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“Trips and Neurotransmitters: Discovering Principled Patterns across 6,850 Hallucinogenic Experiences”, Ballentine et al 2022

“Trips and neurotransmitters: Discovering principled patterns across 6,850 hallucinogenic experiences”⁠, Galen Ballentine, Samuel Freesun Friedman, Danilo Bzdok (2022-03-16; ; similar):

Psychedelics probably alter states of consciousness by disrupting how the higher association cortex governs bottom-up sensory signals. Individual hallucinogenic drugs are usually studied in participants in controlled laboratory settings.

Here, we have explored word usage in 6,850 free-form testimonials [from Erowid] about 27 drugs through the prism of 40 neurotransmitter receptor subtypes, which were then mapped to 3-dimensional coordinates in the brain via their gene transcription levels from invasive tissue probes.

Despite high interindividual variability, our pattern-learning approach delineated how drug-induced changes of conscious awareness are linked to cortex-wide anatomical distributions of receptor density proxies. Each discovered receptor-experience factor spanned between a higher-level association pole and a sensory input pole, which may relate to the previously reported collapse of hierarchical order among large-scale networks.

Co-analyzing many psychoactive molecules and thousands of natural language descriptions of drug experiences, our analytical framework finds the underlying semantic structure and maps it directly to the brain.

“Patient-Driven Findings of Genetic Associations for PANS and PANDAS”, Horvath & Keating 2021

2021-horvath.pdf: “Patient-Driven Findings of Genetic Associations for PANS and PANDAS”⁠, Robert Steve Horvath, Samuel Keating (2021-12-31; ⁠, ; similar):

Background: There are presently very few genetic studies for PANS (Pediatric Acute-Onset Neuropsychiatric Syndrome) or PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections). More work in genetic associations for PANS and PANDAS (P/​P) is needed to increase understanding of these debilitating childhood disorders that have a range of presentations.

Objective: This work represents a novel approach that aims to determine genetic associations between P/​P and other diseases, disorders and traits (hereafter referred to as phenotypes).

Methods: Consumer genetic data (23andMe⁠, AncestryDNA) for 155 patients with P/​P were obtained from consenting parents over a period from 2018 to 2020. An analysis plan for this work was registered at Open Science Framework⁠, additional genotypes imputed using Impute.me⁠, and polygenic risk scores for 1,702 phenotypes calculated for each of the 155 P/​P patients.

Results: One-sample t-tests performed across the 155 individual risk scores revealed that P/​P is statistically-significantly associated with 21 different groups of Single Nucleotide Polymorphisms (SNPs) that are in turn associated with 21 phenotypes. Some of the 21 phenotypes (see Table 3) are previously known to be related to or associated with P/​P: a group of SNPs associated with Tourette’s Syndrome⁠, and another group associated with autism spectrum disorder or Schizophrenia⁠, and a third associated with “feeling nervous” yielded t-tests with p-values of 1.2 × 10−5, 1.2 × 10−11 and 1.0 × 10−5 respectively for association with the P/​P data. This validated our analysis methodology. Our analysis also revealed novel genetic associations such as between P/​P and plasma anti-thyroglobulin levels (p = 1.3 × 10−7), between P/​P and triglycerides (p = 5.6 × 10−6), and between P/​P and Lewy body disease (p = 7.8 × 10−6), inviting further investigation into the underlying etiology of P/​P.

Conclusion: P/​P is associated with many phenotypes not previously recognized as being connected to P/​P. Further work on these connections can lead to better understanding of P/​P.

[Keywords: PANS genetic associations, PANS polygenic risk score, consumer genetics tests, imputation]

“Results of a 5-Year n-of-1 Growth Hormone Releasing Hormone Gene Therapy Experiment”, Hanley et al 2021

2021-hanley.pdf: “Results of a 5-Year n-of-1 Growth Hormone Releasing Hormone Gene Therapy Experiment”⁠, Brian P. Hanley, Keith Brewer, George Church (2021-12-16; ):

Here presented for the first time are results showing persistence over a 5+ year period in a human [Brian P. Hanley] who had a hormone gene therapy administered to muscle.

This growth hormone releasing hormone (somatocrinin/​somatoliberin/​GHRH) therapy was administered in 2 doses, a year apart, with a mean after the second dose of 195 ng/​mL (13 × normal, σ = 143, σM = 34, max = 495, min = 53). This level of GHRH therapy appears to be safe for the subject, although there were some adverse events.

Insulin-like growth factor 1 levels were little affected, nor were the growth hormone test results, showing no indications of acromegaly for the hormone homologue used.

Heart rate declined 8 to 13 bpm, persistent over 5 years. Testosterone rose by 52% (σ = 22%, σM = 6%). The high-density lipoprotein/​low-density lipoprotein ratio dropped from 3.61 to mean 2.81 (σ = 0.26, σM = 0.057, max = 3.3, min = 2.5), and triglycerides declined from 196 mg/​dL to mean 94.4 mg/​dL (σ = 21.9, σM = 5.0, min = 59, max = 133, min = 59). White blood cell counts increased, however, the baseline was not strong. CD4 and CD8 mean increased by 11.7% (σ = 11.6%, σM = 3.3%, max = 30.7%, min = −9.6%) and 12.0% (σ = 10.5%, σM = 3.0%, max = 29.1%, min = −6.7%), respectively. Ancillary observations comprise an early period of euphoria, and a dramatic improvement in visual correction after the first dose, spherical correction from baseline (L/​R) −2.25/​−2.75 to −0.25/​−0.5. Over the next 5 years, correction drifted back to −1.25/​−1.75. Horvath PhenoAge epigenetic clock was cut 44.1% post-treatment. At completion, epigenetic age was −6 years (−9.3%), and telomere age was +7 months (+0.9%).

