; the chromatophores reduce translucence even when contracted and they are not numerous enough to allow them to become totally red. Thus, I would guess that these cephalopods are at a disadvantage relative to organisms that specialize in being red or translucent. But, in contrast to the these cephalopods, such specialists would be limited in the light environments that they could use.The translucent and red forms of J. heathi (left) and O. banksii (right). Note that neither the translucent nor the red strategy are complete (image constructed from figures in the paper)Interestingly, the images seem to suggest that J. heathi, which has the deeper distribution, is more able to produce the red colouration that is advantageous where predators hunt using bioluminescence. The authors, however, do not test or discuss this possibility. In the article they do briefly mention that older J. heathi are more common at deeper depths and have greater chromatophore coverage. So, the apparent difference in chromatophore coverage between the two species could be a consequence of either age or depth distribution differences, or perhaps both.Zylinski, S., & Johnsen, S. (2011). Mesopelagic cephalopods switch between transparency and pigmentation to optimize camouflage in the deep Current Biology, 21 (22), 1937-1941 DOI: 10.1016/j.cub.2011.10.014... Read more »
Zylinski, S., & Johnsen, S. (2011) Mesopelagic cephalopods switch between transparency and pigmentation to optimize camouflage in the deep. Current Biology, 21(22), 1937-1941. DOI: 10.1016/j.cub.2011.10.014
by Christian Jarrett in BPS Research Digest
For harassed doctors and stressed-out parents, it can be tempting to treat a challenging child with ADHD (attention deficit hyperactivity disorder) with pills and leave it at that. After all, early results from the one of the largest trials of its kind in the United States - the Multimodal Treatment Study of Children with ADHD (MTA) - showed that behavioural outcomes were better for children given the psychostimulant Ritalin, than for those given psychological treatment. However, follow-up data over several years has shown that the advantages of drug treatment aren't sustained over the longer term. The position of the UK's independent health advisory body, NICE, is that drug treatments for ADHD should only ever be part of a broader treatment package, including psycho-educational sessions for parents (pdf). The hunt continues for the most effective treatment or mix of treatments.
It's in this context that a team of German psychologists, led by Wolf-Dieter Gerber at the University of Kiel, has published a new report looking at the benefits of combining drug treatment for ADHD with an intensive Summer Camp.
Eighteen children with an ADHD diagnosis (aged 9 to 17 years), all on medication, spent 12 days at one such camp, which included social skills training conducted in a playful manner, attention training and sports. Crucially, the camp also incorporated "response cost token-based behaviour training" - that is, the children earned or lost tokens according to whether they followed or broke the camp rules. They were encouraged to compare their token totals each evening and a winner was declared for each day following an "Olympics style" format. At the end of the camp, the tokens could be exchanged for prizes.
A control group of 19 age-matched children with ADHD, also on medication, didn't go to camp, but their parents received a one-and-a-half hour-long psycho-educational session in which they were taught, amongst other things, about using a token strategy in the home.
Six months later, the children from both groups were tested on a range of neuropsychological measures and their outcomes compared with their pre-intervention test performance.
The key finding is that only the Summer Camp kids showed a reduction in the variability of their reaction times. This is significant because highly sporadic reaction times are a hallmark of ADHD, indicative of reduced self control. Moreover, only the Summer Camp group showed significant improvements in selective and sustained attention and the capacity to integrate information. It's likely these cognitive changes were clinically significant. Only those children who received higher ratings from their teachers (in terms of improved impulsivity, hyperactivity and inattention) showed positive changes in the variability of their reaction time scores on the neuropsych tests.
"We believe this study has merit" the researchers said, "as the ADHD Summer Camp can be regarded as a novelty in ADHD treatment. We could find no comparable intervention programmes that included stringent ... [token reward and punishment] techniques."
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Gerber, W., Gerber-von Müller, G., Andrasik, F., Niederberger, U., Siniatchkin, M., Kowalski, J., Petermann, U., and Petermann, F. (2012). The impact of a multimodal Summer Camp Training on neuropsychological functioning in children and adolescents with ADHD: An exploratory study. Child Neuropsychology, 18 (3), 242-255 DOI: 10.1080/09297049.2011.599115
Post written by Christian Jarrett for the BPS Research Digest.
