A new Molecular CT scan could dramatically speed drug discovery

Tuesday, November 6th, 2018

Researchers have adapted a third technique, commonly used to chart much larger proteins, to determine the precise shape of small organic molecules:

The gold standard for determining chemical structures has long been x-ray crystallography. A beam of x-rays is fired at a pure crystal containing millions of copies of a molecule lined up in a single orientation. By tracking how the x-rays bounce off atoms in the crystal, researchers can work out the position of every atom in the molecule. Crystallography can pinpoint atomic positions down to less than 0.1 nanometers, about the size of a sulfur atom. But the technique works best with fairly large crystals, which can be hard to make. “The real lag time is just getting a crystal,” says Brian Stoltz, an organic chemist at the California Institute of Technology (Caltech) in Pasadena. “That can take weeks to months to years.”

The second approach, known as nuclear magnetic resonance (NMR) spectroscopy, doesn’t require crystals. It infers structures by perturbing the magnetic behavior of atoms in molecules and then tracking their behavior, which changes depending on their atomic neighbors. But NMR also requires a fair amount of starting material. And it’s indirect, which can lead to mapping mistakes with larger druglike molecules.

The new approach builds on a technique called electron diffraction, which sends an electron beam through a crystal and, as in x-ray crystallography, determines structure from diffraction patterns. It has been particularly useful in solving the structure of a class of proteins lodged in cell membranes. In this case, researchers first form tiny 2D sheetlike crystals of multiple copies of a protein wedged in a membrane.

But in many cases, efforts to grow the protein crystals go awry. Instead of getting single-membrane sheets, researchers end up with numerous sheets stacked atop one another, which can’t be analyzed by conventional electron diffraction. And the crystals can be too small for x-ray diffraction. “We didn’t know what to do with all these crystals,” says Tamir Gonen, an electron crystallography expert at the University of California, Los Angeles (UCLA). So, his team varied the technique: Instead of firing their electron beam from one direction at a static crystal, they rotated the crystal and tracked how the diffraction pattern changed. Instead of a single image, they got what was more like molecular computerized tomography scan. That enabled them to get structures from crystals one-billionth the size of those needed for x-ray crystallography.

Gonen says because his interest was in proteins, he never thought much about trying his technique on anything else. But earlier this year, Gonen moved from the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia, to UCLA. There, he teamed up with colleagues, along with Stoltz at Caltech, who wanted to see whether the same approach would work not just with proteins, but with smaller organic molecules. The short answer is it did. On the chemistry preprint server ChemRxiv, the California team reported on Wednesday that when they tried the approach with numerous samples, it worked nearly every time, delivering a resolution on par with x-ray crystallography. The team could even get structures from mixtures of compounds and from materials that had never formally been crystallized and were just scraped off a chemistry purification column. These results all came after just a few minutes of sample preparation and data collection. What’s more, a collaboration of German and Swiss groups independently published similar results using essentially the same technique this week.

Energy drinks are associated with mental health problems, anger-related behaviors, and fatigue

Monday, November 5th, 2018

Energy drinks are popular with young men, especially young men in the military, and they may be contributing to mental health problems:

What the authors found was that over the course of the month leading up to the survey, more than 75 percent of soldiers consumed energy drinks. More surprising, however, was that 16 percent “of soldiers in this study reported continuing to consume two or more energy drinks per day in the post-deployment period,” the authors wrote.

High energy drink use, which was classified as consuming two or more drinks per day, was significantly associated with those survey respondents who reported mental health problems, anger-related behaviors and fatigue, the authors found.

Those consuming less than one energy drink per week reported these symptoms at a significantly lower rate.

Also of note is that energy drink use in this Army infantry sample was five times higher than previous studies that analyzed consuming patterns of airmen and the general population’s youth.

The original study is available online.

There’s something different about being blown up

Saturday, November 3rd, 2018

The “routine” treatment for a head injury — whether in Iraq, Afghanistan, or an American emergency room — works, but not for all traumas:

As soon as you enter the emergency room (ER) as a “Head Injury,” your blood pressure and breathing will be stabilized. ER doctors know the procedures and will, if there are signs of increased intracranial pressures, put you into a drug-induced coma to slow any ongoing damage to injured brain cells and protect any of the remaining healthy tissues from undergoing any secondary damage.