[Keywords: GHRH, GRF, GHRF, growth hormone releasing hormone, somatocrinin, somatoliberin, somatorelin⁠, self-experimentation, n-of-1]

…Sans anesthetic, electroporation elicited the remark, “On a POW that would be a war crime.” Available literature greatly understated sensations.

Euphoria: The subject reported being euphoric after the first inoculation, a feeling of “more intense reality” with joyful/​blissful body feelings. One adviser to the study was quite concerned, being of the opinion that euphoria was probably signaling pathology, and so, it was logged as a mild grade 1 adverse event. The subject did not think it was pathological, nor adverse.

Results: Subjective first-person overview

A self-experiment provides for more than an objective observation of the experiment. The subjective experience can also inform us, allowing observations that could be missed. This experiment generated a number of such, and a third person will be dispensed with for this section.

The first inoculation was traumatic, causing strong activation of the quadriceps, and an electrical shock sensation. Inoculation sites on both legs felt “hit with a hammer.” Modifications made the second inoculation go smoothly. This is ascribed to 2 things. Without tetany of muscle cells near the electroporation site, there was no trauma to the muscle from that cause. Also, chilling prevented tissue heating.

I was surprised (because I believed that this dose would be too low to be perceptible) that in the first half-hour, I felt a tingling sensation that I had never experienced. I speculate that this was due to rapid stimulation of gonadotropin release, and the rise in testosterone level fits this idea. The first inoculations were primarily intended as a live test of the protocol. Low dose was serendipitous, as I well may have canceled the experiment and removed the site if the euphoria had continued to increase.

Over the first several days I felt better and better—my legs and whole body felt lively when going cycling, and I wondered if this could plausibly be a placebo effect. This liveliness then went over the edge into euphoria that was so strong I did not care enough to bother putting my foot down as I fell over on my bicycle due to moving too slowly. I think this suggests that GHRH, through receptors in the central nervous system, has an upregulating effect on a range of neurotransmitter receptors in the receptorome.

A curious effect on muscles occurred in the first week that I suspect is connected to later developments. During arm weight work, a sensation occurred as if minuscule spots at or near the attachments of upper body muscles were popping. This slight stinging sensation was so distributed, and so tiny for each of the countless locations, that it didn’t bother me enough to stop. Later, I had old soft tissue injuries recur, a second lumbar disc herniation, then a new shoulder injury. This shoulder injury occurred on a relatively light body weight rep after a maximal weight effort competing with young men in their mid-20s. The injury was not a full tear.

However, there was an unusual event that suggests something more. I had a motorcycle accident at 18, which left me with a gouge in my right kneecap and a lump of collagen/​scar ~0.6 cm thick × 1 cm × 2.5 cm. This lump spontaneously came loose and slipped down under my skin. It was absorbed in a 3-week period.

The first hypothesis about these injuries is that higher exercise tolerance drove my body beyond its current limits. The second hypothesis is based on speculating what saturation levels of this hormone might do to a senescent cell. It may be that senescent cells respond and create weaker tissue, or undergo apoptosis in doing so. A third hypothesis is that there may be an expression level of GHRH that corresponds to childhood, perhaps very young childhood, and triggers some neotenous cell growth pattern.

Because of concerns about further soft tissue effects, in July of 2019, I decided on a course of senolytics (dasatinib 400mg and quercetin 4g per day for 5 days) repeated 2 months later. Since then, there have been no new events. A cycling crash (over 20MPH) shortly after the second course of senolytics resulted in a mild concussion, and no other injuries, despite hitting so hard, that immediately afterward I was sure I had multiple broken bones. I have had cycling accidents in the past, breaking both wrists, a collarbone, etc. This crash was like having an accident in my 20s. As I sprinted to avoid a speeding car, I put too much focus on the car that stopped half-way across the intersection with squealing tires, and caught a pedal on the pillar in the middle of the bike path entrance.

The mental effects were pleasant after the first inoculation and largely so after the second. However, the second inoculation also included disturbing effects. My physiological responses to the world around me changed completely. This isn’t a mental thing, it’s in the body, what the Japanese call the hara. It became apparent that my identity foundation is integral with this. I talked with a psychiatrist, and did meditative exercises intentionally embracing and accepting who I was now. This was difficult, including what most would call nightmares. My unconscious operated like a child’s, piecing metaphors together to understand what I had done. I didn’t feel afraid, I felt unmoored, wondering why I felt no fear. This was probably a dose effect.

An effect I didn’t expect and still remains is that I feel I felt rejuvenated after doing leg work. This isn’t a minor effect. I consistently go in tired and by the end of my workout feel like doing it again. This begins to dissipate 2–3 hours later, and I suspect it is a direct effect of GHRH production triggered by use of the affected muscles. This also signals that upregulation of the myosin gene happens within 20–30 minutes of heavy exercise stimulation.

Sleep improved dramatically, becoming like a teens sleep for a couple of months after first inoculation. This faded, in part, probably from stress, but overall sleep improved. Since 2 months after second inoculation I wake up so hungry I cannot sleep. Eating a sizeable (800–1,000 calories) meal before bed can sometimes get me through 6 hours. However, I should note that my normal exercise schedule is 6–7 days a week, 1–2.5 hours per weekday session and up to 5 hours on weekends.

The GHRH graph shows impressive expression for more than 5 years, the first finding of such long-term expression. After 5 and ½ years, this level of long-term expression does appear to be reasonably safe.

