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Chinese find doughnut-like topology at tipping points, break physics convention

Oct 19 • 4:00 AM EDT • Science • scmp.com

Israel boss shuns politics before Republic of Ireland clash

Israel boss Ran Ben-Shimon insisted he is “not dealing with any politics” ahead of his side’s behind-closed-doors Nations League meeting with the Republic of Ireland in Serbia on Sunday. Republic manager Heimir Hallgrimsson’s press conference on Saturday morning in Backa Topola ended abruptly following a confrontational conclusion, after an Israeli journalist accused Irish players of calling their opponents "monkeys" in Hungary, where the reverse fixture was held.

Oct 3 • 1:48 PM EDT • Politics • sports.yahoo.com

Haoye Qin: Turning disorder into an advantage in nanophotonics

A 2026 Nanophotonics Early Career Awardee, Qin is harnessing topology and engineered disorder to develop compact optical technologies.

Sep 21 • 1:03 AM EDT • Science • advancedsciencenews.com

The Big Holes in Wearable Heart Rate Variability And Readiness Scores

On September 9th, Apple announced it was revamping its Apple Watch Health Sensing System, rolling out a Readiness score (0 to 10), and increasing the frequency of heart rate variability (HRV) outputs 24-fold. This can be viewed as upping its competition with various other consumer wearable sensors. These “readiness scores” as a composite of multiple metrics, with heart rate variability (HRV) being front and center for most. The majority of Americans are now using wearable sensors, which equates to well over 100 million adults. HRV and Readiness scores are increasingly being marketed as a measurement of autonomic nervous system health, a digital marker for future disease, a clock for biological age, and a holistic metric to promote healthspan and even longevity. (Apple also introduced a new longevity tab and “Health Age”.) None of this has been proven. In this edition of Ground Truths I am going to review what we know about heart rate variability and readiness scores. Heart Rate Variability HRV is the variation in normal heart cycle timing. The variability of the heart rate, the barely perceptible millisecond changes in time between consecutive heart beats (see R-R intervals in the Figure below, left panel), is due to interplay between the sympathetic and parasympathetic (vagal nerve) inputs. Distinct from heart rate, individuals with the same heart rate can have very different HRVs. It is a rough reflection of the autonomic nervous system (ANS) activity, inadequate to say whether a person’s ANS function is abnormal. For more than three decades, heart rate variability (HRV) has been measured and several studies have found an association of low HRV and clinical outcomes, particularly a link with higher all-cause and cardiovascular mortality. There have also been less well established links of low HRV to risk of early cognitive impairment, dementia, mental illness, Type 2 diabetes and substance abuse. An important reminder is that HRV is a surrogate marker without any established cause-and-effect relationship. If you increase your HRV, that doesn’t mean it will improve health outcomes. In fact, there is no hard evidence for that. All that work linking to health outcomes was done with electrocardiogram (ECG) derived HRV. Now, in the era of consumer wearables, this is getting assessed differently, by optical pulse (yes, the lights you see) plethysmography (PPG) or what is called pulse rate variability (PRV). They are not the same, as shown below (right panel) and only concordant when the delay between the ECG and pulse is kept constant, which basically means at rest. I should mention there’s also what I will call MPV, a mattress mechanical movement sensor, a derived heart rate variability, that companies like Eight Sleep use, even further away from directly measuring HRV. HRV has not one uniform measurement but many different types of quantification, such as RMSSD, the magnitude of difference between successive R-R intervals of normal sinus beats (N-N) or SDNN, the standard deviation of NN intervals, both in milliseconds. SDNN is one of the so-called frequency domain HRVs (others are LF, HF, LF/HF). Different wearable sensors use different metics; Apple has relied on SDNN and nearly all of the others use RMSSD, which is generally considered the more accurate metric. There’s also the different length of time measured, such as for a matter of minutes, all day, or an overnight’s sleep. Short measurements are especially problematic since they don’t capture enough of respiratory modulation and other factors that influence HRV. Share Ground Truths How well does HRV correlate with PRV? There are very limited studies, especially independently done. One that is commonly cited was conducted by Air Force researchers in only 13 healthy adults assessing Oura ring 3 and 4, Whoop 4.0, and Garmin Fenix 6 and showed a correlation coefficient of 0.88 to 0.97 and a mean absolute percentage error from 6 to 10%. The correlation is not a perfect 1.0, but there’s at least a fairly high level of correlation. HRV is supposed to increase during the night due to takeover of the parasympathetic nervous system, and higher during deep sleep. A recent example of my 1 week, all day “HRV,” and one during sleep is shown below. As you can see, the N of 1 data are inconsistent for the same days from different sensors (Oura, AppleWatch, Fitbit Air, and Eight Sleep) by patterns, absolute numbers, and comparison with prior days and weeks. The largest study in over 8 million Fitbit users (the old version, not Google Fitbit Air, introduced in May 2026) gives you a sense of the effect of age, sex, and the 2 different main HRV (here PRV) metrics, with RMSSD on the left and SDRR (=SDNN) on the right below. That study, from data collected in 2018, is a major outlier, since all the more recent ones are tiny with respect to sample size. Many of the companies have not had independent evaluation of their HRV, such as Eight Sleep, but have published a low standard error on their website. There are some other published studies on the correlation between HRV and PRV, but they are all small and only in healthy adults. A scoping review emphasized the lack of study in underrepresented individuals, including the aged, people of color (which affects the PPG signal), and individuals who are underweight or obese. Add the typical adult age 60 plus with one or more chronic diseases. For example, one study in over 900 adults found poor correlation of HRV and PRV, non-uniformly underestimated across many chronic diseases (cardiovascular, endocrine, neurological, respiratory, and others), concluding PRV is “an invalid surrogate for HRV.” A recent systematic review of 43 studies comparing