Tuesday, October 27, 2020

The end of an expanding epidemic cannot be precisely forecast

A sobering analysis from Castro et al.:  

Significance

Susceptible–infected–removed (SIR) models and their extensions are widely used to describe the dynamics of infection spreading. Certain generic features of epidemics are well-illustrated by these models, which can be remarkably good at reproducing empirical data through suitably chosen parameters. However, this does not assure a good job anticipating the forthcoming stages of the process. To illustrate this point, we accurately describe the propagation of COVID-19 in Spain using one such model and show that predictions for its subsequent evolution are disparate, even contradictory. The future of ongoing epidemics is so sensitive to parameter values that predictions are only meaningful within a narrow time window and in probabilistic terms, much as what we are used to in weather forecasts.
Abstract
Epidemic spread is characterized by exponentially growing dynamics, which are intrinsically unpredictable. The time at which the growth in the number of infected individuals halts and starts decreasing cannot be calculated with certainty before the turning point is actually attained; neither can the end of the epidemic after the turning point. A susceptible–infected–removed (SIR) model with confinement (SCIR) illustrates how lockdown measures inhibit infection spread only above a threshold that we calculate. The existence of that threshold has major effects in predictability: A Bayesian fit to the COVID-19 pandemic in Spain shows that a slowdown in the number of newly infected individuals during the expansion phase allows one to infer neither the precise position of the maximum nor whether the measures taken will bring the propagation to the inhibition regime. There is a short horizon for reliable prediction, followed by a dispersion of the possible trajectories that grows extremely fast. The impossibility to predict in the midterm is not due to wrong or incomplete data, since it persists in error-free, synthetically produced datasets and does not necessarily improve by using larger datasets. Our study warns against precise forecasts of the evolution of epidemics based on mean-field, effective, or phenomenological models and supports that only probabilities of different outcomes can be confidently given.

Monday, October 26, 2020

Machine learning detects online influence campaigns.

Maybe there is light at the end of the tunnel in the struggle to determine when malign information or online influence campaigns are being spread on social media platforms. Alizadeh and collaborators summarize in a Washington Post article their use of machine learning techniques, described in more detail in an article in Science Advances. They also point to promising techniques being developed by other scholars.
There’s no single solution, but there is a path forward
Unfortunately, this means there is no single model for finding foreign influence campaigns. Social media usage is dynamic. Normal users are always responding to current events and trolls are continually adapting and trying new tactics.
While we did not find a stable set of characteristics that allow us to detect all campaigns, we did find a method for detecting these campaigns based on the fact that troll content is almost always different in detectable ways. And machine learning allows us to find those differences at scale. Other scholars have developed promising techniques, as well.
The day when we can have a “daily report” of online influence campaigns to inform citizens may not be as far away as it would seem.
Here is the abstract from their Science Advances article:
We study how easy it is to distinguish influence operations from organic social media activity by assessing the performance of a platform-agnostic machine learning approach. Our method uses public activity to detect content that is part of coordinated influence operations based on human-interpretable features derived solely from content. We test this method on publicly available Twitter data on Chinese, Russian, and Venezuelan troll activity targeting the United States, as well as the Reddit dataset of Russian influence efforts. To assess how well content-based features distinguish these influence operations from random samples of general and political American users, we train and test classifiers on a monthly basis for each campaign across five prediction tasks. Content-based features perform well across period, country, platform, and prediction task. Industrialized production of influence campaign content leaves a distinctive signal in user-generated content that allows tracking of campaigns from month to month and across different accounts.

Friday, October 23, 2020

Unethical amnesia

An interesting study from Galeotti et al. (open source):