“Amateur Hour: Improving Knowledge Diversity in Psychological and Behavioral Science by Harnessing Contributions from Amateurs”, Mohlhenrich & Krpan 2021

2021-mohlhenrich.pdf: “Amateur hour: Improving knowledge diversity in psychological and behavioral science by harnessing contributions from amateurs”⁠, Erik Mohlhenrich, Dario Krpan (2021-11-30; ⁠, ; similar):

  • Low knowledge diversity is an important issue affecting psychological science.
  • We propose this issue could be resolved by harnessing contributions from amateurs.
  • We outline 6 “blind spots”—neglected areas in which amateurs could contribute.
  • We discuss how amateur contributions could be practically achieved.

Contemporary psychological and behavioral science suffers from a lack of diversity regarding the key intellectual activities that constitute it, including its theorizing, empirical approaches, and topics studied. We refer to this type of diversity as knowledge diversity.

To fix the knowledge diversity problem, scientists have proposed several solutions that would require transforming the field itself—an endeavor that can realistically be realized only in the long term. In this article, we propose that knowledge diversity could also be attained in the short term without transforming the field itself—by harnessing contributions from amateurs who can explore diverse aspects of psychology that are neglected in academia.

We identify 6 such “blind spot” areas within which amateurs could contribute and discuss how this could be practically achieved.

Blind spot

Description

Long-term projects

Projects (eg. theory development, research pursuit) that require dedication over a long period of time with uncertain payoffs.|

Basic observational research

Conducting observational studies that aim to identify new phenomena or characterize the generalizability of already known phenomena.

Speculation

Making speculations that are not limited by current methodological or other practical considerations.|

Interdisciplinary projects

Projects that combine diverse areas of psychology (and potentially other disciplines) and do not involve working within a specific area of expertise or topic.|

Aimless projects

Projects that do not have pre-determined goals or planned outcomes and evolve in any direction in which pursuing psychology-related ideas takes the person.|

Uncommon research areas

Research areas that are neglected by psychological scientists.|

Table 1: Blind spots that are not incentivized in academia and could be addressed by amateur psychologists to increase knowledge diversity in psychological and behavioral science.

We hope that our article will inspire professionals and academic institutions to be more open toward amateur contributions to create a diverse body of knowledge.

[Keywords: amateurs, knowledge diversity, psychology, blind-spots, inclusivity]

“Personalized Machine Learning of Depressed Mood Using Wearables”, Shah et al 2021

“Personalized machine learning of depressed mood using wearables”⁠, Rutvik V. Shah, Gillian Grennan, Mariam Zafar-Khan, Fahad Alim, Sujit Dey, Dhakshin Ramanathan, Jyoti Mishra et al (2021-06-09; ⁠, ; similar):

Depression is a multifaceted illness with large interindividual variability in clinical response to treatment. In the era of digital medicine and precision therapeutics, new personalized treatment approaches are warranted for depression.

Here, we use a combination of longitudinal ecological momentary assessments of depression, neurocognitive sampling synchronized with electroencephalography⁠, and lifestyle data from wearables to generate individualized predictions of depressed mood over a 1-month time period. This study, thus, develops a systematic pipeline for N-of-1 personalized modeling of depression using multiple modalities of data. In the models, we integrate 7 types of supervised machine learning (ML) approaches for each individual, including ensemble learning and regression-based methods. All models were verified using 4× nested cross-validation⁠.

The best-fit as benchmarked by the lowest mean absolute percentage error, was obtained by a different type of ML model for each individual, demonstrating that there is no one-size-fits-all strategy. The voting regressor, which is a composite strategy across ML models [which simply averages the model predictions], was best performing on-average across subjects. However, the individually selected best-fit models still showed statistically-significantly less error than the voting regressor performance across subjects. For each individual’s best-fit personalized model, we further extracted top-feature predictors using Shapley statistics. Shapley values revealed distinct feature determinants of depression over time for each person ranging from co-morbid anxiety⁠, to physical exercise, diet, momentary stress and breathing performance, sleep times, and neurocognition.

In future, these personalized features can serve as targets for a personalized ML-guided, multimodal treatment strategy for depression.

“Citizen Science: Asking Questions of Psychedelic Microdosing”, Cameron 2021

“Citizen Science: Asking questions of psychedelic microdosing”⁠, Lindsay P. Cameron (2021-03-02; ; backlinks; similar):

A citizen science approach to research has shown that the improvements in mood and cognition associated with psychedelic microdosing are likely due to a placebo effect⁠.

…Now, in eLife, Balász Szigeti (Imperial College) and colleagues report how they have taken a citizen science approach to enroll 191 participants in a trial, and then used a clever experimental protocol to blind these participants to the experimental conditions (Szigeti et al 2021). Participants were split into 3 groups and took doses for 4 weeks: the first group microdosed, the second group took only placebo, and the last group had 2 weeks of microdoses and 2 weeks of placebo (Figure 1)…Surveys were given to participants at the start of the study, at multiple points during the investigation, and afterwards to measure a wide range of psychological outcomes including creativity, emotional state, mood, energy, well-being, mindfulness, openness, neuroticism and paranoia. Critically, their method enabled a placebo-controlled study, with a large sample size and realistic drug-use practices (albeit with drug samples that vary in purity and dose). This is the largest placebo-controlled microdosing study to date.

While Szigeti et al confirm anecdotal reports that microdosing improves mood and cognitive functions, there was no statistically-significant difference between the microdosing group and the placebo-treated group. This suggests that effects associated with psychedelic microdosing can be explained by the placebo effect. Consistent with this, participants scored statistically-significantly higher on the surveys when they believed they had taken a microdose.

So, does the dose of a psychedelic compound have to be strong enough to cause hallucinations in order to have a therapeutic effect? The results of Szigeti et al suggest that the answer to this question is yes.

