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“AI polls” are fake polls

A few weeks after Donald Trump’s second presidential win, I took the train up from London (where I was living at the time) to Oxford to attend a conference on polls and forecasts of the 2024 election. Most of the attendees were pollsters or academics, but I also watched presentations from Aaru and Electric Twin, two companies that do what is interchangeably called synthetic sampling, silicon sampling, or synthetic audiences. Stripped of startup jargon, that means they use large language models (LLMs) to simulate responses to public opinion polls by having AI agents take on the role of survey respondents. I had already heard of Aaru thanks to some articles with eye-catching headlines like “No people, no problem: AI chatbots predict elections better than humans” in the months leading up to Election Day. The founders were making some big, some might even say far-fetched claims, such as: “within two years, we will simulate the entire globe — from the way crops are grown in Ukraine to how that impacts production of oil in Iraq, trade through the strait of Malacca, and elections for the mayor of Baltimore.” When Semafor asked Aaru’s cofounders — Cameron Fink and Ned Koh — about my boss, they said “we respect all those who came before us.” Nate (as he so often does) shared his thoughts on Twitter: Fink and Koh were relatively good-natured about this back-and-forth when we spoke at Oxford. They even offered to mail me one of the t-shirts featuring Nate’s quote they apparently had made. I never took them up on the offer, which I now somewhat regret. These synthetic sampling companies fell off my radar for a while, but they do still exist. In fact, Aaru recently received a $1 billion valuation. Is what they’re doing anywhere close to the most important frontier in AI development? Not by a longshot, especially when Anthropic just developed a model so adept at exploiting software vulnerabilities that it’s only being released to 40 companies. Still, silicon sampling is increasingly finding its way into public polling. Axios reported in March that “a majority of people trust their own doctors and nurses” based on findings from Aaru — without mentioning that the “people” in that sentence were actually LLMs. Around the same time, the Public Sentiment Institute “boosted” their online sample of 373 real survey respondents with 114 AI agents.1 (Spoiler alert: even the co-founder of Electric Twin doesn’t think that’s a particularly defensible approach.) Polling companies like Qualtrics and Ipsos are also developing synthetic data panels. So, what should we make of these … “polls”? Let’s get one thing out of the way: whatever they are, they’re not polls in the way that term is usually defined. Subscribe You can’t replace polls with AI On one hand, using LLMs to essentially make up fake survey respondents sort of sounds like the dumbest idea ever, one that will at best imperfectly replicate real polls while introducing all sorts of biases. On the other hand, with LLMs improving at a remarkable, perhaps even alarming rate, maybe that means I’m a dinosaur at the ripe old age of 24 because I still want to rely on polls that talk to actual people. I’m not going to argue that synthetic samples are completely useless. In fact, as I’ll return to later, there is evidence that some techniques can replicate topline survey results quickly and cheaply. But the marketing from certain companies can be slightly optimistic. “No traditional poll will exist by the time the next general election occurs,” said Fink in 2024. We’re just 206 days away from the midterms, and based on the fact that I still have to collect a bunch of polls every day, I’d say he should have run that prediction by a sample of AI agents before the interview.2 To see why synthetic samples can’t replace polls, here’s a quick primer on how they work. The simplest version of these models involves taking a LLM (like ChatGPT or Claude), giving it a demographic profile (e.g., a white, college-educated woman who lives in Utah and makes $70k a year), and then asking it to respond to a survey question. You repeat that process a few thousand times using different demographic profiles and end up with a sample of synthetic survey responses. The actual models used by private companies are more sophisticated than this, usually because they incorporate more hypothesized demographic characteristics for each agent and provide them with extra information. Aaru, for example, feeds agents a diet of news and information they’d be likely to consume, while Electric Twin incorporates their customers’ proprietary data about the audience they’re trying to replicate. The way Ben Warner, the co-founder of Electric Twin, explained it to me was “we have a large amount of data on […] for instance, 5,000 people. Can we make an accurate prediction of how they would respond to another question?” Still, it should be obvious why synthetic samples can’t replace polls. Polling is fundamentally a data collection process. We might use surveys to make predictions by feeding them into election forecasts, but the main purpose of a poll isn’t prediction, it’s gathering new data about what people think and how they feel. Silicon sampling, on the other hand, produces no new data. It’s simply a model: you input LLM training data, demographic prompts, and a bunch of other information, and it spits out a prediction for what a poll would say. We love models here, but models aren’t polls. That difference is an important philosophical sticking point for most pollsters I talk to. “I think politics should stay away from [synthetic sampling], because we’re trying to […] represent the voice of the people,” said Natalie Jackson, a vice president at GQR Insights. Democratic pollster John Hagner told me: “I think I’m just incredibly skeptical of this idea. I don’t think it’s research. At that point, you’re asking the machine to tell you what you already believe.” Hagner has seen some presentations of early synthetic sampling experiments, but so far, “if it’s being used in a campaign, people are keeping it incredibly quiet.”3 But Eli, I hear you saying, aren’t polls themselves increasingly governed by modeling decisions? Indeed they are: pollsters’ choices on which sampling method to use, how to define their likely voter models, and how to weight their samples can and do lead to dramatic differences in the results they publish. Aaru even referenced these limitations in the methodology statement included with that maternal mortality “poll” — although I’m using the term “methodology statement” loosely here, because it doesn’t really explain how the model works at all. We can ignore the (frankly preposterous) implication that synthetic sampling isn’t subject to a separate set of biases. The important point is that there’s still a meaningful difference between using weighting and other statistical techniques on actual polling data and using a model to predict what a poll would say. The latter is far closer to election forecasts or techniques like MRP — potentially useful models, but not a replacement for polls.4 To be fair, other synthetic sampling companies are perfectly happy with the distinction between polls and models. Warner compared polling and synthetic sampling to different tools in a toolbox. “The mistake I think we make is we think that these new tools should either work in exactly the same way or somehow replace these old tools,” he said. “Rather than thinking of it as, okay, so we’ve always had the hammer, we’ve always had the screwdriver, now we’ve got a saw. But don’t use a saw to try [to] do the job of a hammer.” A quick comment from Nate Eli didn’t ask me for a comment — rather rude of him, don’t you think? But since I’m editing this story, I figured I’d add a few quick thoughts