... Read more »
Gerber, W., Gerber-von Müller, G., Andrasik, F., Niederberger, U., Siniatchkin, M., Kowalski, J., Petermann, U., & Petermann, F. (2012) The impact of a multimodal Summer Camp Training on neuropsychological functioning in children and adolescents with ADHD: An exploratory study. Child Neuropsychology, 18(3), 242-255. DOI: 10.1080/09297049.2011.599115
by Jaime Menchén in United Academics
This image is a reconstruction of a lizard’s skeleton in three dimensions, showing how the ‘armor’ is formed.... Read more »
Greenbaum, E., Stanley, E., Kusamba, C., Moninga, W., Goldberg, S., & Bursey, C. (2012) A new species of (Squamata: Cordylidae) from the Marungu Plateau of south-eastern Democratic Republic of the Congo. African Journal of Herpetology, 61(1), 14-39. DOI: 10.1080/21564574.2012.666505
by John Ankers in Too Many Live Wires
The liquorice root is full of surprises. Chewed as a breath freshener in Italy and a sweet in Sweden (and the north of England), this little brown stick has also been used as a remedy for mouth ulcers for thousands of years.
New research has identified a natural chemical extracted from the liquorice root that could be used to treat Type II diabetes.... Read more »
Weidner, C., de Groot, J., Prasad, A., Freiwald, A., Quedenau, C., Kliem, M., Witzke, A., Kodelja, V., Han, C., Giegold, S.... (2012) From the Cover: Amorfrutins are potent antidiabetic dietary natural products. Proceedings of the National Academy of Sciences, 109(19), 7257-7262. DOI: 10.1073/pnas.1116971109
by Duncan Hull in O'Really?
The Life Scientific is a series of interviews by Jim Al-Khalili of well known scientists. It’s a bit like Desert Island Discs without the music and with more interesting guests. If you missed them on the radio, you can download the lot as a podcast. Here’s a good example of an interview with John Sulston on the Physics vs. Stamp Collecting debate:... Read more »
Ihde, A. (1964) Rutherford at Manchester (Birks, J. B., ed.). Journal of Chemical Education, 41(11). DOI: 10.1021/ed041pA896
Birks, J., & Segrè, E. (1963) Rutherford at Manchester. Physics Today, 16(12), 71. DOI: 10.1063/1.3050668
Goldhammer, P. (1963) Rutherford at Manchester. J. B. Birks, Ed. Heywood, London, 1962; Benjamon, New York, 1963. x 364 pp. Illus. $ 12.50. Science, 142(3594), 943-944. DOI: 10.1126/science.142.3594.943-a
by Lutz Kraushaar in Chronic Health
Briefly
There were always two types of cholesterol, the good and the
bad. Until now. A large new study tells us that good cholesterol might have
been an impostor. That's food for the media types. For those who think before
they type, the real news is that we are finally getting closer to uncovering
the impostors. Thanks to the genetics revolution which seems to be paying off
in an unexpected area.
HDL - The Knight in Shining Armor
In the cholesterol universe there are two camps: good
cholesterol, also known as HDL, and bad cholesterol, often referred to as
non-HDL cholesterol. The latter comes in a variety of flavors, of which LDL is
the most prominent and best known. From many large observational studies we
know that high levels of LDL and low levels of HDL associate with an elevated
risk for heart disease and stroke. Certain limits have been derived from these
studies, above which your LDL shouldn't rise and below which your HDL shouldn't
fall. The magic level for HDL is 60 mg/dL blood. Above that limit, we are
assured, HDL will even offset some other risk factor, such as age or being of
the male persuasion. Given that a large percentage of people fail to achieve
these desirable levels, researchers have been eagerly sourcing for
pharmaceutical means to increase HDL. Now a new study tells us, that HDL might
have to be stripped off its White-Knight title, much for the same reason as
"Dr." Karl-Theodor zu Guttenberg, the former German defense minister,
had to be stripped off his doctorate last year: for being an impostor.
Epidemiology 101
If you have been following biomedical research for a couple
of years, you will have noticed that results are often conflicting. So, you
might discount the findings of one study if hundreds of others come to a
different conclusion. Only in this case you should pay closer attention,
because what Voight and colleagues have produced strikes at the foundation of
how we do research in epidemiology, the science which studies the health of
populations [1].
To appreciate the gravity of the
situation, I need to familiarize you with a basic concept of epidemiological
studies: Confounding. I'll use a very simple and hypothetical example.