“Follow-up: I Found Two Identical Packs of Skittles, among 468 Packs With a Total of 27,740 Skittles”, Farmer 2019

“Follow-up: I found two identical packs of Skittles, among 468 packs with a total of 27,740 Skittles”⁠, E. R. Farmer (2019-04-06; ; similar):

This is a follow-up to a post from earlier this year discussing the likelihood of encountering two identical packs of Skittles, that is, two packs having exactly the same number of candies of each flavor. Under some reasonable assumptions, it was estimated that we should expect to have to inspect “only about 400–500 packs” on average until encountering a first duplicate. This is interesting, because as described in that earlier post, there are millions of different possible packs– or even if we discount those that are much less likely to occur (like, say, a pack of nothing but red Skittles), then there are still hundreds of thousands of different “likely” packs that we might expect to encounter.

So, on 12 January of this year, I started buying boxes of packs of Skittles. This past week, “only” 82 days, 13 boxes, 468 packs, and 27,740 individual Skittles later, I found the following identical 2.17-ounce packs.

…this seemed like a great opportunity to demonstrate the predictive power of mathematics. A few months ago, we did some calculations on a cocktail napkin, so to speak, predicting that we should be able to find a pair of identical packs of Skittles with a reasonably—and perhaps surprisingly—small amount of effort. Actually seeing that effort through to the finish line can be a vivid demonstration for students of this predictive power of what might otherwise be viewed as “merely abstract” and not concretely useful mathematics.

“ZMA Sleep Experiment”, Branwen 2017

ZMA: “ZMA Sleep Experiment”⁠, Gwern Branwen (2017-03-13; ⁠, ⁠, ⁠, ; backlinks; similar):

A randomized blinded self-experiment of the effects of ZMA (zinc+magnesium+vitamin B6) on my sleep; results suggest small benefit to sleep quality but are underpowered and damaged by Zeo measurement error/​data issues.

I ran a blinded randomized self-experiment of 2.5g nightly ZMA powder effect on Zeo-recorded sleep data during March-October 2017 (n = 127). The linear model and SEM model show no statistically-significant effects or high posterior probability of benefits, although all point-estimates were in the direction of benefits. Data quality issues reduced the available dataset, rendering the experiment particularly underpowered and the results more inconclusive. I decided to not continue use of ZMA after running out; ZMA may help my sleep but I need to improve data quality before attempting any further sleep self-experiments on it.

“Self-Blinded Mineral Water Taste Test”, Branwen 2017

Water: “Self-Blinded Mineral Water Taste Test”⁠, Gwern Branwen (2017-02-15; ⁠, ⁠, ; backlinks; similar):

Blind randomized taste-test of mineral/​distilled/​tap waters using Bayesian best-arm finding; no large differences in preference.

The kind of water used in tea is claimed to make a difference in the flavor: mineral water being better than tap water or distilled water. However, mineral water is vastly more expensive than tap water.

To test the claim, I run a preliminary test of pure water to see if any water differences are detectable at all. Compared my tap water, 3 distilled water brands (Great Value, Nestle Pure Life, & Poland Spring), 1 osmosis-purified brand (Aquafina), and 3 non-carbonated mineral water brands (Evian, Voss, & Fiji) in a series of n = 67 blinded randomized comparisons of water flavor. The comparisons are modeled using a Bradley-Terry competitive model implemented in Stan; comparisons were chosen using an adaptive Bayesian best-arm sequential trial (racing) method designed to locate the best-tasting water in the minimum number of samples by preferentially comparing the best-known arm to potentially superior arms. Blinding & randomization are achieved by using a Lazy Susan to physically randomize two identical (but marked in a hidden spot) cups of water.

The final posterior distribution indicates that some differences between waters are likely to exist but are small & imprecisely estimated and of little practical concern.

“Sensory Augmentation: Integration of an Auditory Compass Signal into Human Perception of Space”, Schumann & O’Regan 2017

“Sensory augmentation: integration of an auditory compass signal into human perception of space”⁠, Frank Schumann, J. Kevin O’Regan (2017-02-04; ⁠, ; similar):

Bio-mimetic approaches to restoring sensory function show great promise in that they rapidly produce perceptual experience, but have the disadvantage of being invasive. In contrast, sensory substitution approaches are non-invasive, but may lead to cognitive rather than perceptual experience.

Here we introduce a new non-invasive approach that leads to fast and truly perceptual experience like bio-mimetic techniques. Instead of building on existing circuits at the neural level as done in bio-mimetics, we piggy-back on sensorimotor contingencies at the stimulus level. We convey head orientation to geomagnetic North, a reliable spatial relation not normally sensed by humans, by mimicking sensorimotor contingencies of distal sounds via head-related transfer functions.

We demonstrate rapid and long-lasting integration into the perception of self-rotation. Short training with amplified or reduced rotation gain in the magnetic signal can expand or compress the perceived extent of vestibular self-rotation, even with the magnetic signal absent in the test. We argue that it is the reliability of the magnetic signal that allows vestibular spatial recalibration, and the coding scheme mimicking sensorimotor contingencies of distal sounds that permits fast integration.

Hence we propose that contingency-mimetic feedback has great potential for creating sensory augmentation devices that achieve fast and genuinely perceptual experiences.

…Our novel iPhone based sensory augmentation device [hearSpace] measures head orientation to North via orientation sensors (compass, gyro, accelerometer) integrated into a headphone and transforms their output into a spatial sound using a sound engine based on head-related transfer functions (HRTF) (Figure 1A, Figure 1B). A recording of a waterfall serves as the sound source which provides the ecological semantics of a natural sound coming from a distance. Further, the sound has a pink-noise like frequency spectrum which is pleasant to hear. The waterfall sound is reliably situated in the direction of magnetic North, moving in such a way as to compensate the movements of the head. This artificial sensorimotor contingency: (1) allows aligning the head with a global reference, creating a reliably stable artificial external reference for the eyes, ears and the vestibular system, and (2) provides an intuitive sensory code that mimics the acoustic characteristics of distal sounds.

