The cumulative effect of reporting and citation biases on the apparent efficacy of treatments: the case of depressionFigure 1 demonstrates the cumulative impact of reporting and citation biases. Of 105 antidepressant trials, 53 (50%) trials were considered positive by the FDA and 52 (50%) were considered negative or questionable (Fig. 1a). While all but one of the positive trials (98%) were published, only 25 (48%) of the negative trials were published. Hence, 77 trials were published, of which 25 (32%) were negative (Fig. 1b). Ten negative trials, however, became ‘positive’ in the published literature, by omitting unfavorable outcomes or switching the status of the primary and secondary outcomes (Fig. 1c). Without access to the FDA reviews, it would not have been possible to conclude that these trials, when analyzed according to protocol, were not positive. Among the remaining 15 (19%) negative trials, five were published with spin in the abstract (i.e. concluding that the treatment was effective). For instance, one article reported non-significant results for the primary outcome (p = 0.10), yet concluded that the trial ‘demonstrates an antidepressant effect for fluoxetine that is significantly more marked than the effect produced by placebo’ (Rickels et al., 1986). Five additional articles contained mild spin (e.g. suggesting the treatment is at least numerically better than placebo). One article lacked an abstract, but the discussion section concluded that there was a ‘trend for efficacy’. Hence, only four (5%) of 77 published trials unambiguously reported that the treatment was not more effective than placebo in that particular trial (Fig. 1d). Compounding the problem, positive trials were cited three times as frequently as negative trials (92 v. 32 citations in Web of Science, January 2016, p < 0.001, see online Supplementary material for further details) (Fig. 1e). Among negative trials, those with (mild) spin in the abstract received an average of 36 citations, while those with a clearly negative abstract received 25 citations. While this might suggest a synergistic effect between spin and citation biases, where negatively presented negative studies receive especially few citations (de Vries et al., 2016), this difference was not statistically significant (p = 0.50), likely due to the small sample size. Altogether, these results show that the effects of different biases accumulate to hide non-significant results from view.
Quantum science turns social -- ScienceDailyWhy could players without any formal training in experimental physics manage to find surprisingly good solutions? One hint came from an interview with a top-player, a retired Italian microwave systems engineer. He said, that for him participating in the Alice Challenge reminded him a lot of his previous job as an engineer. He never attained a detailed understanding of microwave systems but instead spent years developing an intuition of how to optimize the performance of his "black-box." "We humans may develop general optimization skills in our everyday work life that we can efficiently transfer to new settings. If this is true, any research challenge can in fact be turned into a citizen science game," said Jacob Sherson, head of the ScienceAtHome project at Aarhus University. It still seems incredible that untrained amateurs using an unintuitive game interface outcompete expert experimentalists. One answer may lie in an old Herbert Simon quote: "Solving a problem simply means representing it so as to make the solution transparent."
Research: Adequate statistical power in clinical trials is associated with the combination of a male first author and a female last author | eLifeHere we investigate whether the statistical power of a trial is related to the gender of first and last authors on the paper reporting the results of the trial. Based on an analysis of 31,873 clinical trials published between 1974 and 2017, we find that adequate statistical power was most often present in clinical trials with a male first author and a female last author (20.6%, 95% confidence interval 19.4-21.8%), and that this figure was significantly higher than the percentage for other gender combinations (12.5-13.5%; P<0.0001). The absolute number of female authors in clinical trials gradually increased over time, with the percentage of female last authors rising from 20.7% (1975-85) to 28.5% (after 2005). Our results demonstrate the importance of gender diversity in research collaborations and emphasize the need to increase the number of women in senior positions in medicine.
Pharma’s broken business model — Part 2: Scraping the barrel in drug discovery – Endpoints NewsAccording to the Human Protein Atlas, there are 19,613 proteins encoded by the human genome. Of these, 14,545 (74%) have no known link or relationship with disease, which rules them out as potential new drug targets because they fail to meet criterion 1 above. Perhaps these proteins are non-essential, as any deficiencies can be compensated by other proteins or pathways; or perhaps they are essential, however any deficiencies are lethal before birth so they never have the chance to cause any disease. In any case, we have no reason to believe that targeting these proteins will do anything for any known human disease. Now of the 5,068 proteins that have any link to disease, 3,131 (16% of all human proteins) are considered to be “undruggable”, either because they have no obvious pocket capable of binding small molecule drugs, or because they are intracellular and thus inaccessible to large proteins that cannot penetrate the cell membrane. We must rule out these proteins as potential new drug targets because we currently have no way to target them, so they fail to meet criterion 2 above.