Let's say we are interested to know the causes of health and
disease in children in the hypothetical and impoverished state of Maladipore.
The figure to the left represents our astonishing finding that children growing
up in a household which owns a TV are significantly less likely to die during
childhood than children growing up without the boob tube. The correlation
between TV ownership status and survival are very strong and compelling.
On the
face of it we could now recommend the prime minister to improve the health of
the nation by simply installing a TV in every household in which there are
children. If we know that this is nonsense, we take our epidemiology tools and
look for another factor which has an influence on TV ownership AND on survival
rate.
And so we discover that wealth is this third factor. We call it a
confounder. Wealth has confounded our original finding because the wealthy can
afford a TV and they can also afford medical care and immunization for their
children. Whereas the inability to buy a TV certainly reflects the inability to
buy medical care, too. When we repeat our analysis of the data, which we
gathered during our observational study, we find that the link between TV
ownership and survival disappears once we bring the third variable, wealth,
into the equation. Clearly, providing every household with a TV wouldn't have reduced
the rate of child deaths. Greater wealth however will.
In the case of Maladipore, common sense is all it takes to
suspect and find the confounder. In real life it is almost never as simple.
When we find an association between cholesterol and heart disease, then we
typically have some idea about the way cholesterol might contribute to heart
disease. At that stage our ideas are merely hypothetical. The classic way of
investigating them is through clinical trials in which we randomize
participants into 2 groups, one in which we lower (bad) cholesterol and another
in which we don't, the control group. Then we observe them for a period and
note the rate at which people in both groups develop heart disease or die from
it. If we find that the control group, the one which didn't receive the benefit
of having its cholesterol lowered, has a significantly higher rate of falling
ill, we conclude that lowering cholesterol is the way to go. Sounds easy, but
it isn't. For several reasons. In the case of cholesterol, the time between
developing high bad, or low good, cholesterol and suffering a heart attack or
stroke is measured in decades rather than in years. We also cannot just
experiment with people as we would like to in the name of science. Ethics
boards look very closely at the potential risks and benefits associated with
what we do in trials. We cannot simply withhold treatment from a control group,
with scientific curiosity as the motivation. With these obstacles, we had to draw our conclusions from
observational studies, which tell us a lot about associations but nothing about
cause and effect. Until now, we simply had no other choice. But not any more:
It's Mendel All Over Again
With larger and larger databases being
developed from genetic research we can now do something else: Mendelian randomization
studies. Which is what Voight and colleagues did. The concept behind it is
amazingly simple and elegant, though not as brand new as you might think. It
has been named after Gregor Mendel, the father of modern genetics, who first
observed and described how traits are inherited. As
always, a concept is best understood using an example. In the 1980s some
researchers thought that very low cholesterol levels might increase the risk of
cancer. There was definitely an association being observed between cancer and
low cholesterol, but nobody knew which was the cause and which the effect. Or
whether there was a third confounding variable, as yet unknown. Now, you can't
make a study in which you lower the cholesterol in some people, just to see
whether they will develop cancer. Go
and find volunteers for that one.
... Read more »
Voight, B., Peloso, G., Orho-Melander, M., Frikke-Schmidt, R., Barbalic, M., Jensen, M., Hindy, G., Hólm, H., Ding, E., Johnson, T.... (2012) Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. The Lancet. DOI: 10.1016/S0140-6736(12)60312-2
by erichorow in peer-reviewed by my neurons
If I ever stumble upon a wish-granting genie, my first wish will be to have the motivation necessary to accomplish all of my goals. Motivation is like salt or nice weather — it makes everything better. Well, almost everything. A new study by psychologists from Ghent University in Belgium and the University of Maryland suggests that [...]... Read more »
Roets, A., Van Hiel, A., & Kruglanski, A. (2012) When motivation backfires: Optimal levels of motivation as a function of cognitive capacity in information relevance perception and social judgment. Motivation and Emotion. DOI: 10.1007/s11031-012-9299-0
by Tetyana Pekar in Science of Eating Disorders
Journalists like to report on novel and exciting findings regardless of how likely they are to be replicated or how well they fit in with everything else we know about that topic. It is an all too common occurrence that a small pilot study which has favourable results, creates a buzz in and gets into our heads, only to produce negative or unfavourable results once the sample size is increased. But the latter, negative finding, rarely makes it to the printing press. So we are left thinking the results of the pilot study are correct when they might be an outlier, or just a false positive.