Significance

Using large-scale incentivized online experiments, we tested two possible origins of individuals’ forgetting about their past cheating behavior in a mind game. We found that purely hedonic considerations, such as the maintenance of a positive self-image, are not sufficient to motivate unethical amnesia, but the addition of an instrumental value to forgetting triggers such amnesia. Individuals forget their past lies more when amnesia can serve as an excuse not to engage in future morally responsible behavior. These findings shed light on the interplay between dishonesty and memory and suggest further investigations of the cost function of unethical amnesia. A policy implication is that improving ethics requires making unethical amnesia more difficult for individuals.
Abstract
Humans care about morality. Yet, they often engage in actions that contradict their moral self. Unethical amnesia is observed when people do not remember or remember less vividly these actions. This paper explores two reasons why individuals may experience unethical amnesia. Forgetting past unethical behavior may be motivated by purely hedonic or affective reasons, such as the willingness to maintain one’s moral self-image, but also by instrumental or strategic motives, in anticipation of future misbehavior. In a large-scale incentivized online experiment (n = 1,322) using a variant of a mind game, we find that hedonic considerations are not sufficient to motivate the forgetting of past cheating behavior. This is confirmed in a follow-up experiment (n = 1,005) in which recalls are elicited the same day instead of 3 wk apart. However, when unethical amnesia can serve as a justification for a future action, such as deciding on whether to keep undeserved money, motivated forgetting is more likely. Thereby, we show that motivated forgetting occurs as a self-excuse to justify future immoral decisions.

Thursday, October 22, 2020

Compassion research

I want to point to a recent "Making Sense" podcast titled "The power of compassion" in which Sam Harris interviews James R. Doty, a Stanford neurosurgeon who is director of the Center for Compassion and Altruism Research and Education at Stanford University School of Medicine. Doty is an inventor, entrepreneur and philanthropist who has given support to a number of charitable organizations, is on the Board of Directors of a number of non-profit foundations, is chairman of the Dalai Lama Foundation, vice-chair of the Charter for Compassion International, and is on the International Advisory Board of the Council for the Parliament of the World’s Religions. He also writes for The Huffington Post. 

I found a brief tour of the website of the Center for Compassion and Altruism Research and Education to be most instructive. It points to numerous sources of compassion research and training. Doty's website points to his book "Into the Magic Shop," which is discussed in the podcast.

Wednesday, October 21, 2020

5 Minutes That Will Make You Love Baroque Music - Calming sounds for our times

The New York Times offers another installment in its series that asks prominent artists to choose the five minutes or so they would play to make their friends fall in love with a particular category of music, such as  classical music, the piano, opera, the cello, Mozart, 21st-century composers, the violin...and now, Baroque Music. I found listening through the 16 selections chosen from the work of Bach, Handel, Purcell, Monteverdi, Scarlatti and others to be a wonderful calming antidote to my usual brain noise.

Tuesday, October 20, 2020

Correlation between increased COVID-19 cases and support for political leaders.

Yam et al. (open source) offer an interesting analysis. (I do hope that the help to incumbent governments offered by COVID-19 they note for many countries and contexts doesn't significantly apply to the upcoming U.S. presidential election!)  

Significance

Amid the present COVID-19 pandemic, we find that many citizens around the world “rally ‘round the flag” and increase their support for their respective political leaders. We observe these findings among countries that are culturally and geographically diverse, and even among leaders who are strongly disliked by citizens prior to the pandemic. Our findings could have important voting implications during or immediately after the pandemic. As an example, the Korean ruling party won the most seats in the house by any party since 1960 in an election held during the pandemic in April 2020. COVID-19 might thus serve as a catalyst to help some incumbent governments.
Abstract
COVID-19 has emerged as one of the deadliest and most disruptive events in recent human history. Drawing from political science and psychological theories, we examine the effects of daily confirmed cases in a country on citizens’ support for the political leader through the first 120 d of 2020. Using three unique datasets which comprise daily approval ratings of head of government (n = 1,411,200) across 11 world leaders (Australia, Brazil, Canada, France, Germany, Hong Kong, India, Japan, Mexico, the United Kingdom, and the United States) and weekly approval ratings of governors across the 50 states in the United States (n = 912,048), we find a strong and significant positive association between new daily confirmed and total confirmed COVID-19 cases in the country and support for the heads of government. These analyses show that political leaders received a boost in approval in the early months of the COVID-19 pandemic. Moreover, these findings suggest that the previously documented “rally ‘round the flag” effect applies beyond just intergroup conflict.

Monday, October 19, 2020

Another description of how science works.