HRV and PRV found reasonable pooled absolute standardized error (HRV as gold standard) but only 10 of the studies provided quantitative synthesis in ideal conditions. Their main conclusion was similarly cautious: “PPG-derived HRV [PRV] should not be regarded as universally interchangeable with ECG-derived HRV across all devices, populations, and recording contexts.” Factors Affecting HRV and PRV That gets me to the long list of factors that affect HRV (and PRV) besides the device, the type of measurement (RMSSD, SDNN or others), the person’s signal, the sensor site, the duration of data capture, if weighting by sleep stage is used, how artifact is processed and corrected. And this list is not complete!: Oura puts out data from their community of users (who input data) on what affects their overnight HRV. The factors currently provided are: no alcohol (increase 8%), melatonin (increase 2%, float tank (increase 2%), wine (decrease 4%), and party (decrease 14%) in overnight HRV. Must be some big parties! Subscribe What is a PRV measurement good for? It has been falsely characterized as an index of “autonomic balance” and a specific indicator of stress. A 2018 review of the studies available for HRV and its relationship to stress, not using any of the current wearables, found that stress can lower HRV. But so can many other factors. The non-specificity of the signal, indexed to the table above, is striking. Evidence from a UK Biobank study of over 46,000 participants with actual HRV looked at genetically predicted HRV, a genetic risk score, that failed to show the expected HRV-mortality link, indicating that _HRV is likely not causa_l, but rather a reflection of person’s physiologic state. A review of consumer wearable HRV data from 5 longitudinal studies showed that nighttime PRV was not associated with perceived stress, and surprisingly higher HRV, in the largest cohort (N=717 participants), was correlated with higher stress. An Oura ring cohort of 525 first-year college students found a link between overnight PRV and perceived stress, but that was also seen with resting heart rate, sleep, and respiratory rate. Several very small studies have examined the relationship of HRV and athletic injuries or guiding training with mixed, and predominantly negative results. HRV biofeedback training with paced breathing had no significant effect on reducing stress or raising HRV, as demonstrated with sham controlled trials. When HRV for multiple days showed a decline in conjunction with body temperature, the Oura ring published data for prediction of Covid. The WHOOP company sponsored an observational study, published in 2026, of 30,000 users for 72 weeks, without a control group, that reported reduced alcohol intake (5.8 % points) by self-report. That doesn’t tell us much, and particularly about the merits of HRV for behavioral change. If you use the same device and conditions as longitudinal trends for multiple (at least 2-3) weeks that may be the one way to get something useful from the measurements. Data for overnight sleep with minimal motion and using RMSSD is the best proxy for real HRV. The reason to look at trends rather than any given night is that it more likely represents something, even though you won’t know with certainty what the “it” is. Keep in mind there are no data, no peer-reviewed evidence, to show that HRV fluctuation in-person has any correlation with health outcomes. Share Readiness Scores These are proprietary scores that integrate different metrics for each of the wearables: no algorithms have been disclosed. They are unvalidated against health outcomes. In a review of 14 composite health scores of readiness and recovery, HRV contributed 86% to the scores, followed by reading heart rate (79%), physical activity and sleep duration (both at 71%). That review noted the substantial variability in measurement protools and lack of standardization. Sleep staging is notoriously inconsistent and inaccurate by these sensors, which adds further to the HRV uncertainties for what the scores, which use sleep stage data, mean. Only resting heart rate has been shown consistently across devices to be extremely accurate. I’ve made a Table to summarize what we know about which metrics are included, the scores, any peer-reviewed studies that compared the readiness score with health outcomes, and the corresponding (if any, NA-not available) citation. You will note that some companies do not use the term “readiness," such as WHOOP for recovery, and Garmin, which has 2 different scores, one of which is Body Battery. Eight Sleep uses the term “Fitness Score.” They all include HRV; Apple includes a new metric they call “Recovery HRV” which among other components uses 7-days of sleep, but it is unclear what this means or how it is differentiated from other scores (there are clearly no data for outcomes). We have no knowledge of how the different components are weighted or whether any of these scores are better than resting heart rate, HRV alone, physical activity, or any other single metric. Since none of these are standardized, they are not interchangeable, so if you get a 90 for Oura that has no relationship to a 90 on a Google Fitbit Air. Notably, the company can update its algorithm for readiness score at any point without notification to device users. Without any useful evidence of actionability for these scores or established relationship with health outcomes, it is hard to make a case for their value. At the Apple recent announcement they showed their Readiness score (0-10) on the watch (Figure below) but there are no published data on this score, not even on their website. It’s available only on their new Watch Series 12 or Ultra 4 [of course, ;-)]. That exemplifies the problems with these scores, lack of data and evidence for being meaningful to promote health. Perhaps the best study (which isn’t saying much) is the WHOOP Recovery for golfer performance, because it did correlate with an objective outcome, even though there was no control group and the authors were all from the company. Among the 389 pro golfers, an absolute 10-per cent point increase in Recovery score was associated with about 0.5 fewer strokes per round. But that’s hardly a health outcome! WHOOP is also conducting a study in over 2,700 runners to see if their recovery score will be linked to less injuries and improved performance, but that is not yet published and has no control group or randomization. Putting This in Context For two decades I’ve been enthusiastic about the potential for digital health and particularly wearable biosensors. Over the years, we’ve seen some great progress for their ability to promote physical activity and accurately detect atrial fibrillation (the first FDA cleared deep learning AI for