A calcium channel blocker will be administered to help stabilize the outer membranes of the injured nerve cells to maintain normal intracellular metabolism. If your blood pressure becomes too high, ER personnel will lower the pressures to protect against any re-bleeding or the expansion of any blood clots that have already formed within the brain following the initial injury. If the pressures are too low, which can further decrease the blood flow to what remains of the undamaged brain tissues – itself leading to more neurological damage, medications will be given to raise the pressures to maintain adequate blood flow to the brain and central nervous system despite the injury.

Those parts of the brain not damaged still have to receive their usual amounts of oxygen and nutrients. But even with all this care after a traumatic brain injury, recovery is always one of those medically “iffy” things.

If the brain continues to swell, damaging as yet undamaged parts of the brain, the neurosurgeons will begin IV fluids of 8 to 12% saline to control swelling. If that doesn’t work, they will add an IV diuretic to drain the body of fluids in an effort to keep down the increasing intracranial pressures that may continue to compress arteries, cutting off oxygen to the still healthy brain cells. If the hypertonic fluids and diuretics fail to work, they will take you to the operating room and neurosurgeons will remove the top of the skull to allow the brain to swell without compressing and damaging any of the still undamaged underlying tissues.

Since the brain is in a closed space, the overriding idea behind removing the top of the skull is to relieve any increasing intra-cranial pressures that would surely further damage the tissues of the physically compressed brain. Such a development would be even more damaging to tissues as the decreased delivery of oxygen would impair the still undamaged brain tissues. When the swelling has finally decreased and the brain is back to normal size, the neurosurgeons will simply put back that part of the skull removed and wait for the patient to recover.

All of this works and has worked hundreds of times in military surgical hospitals and in emergency rooms and major trauma centers around the country. It certainly works if the patient has been shot in the head.

[...]

But what we have learned from the battlefields of our newest wars is that the brain damage from an IED appears to be a different kind of traumatic brain injury.

Treatments at an earlier time regarded as usual for head injuries do not work. There is clearly something different and so unexpected going on down at the cellular or sub-cellular level of the brain following exposure to a pressure wave that is not the same as hitting your head on the pavement, falling in a bathroom, or being shot in the head. There is simply something fundamentally different about being blown up.

Stop when you’re almost finished

Friday, November 2nd, 2018

Performance psychologist Noa Kageyama recommends harnessing resumptive drive, or the Zeigarnik effect, to get yourself to practice when you don’t feel like it:

Bluma Zeigarnik described a phenomenon way back in 1927, in which she observed while sitting in a restaurant that waiters seemed to have a selective memory. As in, they could remember complicated customers’ orders that hadn’t yet been filled, but once all the food had been served (or maybe when the bill was paid?), it’s as if the order was wiped from their memory.

Back in her lab, she found that indeed, participants were much more likely to remember tasks they started but didn’t finish, than tasks that were completed (hence, the Zeigarnik effect).

Another form of the Zeigarnik effect — and the one more relevant to what we’re talking about here — is the observation that people tend to be driven to resume tasks in which they were interrupted and unable to finish.

Researchers at Texas Christian University & University of Rochester ran a study on this form of the Zeigarnik effect.

Subjects were given eight minutes to shape an eight-cube, three-dimensional puzzle into five different forms. They were told to work as quickly as possible, and given three minutes to complete the first two puzzles as practice.

Then they were given five minutes to solve the last three puzzles.

The researchers deliberately made the second practice puzzle difficult — one that was unlikely to be solved within the time available. And just as they had hoped, only 6 of the 39 participants solved the difficult puzzle.

After their time was up, the participants had eight minutes of free time to do as they wished while the researcher running the experiment left the room to retrieve some questionnaires they accidentally forgot to bring, saying they would be back in “5 or 10 minutes.” This was all a ruse, of course, to see what the participants would do when left alone.

Despite there being other things in the room to do (e.g. a TV, magazines, newspaper, etc.), 28 of the 39 participants (72%) resumed working on the puzzles.

[...]

Of the six who completed the difficult puzzle, only one (17%) resumed working on the puzzles (and did so for one minute and 18 seconds).

Of the 33 who did not complete the challenging puzzle, 27 (82%) resumed working on the puzzle, and on average, spent more than two and a half times as long (3:20) working on the puzzles.

So, when interrupted in the middle of a task, not only were participants more motivated to resume working on that task, but they also continued working on it for much longer.

[...]

So instead of thinking about practicing for an hour, or having to work on 10 excerpts, or memorize a concerto, just tune your instrument. Or play a scale really slowly. Or set the timer for five minutes and pick one little thing to fix. And if at the end of five, you don’t feel like continuing, put your instrument away and try again later.