“Banner Ads Considered Harmful”, Branwen 2017

Ads: “Banner Ads Considered Harmful”⁠, Gwern Branwen (2017-01-08; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

9 months of daily A/​B-testing of Google AdSense banner ads on Gwern.net indicates banner ads decrease total traffic substantially, possibly due to spillover effects in reader engagement and resharing.

One source of complexity & JavaScript use on Gwern.net is the use of Google AdSense advertising to insert banner ads. In considering design & usability improvements, removing the banner ads comes up every time as a possibility, as readers do not like ads, but such removal comes at a revenue loss and it’s unclear whether the benefit outweighs the cost, suggesting I run an A/​B experiment. However, ads might be expected to have broader effects on traffic than individual page reading times/​bounce rates, affecting total site traffic instead through long-term effects on or spillover mechanisms between readers (eg. social media behavior), rendering the usual A/​B testing method of per-page-load/​session randomization incorrect; instead it would be better to analyze total traffic as a time-series experiment.

Design: A decision analysis of revenue vs readers yields an maximum acceptable total traffic loss of ~3%. Power analysis of historical Gwern.net traffic data demonstrates that the high autocorrelation yields low statistical power with standard tests & regressions but acceptable power with ARIMA models. I design a long-term Bayesian ARIMA(4,0,1) time-series model in which an A/​B-test running January–October 2017 in randomized paired 2-day blocks of ads/​no-ads uses client-local JS to determine whether to load & display ads, with total traffic data collected in Google Analytics & ad exposure data in Google AdSense. The A/​B test ran from 2017-01-01 to 2017-10-15, affecting 288 days with collectively 380,140 pageviews in 251,164 sessions.

Correcting for a flaw in the randomization, the final results yield a surprisingly large estimate of an expected traffic loss of −9.7% (driven by the subset of users without adblock), with an implied −14% traffic loss if all traffic were exposed to ads (95% credible interval: −13–16%), exceeding my decision threshold for disabling ads & strongly ruling out the possibility of acceptably small losses which might justify further experimentation.

Thus, banner ads on Gwern.net appear to be harmful and AdSense has been removed. If these results generalize to other blogs and personal websites, an important implication is that many websites may be harmed by their use of banner ad advertising without realizing it.

“Digital Health: Tracking Physiomes and Activity Using Wearable Biosensors Reveals Useful Health-Related Information”, Li et al 2016

“Digital Health: Tracking Physiomes and Activity Using Wearable Biosensors Reveals Useful Health-Related Information”⁠, Xiao Li, Jessilyn Dunn, Denis Salins, Gao Zhou, Wenyu Zhou, Sophia Miryam Schüssler-Fiorenza Rose, Dalia Perelman et al (2016-12-05; ; similar):

A new wave of portable biosensors allows frequent measurement of health-related physiology. We investigated the use of these devices to monitor human physiological changes during various activities and their role in managing health and diagnosing and analyzing disease.

By recording over 250,000 daily measurements for up to 43 individuals, we found personalized circadian differences in physiological parameters, replicating previous physiological findings. Interestingly, we found striking changes in particular environments, such as airline flights (decreased peripheral capillary oxygen saturation [SpO2] and increased radiation exposure). These events are associated with physiological macro-phenotypes such as fatigue, providing a strong association between reduced pressure/​oxygen and fatigue on high-altitude flights.

Importantly, we combined biosensor information with frequent medical measurements and made two important observations: First, wearable devices were useful in identification of early signs of Lyme disease and inflammatory responses; we used this information to develop a personalized, activity-based normalization framework to identify abnormal physiological signals from longitudinal data for facile disease detection. Second, wearables distinguish physiological differences between insulin-sensitive and insulin-resistant individuals. Overall, these results indicate that portable biosensors provide useful information for monitoring personal activities and physiology and are likely to play an important role in managing health and enabling affordable health care access to groups traditionally limited by socioeconomic class or remote geography.

“CO2/ventilation Sleep Experiment”, Branwen 2016

CO2: “CO2/ventilation sleep experiment”⁠, Gwern Branwen (2016-06-05; ⁠, ⁠, ⁠, ; backlinks; similar):

Self-experiment on whether changes in bedroom CO2 levels affect sleep quality

Some psychology studies find that CO2 impairs cognition, and some sleep studies find that better ventilation may improve sleep quality. Use of a Netatmo air quality sensor reveals that closing my bedroom tightly to reduce morning light also causes CO2 levels to spike overnight to 7x daytime levels. To investigate the possible harmful effects, I run a self-experiment randomizing an open bedroom door and a bedroom box fan (2x2) and analyze the data using a structural equation model of air quality effects on a latent sleep factor with measurement error⁠.

“Catnip Immunity and Alternatives”, Branwen 2015

Catnip: “Catnip immunity and alternatives”⁠, Gwern Branwen (2015-11-07; ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

Estimation of catnip immunity rates by country with meta-analysis and surveys, and discussion of catnip alternatives.

Not all cats respond to the catnip stimulant; the rate of responders is generally estimated at ~70% of cats. A meta-analysis of catnip response experiments since the 1940s indicates the true value is ~62%. The low quality of studies and the reporting of their data makes examination of possible moderators like age, sex, and country difficult. Catnip responses have been recorded for a number of species both inside and outside the Felidae family; of them, there is evidence for a catnip response in the Felidae, and, more uncertainly, the Paradoxurinae, and Herpestinae.

To extend the analysis, I run large-scale online surveys measuring catnip response rates globally in domestic cats, finding high heterogeneity but considerable rates of catnip immunity worldwide.