rather than putting words in his mouth. Beyond the frequently misleading marketing, what bothers me about the AI “poll” hype is that as AI tools make statistical inference cheaper and/or better (note that these are not synonyms) that actually increases the comparative value of collecting original data. You might be able to train a model to make a reasonable estimate of what some hard-to-reach poll respondent would say — say, a young Black man who voted for Trump. (Such a person checks a number of boxes for a voter who is usually hard to reach in surveys.) Indeed, this is closely related to what models like the Silver Bulletin forecast already do. They essentially smooth out the kinks in noisy survey data by making inferences based on past voting patterns or national polls or surveys of other states. But you don’t actually know what these voters think unless you’re reaching them directly. If there’s a shift in opinion among this subgroup, you’re not going to detect it. So if I were running a campaign, I’d invest more in going the extra mile to find a representative sample of those voters. And then I’d hire some smart quants — or Claude? — to figure out the implications for campaign strategy based on proprietary data that my competitors didn’t have access to. -Nate Silver Are these models any good? If synthetic surveys are just a new type of model, the next obvious question is whether the models are at least accurate. The answer very much depends on who you ask. On one end of the spectrum, you have the maximalist argument that synthetic sampling is more accurate than actual polls. “It’s an incredibly challenging problem to go to someone and say ‘hey, we’re going to be more accurate at predicting human behavior than you, even when you talk to your customers directly’,” Koh recently told CNBC. In his view, synthetic sampling isn’t a saw to polling’s hammer, it’s “magic.” There’s certainly evidence that synthetic samples can replicate certain survey toplines. But if Aaru does have any examples of their approach outperforming the polls, they’re keeping those to themselves.5 Aaru’s 2024 election model, for example, had Kamala Harris leading in Michigan, Nevada, Pennsylvania, and Wisconsin on November 4th. And although they’ve since taken down their forecast page, they gave Harris a 50.5 percent chance of winning the race on November 2nd.6 After the election, Fink told Semafor he was happy enough with those results because they were “within margin of error,” a term that is completely meaningless when applied to a “sample” of AI agents. And of course, Aaru says their models have improved since 2024, so supposedly now they’d be more accurate than the polls? Still, their stronger argument is on cost: “We are significantly faster and cheaper than traditional polling, and still more accurate,” said Fink. The first two claims are undeniably true, but the third brings us to the opposite end of the spectrum. Both Jackson and Hagner are skeptical that these models are reliable for anything beyond replicating common survey toplines. “I just […] don’t think the machines are what we want when we’re looking for nuanced views. My example on this is people in Arizona and Nevada in 2024 who voted for Trump and voted for expanding abortion in their states on ballot initiatives,” said Jackson. Hagner identified another issue. Maybe the synthetic respondents, like sycophantic LLMs, are inhuman in one important way: they’re too nice. “The reports that have come through at the meetings that I’ve been at are that the early experiments on this, they cannot get respondents to be as racist or sexist or, frankly, as negative as human respondents,” he said. Academic research mostly agrees on this point. While there are some papers that show promising results when using LLMs to replicate polling data, most show that LLMs suffer from various quirks like producing too few “don’t know” responses and can seriously overpredict the favorability of politicians like Donald Trump and Kamala Harris. They also seem to struggle with too little variation between demographic subgroups, so the difference in predicted opinion between Democrats and Republicans, for example, is too small. When I asked Warner about these studies, his response to these papers was that just because academics can’t get synthetic sampling to work doesn’t mean that the technique doesn’t work in general. “Actually, the argument is, okay, yours does not [work]. That does not mean […] for this complex set of machinery, which uses a lot of investment, a lot of time, a lot of money, you can’t get it to work.” Cards on the table, I’m somewhat sympathetic to this argument because academics aren’t exactly great at making election forecasts. Usually, the people with skin in the game are the most accurate. Warner’s argument is that the approach Electric Twin takes — which includes, for example, making multiple predictions for each synthetic respondent using different models and prompts and subsequently averaging those to get a final prediction in a sort of ensemble forecast — produces better results than the simpler academic models. Warner shared a comparison between his method and the method from a recent academic paper with me, and Electric Twin was indeed able to get more accurate replication. But even still, he acknowledged that synthetic sampling “is not a crystal ball.” “If you asked me, do I think using other data sources will be more accurate than asking somebody who they will vote for, I would probably say no. But if you asked me ‘would your system be useful for our turnout modeling today?’ I would say yes.” For better or worse, it looks like the method is already getting more popular in the market research world. Most of the clients Aaru touts these days are businesses like EY and McDonald’s. And AI will probably begin to pop up in other parts of the political polling process. Pollsters are already using it to code open-ended survey responses, and some firms, like YouGov, are testing using LLMs to ask survey respondents questions. More worryingly, one danger to actual polls is that AI agents can be used to infiltrate online surveys. Most online polls use various checks to prevent that from happening, but there’s conflicting evidence on how effective those filters are and how prevalent AI agents currently are in online panels. If those agents ever become impossible to detect, it might spell the end of online polling, but the solution isn’t to replace all of your respondents with ChatGPT. Silver Bulletin is a reader-supported publication. To receive new posts and support our work, consider becoming a subscriber. Subscribe 1 That particular poll obviously doesn’t meet Silver Bulletin standards for aggregation. But we exclude all Public Sentiment Institute polls from our averages because we classify them as an amateur polling firm. 2 You could argue that Fink meant the next presidential election, but (a) I’m also confident we’ll still have real polls in 2028 and (b) in that case he should have asked an LLM to define “general election.” 3 Quick caveat: that’s reporting from a Democratic pollster. It’s possible that Republicans are more willing to use AI in political campaigns. 4 Indeed, Silver Bulletin does not include “polls” produced by MRP in our forecasts or averages, and we think it’s extremely misleading when their practitioners describe them in a way that suggests original data had been collected among a large number of states or Congressional districts. 5 A recent report from Aaru and EY did show two examples of a synthetic estimate being closer than a survey to a real-world benchmark — but I’d take those findings with a grain of salt because the report reads more like an ad and didn’t involve any sort of prediction being made ahead of time. 6 For comparison, our odds for Harris on the same day were 48.2 percent.