Joshua Rothman does a review of a new book by Michael Strevens, a philosopher at New York University,"The Knowledge Machine: How Irrationality Created Modern Science". Strevens, noting that science is objective while scientists are not, asks whether an "iron rule" can explain how they changed the world anyway. I'm passing on some central points with a few clips of text, and suggest you read the whole review, which describes the contexts of several scientific breakthroughs.

In school, one learns about “the scientific method”—usually a straightforward set of steps, along the lnes of “ask a question, propose a hypothesis, perform an experiment, analyze the results.” ....Two twentieth-century philosophers of science, Karl Popper and Thomas Kuhn, are widely held to have offered the best accounts of this process. Popper maintained that scientists proceed by “falsifying” scientific claims—by trying to prove theories wrong. Kuhn, on the other hand, believed that scientists work to prove theories right, exploring and extending them until further progress becomes impossible. These two accounts rest on divergent visions of the scientific temperament. For Popper, Strevens writes, “scientific inquiry is essentially a process of disproof, and scientists are the disprovers, the debunkers, the destroyers.” Kuhn’s scientists, by contrast, are faddish true believers who promulgate received wisdom until they are forced to attempt a “paradigm shift”—a painful rethinking of their basic assumptions.
The allocation of vast human resources to the measurement of possibly inconsequential minutiae is what makes science truly unprecedented in history. Why do scientists agree to this scheme? Why do some of the world’s most intelligent people sign on for a lifetime of pipetting?
Strevens thinks that they do it because they have no choice. They are constrained by a central regulation that governs science, which he calls the “iron rule of explanation.” The rule is simple: it tells scientists that, “if they are to participate in the scientific enterprise, they must uncover or generate new evidence to argue with”; from there, they must “conduct all disputes with reference to empirical evidence alone.” Compared with the theories proposed by Popper and Kuhn, Strevens’s rule can feel obvious and underpowered. That’s because it isn’t intellectual but procedural. “The iron rule is focused not on what scientists think,” he writes, “but on what arguments they can make in their official communications.” Still, he maintains, it is “the key to science’s success,” because it “channels hope, anger, envy, ambition, resentment—all the fires fuming in the human heart—to one end: the production of empirical evidence.”
Strevens arrives at the idea of the iron rule in a Popperian way: by disproving the other theories about how scientific knowledge is created. The problem isn’t that Popper and Kuhn are completely wrong. It’s that scientists, as a group, don’t pursue any single intellectual strategy consistently. Exploring a number of case studies—including the controversies over continental drift, spontaneous generation, and the theory of relativity—Strevens shows scientists exerting themselves intellectually in a variety of ways, as smart, ambitious people usually do. Sometimes they seek to falsify theories, sometimes to prove them; sometimes they’re informed by preëxisting or contextual views, and at other times they try to rule narrowly, based on the evidence at hand.
Why did the iron rule emerge when it did? Strevens takes us back to the Thirty Years’ War, which concluded with the Peace of Westphalia, in 1648. The war weakened religious loyalties and strengthened national ones...As Isaac Newton wrote, “The laws of God & the laws of man are to be kept distinct.” These new, “nonoverlapping spheres of obligation,” Strevens argues, were what made it possible to imagine the iron rule. The rule simply proposed the creation of a third sphere: in addition to God and state, there would now be science.
The iron rule—“a kind of speech code”—simply created a new way of communicating, and it’s this new way of communicating that created science. The subjectivists are right, he admits, inasmuch as scientists are regular people with a “need to win” and a “determination to come out on top.” But they are wrong to think that subjectivity compromises the scientific enterprise. On the contrary, once subjectivity is channelled by the iron rule, it becomes a vital component of the knowledge machine. It’s this redirected subjectivity—to come out on top, you must follow the iron rule!—that solves science’s “problem of motivation,” giving scientists no choice but “to pursue a single experiment relentlessly, to the last measurable digit, when that digit might be quite meaningless.”

Friday, October 16, 2020

Want to feel better? Make a fake smile by holding a pencil in your teeth.