consumers). That work was the subject of rigorous research. But there are holes in the data and evidence for other metrics. One notable one is the “VO2 max” story that I wrote about earlier this year. At that time many subscribers asked me to cover heart rate variability, which I finally got to here. When I dived into the research and publication for HRV and readiness scores, I expected to find at least some that were of high quality and demonstrated their utility by linkage to health outcomes. To my surprise, I found none. The wearable sensor measurements for HRV (PRV) are, for the most part, accurate, but that validation work has only been done in small studies of healthy adults and does not take into account the long list of factors, from the device, software side, and the user side, that affect HRV measurements. Moreover, this metric chiefly relies on optical sensing and, as we have learned for heart rate PPG sensing, may be less accurate in people of color. Keep in mind that all of the health outcome association evidence comes from ECG-derived HRV; none are from wearable sensor data. I will repeat the key point: there's no peer-reviewed evidence to show that in-person HRV fluctuation—or efforts to raise your HRV— has any correlation with health outcomes. For those of you who look at your HRV on awakening, or even 2+ week trends of it being low, I hope this context helps to relieve any anxiety. Yes, low HRV (not PRV) has been shown to increase risk of some diseases as summarized above. But efforts to raise your HRV—a surrogate metric— has not been established for improving any health outcomes. HRV does not have any evidence of causality (the genetic evidence actually goes against this possibility). In this summary, I have not included data for other wearable sensors such as Polar, Samsung, Withings, Suunto, Amazfit, Coros, Ultrahuman, or additional mattress sensors. These are beyond my first-hand experience, and as far as I know from my in-depth review none have any peer-reviewed published data that differ from the 6 sensors I’ve reviewed here. From the points I’ve gone over above, we’re not ready for readiness scores. Besides being proprietary, they are predominantly based on metrics that have their own issues. It’s compounding the problem, like building a house without a solid foundation that has never undergone a rigorous inspection, and then selling it. Like I mentioned for PRV, you can look at trends over weeks rather than any single day, to get a handle, but even that may not be helpful. There’s simply no evidence that these scores meaningfully relate to health outcomes. I’d emphasize they might, but that requires doing prospective or randomized studies to prove it. None exist. There’s great promise for HRV/PRV utility_. For example**,**_ Prof Maiken Nedergaard, who discovered the brain glymphatics that are essential in eliminating metabolic waste products from the brain during sleep, has posited that HRV could be a non-invasive marker for neuromodulator oscillations, brain-body regulatory circuits, and brain clearance. That would be extremely useful, but like everything else on HRV and readiness scores it requires solid research and validation. The lay media isn’t helping much to get the story straight. Earlier this year The Economist published a piece entitled “The most useful indicator of your overall health” which ordained HRV as an “accumulated stress score.” That’s akin to the false assertion about VO2max: “V02 max is the singular most powerful marker for longevity.” As I’ve summarized here, that is not established. The fact is that so many things can lower HRV, including physical exercise (especially an intense workout), reduced sleep quality, stress, the list above, no less the device, signal, and software. Whatever fluctuations observed have not been correlated with any health outcome. Sadly, “datamaxxers” are widely using HRV and readiness scores that have never been validated to mean anything. We already know that for some people using the sensors for sleep metrics, it can induce “orthosomnia,” an obsession to get high sleep quality, with associated high levels of anxiety. In an experiment done by a company to promote sleep quality for its employees, “For those employees who did use the trackers, many reported feeling perfectly rested until their tracker told them they had had a terrible night. Others were told that they had slept like a baby when they had actually been lying awake worrying about the quality of their sleep. “ The same problem can result from preoccupation with HRV or readiness scores, with anxiety that would lead to further reduction in both. It you are using a wearable like >100 million American adults, it’s OK to look at these data, but contextualized with the major caveats reviewed here. If you are one to require evidence that HRV or readiness scores are linked to health outcomes, you may not even want to look. The companies make it hard to turn them off! Let me end with the companies that make and sell wearables. Apple’s doubling down on HRV (24-fold more reporting and heart rate very 5 seconds) and introduction of a Readiness score tells us that consumers have bought into these metrics and they are joining the club. However, all of this is occurring with a backdrop of tens millions of users, claims about the data that are not backed up by adequate evidence, marketing way out in front of whatever limited data exists, and not being transparent about their readiness score algorithms. The companies can well afford to do the research that is needed to connect these metrics with health outcomes show, once and for all, that increasing HRV or using readiness scores promotes our health. If they believed and invested in the products they are selling, we’d not be in this position of not knowing. That’s essentially where we are with HRV and readiness scores. Perhaps someday this will change and we’ll have good reason to embrace them. NB: I wrote this post. No AI. I have no conflicts of interest with any of its content. Loading... Ground Truths has 215,000 subscribers from every US state and 214 countries. There are over 300,000 followers of Ground Truths so more than 90,000 folks who can easily convert to be free subscribers. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. If you’re not a subscriber, please join! If you found this interesting PLEASE share it! Share Ground Truths The proceeds from all voluntary paid subscriptions go to support our summer internship program. It enabled us to accept and support a record number of 62 summer interns that joined us in 2026! These are high school, college and medical students selected from thousands of applicants. We couldn’t do this expanded program without the funds coming in through Ground Truths. Thank you!