Don’t feel like studying? Just crack open the book. Work on one math problem. Write three sentences of your essay. Create two flash cards.

Second, once you’ve finally gotten yourself into the mood to practice or study, try stopping in the middle of a task. Meaning, if you’re working on a tricky passage that has you stumped, test out a few solutions, but leave yourself a few possible solutions remaining before taking a practice break. Stop when you’re almost finished solving the math problem. Or in the middle of a sentence.

It’s not necessary to have a brain disorder in order to control one’s fear

Wednesday, October 31st, 2018

Scientists are starting to understand the biology of bravery:

Most of the science focuses on the amygdala, the almond-shaped structure deep in the brain (one on each side) that generates such feelings as fear and anxiety. In 2005, a team led by Gleb Shumyatsky at Rutgers University reported in the journal Cell that stathmin, a protein produced by the STMN1 gene, has an important role in the amygdala. Mice that were bred not to have the protein explored more of a new environment. They lacked what the researchers called “innate fear” and were unable to form memories of fear-inducing events.

The researchers also manipulated the gene as a kind of “volume” control, producing different levels of stathmin, which in turn resulted in different levels of fear in the mice. In 2010, researchers led by Burkhard Brocke at the Institute of Psychology II in Germany found that people with an exaggerated response to fear had mutations in the gene that controls this volume switch.

As for how we overcome fear, scientists have found brain structures that appear to resist the prompting of the amygdala. In a 2010 study published in the journal Neuron, the neurobiologist Uri Nili at the Weizmann Institute in Israel scanned the brains of research subjects who were afraid of snakes as they decided whether or not to move a live snake closer or farther away on a conveyor belt. The more people were able to overcome their fear and move the snake closer, the more activity they showed in the sgACC, a brain region that sits between the amygdala and the hypothalamus, which stimulates the release of hormones. A control group that wasn’t scared of snakes didn’t show such activity.

Hormones released in the amygdala itself also have been shown to affect bravery. Oliver Bosch, a neurobiologist at the University of Regensburg in Germany, studies maternal instinct in mammals and has found that oxytocin is released in the amygdala when a mother faces a danger to herself and her children. This hormone, in turn, blocks the production of a hormone called CRH, which primes the body for action but can generate feelings of fear and anxiety. It is this sort of hormonal override that would have given Angie Padron, the mother in Florida, the instant courage to confront her assailants. As she herself said of the incident, her instincts just kicked in.

Indeed, taking the amygdala entirely out of the picture can virtually eliminate fear. Justin Feinstein, a clinical neuropsychologist at the Laureate Institute for Brain Research at the University of Tulsa, works with three women, known in the literature just by their initials, who have Urbach-Wiethe disease, a rare genetic disorder that destroys the amygdala. One of them, SM, has never experienced fear in her adult life. A man once threatened her by putting a gun to her head and shouting “Bam!” She didn’t flinch.

Of course, it’s not necessary to have a brain disorder in order to control one’s fear, even in the face of heart-stopping danger. Consider Alex Honnold, the climber who has scaled the 3,000-foot El Capitan in Yosemite National Park without ropes (as featured in the new documentary, “Free Solo”) and made other notable ascents. In 2016, Mr. Honnold’s brain was scanned by neuroscientist Jane Joseph at the Medical University of South Carolina in Charleston. When exposed to images that excite the amygdala in most people, his brain scans showed no response. What’s unclear is whether this capacity predates and enables his daredevil climbing or has been created by it.

[...]

But the amygdala isn’t the only candidate for controlling fear. In a study published earlier this month in the journal Nature Communications, Sanja Mikulovic and colleagues at Uppsala University in Sweden showed that cells called OLM neurons produce theta brain waves, which are seen during meditation and when you feel safe despite a threat in the environment. By manipulating those cells in laboratory mice, the scientists were able to dial up a mouse’s willingness to venture into unexplored areas and tamp down its indications of anxiety, even when smelling a cat. Nicotine also stimulates OLM neurons in humans, a reason that some people chain-smoke to relieve stress.

We know, too, that training and conditioning alters pathways in the brain and can help to mitigate stress and promote calm in fearful situations. A study published in the journal PLOS Biology last year showed, for example, how training instills a kind of autopilot setting. Researcher Sirawaj Itthipuripat at the University of California, San Diego, measured brain activity when people were learning a task and found that less was needed after training, though improvement in performance remained. Another recent paper connected that idea to how people respond to uncertainty and threats. A team of German and Greek researchers completed a nine-month longitudinal study, published in the journal Science Advances, that showed some forms of training changed structures in the cortex and reduced secretions of the stress hormone cortisol.