Neat work by Marmolejo-Ramos et al in Experimental Psychology, Research subjects who forced their facial muscles to replicate the movement of a smile by holding a pen between their teeth altered their perception to see the world in a more positive way, and to have a lower threshold for the perception of happy expression in facial stimuli. This correlated with changes in activity of the amygdala, an emotion regulation center in the brain. I pass on their abstract (motivated readers can obtain the whole article by emailing me):
In this experiment, we replicated the effect of muscle engagement on perception such that the recognition of another’s facial expressions was biased by the observer’s facial muscular activity (Blaesi & Wilson, 2010). We extended this replication to show that such a modulatory effect is also observed for the recognition of dynamic bodily expressions. Via a multilab and within-subjects approach, we investigated the emotion recognition of point-light biological walkers, along with that of morphed face stimuli, while subjects were or were not holding a pen in their teeth. Under the “pen-in-the-teeth” condition, participants tended to lower their threshold of perception of happy expressions in facial stimuli compared to the “no-pen” condition, thus replicating the experiment by Blaesi and Wilson (2010). A similar effect was found for the biological motion stimuli such that participants lowered their threshold to perceive happy walkers in the pen-in-the-teeth condition compared to the no-pen condition. This pattern of results was also found in a second experiment in which the no-pen condition was replaced by a situation in which participants held a pen in their lips (“pen-in-lips” condition). These results suggested that facial muscular activity alters the recognition of not only facial expressions but also bodily expressions.

Thursday, October 15, 2020

Physics of virus transmission by speaking droplets

Some clarity from Netz and Eaton (open source) on a scientifically contentious politicized issue:
To make the physics of person-to-person virus transmission from emitted droplets of oral fluid while speaking easily understood, we present simple and transparent algebraic equations that capture the essential physics of the problem. Calculations with these equations provide a straightforward way of determining whether emitted droplets remain airborne or rapidly fall to the ground, after accounting for the decrease in droplet size from water evaporation. At a relative humidity of 50%, for example, droplets with initial radii larger than about 50 μm rapidly fall to the ground, while smaller, potentially virus-containing droplets shrink in size from water evaporation and remain airborne for many minutes. Estimates of airborne virion emission rates while speaking strongly support the proposal that mouth coverings can help contain the COVID-19 pandemic.
From the text of the article:
A few examples are instructive. In the absence of water evaporation, droplets placed initially at z0 = 1.5 m (the average height above ground for the mouth of a standing human adult) with radii of 1, 10, or 100 μm will require 1.3 × 104 s (∼3.5 h), 130 s, and 1.3 s, respectively, to fall to the ground.
After an analysis of the number of emitted virions while speaking (Table 1):
Overall, the above analysis strongly supports the concept that simply speaking can be a major mechanism of person-to-person COVID-19 transmission and that covering the mouth in public, as suggested by the work of Anfinrud and coworkers (11⇓–13) and others (10, 17), could help to more rapidly contain and potentially end the pandemic.

Wednesday, October 14, 2020

MindBlog starts another anti-aging self experiment.

I've done a bit more reading on alpha-ketoglutarate, a natural component of the Krebs biochemical cycle that generates body energy and whose levels normally decline with aging. It was the subject of a recent post pointing to studies indicating the positive effects of its supplementation on health and longevity in mice.  So...I have started taking 300 mg capsules of the stuff with my other breakfast supplements. I decided to pass on the pricey 'Rejuvant Life Tabs', containing 1000 mg and offered by Ponce de Leon Health, a company set up by some of the researchers, and instead got the compound from Kirkman, one of the supplement providers. I'm inclined not to be too paranoid about their sending sawdust instead of the real product.  I noted that I could buy the >98% pure dry powder from the Sigma-Aldrich company, the supplier my biochemisty lab used for over 30 years, but decided the hassle of dealing with bulk powder wasn't worth it.  The compound is quite acidic, so best taken as the Calcium or Magnesium salt and with a meal.  I had an unhappy tummy when I tried it without food.  

I will continue taking the compound, will report imagined positive or negative effects as addenda to this post.  Undesirable side effects will lead me to discontinue the supplement, as was the case with my 2010 (Acetyl L-carnitine, alpha-lipoic acid, and the B-vitamin biotin) and 2016 (pterostilbene and nicotinamide riboside) self experiments.  The latter, like a 2008 experiment with resveratrol was terminated because of increasing arthritic symptoms. The 2008 post had 33 comments reporting negative effects resveratrol.