Sep 19 • 10:05 AM EDT • Technology • erictopol.substack.com

Scientists solve ‘mystery-signal’ hidden in quantum material

Researchers have solved the years-long mystery about the origins of the ‘beating’ signal in the topological insulator (TI) nanowires.

Sep 4 • 9:37 AM EDT • Science • interestingengineering.com

Scientists discover asymmetric diffusion of magnetic skyrmions in simulations

Magnetic skyrmions are nanoscale spin textures that can behave like particles and move and diffuse in real space. This makes them promising information carriers for future memory and computing technologies. A new computational study in npj Spintronics shows how geometry and topology can guide asymmetric thermal diffusion of magnetic skyrmions, offering insights for unlocking unconventional computing paradigms, including future stochastic and neuromorphic computing devices for more efficient artificial intelligence (AI) applications.

Aug 24 • 8:00 PM EDT • Science • eurekalert.org

No, AI Probably Won’t Cure Cancer Anytime Soon, Scientists Say

Eric Topol is a prominent cardiologist known for his research into deploying AI and other technologies to improve healthcare. He considers himself a Demis Hassabis superfan, and when I spoke to him, he enthusiastically recounted scoring a blurb from the Google DeepMind chair for “Super Agers,” ...

Aug 22 • 10:17 AM EDT • Science • theinformation.com

Sevastopol Forming New Business Association

Business representatives and a Town of Sevastopol ad hoc committee are working toward the formation of a new Sevastopol Business Association. The committee was scheduled to meet Aug. 19 for an […]

Aug 20 • 1:00 PM EDT • Business • doorcountypulse.com

Czinger debuts topology-optimized brakes with 21C Spyder

Czinger used topological design and additive manufacturing to make the brakes.

Aug 14 • 3:01 AM EDT • Technology • arstechnica.com

John Pardon Untangles the Theoretical Loops

The mathematics professor has won a prestigious Fields Medal for his work at the intersection of geometry, topology and physics.

Jul 23 • 10:19 AM EDT • Science • nytimes.com

Plutonium compound unlocks rare topological quantum behavior with potential nuclear science applications

Plutonium is one of the most complex elements in the periodic table. First synthesized and isolated in 1940 by scientists at the University of California, Berkeley, plutonium has been studied closely ...

Jun 29 • 7:30 PM EDT • Science • phys.org

A new paper argues Microsoft exaggerated its quantum claims a year ago

A peer-reviewed critique of Majorana 1 claims Microsoft did not conclusively demonstrate a working topological qubit. Microsoft disagrees.

Jun 24 • 4:54 PM EDT • Technology • theverge.com

‘I can’t keep this up’: Sebastopol BBQ owner looks for path forward amid enforcement, complaints

A&M BBQ pitmaster Kris Austin is driving 30 miles a day in his diesel truck to shuttle food from his commercial smokers to his restaurant in order to comply with Sebastopol’s zoning code.

Jun 3 • 7:01 PM EDT • Business • pressdemocrat.com

Microsoft’s quantum chip got an upgrade. Critics are still skeptical

Swapping materials in its Majorana 2 chip boosted the effectiveness of quantum bits that rely on the math of topology to reduce errors, Microsoft says.

Jun 2 • 2:15 PM EDT • Science • sciencenews.org

Top Links 1112 Semiconductor decoupling. Powell's politics. Industrializing Ogaden. Free trade and the Magna Carta.

Thank you for your support of Chartbook. Your generosity keeps this show on the road. Feliks Topolski, 1907-1989 8th Army’s Front, Italy 1944 Semiconductor decoupling

May 25 • 6:21 AM EDT • Politics • adamtooze.substack.com

Network topology of the gut microbiome associates with metabolic health in obesity

Nature Communications - Here, the authors show that microbiome network topology associates with metabolic health across obesity phenotypes, with reduced connectivity in metabolically unhealthy...

May 12 • 8:00 PM EDT • Health • nature.com

Quantum topology emerges at near field

Light: Science & Applications - Near-field nanophotonics platform with spin-orbital coupling enables single-photon skyrmions with robust topological structures for high-dimensional quantum...