Newfound 'organ' had been missed by standard method for visualizing anatomy -- ScienceDailyThe researchers say that no one saw these spaces before because of the medical field's dependence on the examination of fixed tissue on microscope slides, believed to offer the most accurate view of biological reality. Scientists prepare tissue this examination by treating it with chemicals, slicing it thinly, and dying it to highlight key features. The "fixing" process makes vivid details of cells and structures, but drains away any fluid. The current research team found that the removal of fluid as slides are made causes the connective protein meshwork surrounding once fluid-filled compartments to pancake, like the floors of a collapsed building.
Redactions in protocols for drug trials: what industry sponsors concealedJournal of the Royal Society of Medicine - Mikkel Marquardsen, Michelle Ogden, Peter C. Gøtzsche, 2018In the first systematic review comparing protocols with published trial reports, we found that at least one primary outcome had been changed, introduced or omitted in two-thirds of the reports, and this change was not mentioned in a single published report.4
Reading on electronic devices may interfere with science reading comprehension -- ScienceDaily"The more time the participants reported on using e-devices per day -- for instance, reading texts on their iPhone, watching TV, playing internet games, texting, or reading an eBook -- the less well they did when they tried to understand scientific texts," said Li. "There are a lot of positive uses for electronic devices and I'm an advocate of digital learning, but when it comes to understanding of science concepts through reading, our take is that it's not helpful." Li said the way people read on electronic devices may encourage them to pick up only bits and pieces of information from the material, while the comprehension of scientific information requires a more holistic approach to reading where the reader incorporates the information in a relational and structured way. "This is sort of speculation, because, so far, this is only a correlation -- When you are writing a text on a smartphone, for example, you use very short sentences and you abbreviate a lot, so it's fragmented," said Li. "When you're reading such a text, you're getting bits of information here and there and not always trying to connect the material. And I think that might be the main difference, when you're reading expository scientific texts you need to be connecting and integrating the information."
Recentering the universeIt was this hierarchy—so central to Western cosmology for so long that, even today, a ten-year-old could intuitively get much of it right—that was challenged by the most famous compendium of all: Denis Diderot and Jean le Rond d’Alembert’s eighteen-thousand-page Encyclopédie. Published between 1751 and 1772, the Encyclopédie was sponsored by neither the Catholic Church nor the French monarchy and was covertly hostile to both. It was intended to secularize as well as to popularize knowledge, and it demonstrated those Enlightenment commitments most radically through its organizational scheme. Rather than being structured, as it were, God-down, with the whole world flowing forth from a divine creator, it was structured human-out, with the world divided according to the different ways in which the mind engages with it: “memory,” “reason,” and “imagination,” or what we might today call history, science and philosophy, and the arts. Like alphabetical order, which effectively democratizes topics by abolishing distinctions based on power and precedent in favor of subjecting them all to the same rule, this new structure had the effect of humbling even the most exalted subjects. In producing the Encyclopédie, Diderot did not look up to the heavens but out toward the future; his goal, he wrote, was “that our descendants, by becoming more learned, may become more virtuous and happier.”
Bayes' theoremDespite the apparent accuracy of the test, if an individual tests positive, it is more likely that they do not use the drug than that they do. This surprising result arises because the number of non-users is very large compared to the number of users; thus, the number of false positives outweighs the number of true positives. To use concrete numbers, if 1000 individuals are tested, there are expected to be 995 non-users and 5 users. From the 995 non-users, 0.01 × 995 ≃ 10 false positives are expected. From the 5 users, 0.99 × 5 ≈ 5 true positives are expected. Out of 15 positive results, only 5, about 33%, are genuine. This illustrates the importance of base rates, and how the formation of policy can be egregiously misguided if base rates are neglected. The importance of specificity in this example can be seen by calculating that even if sensitivity is raised to 100% and specificity remains at 99% then the probability of the person being a drug user only rises from 33.2% to 33.4%, but if the sensitivity is held at 99% and the specificity is increased to 99.5% then probability of the person being a drug user rises to about 49.9%.
Why Are There No Biological Tests in Psychiatry? - Scientific American Blog NetworkThe problem of teasing out heterogeneous clinical presentations in psychiatry is compounded by the fact that they also have heterogeneous underlying mechanisms. There will not be one pathway to schizophrenia; there may be dozens, perhaps hundreds. Biological tests that appear to be associated with schizophrenia are never useful for making the diagnosis because they always show more variability within the category than between categories. And seemingly intriguing findings usually don't replicate.