As a piece of practical advice for cat-hallucinogen sommeliers, I treat catnip response & finding catnip substitutes as a decision problem, modeling it as a Markov decision process where one wishes to find a working psychoactive at minimum cost. Bol et al 2017 measured multiple psychoactives simultaneously in a large sample of cats, permitting prediction of responses conditional on not responding to others. (The solution to the specific problem is to test in the sequence catnip → honeysuckle → silvervine → Valerian⁠.)

For discussion of cat psychology in general, see my Cat Sense review.

“Bacopa Quasi-Experiment”, Branwen 2014

Bacopa: “Bacopa Quasi-Experiment”⁠, Gwern Branwen (2014-05-06; ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

A small 2014-2015 non-blinded self-experiment using Bacopa monnieri to investigate effect on memory/​sleep/​self-ratings in an ABABA design; no particular effects were found.

Bacopa is a supplement herb often used for memory or stress adaptation. Its chronic effects reportedly take many weeks to manifest, with no important acute effects. Out of curiosity, I bought 2 bottles of Bacognize Bacopa pills and ran a non-randomized non-blinded ABABA quasi-self-experiment from June 2014 to September 2015, measuring effects on my memory performance, sleep, and daily self-ratings of mood/​productivity. For analysis, a multi-level Bayesian model on two memory performance variables was used to extract per-day performance, factor analysis was used to extract a sleep index from 9 Zeo sleep variables, and the 3 endpoints were modeled as a multivariate Bayesian time-series regression with splines. Because of the slow onset of chronic effects, small effective sample size, definite temporal trends probably unrelated to Bacopa, and noise in the variables, the results were as expected, ambiguous, and do not strongly support any correlation between Bacopa and memory/​sleep/​self-rating (+/​-/​- respectively).

“2013 LLLT Self-experiment”, Branwen 2013

LLLT: “2013 LLLT self-experiment”⁠, Gwern Branwen (2013-12-20; ⁠, ⁠, ; backlinks; similar):

An LLLT user’s blinded randomized self-experiment in 2013 on the effects of near-infrared light on a simple cognitive test battery: positive results

A short randomized & blinded self-experiment on near-infrared LED light stimulation of one’s brain yields statistically-significant dose-related improvements to 4 measures of cognitive & motor performance. Concerns include whether the blinding succeeded and why the results are so good.

“Lunar Circadian Rhythms”, Branwen 2013

Lunar-sleep: “Lunar circadian rhythms”⁠, Gwern Branwen (2013-07-26; ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

Is sleep affected by the phase of the moon? An analysis of several years of 4 Zeo users’ sleep data shows no lunar cycle.

I attempt to replicate, using public Zeo-recorded sleep datasets, a finding of a monthly circadian rhythm affecting sleep in a small sleep lab. I find only small non-statistically-significant correlations, despite being well-powered⁠.

“2013 Lewis Meditation Results”, Branwen 2013

Lewis-meditation: “2013 Lewis meditation results”⁠, Gwern Branwen (2013-07-12; ⁠, ⁠, ; backlinks; similar):

Multilevel modeling of effect of small group’s meditation on math errors

A small group of Quantified Selfers tested themselves daily on arithmetic and engaged in a month of meditation. I analyze their scores with a multilevel model with per-subject grouping, and find the expect result: a small decrease in arithmetic errors which is not statistically-significant⁠, with practice & time-of-day effects (but not day-of-week or weekend effects). This suggests a longer experiment by twice as many experimenters in order to detect this effect.

“Magnesium Self-Experiments”, Branwen 2013

Magnesium: “Magnesium Self-Experiments”⁠, Gwern Branwen (2013-05-13; ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

3 magnesium self-experiments on magnesium l-threonate and magnesium citrate.

Encouraged by TruBrain’s magnesium & my magnesium l-threonate use, I design and run a blind random self-experiment to see whether magnesium citrate supplementation would improve my mood or productivity. I collected ~200 days of data at two dose levels. The analysis finds that the net effect was negative, but a more detailed look shows time-varying effects with a large initial benefit negated by an increasingly-negative effect. Combined with my expectations, the long half-life, and the higher-than-intended dosage, I infer that I overdosed on the magnesium. To verify this, I will be running a followup experiment with a much smaller dose.

“Caffeine Wakeup Experiment”, Branwen 2013

Caffeine: “Caffeine wakeup experiment”⁠, Gwern Branwen (2013-04-07; ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

Self-experiment on whether consuming caffeine immediately upon waking results in less time in bed & higher productivity. The results indicate a small and uncertain effect.

One trick to combat morning sluggishness is to get caffeine extra-early by using caffeine pills shortly before or upon trying to get up. From 2013-2014 I ran a blinded & placebo-controlled randomized experiment measuring the effect of caffeine pills in the morning upon awakening time and daily productivity. The estimated effect is small and the posterior probability relatively low, but a decision analysis suggests that since caffeine pills are so cheap, it would be worthwhile to conduct another experiment; however, increasing Zeo equipment problems have made me hold off additional experiments indefinitely.

“Perceiving Invisible Light through a Somatosensory Cortical Prosthesis”, Thomson et al 2013

“Perceiving invisible light through a somatosensory cortical prosthesis”⁠, Eric E. Thomson, Rafael Carra, Miguel A.L. Nicolelis (2013-02-12; ⁠, ; similar):

Sensory neuroprostheses show great potential for alleviating major sensory deficits. It is not known, however, whether such devices can augment the subject’s normal perceptual range.

Here we show that adult rats can learn to perceive otherwise invisible infrared light through a neuroprosthesis that couples the output of a head-mounted infrared sensor to their somatosensory cortex (S1) via intracortical microstimulation. Rats readily learn to use this new information source, and generate active exploratory strategies to discriminate among infrared signals in their environment. S1 neurons in these infrared-perceiving rats respond to both whisker deflection and intracortical microstimulation, suggesting that the infrared representation does not displace the original tactile representation.