May 7 • 8:00 PM EDT • Science • nature.com

The expert on 'super aging' breaks down the science — and grift

From peptides and protein to sleep hygiene and vaccines, what actually helps you age well? Physician Eric Topol breaks down the science — and the myths — of longevity and anti-aging.

May 1 • 9:59 AM EDT • Science • wesa.fm

Topological control of chirality and spin with structured light

Light: Science & Applications - Pancharatnam topological charge drives deterministic spin-orbit interactions in paraxial free space, inducing tunable optical chirality and radial spin...

Apr 23 • 8:00 PM EDT • Science • nature.com

A look at 'super agers' and the science behind longer, sharper lives

For thousands of years, humans have tried to avoid growing old. Billions are spent every year on potions and procedures to make us look younger, feel younger and think younger. It’s a hugely profitable, but ultimately fruitless hunt. But science has started to zero in on some proven techniques. Horizons moderator William Brangham explores that with Dr. Eric Topol and Dr. Sandra Weintraub.

Apr 17 • 7:00 PM EDT • Science • pbs.org

Aerospace engineer who worked on Artemis II thanks middle school science teachers

A little more than a decade ago, Nate Eller was an standout student at Twin Hills Middle School in Sebastopol. Today, he’s an aerospace engineer at NASA who played a role in the Artemis II mission.