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Marathon has sold 1.2M copies across Steam, PS5, and Xbox

Alinea Analytics estimates show that Marathon has generated gross revenues of $55M via 1.2M copies sold on Steam, PS5, and Xbox: Looking at the split between Steam, PS5, and Xbox, Steam is clearly the main platform for Marathon, accounting for a little under 70% of the audience (800K copies sold). Meanwhile, PS5 takes about 19% (217K) and Xbox (including console, PC, and cloud) accounts for a bit over 11% or 133K. Marathon is technically a first-party Sony title, so seeing the home console struggle to break 20% of the volume is a notable data point for the ongoing platform-agnostic debate. PlayStation Studios online games will almost certainly continue being multiplatform (despite Sony reportedly pulling back on PC releases). Subscribe for free to get the most accurate games estimates in your inbox twice a week 🫶 Subscribe As for Marathon, the consensus among hardcore players who pushed through the awkward onboarding phase – myself included – is that it’s fantastic. The gunplay, aesthetic, and presentation are among the best in the shooter genre. A great game doesn’t always equal an immediate hit, though, as shown by our estimates. Things are looking lukewarm right now. But this might be one of those marathon-not-a-sprint situations. Had to, didn’t I? Why wasn’t Marathon a hit on the same level as Arc Raiders? One topic that came up in a lot of conversations at GDC this year was why Marathon hasn’t hit the same stratosphere as Arc Raiders. On paper, they’re both extraction shooters, and Marathon has the Bungie pedigree – the house that built the gold standard for gunplay in Halo and Destiny. Marathon’s neon-futuristic aesthetic also distinguishes itself from the gritty realism of Tarkov or the post-apocalyptic hope of ARC Raiders. But vibes can only get you so far for first impressions if the onboarding feels like a brick wall. Marathon is a sweaty PvP-focused experience with a first-time user experience and UI that I can only describe as dreadful. Players are dropped into a complex ecosystem where the UI, though visually striking, is functionally uninformative, forcing users to manually hover over nondescript, identical icons just to identify basic gear or weapon mods. This lack of clarity is compounded by punishing mechanics like a severe heat gauge for movement and a scarcity of vital resources, all without a clear tutorial or a low-stakes mode to learn the ropes. Most people – even top streamers and veteran shooter players – have no idea what’s going on in Marathon at first. Arc is on the complete other end of the spectrum. As we covered here and here, Arc Raiders offers a more collaborative, approachable loop where players often work together toward shared goals. And the objectives are instantly clear. To many players, this contrast only emphasised Marathon’s issues, especially during the testing period. Players understand the Arc Raiders loop within 30 minutes, while Marathon acts as a massive filter, chewing up newcomers and spitting them out before they can experience the depth of Bungie’s signature gunplay. What I’m getting at here is that the poor first-time user experience of Marathon’s Server Slam likely stifled launch sales, while the opposite was true for Arc. Let’s look at the pre-launch copies sold for each game during their respective Server Slams (launch-aligned) : Looking at the trajectory: Arc Raiders saw a massive 80% jump in copies sold during its three-day Server Slam (day -13 to -11). Players jumped in, realised the water was fine, and immediately opened their wallets. Marathon, meanwhile, saw a 49% increase in the four days following its Slam (Day -7 to -3). At the time of each game’s respective launch, Arc Raiders had nearly double the Steam footprint of Marathon – and word of mouth only continued to grow. Bungie could have had more time to fix the onboarding process had the beta happened earlier. But Marathon launched three days after the beta finished. These factors limited the launch sales quite a bit, I reckon. Marathon has found a niche audience, though Despite the friction-heavy start, the data suggests that those who survived Marathon’s onboarding are loving life. We’ve been tracking cross-platform DAUs, and while there’s the expected post-launch leakage, many players are sticking with it. After peaking at 478K total DAUs on its first Saturday, Marathon has settled into a respectable rhythm, holding 345K DAUs as of yesterday and averaging 380K DAUs across the weekend. Steam continues to do the heavy lifting here, consistently accounting for the lion’s share of the daily players. Players have been putting in the hours, too: On Steam, Marathon’s average playtime has climbed to 27.8 hours, significantly outpacing the console averages on PS5 (16.5h) and Xbox (17.3h). Even more telling than the averages: 22% of the Steam audience has surged past the 50-hour mark, and nearly 7% have already logged over 100 hours. Subscribe for free to get the most accurate games estimates in your inbox twice a week 🫶 Subscribe This data suggests that once the Bungie magic clicks, it hooks players deeper than the average extraction shooter. There’s also started to be a shift in the game’s discourse. Marathon launched as one of those games that’s cool to hate. But as Marathon’s 100-hour club grows, we’re seeing conversations