Military training is partly designed to hold fear in check when carrying out missions that risk death and injury, as well as in the case of disaster. Dave Henson’s training before he deployed to Afghanistan helped him to stay composed while detecting and disarming improvised explosives. Then, a year into his tour, Mr. Henson stepped on an IED. He lost both of his legs.

Once the immediate shock of the blast receded, he found himself reciting the process that he had been trained to follow in the event of a casualty scenario. “The training definitely kicked in,” he says; it distracted him from the pain.

Wired to look for chances to earn money

Monday, October 29th, 2018

Americans have a blind spot when it comes to saving:

Americans seem to excel at working. But saving? Not so much. As of last year, the median American household had only $1,100 saved for retirement, according to an analysis from the Federal Reserve Bank of St. Louis.

While many factors likely contribute to the poor U.S. savings rate, a recent Cornell University study published in the journal Nature Communications pointed to another factor that may be at least partially to blame: our brains. More specifically, the researchers found that our brains may be wired to look for chances to earn money — but fail to recognize chances to save, even when they are right in front of us.

The study measured something we can’t usually measure ourselves: how much attention we pay to earning and saving opportunities. First, participants had to identify colors shown quickly on a computer: one “earning” color that let them gain 30 cents, a neutral color that had no monetary effect and one “saving” color that let them avoid losing 30 cents.

When the “earning” color was shown, a staggering 87.5% of participants identified it more quickly and accurately than when the “saving” color was shown. Even in trials that framed “saving” as earnings that would come slightly later, participants were still better at immediate earning.

In the study’s second part, participants had to identify which color appeared first. Three out of four said they saw the “earning” color appear first — when in fact, the “saving” color did. This suggests our “earning” bias may even be strong enough to warp our perception of time.

It’s just plain good science fiction and it satisfies

Friday, October 26th, 2018

I haven’t read The Da Vinci Code — or any other conspiracy thrillers, now that I think of it — but I have to assume that Hans G. Schantz‘s Hidden Truth series reads like Dan Brown’s bestselling novel — but with physics taking the place of theology.

Schantz can credibly weave physics into his story, because he is a trained physicist and “wrote the book” on The Art and Science of Ultra-Wideband Antennas, and the first book definitely made me want to know more about the pioneers of electromagnetic theory — many of whom did die young or inexplicably left the field.

But the real draw — or drawback — of the novel is that it is unambiguously conservative and especially anti-Progressive. This makes it a bit of a guilty pleasure, if you ascribe to Jordan Peterson’s point about art versus propaganda:

Neovictorian reviewed the second book, and I think he reviewed it well:

It’s fun, it’s well written, it’s just plain good science fiction and it satisfies. Also, it’s a practical guide to understanding, infiltrating and grandly screwing with college SJWs. After you’ve read it, buy a copy (of both volumes) for your friends and children at school! Buy copies for younger kids, too. These books show how young people should conduct themselves with honor and perseverance, and not through preaching, but through example.

I may have to read Neovictorian’s own Sanity next.

There were balloons, and the whole class got to have ice-cream

Monday, October 22nd, 2018

Eight-year-old Saga Vanecek’s first-hand account — “as told to Moya Sarner” — of how she pulled a 1,500-year-old sword out of a lake is as adorable as you could hope:

Daddy was begging me to rush so he could watch the World Cup final, but I like to take my time about things so I ignored him.

I was crawling along the bottom of the lake on my arms and knees, looking for stones to skim, when my hand and knee felt something long and hard buried in the clay and sand. I pulled it out and saw that it was different from the sticks or rocks I usually find. One end had a point, and the other had a handle, so I pointed it up to the sky, put my other hand on my hip and called out, “Daddy, I’ve found a sword!”

I felt like a warrior, but Daddy said I looked like Pippi Longstocking. The sword felt rough and hard, and I got some sticky, icky brown rust on my hands. It started to bend and Daddy splashed up to me, and said I should let him hold it. It was my sword and now he was taking it away! I gave it to him in the end.

I ran to my mamma and my mormor — my grandma — and some other relatives who were all sitting outside having fika, which is Swedish for having a sit-down with coffee and cookies. I was yelling, “I found a sword, I found a sword!” Daddy went to show it to our neighbours, whose family has lived in the village for more than 100 years, and they said it looked like a Viking sword. Daddy didn’t get to watch the football in the end.

[...]