And, a necessary comment regarding Ponce de Leon Health and other purveyors of life extension elixirs:

You're gonna die..there is compelling evidence that none of us will make it past ~120 years of age.   

 



Tuesday, October 13, 2020

Can podcasts make us happy?

Alexandra Schwartz offers some comments on two positive psychology podcasts that take a quantitative view of the quest to be happy. I suggest you read the whole article in the New Yorker. Here are a few clips:
...There are well-being podcasts galore, but the ones that seemed most worthy of consideration for limited listening time are hosted by psychologists and neuroscientists who have professional purchase on the subject.
Laurie Santos, the host of “The Happiness Lab,” podcast which is produced by Pushkin, is an upbeat Yale psychologist whose course Psychology and the Good Life is the most popular class in the college’s three-hundred-year history...One reason for such popularity is obvious: like the rest of us, but more so, undergrads are under-rested and overworked, and need help making their lives more of a joy and less of a misery. Another reason becomes clear when you listen to the podcast: the class is a gut.
The Science of Happiness” is hosted by Dacher Keltner, a psychologist who runs Berkeley’s Greater Good Science Center, which co-produces his podcast with PRX. The show, currently in its sixth season, is straightforward about its self-help proposition; episodes have alluring titles like “Do You Want to Be More Patient?” and “How to Love People You Don’t Like.”
Listeners seem to enjoy these podcasts. Their iTunes ratings are high. They have similar strong points; both hosts are accomplished and likable, and you tend to learn a little something, even if you already knew it. (You probably understood that too much of a good thing reduces your pleasure in it; now you can call that the “hedonic treadmill.”) And they have similar flaws. The main one, I’m sorry to say, is that they are boring. An oddity of the scientific approach to happiness is that it can seem, to the laypeople among us, to be reinventing a wheel that has been turned, for thousands of years, by the world’s great religions, philosophers, novelists, and poets. Santos recognizes this; the show is currently in a “mini-season” that deals with thinkers such as Aristotle, Plato, Epictetus, and the Buddha.
Her points about becoming habituated to and bored by a particular presentation regime mirror my own experience with the two instructional apps I have reviewed on MindBlog, Waking Up, and Healthy Minds.

Monday, October 12, 2020

Our looming societal bereavement.

Some ramblings prompted by reading Andrew Sullivan't Weekly Dish piece "Dreaming of a Landslide" : 

As eager as I am to see Trump lose the presidential election, I realize I will have withdrawal symptoms - feel an emptiness from the loss of the constant entertainment provided by the media's obsessive focus on the attention grabbing orange clown's reality show. I will miss the horrified fascination I felt each time my prediction that 'surely it can't get any worse than this' was yet again proved wrong. 

One thing we can be very sure of is that a Biden presidency is going to be majorly boring in comparison. Extreme behaviors and political positions grab our attention, competent, sane, non-ideological problem solving does not. Polarization pays, driving the media quest for incendiary content that increases clicks What might rise as our new shiny object, our new circus? Schadenfreude over the tyrant's fall may suffice for awhile, but maybe people will finally fatigue from the divisiveness and decide to just get along with each other. 

Some rearranged clips illustrating conservative Andrew Sullivan's sentiments:

...a landslide is the only thing that can possibly, finally break the far right fever that has destroyed the GOP as a legitimate right-of-center political party, and turned it into a paranoid, media-driven, fact-free festival of fear and animus...A thumping defeat of the president, a serious shellacking, could help remove the tarnished toxicity of Trump from an agenda that, under younger leadership, could spawn a new, multicultural right-of-center majority...a reformist conservatism would seek to “level up” a society wracked by hyper-global capitalism...move toward defending the unskilled, protecting working families, guarding entitlements, resisting urban wokeness, checking free trade absolutism, restraining overseas intervention, and curtailing mass immigration.