around its mechanical merit outweigh the negativity. Several high-profile creators, who were initially vocal critics, have spent the last week coming around on the mechanical depth of the endgame. It’s a subtle but positive signal; the hate train is losing steam, and a new narrative about the game is emerging. Bungie faithfuls unite Another interesting metric in Marathon’s first few weeks is who, exactly, is playing. Bungie leans heavily on its prestige as the “makers of Halo and Destiny,” in its marketing, and that message has clearly hit the mark. On Steam, the gravity (hammer) of Bungie’s previous work is unavoidable. A staggering 78.2% of Marathon players also played Destiny 2. The trend carries across other platforms, with 74.2% of PS5 players and 82.7% of Xbox players also having played Destiny 2. The Halo legacy lives on, it seems. More on that in a bit. While Destiny 2 went free to play, these numbers still represent a high-intent migration of a fanbase that trusts Bungie’s specific brand of kinetic gunplay and cryptic world-building. The Xbox data adds another layer of legacy. About 85.7% of Marathon players on Xbox have played Halo Infinite, while over half of the Steam audience has spent time in Halo Infinite and 36.1% in the Master Chief Collection (a paid collection of the old Bungie-made legacy games). Interestingly, we see a 55.9% overlap with ARC Raiders on Steam. Overlap is even higher there on PlayStation (60.5%) and Xbox (66.5%). And there’s also significant crossover with Helldivers 2 on all platforms, too. Subscribe for free to get the most accurate games estimates in your inbox twice a week 🫶 Subscribe Bungie has found some of its fans with Marathon, and the challenge now is keeping this engaged in a high-stakes PvP environment when they’ve spent the last decade primarily enjoying the power fantasies of PvE. On that note… Go the full 26 miles? Or cut and run? Time for some could’ve, should’ve, would’ve. These things would have improved Marathon’s performance at launch: A more robust onboarding process, perhaps in the form of a short single-player/PvE campaign. We know Bungie fans love this stuff. A traditional arena-based mode akin to Destiny’s Crucible could have been a bridge for the cautious players who’d have been otherwise deterred by the Server Slam. It’s also a great palate cleanser after getting merked. Introducing a dedicated PvE environment would have similarly diversified the conversation and lowered the barrier for the Bungie faithful who found the pure PvP extraction loop too abrasive. PvE is safer than PvP these days. There’s an argument that a thin PvE mode would have just felt like a budget Destiny, potentially hurting the brand more. But given how dire the FTUE is, I think it would have been a net positive. Any kind of tutorialised loop that demystifies the stakes, really. While there is merit in a studio sticking firmly to a singular creative vision, and going all in on the hardcore extraction loop. Less forgiving is the technical reality is that the user interface and first-time user experience (FTUE) were not at a commercial standard for launch. Subscribe for free to get the most accurate games estimates in your inbox twice a week 🫶 Subscribe In a landscape where player time is oversaturated and the most contested currency, a flawed FTUE is a critical failure point. But it’s not all doom and gloom, as Marathon has an incredible, unique gameplay loop, suggesting that financial success is still attainable if Bungie can pivot effectively. Bungie and PlayStation now face a difficult strategic crossroads, though – one within a challenging games market. They could: Double down on Marathon with a long-term Rainbow Six Siege- or No Man’s Sky-style recovery plan, which is something I heard Last Stand Media’s Chris Maldonado mention last week. While this could be a sunk-cost fallacy in action, it could eventually yield the audience the game’s mechanical depth deserves. Shift focus toward the inevitable Destiny 3 or another project, mitigating the escalating opportunity cost and cutting their losses, so to speak. Doing both is an expensive proposition, given the high overhead and burn rate of operating out of Bellevue, Washington. With Sony recently demonstrating a lower threshold for underperforming studios and projects, the margin for error has vanished. Whatever happens, the next six months will determine whether Marathon becomes a cornerstone of Sony’s live-service portfolio or a cautionary tale of vision exceeding accessibility. I’m hoping it’s the former, because Marathon rocks. As always, hit subscribe to get updates on Marathon and other relevant games. Subscribe Want to get your hands on our data for yourself – for free? We’re offering a free trial of our platform for games companies. Send us a message here, or reply to this email, and we’ll set you up. The last word Reply to this email – or reach out here – if you have any feedback for the newsletter – or want to request a game for us to cover. [Alinea Analytics boasts the most accurate PC and console estimates in the business. Game makers use our platform to understand their audience, keep an eye on the competition, monitor sales trends, and spot new opportunities. We equip game studios and financial institutions with accurate data and the confidence to make smarter, data-driven decisions. Want to talk about all things games market data? We’d love to chat!]