She made me promise not to tell anyone because she and other archaeologists wanted to see if there was anything else buried in the lake; they didn’t want anyone else to come and take the treasures.

[...]

Then they announced the news and I could finally tell everyone at school. I came back from gym class and the whiteboard said, “Saga’s sword” and there were balloons, and the whole class got to have ice-cream.

Some Russian guy tried it 15 years ago

Thursday, October 18th, 2018

The origin of Blue Origin sounds fascinating:

Jeff Bezos remembers being 5 years old and watching the Apollo 11 moon landing on a black-and-white television. The event triggered a lifelong obsession. He spent his boyhood in Houston and moved to Florida by high school, but he passed his summers on his grandparents’ farm in rural Cotulla, Texas. There, his grandfather — a former top Defense Department official — introduced him to the extensive collection of science fiction at the town library. He devoured the books, gravitating especially to Robert Heinlein and other classic writers who explored the cosmos in their tales.

When he was a junior at Miami’s Palmetto Senior High School, his physics teacher, Deana Ruel, tasked the students with designing a piece of playground equipment. Bezos’ idea was to build one in low gravity. “One day I’m going to be the first one to have an amusement park on the moon,” he told Ruel. He promised her a ticket. For a newspaper profile, Bezos spouted O’Neillian talking points to a local reporter curious about his space obsession: “The Earth is finite, and if the world economy and population is to keep expanding, space is the only way to go.”

Bezos went to Princeton, where he attended seminars led by O’Neill and became president of the campus chapter of Students for the Exploration and Development of Space. At one meeting, Bezos was regaling attendees with visions of hollowing out asteroids and transforming them into space arks when a woman leapt to her feet. “How dare you rape the universe!” she said, and stormed out. “There was a pause, and Jeff didn’t make a public comment,” says Kevin Polk, another member of the club. “But after things broke up, Jeff said, ‘Did she really defend the inalienable rights of barren rocks?’”

After Princeton, Bezos put his energies toward finance, working at a hedge fund. He left it to move to Seattle and start Amazon. Not long after, he was seated at a dinner party with science fiction writer Neal Stephenson. Their conversation quickly left the bounds of Earth. “There’s sort of a matching game that goes on where you climb a ladder, figuring out the level of someone’s fanaticism about space by how many details they know,” Stephenson says. “He was incredibly high on that ladder.” The two began spending weekend afternoons shooting off model rockets.

In 1999, Stephenson and Bezos went to see the movie October Sky, about a boy obsessed with rocketry, and stopped for coffee afterward. Bezos said he’d been thinking for a long time about starting a space company. “Why not start it today?” Stephenson asked. The next year, Bezos incorporated a company called Blue Operations LLC. Stephenson secured space in a former envelope factory in a funky industrial area in south Seattle. Other early members of the team included Pablos Holman, a self-described computer hacker, and serial inventor Danny Hillis, who had crafted a proposal to build a giant mechanical clock that would run for 10,000 years. Bezos also recruited Amazon’s general counsel, Alan Caplan, a fellow space nerd. (“We both agreed we’d like to retire on Mars,” Caplan says.) These people were more thinkers than rocketeers, but at Blue Origin’s start the point was to brainstorm: Had any ideas been overlooked that could shake up space travel the way the internet had upended terrestrial commerce?

Another early participant was George Dyson, a science historian and son of physicist Freeman Dyson. At the 1999 PC Forum, an elite tech event run by Dyson’s sister, Esther, Bezos made a beeline for George, who had been writing about a little-known 1950s venture called Project Orion. Project Orion sought to propel space vehicles with atomic bomb explosions, and Bezos wanted to know all about it. As Dyson recalls, Bezos saw Orion as “his model for a small group of crazy people deciding to go into space without the restrictions of being an official government project.” (Bezos later reviewed Dyson’s book on Amazon—something he’s done only three times in the company’s history.) Some months later, Stephenson asked Dyson if he would consult for the company. Then he asked him to join Blue.

When Dyson signed on, he says, Blue Origin felt like Wernher von Braun’s Society for Space Travel. Like that amateur group of dazzling scientists, Blue resembled a club more than a company. Its members were obsessed with finding an alternative to chemical combustion, which is a woefully inefficient way to propel rockets on interplanetary journeys. “We went through a long list of not-quite-crazy but way-out-there projects at the beginning,” Dyson says.