Why Abstract Art Stirs Creativity in Our Brains - Facts So Romantic - Nautilus“Creativity is for amateurs. We go out there and we solve problems. We set tasks for ourselves and we solve them.” I think the similarities are really becoming quite obvious. Certainly in the abstract expressionists—the New York group—they all ended up doing very different things when they started doing it, and they did it step-by-step as they moved from figuration to abstraction, becoming progressively more abstract in distinctively different ways.
100 billion neurons, unsourcedShe then returned to her alma mater to train young scientists in communication—with an allowance to pursue research if she were so inclined. She was inspired to do so by the pervasive myths about the brain she kept encountering, such as that we use only 10 percent of our capacity. Moreover, none of the distinguished neuroscientists she asked could tell her the source for the claim that there were 100 billion neurons in the brain, which they all believed.
Characterizing a psychiatric symptom dimension related to deficits in goal-directed control | eLifeProminent theories suggest that compulsive behaviors, characteristic of obsessive-compulsive disorder and addiction, are driven by shared deficits in goal-directed control, which confers vulnerability for developing rigid habits. However, recent studies have shown that deficient goal-directed control accompanies several disorders, including those without an obvious compulsive element.
How big was that quakeA thirty-second earthquake generally has a magnitude in the mid-sevens. A minute-long quake is in the high sevens, a two-minute quake has entered the eights, and a three-minute quake is in the high eights. By four minutes, an earthquake has hit magnitude 9.0.
"The Dress" is the perfect mirror for the subjective, fractured InternetThe fact that a single image could polarize the entire Internet into two aggressive camps is, let’s face it, just another Thursday. But for the past half-day, people across social media have been arguing about whether a picture depicts a perfectly nice bodycon dress as blue with black lace fringe or white with gold lace fringe. And neither side will budge. This fight is about more than just social media—it’s about primal biology and the way human eyes and brains have evolved to see color in a sunlit world.
Certainly for artists of all stripes, the unknown, the idea or the form or the tale that has not yet arrived, is what must be found. It is the job of artists to open doors and invite in prophesies, the unknown, the unfamiliar; it’s where their work comes from, although its arrival signals the beginning of the long disciplined process of making it their own. Scientists too, as J. Robert Oppenheimer once remarked, “live always at the ‘edge of mystery’ – the boundary of the unknown.” But they transform the unknown into the known, haul it in like fishermen; artists get you out into that dark sea.
Critics have pointed out that Dr. Keys violated several basic scientific norms in his study. For one, he didn't choose countries randomly but instead selected only those likely to prove his beliefs, including Yugoslavia, Finland and Italy. Excluded were France, land of the famously healthy omelet eater, as well as other countries where people consumed a lot of fat yet didn't suffer from high rates of heart disease, such as Switzerland, Sweden and West Germany. The study's star subjects—upon whom much of our current understanding of the Mediterranean diet is based—were peasants from Crete, islanders who tilled their fields well into old age and who appeared to eat very little meat or cheese. As it turns out, Dr. Keys visited Crete during an unrepresentative period of extreme hardship after World War II. Furthermore, he made the mistake of measuring the islanders' diet partly during Lent, when they were forgoing meat and cheese. Dr. Keys therefore undercounted their consumption of saturated fat. Also, due to problems with the surveys, he ended up relying on data from just a few dozen men—far from the representative sample of 655 that he had initially selected. These flaws weren't revealed until much later, in a 2002 paper by scientists investigating the work on Crete—but by then, the misimpression left by his erroneous data had become international dogma.
“The mentality of fission is that there is a systematic process—you define your loads, your criteria, and then you produce a design,” Chiocchio told me. “At the beginning, at ITER, sometimes I would ask my boss, ‘Can you tell me what the main requirements are for this component?’ And he would say, ‘What are you talking about? Try to find a solution.’ It was a bit more of a, let’s say, creative engineering environment.”
In the winter of 1976-77, they point out, the temperature in Chicago stayed below freezing for 43 days straight, and in 1985 the city had a below-freezing stretch of 40 days. The longest stretch so far this winter was 11 days. Similarly, New York’s longest stretch below freezing this year has been six days, less than half as long as the freezing periods in the 1970s.Perhaps this is the real reason everyone is panicking about the cold: Winters have become so mild over the past 20 to 30 years that a blast of Arctic air feels extraordinary. “If you were 10 years old when this last happened and now you’re 40, that’s quite a chunk of your life,” Mr. Henson said.