Mar 24 • 2:06 PM EDT • Technology • alineaanalytics.substack.com

Football's greatest showboaters ranked: Ronaldinho, Neymar, Balotelli, Kerlon

We all love to watch the players with the flicks and tricks, the mavericks with the magic manoeuvres. Here, BBC Sport ranks football's top showboaters.

Mar 24 • 4:05 AM EDT • Sports • bbc.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

Luka Doncic Explains Controversial Exchange with Goga Bitadze Before Suspension

Luka Doncic did not let up on Saturday night, leading the Los Angeles Lakers to a 105-104 win over the Orlando Magic. Doncic has been on an absolute heater of late, and he kept his foot on the gas against the Magic. The Lakers improved to 46-25 and remain third in the Western Conference.

Mar 21 • 11:33 PM EDT • Sports • sports.yahoo.com

LeBron James breaks record for most NBA games played

LeBron James broke the NBA record for most regular-season games played on Saturday, taking the court for his 1,612th when the Los Angeles Lakers tipped off against the Orlando Magic.James, playing his unprecedented 23rd season, already holds a host of NBA records, including points scored, field goals made and field goals attempted and the longest streak of regular-season games with at least 10 points scored -- 1,297 -- in history.

Mar 21 • 7:22 PM EDT • Sports • sports.yahoo.com

Lakers release injury report for Saturday's game versus Magic

One of the Lakers' three stars could miss Saturday's game against the Magic.