Those were hashed out at Blue Origin’s monthly Saturday all-hands meetings. The sessions began at 9 and lasted all day. Bezos rarely missed one. “It was almost incomprehensible how technically engaged Jeff was in every part of the discussion,” Dyson says. “It wasn’t like, ‘Oh, we’ll leave the hydrogen-flow control valve question to the hydrogen-flow control valve people.’ Whatever the question was, Jeff would have technical knowledge and be involved.”

But as the Blue Origin team experimented with eccentric ways to heave things upward, they began to realize there was a reason big tubes full of chemical fuel had persisted. Every new tack proved infeasible, because of cost, risk, or technical complexity. “You can work really hard and come up with what you think is a super original idea, and you always find out that some Russian guy tried it 15 years ago,” Stephenson says.

That rubber-ducking rubber-ducker!

Tuesday, October 16th, 2018

Anyone who has ever tried to solve a problem knows that the surest way to solve it is to call someone over and then explain how it just doesn’t make sense. That someone doesn’t even have to be a real person. (The Pragmatic Programmer calls this rubber-ducking, since explaining all your problems to a cute little toy works just fine.)

A group of researchers studied how to maximize the talking-aloud effect:

109 participants were tasked with solving different variations of the Tower of Hanoi puzzle (try it yourself right here) in the fewest number of moves, before being given a final test on the most challenging variation (to see how effectively they could transfer what they’ve learned to a new problem).

Participants were randomly assigned to one of five groups, each of which was designed to test a different kind of thinking aloud.

Before each move, the “metacognitive” group was asked to answer questions like “How are you deciding which disk to move next?” or “How do you know that this is a good move?” The idea was to get them to adopt a higher-level process focus, by thinking about what they were doing (consciously monitoring performance) and how they were doing — i.e. whether the move was a good one or not (evaluating success/failure/effectiveness).

The “if-then” group’s instructions were a little more rigidly structured, but similarly intended to get them focused on the problem-solving process: “Before each move, I want you to tell me where you are going to move each disk, and why. Specifically, I want you to state this in an ‘if-then’ statement, for example, ‘if I move this disk to this peg, then this will happen’.”

The “problem-focused” group was asked to answer questions like “What is the goal of the problem?” or “What are the rules of the problem?” before each move. The idea was to give them some structure, but not at the higher process level of the other two groups.

The “think-aloud” control group was given no real structure to guide their thinking, but simply told to “think out loud while you are solving this problem. Try to keep talking as much as you can so that I can hear what you are thinking about as you solve the problem.”

The “silent” control group was given no additional instructions beyond the standard instructions for the puzzle, so did no verbalizing of their thoughts.

[...]

On average, the control groups (silent and think-aloud) made more mistakes than the two process-focused (metacognitive and if-then) groups. This was true for every variation of the puzzle during the practice trials — from the easiest 2-disk version to the more complex 5-disk version.

Then, when the participants were tested on their ability to solve the most challenging 6-disk puzzle (to see how effectively they could transfer what they learned from the practice puzzles), the control groups made an average of 2.5 error moves for every correct move vs. just 1 error move for the process-focused groups.

The problem-focused group fared somewhere in the middle. Better than the control groups, but not as good as the process-focused groups.

[...]

1. Unless we are guided, we tend not to focus on or engage in process-level thinking. It’s more natural for us to simply execute a skill, stop, and repeat the skill on “autocorrect” mode until the problem seems to go away. Like playing a passage over and over until it sounds better. Hitting forehand volleys over and over until we get into a groove and everything seems peachy.

Except that in “solving” problems on this implicit level, while we may be able to work ourselves up to a pretty high level of performance in the short term, it involves making more mistakes during the process, and we don’t actually figure out what the solution is, so therefore can’t apply it very effectively to future problems that we might encounter.

2. When, on the other hand, we focus on what we are doing and why we are doing it (whether we are verbalizing these out loud or not), we can not only solve problems more efficiently, but transfer those solution to similar new problems we might encounter later.

How experts get even better

Monday, October 15th, 2018

A team of researchers in the UK asked expert and intermediate players of Gaelic football to perform 10 kicks from the ground (like a penalty kick in soccer) and 10 from their hands (like punting a football) at target zones on the gym wall for points and then had the players practice for 15 minutes, once per week, for four weeks, to compare how experts practice versus non-experts:

Experts work on their weaker areas; intermediates work on their stronger skill.

The experts spent a greater percentage of their time working on their weaker kick — 66% of the time, compared to the intermediate athletes who devoted only 27% of their time to improving their weaker kick.