Hence, sensory cortical prostheses, in addition to restoring normal neurological functions, may serve to expand natural perceptual capabilities in mammals.

“Potassium Sleep Experiments”, Branwen 2012

Potassium: “Potassium sleep experiments”⁠, Gwern Branwen (2012-12-21; ⁠, ⁠, ⁠, ; backlinks; similar):

2 self-experiments on potassium citrate effects on sleep: harm to sleep when taken daily or in the morning

Potassium and magnesium are minerals that many Americans are deficient in. I tried using potassium citrate and immediately noticed difficulty sleeping. A short randomized (but not blinded) self-experiment of ~4g potassium taken throughout the day confirmed large negative effects on my sleep. A longer followup randomized and blinded self-experiment used standardized doses taken once a day early in the morning, and also found some harm to sleep, and I discontinued potassium use entirely.

“The Iron Law Of Evaluation And Other Metallic Rules”, Rossi 2012

1987-rossi: “The Iron Law Of Evaluation And Other Metallic Rules”⁠, Peter H. Rossi (2012-09-18; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

Problems with social experiments and evaluating them, loopholes, causes, and suggestions; non-experimental methods systematically deliver false results, as most interventions fail or have small effects.

“The Iron Law Of Evaluation And Other Metallic Rules” is a classic review paper by American “sociologist Peter Rossi⁠, a dedicated progressive and the nation’s leading expert on social program evaluation from the 1960s through the 1980s”; it discusses the difficulties of creating an useful social program⁠, and proposed some aphoristic summary rules, including most famously:

  • The Iron law: “The expected value of any net impact assessment of any large scale social program is zero”
  • the Stainless Steel law: “the better designed the impact assessment of a social program, the more likely is the resulting estimate of net impact to be zero.”

It expands an earlier paper by Rossi (“Issues in the evaluation of human services delivery”⁠, Rossi 1978), where he coined the first, “Iron Law”.

I provide an annotated HTML version with fulltext for all references, as well as a bibliography collating many negative results in social experiments I’ve found since Rossi’s paper was published (see also the closely-related Replication Crisis).

“LSD Microdosing RCT”, Branwen 2012

LSD-microdosing: “LSD microdosing RCT”⁠, Gwern Branwen (2012-08-20; ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

Self-experiment with sub-psychedelic doses of LSD; no benefit

Some early experimental studies with LSD suggested that doses of LSD too small to cause any noticeable effects may improve mood and creativity. Prompted by recent discussion of this claim and the purely anecdotal subsequent evidence for it, I decided to run a well-powered randomized blind trial of 3-day LSD microdoses from September 2012 to March 2013. No beneficial effects reached statistical-significance and there were worrisome negative trends. LSD microdosing did not help me.

“Treadmill Desk Observations”, Branwen 2012

Treadmill: “Treadmill desk observations”⁠, Gwern Branwen (2012-06-19; ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

Notes relating to my use of a treadmill desk and 2 self-experiments showing walking treadmill use interferes with typing and memory performance.

It has been claimed that doing spaced repetition review while on a walking treadmill improves memory performance. I did a randomized experiment August 2013 – May 2014 and found that using a treadmill damaged my recall performance.

“A/B Testing Long-form Readability on Gwern.net”, Branwen 2012

AB-testing: “A/B testing long-form readability on Gwern.net”⁠, Gwern Branwen (2012-06-16; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

A log of experiments done on the site design, intended to render pages more readable, focusing on the challenge of testing a static site, page width, fonts, plugins, and effects of advertising.

To gain some statistical & web development experience and to improve my readers’ experiences, I have been running a series of CSS A/​B tests since June 2012. As expected, most do not show any meaningful difference.

“Redshift Sleep Experiment”, Branwen 2012

Redshift: “Redshift sleep experiment”⁠, Gwern Branwen (2012-05-09; ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

Self-experiment on whether screen-tinting software such as Redshift/​f.lux affect sleep times and sleep quality; Redshift lets me sleep earlier but doesn’t improve sleep quality.

I ran a randomized experiment with a free program (Redshift) which reddens screens at night to avoid tampering with melatonin secretion & the sleep from 2012–2013, measuring sleep changes with my Zeo⁠. With 533 days of data, the main result is that Redshift causes me to go to sleep half an hour earlier but otherwise does not improve sleep quality.

“Metamagical Themas: Sanity and Survival”, Hofstadter 2012

1985-hofstadter: “Metamagical Themas: Sanity and Survival”⁠, Douglas Hofstadter (2012-04-16; ⁠, ⁠, ⁠, ; backlinks; similar):

3 essays by AI researcher Douglas Hofstadter exploring cooperation/​game theory/​‘superrationality’ in the context of the failure of political coordination to prevent global nuclear war

The following 3 essays were prepared from pages 737–780 of an ebook of Metamagical Themas: Questing for the Essence of Mind and Pattern (1985) by Douglas Hofstadter⁠, an anthology of articles & essays primarily published in Scientific American “between January 1981 and July 1983”. (I omit one entry in “Sanity and Survival”, the essay “The Tumult of Inner Voices, or, What is the Meaning of the Word ‘I’?”, which is unconnected to the other entries on cooperation/​decision theory⁠/​nuclear war.) All hyperlinks are my insertion.

They are interesting for introducing the idea of ‘superrationality’ in game theory⁠, an attempt to devise a decision theory/​algorithm for agents which can reach global utility maxima on problems like the prisoner’s dilemma even in the absence of coercion or communication which has partially inspired later decision theories like UDT or TDT⁠, linking decision theory to cooperation (eg. Oesterheld 2017) & existential risks (specifically, nuclear warfare), and one networking project⁠.