Mar 20 • 10:24 PM EDT • Sports • sports.yahoo.com

Thunder first NBA side to clinch play-off place

Shai Gilgeous-Alexander enjoys 40-point night as the Oklahoma City Thunder beat the Orlando Magic and become the first NBA team to secure a play-off berth.

Mar 18 • 3:03 AM EDT • Sports • sports.yahoo.com

Gilgeous-Alexander scores 40 as Thunder clinch playoff berth

Shai Gilgeous-Alexander delivered a 40-point scoring performance as the Oklahoma City Thunder became the first team to punch their ticket to the NBA playoffs with a 113-108 defeat of the Orlando Magic on Tuesday.Reigning NBA Most Valuable Player Gilgeous-Alexander saluted the Thunder's resilience after a mixed first-half performance.

Mar 18 • 12:31 AM EDT • Sports • sports.yahoo.com

Thunder's Alex Caruso receives technical foul for using shoe to block shot in win over Magic

Mar 17 • 9:54 PM EDT • Sports • sports.yahoo.com

Hawks fans sport Magic City gear despite canceled promotion

Hawks fans showed up in Magic City gear Monday night even though the NBA shut down the team's short-lived promotion with the well-known adult entertainment club.

Mar 17 • 9:09 AM EDT • Sports • espn.com

Magic mushroom-infused products appear in Colorado gas stations – what public health officials want consumers to know

Hallucinogenic chocolate bars were removed from six Denver-area gas stations.

Mar 17 • 8:26 AM EDT • Health • theconversation.com

Bills news: How DJ Moore fits with Buffalo

DJ Moore expects that teaming up with Josh Allen will lead to some magical moments, especially when plays break down.

Mar 13 • 10:59 AM EDT • Sports • sports.yahoo.com

World’s thinnest foldable phone is looking to challenge Samsung with a very striking price tag

The foldable phone race is heating up with Honor's latest Magic V6 contender, and it looks like a challenge to Samsung as the world's thinnest foldable phone

Mar 13 • 8:08 AM EDT • Technology • supercarblondie.com

Where did magic mushrooms come from? Scientists just got closer to an answer

Scientists just discovered a new species of magic mushroom, Psilocybe ochraceocentrata, that appears to have shared a common ancestor with the popular Psilocybe cubensis some 1.5 million years ago.

Mar 11 • 5:00 AM EDT • Science • scientificamerican.com

NBA cancels Hawks' plans to celebrate Magic City adult entertainment club

Atlanta announced the plan last month, saying the team would pay tribute to an “iconic cultural institution.”

Mar 9 • 6:36 PM EDT • Entertainment • nbcmiami.com

NBA cancels Atlanta Hawks' Magic City event, citing 'significant concerns' about strip club promotion

Spurs center Luke Kornet was among those who spoke out against the scheduled event

Mar 9 • 5:53 PM EDT • Sports • cbssports.com

NBA cancels Atlanta Hawks’ plans to celebrate famed Magic City adult entertainment club

The NBA has called off the Atlanta Hawks' plans for a night celebrating the city's famed Magic City adult entertainment club, saying it did so because of “concerns” from many across the league.

Mar 9 • 5:49 PM EDT • Entertainment • wtop.com

NBA cancels Atlanta Hawks' plans to celebrate famed Magic City adult entertainment club

The NBA has called off the Atlanta Hawks’ plans for a night of celebrating the city’s famed Magic City adult entertainment club, saying it was responding to “concerns” from many […]

Mar 9 • 5:48 PM EDT • Entertainment • wabe.org

NBA cancels Atlanta Hawks’ promotion with Magic City adult entertainment club after backlash

The NBA has canceled a popular Atlanta Hawks promotion with Magic City after receiving some backlash.

Mar 9 • 5:34 PM EDT • Entertainment • walb.com

NBA cancels Atlanta Hawks’ promotion with Magic City adult entertainment club

The NBA has canceled a popular Atlanta Hawks promotion with Magic City after receiving some backlash.

Mar 9 • 5:34 PM EDT • Entertainment • atlantanewsfirst.com

Legendary magician ends Vegas residency after over two decades

The legendary illusionist announced his final show at MGM will be on April 30, 2026.

Mar 6 • 12:47 PM EST • Entertainment • pennlive.com

Cooper Flagg reaches 1,000 career points in return to Mavericks' lineup vs. Magic

Mar 5 • 7:30 PM EST • Sports • sports.yahoo.com

There is no magic formula for business success, Texas A&M researcher finds

Mays Business School professor highlights flexibility and learning from mistakes as essential for professional growth.