Not surprisingly, the experts demonstrated significant improvement on their weaker kick from the pre-test to the post-test (improving from 14.4 points to 19.9 points). Their improvement was also more permanent, as their scores remained stable 6 weeks later on the retention test (19.4 points at retention test).

Conversely, while the intermediate players did make significant improvements to their stronger kick from pre-test to post-test (8 points to 14.7 points), their improvement was less stable, as they regressed on the retention test (12.7). And more importantly perhaps, their weaker kick did not improve at all.

Experts put in fewer repetitions, but expend more effort and energy on each one.

Both expert and intermediate footballers spent the same total amount of time practicing, but experts logged fewer practice attempts than the intermediate group (43.9 vs 56.4 practice attempts).

However, results from the effort and enjoyment assessments suggest that the elite performers expended more effort on each practice attempt.

Specifically, the experts rated their practice sessions as being less enjoyable than the intermediate players (57.7% for the experts vs. 75.8% for the intermediates, where a rating of 65-70% equals riding on an exercise bike at a comfortable pace for 20 minutes).

The experts also rated their practice as requiring more mental effort than the intermediate players (57.9% vs. 30.7%, where higher scores=more effort).

The experts rated their practice as requiring more physical effort as well (58.8% vs. 46.8%, where higher scores=more effort).

This is likely due to the experts and intermediate players’ focus on weaker vs. stronger skills. The more repetitions the experts did of their weaker kick, the less enjoyable they rated their practice time to be. And the more repetitions the intermediate players did of their stronger kick, the easier and less effortful they found their practice to be.

Experts do more planning before each practice attempt.

Based on the voice recordings of their spoken-aloud thoughts during practice, the researchers found that experts did more thinking and planning before each practice attempt.

On average, the experts made almost twice as many statements per attempt than their intermediate counterparts (3.3 statements vs 1.7 statements). In particular, they made more “monitoring and planning” statements before each kick. In other words, they seemed to be able to better utilize feedback from the previous kick and form a clearer plan for what they were going to do in the subsequent kick.

Experts do more random practice.

Experts spent less time engaged in a “blocked” style of practice — spending 17% of their practice sessions in this format, as compared with 22% for the intermediate players. Note: For this study, blocked practice was defined as spending at least 60% of the practice attempts in one 5-minute block on just one kick, with only one switch between kicks per 5-minute block.

The expert footballers also spent more time engaged in “random” practice — with 26% of their practice being considered random, compared with the intermediates who at 3%, did almost none of this kind of practice. Note: For this study, random practice was defined as 4 or fewer consecutive trials before switching to the other kick. Or in other words, to be considered random practice, athletes could do no more than 4 kicks of the same kind in a row.

Learn at night and relearn in the morning

Friday, October 12th, 2018

We already know that (1) spacing practice out results in better learning and long-term retention than cramming it all together, and (2) sleep enhances learning and long-term retention.

A team of French researchers combined these two effects into a simple practice scheduling hack:

Two groups of 20 participants were tasked with learning the French translations of 16 Swahili words. All 40 participants went through the same exact training, but there was one teensy difference.

One group (“wake” group) had their first study session at 9am, and their relearning session at 9pm on the same day. The other group (“sleep” group) had their first study session at 9pm, and their relearning session at 9am the following morning.

[...]

The researchers kept track of how much practice the participants needed to get all 16 translations correct. The sleep group got to perfect recall in about half the time that it took the wake group (3.05 cycles through the list vs. 5.80 cycles). Plus, every single participant in the sleep group got a perfect score within 5 attempts, whereas 75% of the wake group needed more practice.

[...]

A full half a year later, the sleep group continued to out-remember the wake group (8.67 correct vs. 3.35).

Dementia starts in the ICU

Thursday, October 11th, 2018

Doctors are gradually realizing that a trip to the intensive care unit can lead to serious memory problems:

This dementia, a side-effect of intensive medical care, can be permanent. And it affects as many as half of all people who are rushed to the ICU after a medical emergency. Considering that 5.7 million Americans end up in intensive care every year, this is a major problem which, until recently, has been poorly appreciated by medical caregivers.

[...]

“This is a huge problem,” says Dr. E. Wesley “Wes” Ely, an intensive care specialist who heads that effort. He says post-ICU syndrome — a cluster of cognitive symptoms that can include anxiety, depression and PTSD, as well as delirium — affects 30 to 50 percent of all patients who are rushed to the ICU because of a medical emergency. That’s including younger patients who had no prior mental challenges. And in some of those patients, dementia soon follows.