Apr 11 • 10:30 AM EDT • Science • pressdemocrat.com

Your Thymus and Your Healthspan

Our thymus gland plays a central role in the development or our immune system, specifically for supporting T cell development (how these cells got their name, maturation and differentiation in the thymus) and discriminating between self and foreign, non-self antigen proteins with production of dendritic cells. As we age, our thymus gland shrinks—the process known as involution—with progressive change from spongy to fatty tissue, with loss of functionality. But this process, with respect to timeline and extent, markedly varies from one person to the next. And to make things even more complicated, our thymus gland anatomy and precise location in the chest also is highly variable. So the famous Frank Netter diagrams from the 1960s (such as at left below) don’t capture the remarkable heterogeneity that a random set of 12 chest CT scans (below at right). What I consider as 2 landmark papers in Nature this week (here and here) used AI to quantify health of the thymus in 2 large cohorts, and then correlate the metric to a broad array of health outcomes. In this edition of Ground Truths, I’m going to cover three questions: (1) How was thymus health determined by AI?; (2) How is thymus health linked to key clinical outcomes? and (3) Are there ways we can promote a healthy (aka rejuvenate) thymus gland in our later years? Subscribe 1. How was thymus health determined by AI? This was accomplished by extensive work developing and validating an AI pipeline for 2 stages, the first for localization and segmentation of the thymus bed, and the second to quantify a digital marker, termed the thymic health score. There’s a lot to this algorithmic development, so I won’t go into all the details, but just provide a rudimentary outline of what was done. The 1st stage used supervised learning with 2 radiologists reviewing 2,461 chest CT scans. That work trained a 3D U-Net model to automatically identify the thymic bed’s 3D cropped region using center of mass coordinates, which reached 99.8% accuracy. The 2nd stage used a foundation model that was pre-trained with SwAV (which stands for Swapping Assignment between multiple Views), a self-supervised model, that generated a high-dimensional thymus representation of 4,096 features. That compares to the radiology reductionist and subjective scoring of 0 to 3 where 0 means the thymus is fully degenerated and fatty, and 3 is considered dense, intact glandular soft tissue. Notably, the self-supervised learning (SSL) performance was superior to supervised (AUC ~0.75 vs 0.55, respectively) reflecting the shallowness of the 0-3 classifier vs SSL’s holistic, self-taught AI. The thymic health score ranged from 0 to 100, with the highest number indexed to fully preserved thymic health. The algorithmic work extended to explainability with both Shapely value distribution, meaning the model was holistic not relying on any “magic” pixel, and occlusion sensitivity, demonstrating the model’s performance was not affected by ribs, sternum, lung tissue, but rather focused on the thymic bed directly. Below are a few saliency maps from the occlusion sensitivity that indicate the thymic bed focus, not affected by neighboring structures, using the jet color scale. Now the AI was ready for processing ~25,000 CT scans, each over 30 MB files, from the 2 large participant cohorts to provide a thymic health score, it did so in less than 14 hours, which is less than 2 seconds per scan! Share 2. How is thymus health linked to key clinical outcomes? The two cohorts were the National Lung Screening Trial, NLST (N=25,031) and the Framingham Heart Study, FHS (N=2,581) each with baseline demographics and long term follow up of >12 years for health outcomes. From the NSLT, you can see below that increased age and body-mass index were correlated to reduced thymic health. And, overall, men had reduced thymic health scores compared with women. There are a lot of graphs in the paper for outcomes, for both the NLST and FHS cohorts. To simplify the major outcomes, below is a composite Figure with striking reduction of all-cause mortality and for the different causes of death. The results were consistent between the 2 cohorts. For example, the cardiovascular mortality hazard ratio average was 0.57 in NLST and 0.38 in FHS (weighted to be 0.53 for the aggregate). The reduction of mortality also extended to digestive diseases and pulmonary disease (data not shown below). Lung cancer incidence was reduced by 36% for high vs low thymic health (Figure below, with a panel -incidence and b panel-mortality, adjusted for age, sex, BMI, smoking status). Notably, there was a smoker’s paradox: lower incidence and improved survival for lung cancer in smokers who had a high thymus health score. Smoking was associated with lower thymic scores whereas alcohol was not. Higher thymic health was linked to higher HDL cholesterol, lower triglycerides, lower fasting blood glucose, and lower systolic and diastolic blood pressure. Inflammation biomarkers, such as C-reactive protein and interleukin-6, were elevated in the people with lower thymic health scores. In their second paper, the same team looked at the relationship between thymic score and outcomes for 3,476 patients receiving cancer immunotherapy. The non-small cell lung cancer progression-free survival was reduced in patients with low thymic health score. A parallel relationship for survival was seen for other types of cancer including melanoma, breast, and kidney with a 44% lower risk among high thymic scores (Figure). A similar pattern was seen with different immune checkpoint inhibitors. The thymus health score outperformed programmed death ligand-1 (PD-L1)and tumor mutation burden (TMB) assay of the tumor and was an independent prognostic marker of progression-free survival. In this dataset, a direct connect with thymus score and adaptive immune function was noted with a correlation before cancer treatment for both T-cell diversity and thymus T-cell production (a metric known as T cell receptor excision circles). Thymus Removal Study There is a highly relevant citation about thymus function before moving onto ways to rejuvenate it. In 2023, a very important study of thymus removal during cardiothoracic surgery was published, with 1146 patients undergoing thymus removal vs 1146 matched controls (mean age 55 years). The adverse outcomes for thymus removal were striking, with a 2.9 higher risk of all-cause mortality and doubling of cancer incidence, 1.5 fold increase in cancer mortality, and 1.5-fold increase in autoimmune diseases. The immune function showed marked compromise after thymus removal, as reflected by CD4+ and CD8+ T cells (Figure below) Share Ground Truths 3. Are there ways we can promote a healthy (aka rejuvenate) thymus gland in our later years? In recent months we’ve learned a lot about the process of thymus involution and the pathways by which this may be modulated. Thymus involution is primarily due to loss to thymus epithelial cells (TECs) and there are 2 subtypes with different functions: the cortical, responsible for positive selection of T cells, and the medullary, for negative selection. When adipose tissue infiltrates the thymus, thymic adipocytes are pro-inflammatory, knocking out T-cell output. Likewise, systemic inflammation, or “inflammaging,” from smoking, obesity, and chronic stress promote thymic adipocytes. Now, from