Mar 5 • 10:37 AM EST • Business • stories.tamu.edu

Ducks comeback magic runs out to sturdy, league-leading Avalanche

Anaheim allowed the first goal of the game for the fourth straight game out of the Olympic break, but Colorado showed its mettle as the NHLs' top team to bolster and button down that early lead en route to a 5-1 victory.

Mar 4 • 2:17 AM EST • Sports • sports.yahoo.com

The Science-Backed Method to Hit Perfect Pickleball Drops Every Time

The third shot drop isn't magic; it's mechanics. Get the science right, and suddenly that impossible shot becomes far more manageable.

Mar 3 • 1:16 PM EST • Science • thedinkpickleball.com

NBA player Luke Kornet calls on Hawks to cancel promotion with Magic City adult entertainment club

By The Associated Press (AP) — Luke Kornet called on the Atlanta Hawks to cancel their upcoming collaboration with Magic City, saying he and other NBA players were surprised by the team'

Mar 2 • 8:22 PM EST • Entertainment • wtop.com

Experience pop folk magic with Dar Williams at the Englert

Singer-songwriter Dar Williams’ forthcoming studio album, “Hummingbird Highway,” illustrates a period of rebirth and renewal in 2025. Despite a challenging battle with breast cancer and political unrest, Williams demonstrates resilience and gratitude.

Mar 2 • 3:00 PM EST • Entertainment • thegazette.com

Return to New York

Learn how Magic brought turtle power to the Big Apple with Magic: The Gathering® | Teenage Mutant Ninja Turtles.

Mar 2 • 11:00 AM EST • Technology • magic.wizards.com

Lenovo Unveils an Attachable AI Agent 'Companion' for Their Laptops

As the Mobile World Conference begins in Spain, Lenovo brought a new attachable accessory for their laptops — an AI agent. CNET reports: The little circular module perches on the top of your Lenovo laptop display, attached via the magnetic Magic Bay on the rear. The module is home to an adora...

Mar 1 • 7:00 PM EST • Technology • mobile.slashdot.org

Honor MagicBook Pro 14 2026 Laptop Review - OLED all-rounder impresses with Panther Lake

Notebookcheck review of the Honor MagicBook Pro 14 2026 with Intel Core Ultra 5 338H & Arc B370 and 120 Hz OLED touchscreen.

Mar 1 • 8:03 AM EST • Technology • notebookcheck.net

The iPad Pro Has Its First Worthy Android Replacement

Honor’s brand-new MagicPad 4 may turn out to be the best alternative to Apple’s M5 iPad Pro: Here’s what this Android flagship tablet can offer.

Mar 1 • 8:01 AM EST • Technology • bgr.com

4 Costco Tablet Accessories That Will Level Up Your iPad

Top Costco iPad accessory picks include the Apple Pencil Pro, Magic Keyboard, a 20,000 mAh power bank, and the latest AirTags for tracking.

Feb 28 • 2:17 PM EST • Technology • bgr.com

Everything announced at MWC 2026: The new Leica Leitzphone by Xiaomi, Honor's ultra-thin MagicPad 4 and more

MWC 2026 is here, with the announcements already flowing before its official start on March 2.

Feb 28 • 12:24 PM EST • Technology • engadget.com

Streaking Reed Sheppard leads Rockets into matchup with Heat

The Houston Rockets were on the verge of completing a stunning rally from a 19-point deficit against the Orlando Magic on Thursday but needed one final push to get over the hump.

Feb 27 • 5:01 PM EST • Sports • cbssports.com

Mutants and Mutagen in Magic: The Gathering® | Teenage Mutant Ninja Turtles

Learn the secrets of the ooze (and Mutagen tokens) with these behind-the-scenes stories from Magic: The Gathering | Teenage Mutant Ninja Turtles.

Feb 27 • 11:00 AM EST • Technology • magic.wizards.com

Two More Studio Display 2 Upgrades Leaked in New Report

Macworld's Filipe Espósito today again reported that Apple appears to be developing two new Studio Display models with different specs. Based on lines of code in "internal Apple files," which likely refers to a macOS Tahoe Kernel Debug Kit that leaked online last year, Espósito continues to believe that both of the new Studio Display models will feature ProMotion, enabling up to a 120Hz refresh rate, as well as HDR support for increased brightness and dynamic range.

Feb 27 • 10:19 AM EST • Technology • macrumors.com

Honor exec showcases Magic V6’s crease-less display

Honor seems to have cracked the "crease code". The teasers for the upcoming Honor Magic V6 keep on coming and the latest one gives us our best look at the...