Given this, I wanted to summarize a review article that provides a critical overview of the current neuroimaging studies in anorexia nervosa. We can use this as an introduction to neuroimaging in AN, to get a sense of the scientific consensus, the trends that emerge from the data and what can we learn from them?... Read more »
Pietrini, F., Castellini, G., Ricca, V., Polito, C., Pupi, A., & Faravelli, C. (2011) Functional neuroimaging in anorexia nervosa: A clinical approach. European Psychiatry, 26(3), 176-182. DOI: 10.1016/j.eurpsy.2010.07.011
by Callum Hackett in For the Ears
Late last year, some researchers in the U.S. conducted a study that tried to determine the changing literary influences on writers, and the story seemed to be making the rounds on the news last week. The essential thesis is this: the influence of classic writers on our contemporaries is not what it used to be. Put in those terms, it sounds rather condemning, as though today’s writers are not reading up on their Chaucer and Milton and so are less culturally informed. That’s certainly how it’s been reported, but what did the researchers really mean? And is the claim even true?
The paper’s basic purpose was to conduct the first large-scale stylometric analysis of literature throughout different periods (i.e. an analysis of different writers’ linguistic styles), which they achieved thanks to the marvellous resources of Project Gutenberg. The most important facet of the study, with the greatest ramifications on the conclusions we can draw from it, is that they focused on content-free words, which they defined as: “the ‘syntactic glue’ of a language: they are words that carry little meaning on their own but form the bridge between words that convey meaning.” Such words include and, but, to, and of.
They narrowed their analysis to 537 authors, all of whom had at least 5 works on Project Gutenberg, though given the copyright laws that govern the texts they’re allowed to archive, they ranged from 1550-1952. Through some fancy linguistic equations and mathematical analysis, they were able to determine that the stylistic influences of preceding writers on their successors has diminished considerably in recent times. However, it’s extremely important to recognise that this concerns stylistic influence - the ands, buts, and ofs that a writer uses. This is how we can estimate the historical position of a line of Joyce and a line of Shakespeare without knowing exactly who we’re reading. It has little to do with the content of their works - their ideas, stories, and arguments - which bear no relation to their sentence structures. It’s quite misleading to even call the effects on style an “influence”, as a writer’s idiosyncratic use of prepositions and conjunctions is more likely a product of the natural evolution of language, driven by many complex social factors, than by the books they read.
Of course, their analysis presented a continuous range of texts spanning 400 years, but to make a statement about anything “modern”, it’s necessary to determine an arbitrary boundary between that and “old” texts. While you or I might intuitively draw this line around 1900, the authors explicitly stated their “modern” writers as extending from 1784, so the results cannot be said to demonstrate an effect that is unique to the writers of today and yesterday - this goes right back to the end of the 18th century. They did go on to make further subdivisions, but this graph from their article demonstrates a paucity of data in some areas despite the number of books they covered:
Here we see that the vast majority of analysis was concentrated on works from around 1830-1930. There were far fewer works from the decades straddling either side of that period, and an extremely small amount from before 1750.
So what exactly can we learn from this paper? Not much. They’re right to suggest that it provides a statistical basis for the common perception that there exist “literary styles of the time”, but these regard linguistic style, not ideological influence or familiarity with classic literature. Our contemporary writers are perfectly able to read as much classic fiction as their forebears while demonstrating smaller amounts of linguistic influence. The reasons for the diminished effect are also inconclusive - while it is most strongly implied that it has to do with reading habits and aesthetic movements, it’s conceivable that the effects of linguistic influence, particularly in English, have been greatly affected by globalisation - a factor not taken into account.
So don’t worry, the writers of today are not necessarily ignorant of their cultural heritage, it’s just journalists once again making tangential, unsubstantiated assumptions about a research article that the researchers gave them no cause for making.
—————
Hughes JM, Foti NJ, Krakauer DC, & Rockmore DN (2012). ‘Quantitative patterns of stylistic influence in the evolution of literature’ Proceedings of the National Academy of Sciences of the United States of America, 109 (20), 7682-6 PMID: 22547796... Read more »
Hughes JM, Foti NJ, Krakauer DC, & Rockmore DN. (2012) 'Quantitative patterns of stylistic influence in the evolution of literature'. Proceedings of the National Academy of Sciences of the United States of America, 109(20), 7682-6. PMID: 22547796
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