“You have somebody coming into the ICU with a previously very well-working brain and they leave critical care not being able to have a good conversation,” Ely says. “They can’t balance their checkbook, they can’t find the names of people at a party and they get very embarrassed, so they start socially secluding themselves. Our patients tell us what a misery this form of dementia is.”

Ely has been tracking his patients for more than a decade through scientific studies such as the BRAIN-ICU study. He says about one third of patients who have cognitive problems following their ICU stay fully recover; another third stay about the same after their dementia sets in — and a third continue to go downhill.

For many, the damage to mental processing is akin to what’s seen with a traumatic brain injury, or in a condition called mild cognitive impairment — or even Alzheimer’s disease.

Researchers don’t yet know how the brain is changing to give rise to these symptoms, or how extended delirium leads to that brain damage; Ely is launching a large study to help tease out some of those mechanisms. What parts of the brain are affected, and how does the damage differ from that caused by other forms of dementia such as Alzheimer’s? One idea he will explore is whether tiny blood clots might be forming in the brain and playing a role the long-term damage.

In the meantime, Ely says, one thing the doctors treating these patients with sudden dementia are certain of is that their mental problems are linked to the degree of delirium they experience while in the ICU.

“Every day you’re delirious, you have about a 35 percent increased risk of this dementia,” he says. “So if you do the math on that — [after] three days of delirium, you have almost a sure thing you’re going to have some elements of the dementia.”

We are willing to suffer more to keep what we have now

Thursday, October 4th, 2018

T. Greer reviews two books by Kenneth Payne on the psychology of strategy — The Psychology of Strategy: Exploring Rationality in the Vietnam War and Strategy, Evolution, and War: From Apes to Artificial Intelligence:

Payne isolates several aspects of human psychology that are especially relevant to strategic decision making. Payne divides these aspects into three broader themes: unconscious biases that affect strategic decision making, interaction between emotions and strategic action, and the critical role that social esteem plays in the psychology of strategy.

[...]

For example, there is strong evidence humans become more certain in our beliefs and in our decisions when angry; the strategic calculations of an angry decision maker will be fundamentally different from a sorrowful one. One of the more intriguing ideas in Payne’s catalog of biases is his interpretation of Clausewitz’s dictum that the defense is stronger than the offense. This is true, Payne argues, because humans are loss averse. We are willing to suffer more to keep what we have now than we are to earn something new. If humans think about territory or international prestige this way, then commanders will be bolder when trying to recover lost ground, and their soldiers will be more determined in defense than on the attack.

The most interesting part of this discussion is Payne’s analysis of honor and esteem. Humans are social animals. The need for the esteem of other humans seems deeply ingrained in human psychology, and statesmen and strategists are not immune to this. In The Psychology of Strategy Payne provides scores of examples of strategic decisions made by Lyndon Johnson, Richard Nixon, and other officials that were made more to bolster the social esteem of the decision maker than to defeat the enemy. For Johnson and his officials, esteem and reputation were often explicitly described as the most important objective in the war — one administration official estimated in a memo that 70% of the reason the U.S. was escalating in Vietnam was to avoid humiliation; the other 30% was divided between the need to keep Vietnam out of Chinese hands and to help the people of South Vietnam live a freer life.

[...]

Esteem, emotion, and cognitive biases are human phenomena. If wars were fought by non-humans they would be fought differently. This is exactly what Payne imagines for the future of war. Artificial intelligence will be a revolution in warfare, Payne claims, because for the first time in man’s evolutionary history, strategy will be freed from the limits of human psychology: “Rather than creating a danger from AI acting strategically against humans, the main effects of AI are likely to be felt from AI acting in our interests.”

Nature has won

Sunday, September 30th, 2018

In reviewing Robert Plomin’s Blueprint: How DNA Makes Us Who We Are, Gregory Cochran says, forget Nature versus Nurture. Nature has won:

Assuming that this work is correct, what does it mean? What are the implications?

It means that we have to completely rethink and rebuild the social sciences. Steven Pinker said: “For most of the twentieth century it was assumed that psychological traits were caused by environmental factors, called nurture.” This was completely wrong. Problems like p-value fishing and the current ‘replication crisis’ are nothing compared to the tsunami that’s coming.

Indeed, social scientists have done such a terrible job that it’s hard to see how the field can be repaired. They wanted the false results they got, and they still do. I’m sure their descendants will as well. Isn’t heritability grand?

We need a different kind of social science researcher, smarter, less emotional, and more curiosity-driven. Intellects vast and cool and unsympathetic. But where will we find them?