Feb 27 • 7:21 AM EST • Technology • gsmarena.com

Magic: The Gathering’s TMNT Unique Pizza Bundle Is Finally Back In Stock Online - Here’s What It Includes

The Magic x TMNT Pizza Bundle is finally back in stock, but is it worth the investment? We dig in.

Feb 27 • 5:46 AM EST • Technology • ign.com

Hawks to collaborate with Atlanta institution for 'Magic City Monday' on March 16

The Hawks will partner with Magic City for "Magic City Monday" on March 16 when the Hawks host the Orlando Magic to celebrate the club's influence on local culture.

Feb 26 • 2:51 PM EST • Entertainment • ajc.com

The Ultimate Guide to Teenage Mutant Ninja Turtles Sealed

The Teenage Mutant Ninja Turtles are coming to a Magic store near you, and they bring a whole new Limited environment with them. This Day 0 guide will give you everything you need for lean, green success at your local Prerelease.

Feb 26 • 12:00 PM EST • Technology • draftsim.com

Rockets vs. Magic prediction, odds, pick

Houston looks to sweep the two-game season series. Check our NBA odds series for the Rockets-Magic prediction and pick.

Feb 26 • 1:07 AM EST • Sports • sports.yahoo.com

Galaxy S26 ‘Now Nudge’ is basically Google Pixel’s Magic Cue, but you’re forced to use Samsung Keyboard

Samsung is completely changing directions this year, and among moves like adding Perplexity as an AI assistant instead of relying...

Feb 25 • 1:08 PM EST • Technology • 9to5google.com

Honor says its 4.8mm thick MagicPad 4 is the world's slimmest Android tablet

Ahead of a full release at Mobile World Conference (MWC), Honor has teased the MagicPad 4 that it calls the world's thinnest Android tablet.

Feb 25 • 6:43 AM EST • Technology • engadget.com

Honor’s new MagicPad 4 is the world’s thinnest Android tablet

At just 4.8mm thick, the MagicPad 4 is also thinner than Apple’s slimmest iPad.

Feb 25 • 5:34 AM EST • Technology • theverge.com

Business Development is Not Magic! How Successful Lawyers Build Thriving Practices

Sustainable practice growth requires intentional strategy, authentic engagement, disciplined follow-up, and a long-term relationship mindset.

Feb 24 • 12:15 PM EST • Business • ipwatchdog.com

Fall Entertainment Guide for the Niagara University Purple Eagles: Live Performances, Broadway Magic, and Historic Venues

Fall Entertainment Guide for the Niagara University Purple Eagles: Live Performances, Broadway Magic, and Historic Venues

Feb 24 • 10:16 AM EST • Entertainment • purpleeagles.com

Lakers reveal injury report for Tuesday's game versus Magic

Will the Lakers be at full strength when they host the Magic on Tuesday?

Feb 23 • 11:04 PM EST • Sports • sports.yahoo.com

Honor Magic V6’s mind-boggling battery is all but confirmed, and Samsung should be worried

The thin chassis and a giant battery of Honor’s upcoming foldable could make the Galaxy Z Fold 8 feel outdated.

Feb 23 • 3:51 PM EST • Technology • phonearena.com

2026 Business Leaders of the Year

Central Massachusetts is full of amazing professionals, each with their own unique skills, talents, and dedication to their companies, industries, and communities. You could make a strong case for hundreds of them to be considered as WBJ’s Business Leader of the Year. Yet, to actually win the award, you need to have that little something extra: a magic spark, an insight no one else sees, years of knowledge that pay off with the right decision at the right time, a leadership style inspiring people to follow, a push for a paradigm shift at a stagnant organization. Business Leader of the Year is WBJ’s oldest award, launched in 1982 when Herb Dunnington of First Safety Fund Bank won the sole award. In the decades since, BLOY has expanded to honor winners from different corners of the economy: small businesses, large businesses, nonprofits, innovation, families. Each of the six winners this year has that something special setting them apart as true leaders in our Central Massachusetts business community: Neelu Mohaghegh’s creativity, Nick Haritos’ compassion, Nicolette Sacco’s adaptability, Julie Bowditch’s energy, Sean Rose’s steadiness, the Vaccaro family’s culture. You can read more about each of them through the links below.

Feb 23 • 1:57 PM EST • Business • wbjournal.com

Heroes of Science and Fiction resurrects Heroes of Might and Magic-style strategy battles

Factions wage war over a distant galaxy until only one remains in this modern take on Heroes of Might and Magic's classic mechanics.

Feb 23 • 7:00 AM EST • Science • store.epicgames.com

Lakers unveil Pat Riley statue next to Magic Johnson and Kareem Abdul-Jabbar

Feb 22 • 8:35 PM EST • Sports • sports.yahoo.com