Friday, October 09, 2020

Partisan polarization about voting by mail during the pandemic

From Lockhart et al., surveys illustrating another depressing feature of our times....
Are voters as polarized as political leaders when it comes to their preferences about how to cast their ballots in November 2020 and their policy positions on how elections should be run in light of the COVID-19 outbreak? Prior research has shown little party divide on voting by mail, with nearly equal percentages of voters in both parties choosing to vote this way where it is an option. Has a divide opened up this year in how voters aligned with the Democratic and Republican parties prefer to cast a ballot? We address these questions with two nationally diverse, online surveys fielded from April 8 to 10 and June 11 to 13, of 5,612 and 5,818 eligible voters, respectively, with an embedded experiment providing treated respondents with scientific projections about the COVID-19 outbreak. We find a nearly 10 percentage point difference between Democrats and Republicans in their preference for voting by mail in April, which had doubled in size to nearly 20 percentage points in June. This partisan gap is wider still for those exposed to scientific projections about the pandemic. We also find that support for national legislation requiring states to offer no-excuse absentee ballots has emerged as an increasingly polarized issue.

Thursday, October 08, 2020

The mystery of American pain - a warning for the future

Case et al. (open source) make the fascinating observation that today's elderly report less pain than those in midlife and predict that tomorrow's elderly will be sicker than today's elderly, with serious implications for healthcare. 

Significance

The elderly in the United States report less pain than those in midlife—suggesting, perhaps, that once people move into old age, their morbidity will fall. Unfortunately, assessing pain by age at one point in time masks the fact that each successive birth cohort reports more pain at any given age than the cohorts that came before it. We cannot use the experience of the elderly today to project pain prevalence of the elderly tomorrow. Today’s elderly have experienced less pain throughout their lives than those in midlife today, who will be tomorrow’s elderly. If these patterns continue, pain prevalence will continue to increase for all adults; tomorrow’s elderly will be sicker than today’s elderly, with serious implications for healthcare.
Abstract
There is an expectation that, on average, pain will increase with age, through accumulated injury, physical wear and tear, and an increasing burden of disease. Consistent with that expectation, pain rises with age into old age in other wealthy countries. However, in America today, the elderly report less pain than those in midlife. This is the mystery of American pain. Using multiple datasets and definitions of pain, we show today’s midlife Americans have had more pain throughout adulthood than did today’s elderly. Disaggregating the cross-section of ages by year of birth and completion of a bachelor’s degree, we find, for those with less education, that each successive birth cohort has a higher prevalence of pain at each age—a result not found for those with a bachelor’s degree. Thus, the gap in pain between the more and less educated has widened in each successive birth cohort. The increase seen across birth cohorts cannot be explained by changes in occupation or levels of obesity for the less educated, but fits a more general pattern seen in the ongoing erosion of working-class life for those born after 1950. If these patterns continue, pain prevalence will continue to increase for all adults; importantly, tomorrow’s elderly will be sicker than today’s elderly, with potentially serious implications for healthcare.

Wednesday, October 07, 2020

Age related cognitive decline and the gut microbiome

Haridy summarizes experiments by D'Amato et al. showing that fecal transplants from old mice to young mice result in the younger animals displaying learning and memory impairments. It would be interesting to expand this work to check whether transferring fecal transplants from young to older mice improved their learning and memory, as is the case with blood transfers from younger to older mice. Here are the background and results sections of the open source research paper

Background

The gut-brain axis and the intestinal microbiota are emerging as key players in health and disease. Shifts in intestinal microbiota composition affect a variety of systems; however, evidence of their direct impact on cognitive functions is still lacking. We tested whether faecal microbiota transplant (FMT) from aged donor mice into young adult recipients altered the hippocampus, an area of the central nervous system (CNS) known to be affected by the ageing process and related functions.
Results
Young adult mice were transplanted with the microbiota from either aged or age-matched donor mice. Following transplantation, characterization of the microbiotas and metabolomics profiles along with a battery of cognitive and behavioural tests were performed. Label-free quantitative proteomics was employed to monitor protein expression in the hippocampus of the recipients. We report that FMT from aged donors led to impaired spatial learning and memory in young adult recipients, whereas anxiety, explorative behaviour and locomotor activity remained unaffected. This was paralleled by altered expression of proteins involved in synaptic plasticity and neurotransmission in the hippocampus. Also, a strong reduction of bacteria associated with short-chain fatty acids (SCFAs) production (Lachnospiraceae, Faecalibaculum, and Ruminococcaceae) and disorders of the CNS (Prevotellaceae and Ruminococcaceae) was observed. Finally, the detrimental effect of FMT from aged donors on the CNS was confirmed by the observation that microglia cells of the hippocampus fimbria, acquired an ageing-like phenotype; on the contrary, gut permeability and levels of systemic and local (hippocampus) cytokines were not affected.