Note: to hide apparatus like the links, you can use reader-mode ().

“LW Anchoring Experiment”, Branwen 2012

Anchoring: “LW anchoring experiment”⁠, Gwern Branwen (2012-02-27; ⁠, ⁠, ; similar):

Do mindless positive/​negative comments skew article quality ratings up and down?

I do an informal experiment testing whether LessWrong karma scores are susceptible to a form of anchoring based on the first comment posted; a medium-large effect size is found. Although the data does not fit the assumed normal distribution so there may or may not be any actual anchoring effect.

“Vitamin D Sleep Experiments”, Branwen 2012

Vitamin-D: “Vitamin D sleep experiments”⁠, Gwern Branwen (2012; ⁠, ⁠, ⁠, ; backlinks; similar):

Self-experiment on vitamin D effects on sleep: harmful taken at night, no or beneficial effects when taken in the morning.

Vitamin D is a hormone endogenously created by exposure to sunlight; due to historically low outdoors activity levels, it has become a popular supplement and I use it. Some anecdotes suggest that vitamin D may have circadian and zeitgeber effects due to its origin, and is harmful to sleep when taken at night. I ran a blinded randomized self-experiment on taking vitamin D pills at bedtime. The vitamin D damaged my sleep and especially how rested I felt upon wakening, suggesting vitamin D did have a stimulating effect which obstructed sleep. I conducted a followup blinded randomized self-experiment on the logical next question: if vitamin D is a daytime cue, then would vitamin D taken in the morning show some beneficial effects? The results were inconclusive (but slightly in favor of benefits). Given the asymmetry, I suggest that vitamin D supplements should be taken only in the morning.

“Zeo Sleep Self-experiments”, Branwen 2010

Zeo: “Zeo sleep self-experiments”⁠, Gwern Branwen (2010-12-28; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

EEG recordings of sleep and my experiments with things affecting sleep quality or durations: melatonin, potassium, vitamin D etc

I discuss my beliefs about Quantified Self⁠, and demonstrate with a series of single-subject design self-experiments using a Zeo. A Zeo records sleep via EEG; I have made many measurements and performed many experiments. This is what I have learned so far:

  1. the Zeo headband is wearable long-term
  2. melatonin improves my sleep
  3. one-legged standing does little
  4. Vitamin D at night damages my sleep & Vitamin D in morning does not affect my sleep
  5. potassium (over the day but not so much the morning) damages my sleep and does not improve my mood/​productivity
  6. small quantities of alcohol appear to make little difference to my sleep quality
  7. I may be better off changing my sleep timing by waking up somewhat earlier & going to bed somewhat earlier
  8. lithium orotate does not affect my sleep
  9. Redshift causes me to go to bed earlier
  10. ZMA: inconclusive results slightly suggestive of benefits

“Nootropics”, Branwen 2010

Nootropics: “Nootropics”⁠, Gwern Branwen (2010-01-02; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar)

“Dual N-Back FAQ”, Branwen 2009

DNB-FAQ: “Dual n-Back FAQ”⁠, Gwern Branwen (2009-03-25; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

A compendium of DNB, WM⁠, IQ information up to 2015.

Between 2008 and 2011, I collected a number of anecdotal reports about the effects of n-backing; there are many other anecdotes out there, but the following are a good representation—for what they’re worth.

“In Defense of Inclusionism”, Branwen 2009

In-Defense-Of-Inclusionism: “In Defense of Inclusionism”⁠, Gwern Branwen (2009-01-15; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

Iron Law of Bureaucracy: the downwards deletionism spiral discourages contribution and is how Wikipedia will die.

English Wikipedia is in decline. As a long-time editor & former admin, I was deeply dismayed by the process. Here, I discuss UI principles, changes in Wikipedian culture, the large-scale statistical evidence of decline, run small-scale experiments demonstrating the harm, and conclude with parting thoughts.

“The Major Role of Clinicians in the Discovery of Off-Label Drug Therapies”, DeMonaco et al 2006

2006-demonaco.pdf: “The Major Role of Clinicians in the Discovery of Off-Label Drug Therapies”⁠, Harold J. DeMonaco, Ayfer Ali, Eric von Hippel (2006-03-01; ⁠, ; backlinks; similar):

Objective: To determine the role of clinicians in the discovery of off-label use of prescription drugs approved by the United States Food and Drug Administration (FDA).

Data Sources: Micromedex Healthcare Series was used to identify new uses of new molecular entities approved by the FDA in 1998, literature from January 1999–December 2003 was accessed through MEDLINE⁠, and relevant patents were identified through the U.S. Patent and Trademark Office.

Data Synthesis and Main Finding: A survey of new therapeutic uses for new molecular entity drugs approved in 1998 was conducted for the subsequent 5 years of commercial availability. During that period, 143 new applications were identified in a computerized search of the literature for the 29 new drugs considered and approved in 1998. Literature and patent searches were conducted to identify the first report of each new application. Authors of the seminal articles were contacted through an electronic survey to determine whether they were in fact the originators of the new applications. If they were, examination of article content and author surveys were used to explore if each new application was discovered through clinical practice that was independent of pharmaceutical company or university research (field discovery) or if the discovery was made by or with the involvement of pharmaceutical company or university researchers (central discovery). 82 (57%) of the 143 drug therapy innovations in our sample were discovered by practicing clinicians through field discovery.

Conclusion: To our knowledge, the major role of clinicians in the discovery of new, off-label drug therapies has not been previously documented or explored. We propose that this finding has important regulatory and health policy implications.

Repeated measures design

Wikipedia

Miscellaneous