preclinical studies, we know about key pathways that account for these processes. Historically, back in 2014, FOXN1 was recognized as a single master transcription factor essential for TEC function, with studies in mice with forced FOXN1 upregulation leading to thymus regeneration. That laid the foundation for potential regrowth of quiescent thymus cells. It took awhile to find pathways to accomplish this goal and to even refute its role as the master regulator. The Liver-Thymus Axis Feng Zhang and his team recently showed that injection of an mRNA vaccine to the liver encoding DLL1, IL-7 and FLT3-L in combination, factors known to support thymopoiesis (Figure), successfully enhanced immune function in aged mice. However, the effect was transient. The FGF21 Story Two reports in 2025 addressed the thymus gland’s production of FGF21, a growth factor (fibroblast growth factor 21) and its control of thymus involution. This growth factor is also produced by the liver, but it doesn’t have impact on the thymus in aged rodent models. In contrast, The liver’s hepatocyte growth factor (HGF) has been shown to reverse senescent TEC structural changes. Growth hormone stimulates production of insulin growth factor-1 (IGF-1) in the liver and the thymus. Two small studies in human participants (TRIIM, for Thymus Regeneration, Immunorestoration, and Insulin Mitigation) of 6 and 50 people, respectively, treated with combined human growth hormone, metformin and DHEA, suggested the potential of slowing epigenetic aging and improving thymus mass and function. But the combination of drugs, small sample, and lack of controls make conclusions murky. Increased thymus FGF21 led to increased CD8 T cells in old mice and extended healthspan and improved physical performance. Building on the previous FOXN1 data, ablation of β-klotho, the obligatory co-receptor for FOXN1, accelerated thymic aging. The benefit to FGF21 was confirmed in a companion paper using an FGF21 knock-in mouse model showing thymus enlargement and increased TECs throughout the lifespan. (schematic Figure below). The accompanying editorial for these 2 papers speculated: “The proposed link between age-associated thymus involution and organismal aging is intriguing, and suggests we might seek to achieve systemic rejuvenation by counteracting thymic involution.” Other Factors Lessons from the Axolotl (Mexican Salamander) In an elegant set of experiments of the axolotl (Figure), known for its complete thymus regeneration after total surgical removal, mediators were identified. Surprisingly FOXN1 was dispensable. But midkine, a growth factor, appeared to be the driver, the initiator of thymus cell growth, survival, and repair. Other components that contributed were Postn+ (periostin-expressing mesenchymal niches) and Ccl19, a chemokine protein from the bloodstream. RANK and RANKL RANK (receptor activator of nuclear factor κB its ligand (RANKL) have been considered key regulators of medullary TECs. In a study of both aged mice and human thymus cell cultures, their key role was confirmed, with multiple benefits of resorting TEC function, recruitment of progenitor cells, and T cell development. Subscribe Summing Up This body of work strongly supports the health of the thymus gland as a critical regulator of human healthspan, not just a correlate or link. The new landmark studies are reinforced by the regenerative biology experimental models that have shown, via an array of mediators, that healthspan of aged mice is at least in part dependent on thymus gland function and its critical role for maintaining adaptive immunity. It sure seems that we’d be better off having an immune reservoir of naive T cells instead of a profile in older adults of exhausted, low quality, memory T cells, with a senescent phenotype. It is striking that we ignored the importance of the thymus gland for many decades. A wake-up call was the results of the thymectomy matched control study reviewed here, with the opposite of high thymic health score improved health outcomes. The convergence of AI and healthspan here is notable. The exceptional and laborious work for developing and validating (no less explaining) the AI to quantify thymus health set the foundation for probing the connect the major health outcomes in two cohorts with extensive follow-up. We’ve never had a way to meaningfully quantify the thymus gland before, so this represents important leverage of supervised, self-supervised, and transformer models. The study wouldn’t have been possible without AI. And it begs the question as to whether there are ways we can maintain our thymus at a high health score. But it’s not so simple to rejuvenate our thymus. There are multiple risks including the induction of autoimmunity, increasing the risk of cancer, and inducing a pro-inflammatory state. For example, factors that increase TEC proliferation could compromise the medulllary negative selection process and leak out auto-reactive (self-attacking) T cells. Thymic cells could be induced to proliferate, but we know, for example, that growth hormone and IGF-1 are associated with an increase risk of cancer. If thymus rejuvenation doesn’t clear out the accumulated senescent cells in older adults, then inflammation within the gland could block the production of TECs. Keeping these risks in mind, we now have identified many ways to keep our thymus healthy as we age that undoubtedly will be tested in clinical trials going forward. Ultimately, the benefit-to-risk tradeoffs will be defined. In the meantime, we have desperately needed an immunome. As I’ve stressed in multiple prior Ground Truths, we have no test in the clinic to assess a patient’s immune status! It was very encouraging for me to get an email from Hugo Aerts, the senior author of the landmark papers in the days after they were published: “I also wanted to say that your Substack on “Why We Need an Immunome” was inspiring for this work. We found it a very compelling perspective and greatly enjoyed reading it.” Just having an assessment of a person’s immune status via a chest CT scan, with millions of these performed per year, might help in guiding the right immunotherapy for cancer (e.g. more intensive, combinations for those with low thymic health scores) and help define people who are increased risk for age-related diseases of cancer, cardiovascular, and neurodegenerative. The main theme of Super Agers is that we now have many layers of data (genetics, proteins, biomarkers, organ clocks that can be integrated via multimodal AI) for us to define a person’s specific risk decades before one of these age-related diseases leads to symptoms, enabling prevention. From the new studies this week, we can add thymus health score as yet another way to understand a person’s risk, a window into their adaptive immune system and healthspan. And perhaps someday we will be able to safely rejuvenate the thymus, or maintain its health through one’s life, and use the thymus health score to monitor. NB: I wrote this post (No A.I.) A Quick Poll Loading... ********************************************************************* Thanks to Ground Truths subscribers (now > 200,000) from every US state and 212 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join! If you found this interesting PLEASE share it! Share Ground Truths Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered. Leave a comment Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026.