Tuesday, October 06, 2020

Bodybuilding supplement promotes healthy aging and extends life span

...at least in mice. I pass on clips from this piece by by Jocelyn Kaiser:
A dietary supplement bodybuilders use to bulk up may have a more sweeping health benefit: Staving off the ravages of old age. Mice given the substance—alpha-ketoglutarate (AKG)—were healthier as they aged, and females lived longer than mice not on the supplement.
AKG is part of the metabolic cycle that our cells use to make energy from food...The molecule grabbed attention as a possible antiaging treatment in 2014, when researchers reported AKG could extend life span by more than 50% in tiny Caenorhabditis elegans worms... In the new study, Gordon Lithgow and Brian Kennedy of the Buck Institute for Research on Aging and colleagues turned to mammals. They gave groups of 18-month-old mice (about age 55 in human years) the equivalent of 2% of their daily chow as AKG until they died, or for up to 21 months. AKG levels in blood gradually drop with age, and the scientists’ aim was to restore levels to those seen in young animals.
Some differences jumped out within a few months: “They looked much blacker, shinier, and younger” than control mice, says Azar Asadi Shahmirzadi, a postdoc at the Buck Institute who did the experiments as a graduate student. In addition, the AKG-fed mice scored an average of more than 40% better on tests of “frailty,” as measured by 31 physiological attributes including hair color, hearing, walking gait, and grip strength. And female mice lived a median of 8% to 20% longer after AKG treatment began than control mice, the group reports today in Cell Metabolism...The AKG-eating mice did not perform better on tests of heart function or treadmill endurance, however, and the tests did not include cognitive performance.
Probing the mechanism for these improvements, the researchers found that female mice receiving AKG produced higher levels of a molecule that tamps down on inflammation. Chronic inflammation can spur many diseases of aging such as cancer, heart disease, arthritis, and dementia.
Kennedy, now also at the National University of Singapore, plans to test AKG in human volunteers soon. Looking at a group of people between the ages of 45 and 65, his group will see whether the molecule improves aging-related biomarkers such as inflammation, arterial hardening, and a type of chemical signature on DNA associated with aging. The company Ponce de Leon Health, where Kennedy serves as chief scientific officer (and Gordon and other paper authors have stock), is running a similar study at Indiana University.
Ponce de Leon Health already sells a formulation of AKG called Rejuvant that it says can “slow the aging process.” Kennedy defends these claims. “We are upfront about the data that we have and do not yet have on the website,” he says. And Brown-Borg notes the Buck Institute team isn’t the first group of aging-focused researchers to start a company to develop an antiaging treatment, an idea she hopes will eventually pan out in clinical trials

Monday, October 05, 2020

Facing major changes that are a predictable and integral part of life.