Mar 22 • 2:18 PM EDT • Health • erictopol.substack.com

Scientists just found a hidden 48-dimensional world in quantum light

A routine quantum optics technique just revealed an extraordinary secret: entangled light can carry incredibly complex topological structures. Researchers found these hidden patterns reach up to 48 dimensions, offering a vast new “alphabet” for encoding quantum information. Unlike previous assumptions, this topology can emerge from a single property of light—orbital angular momentum.

Mar 20 • 8:00 PM EDT • Science • sciencedaily.com

Linux Finally Catches Up to Windows with a Game-Changing Performance Feature

For years, the Linux kernel’s scheduler has been world‑class at balancing loads, yet it missed a crucial, cache‑aware instinct. In modern multi‑core systems, that gap can turn into measurable latency, especially when threads bounce between cores that don’t share the same cache. A new upstream feature, often called Cache Aware Scheduling, is now set to change that equation. A cache‑savvy scheduler arrives At the heart of any OS, the scheduler decides which thread runs where and for how long. In modern CPUs, small private caches (L1 and L2) sit beside each core, while a larger Last Level Cache (LLC, typically L3) is shared among groups of cores. When a task migrates across LLC boundaries, its warm data may vanish from the cache, forcing slower trips to main memory. Cache Aware Scheduling keeps related tasks close to their shared LLC, reducing destructive migrations. By respecting cache topology, the kernel minimizes cold‑start penalties and preserves locality that many workloads desperately need. The result is less thrashing, fewer memory stalls, and more consistent throughput. "Keep tasks close to their data, and the system will keep performance close to its peak." Why this narrows the Windows gap Windows has long leaned on topology‑aware, cache‑sensitive heuristics, especially since the Windows 10 era. That advantage helped Microsoft handle hybrid designs with P‑cores and E‑cores, plus complex cluster and NUMA layouts. With cache awareness integrated upstream, Linux brings parity to this vital dimension, without sacrificing its trademark flexibility. The Linux approach remains deeply configurable, reflecting the ecosystem’s breadth across servers, desktops, and embedded devices. It layers atop existing NUMA‑balancing and energy‑aware logic, refining placement rather than reinventing the wheel. Crucially, it aligns scheduling with the hardware’s real shape, not just with abstract CPU counts. Real‑world gains and who benefits Early tests on Intel Sapphire Rapids platforms point to gains in the 30–45% range for select workloads. Those wins appear in cache‑sensitive tasks like in‑memory analytics, high‑thread compilation, and microservices with tight working‑sets. Games and latency‑bound engines can also feel steadier frame‑times, especially when threads share hot assets. The benefits extend to AMD’s 3D V‑Cache parts, where keeping threads near enlarged cache slices prevents needless misses. Hybrid x86 designs with performance and efficiency cores further profit when cache and core roles are scheduled in concert. Even handhelds running SteamOS can squeeze more out of limited power, translating cache locality into smoother play. Key advantages include: Lower end‑to‑end latency Fewer expensive misses to RAM Better multi‑socket and NUMA behavior Improved energy efficiency More predictable QoS under mixed loads Stronger scaling on dense servers Caveats, tuning, and rollout No scheduler change is purely free, and trade‑offs still exist. Favoring locality can reduce cross‑cluster balance if limits are set too tight. Likewise, fairness and utilization must remain healthy, especially under heterogeneous, bursty workloads. Linux’s implementation is designed to be measured and tunable, not a blunt instrument. It cooperates with energy‑aware scheduling for mobile efficiency, and with NUMA‑balancers on big iron. Expect architecture‑specific refinements as vendors surface richer topology hints and cache‑sharing maps. Upstream integration has begun, with broad distribution adoption likely over the next cycles. Many users will encounter the change through standard kernel updates in 2025–2026, depending on distro cadence. Server‑class kernels may enable or tune it sooner for targeted fleets where cache locality is money in the bank. How to think about performance impact Cache Aware Scheduling amplifies gains when your workload is both CPU‑bound and cache‑sensitive. Think tight inner loops, hot code paths, and datasets that fit snugly in shared LLC. It’s less dramatic for I/O‑bound services or memory‑hungry tasks that blow past cache capacity. Still, even modest locality improvements often translate into smoother tail‑latency, which is where user experience and SLAs typically break. Developers can further help by pinning related threads, batching work, and aligning data to reduce cross‑cluster chatter. The scheduler’s new awareness works best when applications expose good hints. The bottom line By understanding and honoring cache topology, Linux removes a subtle yet costly bottleneck. The kernel’s smarter placement keeps hot data hot and work near where it belongs. That narrows a long‑standing gap with Windows, while preserving the openness and tunability Linux champions. For gamers, creators, and operators, the payoff is practical: more consistent frames, faster builds, and snappier services. For the ecosystem, it’s another step toward hardware‑savvy scheduling that turns transistor complexity into real‑world speed. And for Linux itself, it’s a timely upgrade that matches today’s silicon with tomorrow’s expectations.

Mar 14 • 8:00 AM EDT • Technology • iowaparkleader.com

(Half) Twisted Science: Researchers Build a Molecular Möbius Strip With Only Half the Twist

The Quantum Insider (TQI) is the leading online resource dedicated exclusively to Quantum Computing.

Mar 5 • 3:18 PM EST • Science • thequantuminsider.com

Sebastopol business Soft Medicine Sanctuary closes

Owners announced Saturday will be the business’ final day after the wellness collective said it had ousted its founding majority owner amid allegations of abuse and financial concerns.

Feb 28 • 1:17 PM EST • Business • pressdemocrat.com

Sebastopol business owner ousted after allegations of sexual assault, financial coercion surface

Jonathan Pinkston, an owner of Soft Medicine Sanctuary in Sebastopol, has been ousted from the business after allegations of assault and financial coercion.

Feb 26 • 3:47 PM EST • Business • pressdemocrat.com

Electrons stop acting like particles—and physics still works

Physicists have long relied on the idea that electrons behave like tiny particles zipping through materials, even though quantum physics says their exact position is fundamentally uncertain. Now, researchers at TU Wien have discovered something surprising: a material where this particle picture completely breaks down can still host exotic topological states—features once thought to depend on particle-like behavior.

Jan 15 • 7:00 AM EST • Science • sciencedaily.com

Topological photonics for single-photon sources

Light: Science & Applications - Topological photonics for single-photon sources

Dec 31, 2025 • 7:00 PM EST • Science • nature.com

Human brains have five ‘eras’ across lifespan, scientists say

According to Nature.com, scientists identified four major topological turning points across a lifespan: around 9 years old, 32, 66, and 83.

Nov 30, 2025 • 6:18 PM EST • Science • newsnationnow.com