I pass on clips from another of Arthur Brooks' biweekly articles on "How to Build a Life." Its discussion of major life changes begins with the obvious  major life transition that is being forced upon most of us by the COVID -19 pandemic.
We have been awakening to the reality that the coronavirus pandemic is not a temporary affliction, but an involuntary transition from one way of life to another. Our jobs and personal lives are shifting and, in many cases, will never fully return to “normal.” ...You may never go back to work like before. Dating may never be the same. Your alma mater might go broke and disappear. Will you hug your friends or even shake hands as much as you used to? Perhaps not.
...Even when a transition is completely voluntary, it can be the source of intense suffering, because it involves adapting to new surroundings and changing your self-conception.
If we understand transitions properly, however, we can curb our natural tendency to fight against them—a futile battle, given their inevitability. Indeed, with a shift in mindset, we can make transitions into a source of meaning and transcendence.
Psychologists call the state of being in transition “liminality - you are neither in the state you left nor completely in your new state, at least not mentally. This provokes something of an identity crisis - it raises the question “Who am I?” - which can be emotionally destabilizing.
After interviewing hundreds of people about their life transitions, author Bruce Feiler found that a major change in life occurs, on average, every 12 to 18 months. Huge ones happen three to five times in each person’s life. Some are voluntary and joyful, such as getting married or having a child. Others are involuntary and unwelcome, such as unemployment or life-threatening illness.
...here’s the good news: Even difficult, unwanted transitions are usually seen differently in retrospect than in real time... research  shows that we tend to see past events—even unwanted ones—as net positives over time. Though our brains have a tendency to focus on negative emotions in the present, over the years unpleasant feelings fade more than pleasant feelings do, a phenomenon known as “fading affect bias.”
One of the things we learn by not resisting challenging transitions is how to cope with subsequent life changes - a sense of meaning gained through change makes the rest of life seem more stable.
Difficult periods can also stimulate innovation and ingenuity. A large amount of literature  talks about “post-traumatic growth,” in which people derive long-term benefits from painful experiences, including more appreciation for life, richer relationships, greater resilience, and deeper spirituality. Another manifestation of this growth, according to some newer scholarship, is heightened creativity.
Life changes are painful, but inevitable. And as hard as they may be, we only make things harder—and risk squandering the benefits and lessons they can bring—when we work against them instead of with them...those who benefit the most from painful periods are those who spend time experiencing and processing them. The right strategy is to accept transitions as an integral part of life, and lean into them.

Friday, October 02, 2020

Tipsy microglia binge on synapses - another reason to cut down on the booze

Socodato et al. find that binge-level alcohol intake (about five drinks for an average person) over 10 consecutive days enhances Src-to–tumor necrosis factor (TNF) signaling in prefrontal cortex microglia, which boosts their engulfment capacity and leads to aberrant synaptic pruning, culminating in synapse loss and anxiety-like behavior. Overall, their data suggest that aberrant synaptic pruning by microglia might play an important role in the synaptic transmission deficits elicited by alcohol abuse. Their abstract:
Alcohol abuse adversely affects the lives of millions of people worldwide. Deficits in synaptic transmission and in microglial function are commonly found in human alcohol abusers and in animal models of alcohol intoxication. Here, we found that a protocol simulating chronic binge drinking in male mice resulted in aberrant synaptic pruning and substantial loss of excitatory synapses in the prefrontal cortex, which resulted in increased anxiety-like behavior. Mechanistically, alcohol intake increased the engulfment capacity of microglia in a manner dependent on the kinase Src, the subsequent activation of the transcription factor NF-κB, and the consequent production of the proinflammatory cytokine TNF. Pharmacological blockade of Src activation or of TNF production in microglia, genetic ablation of Tnf, or conditional ablation of microglia attenuated aberrant synaptic pruning, thereby preventing the neuronal and behavioral effects of the alcohol. Our data suggest that aberrant pruning of excitatory synapses by microglia may disrupt synaptic transmission in response to alcohol abuse.

Thursday, October 01, 2020

Acetaminophen increases risk taking

From Keaveney et al.:
Acetaminophen (Tylenol), an analgesic and antipyretic available over-the-counter and used in over 600 medicines, is one of the most consumed drugs in the USA. Recent research has suggested that acetaminophen’s effects extend to the blunting of negative as well as positive affect. Because affect is a determinant of risk perception and risk taking, we tested the hypothesis that acute acetaminophen consumption (1000 mg) could influence these important judgments and decisions. In three double-blind, placebo-controlled studies, healthy young adults completed a laboratory measure of risk taking (Balloon Analog Risk Task) and in Studies 1 and 2 completed self-report measures of risk perception. Across all studies (total n = 545), acetaminophen increased risk-taking behavior. On the more affectively stimulating risk perception measure used in Study 2, acetaminophen reduced self-reported perceived risk and this reduction statistically mediated increased risk-taking behavior. These results indicate that acetaminophen can increase risk taking, which may be due to reductions in risk perceptions, particularly those that are highly affect laden.