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Skokie trustees raise entertainment tax, apply it to Netflix and other streaming services
It’s about to become slightly more expensive to stream television and music in Skokie. The Skokie Board of Trustees voted unanimously on Monday to raise the village’s Amusement Tax and expand its scope to apply to any “video streaming, audio streaming, or remotely accessed online games” that residents use on a rental or subscription basis, […]
Meta is trying to sell AI agents to businesses in latest effort to diversify away from ads
The Meta Business Agent will be included in the company's Meta One paid subscription offerings.
Apple Music could soon get different subscription tiers
As spotted by Aaron Perris, Apple seems to be working on different subscription tiers to Apple Music, based on strings found in the platform’s Android app. Here are the details.
I stopped paying for a PDF editor — these Google Drive hidden features are all I need
I canceled my PDF subscription after discovering these hidden Drive features
Meta Eyes AI Subscriptions While AI Rivals Target Meta’s Ad Business
The social giant wants to make money from its chatbot, but its core business may be at risk.
Meta stock price jumps 3% on plan to sell AI subscriptions
Shares of Meta gained nearly 4% on Wednesday as investors cheered the company's move to start generating recurring revenue from its platforms.
Meta launches Instagram, Facebook, and WhatsApp subscriptions, with more to come, including AI plans
Meta is rolling out paid subscription plans for Instagram, Facebook, and WhatsApp worldwide, while also testing new AI, creator, and business-focused offerings under its broader “Meta One” subscription brand.
Oura Ring 5 leak suggests week-long battery life, the same old subscription story [Gallery]
The Oura Ring 5 picture is becoming clearer as new leaks appear, with details about the health-tracking ring. Thanks to...
Ebola, chemical plants and health, hantavirus, common colds, heat and more
As they say, bugs have ears. Public health has had a relentless May. Chemical plant (near) explosions, Ebola, hantavirus, and that's before you even get to the usual suspects: common colds, heat, and ticks. Here’s an attempt to keep you up to speed and, more importantly, what it means for you and your community. But first, an announcement: World Cup The World Cup starts in 15 days (not like anyone is counting down), and we are hanging TVs in the Health Security Operations Center. It’s going to be a gorgeous, chaotic celebration of basically every culture on earth. And it’s going to take a team effort—from communities to individuals, from public health to health care—to keep people healthy. That’s where you come in. If you’re going to the games or live within 30 miles of a stadium, we would love to hear from you. Sign up for a weekly survey here. Thanks to the more than 1,280 people who have already signed up…you will be hearing from us soon!! Global disease “weather report” Hantavirus: Two more cases The global count of cruise ship passengers with hantavirus has now increased to 13 cases (11 confirmed), with three deaths. The two new cases are overseas and among people who were already quarantining: A crew member in the Netherlands. A Spanish national passenger who was quarantining at home tested positive through daily monitoring. They are now in a biocontainment unit. In the U.S., everyone remains negative. There may be more cases, given that the incubation period of hantavirus (the time from exposure to infection) is 45 days. But this week, we will reach a major milestone: the median incubation window is 18 days, and that will pass on May 29. What this means for you: Your risk from this cruise ship outbreak remains essentially nil at this point. Ebola rages on in Central Africa Big thanks to Dr. Craig Spencer, a humanitarian physician who has treated and survived Ebola, for jumping in to provide the YLE community with an update. Craig, take it from here… The combined confirmed and suspected Ebola cases in DRC are now more than 1,000. All signs are pointing to a very long and catastrophic outbreak in Central Africa: This is a vast undercount. We know this because the test positivity rate is hovering around 50%, only 20% of contacts are being traced (and in some areas, no contacts at all), and more cases keep popping up with no known connection. This all points to widespread and undetected community transmission. This is in only a week of detection. Compared to previous outbreaks, the growth is very fast, as the huge West Africa outbreak in 2016 was first detected at 49 cases and rose to 208 cases a month later. It took four months for that outbreak to reach the size of the current one in the DR Congo. The cases are spread out across 16 health zones. There are now multiple epicenters, making containment very difficult. Next door in Uganda, the case count is seven. While this number is low compared to DRC, a concerning development is that two health care workers recently tested positive with uncertain exposure histories. If they weren’t treating known Ebola cases, this means it’s spreading undetected in Uganda as well. On the ground, backlash, including the burning of health centers, has emerged, a pattern seen in nearly every outbreak and rooted in deep community distrust. It often stems from outside actors working in communities without fully understanding or addressing local priorities. Affected populations may recognize the severity of Ebola while still holding other concerns as more pressing, such as where their loved ones are buried. Community trust is essential to an effective response, but difficult to build during an active emergency. It is best established long before a crisis begins. U.S. priorities are made clear, and may backfire. The U.S. Administration has shown that its first priority is keeping Ebola out, with helping end the outbreak in the DRC a secondary concern. That's meant travel restrictions broader than anything we've imposed before — covering travelers from across the region, and reportedly some green card holders and permanent residents as well. For example, just these past two days, news broke that high-risk American travelers will be subject to a mandatory quarantine in Kenya before they are allowed to return. If an American is infected, the U.S. government plans to send them to a hospital it is standing up from scratch in Kenya. (Currently, Americans who were in the area are allowed to return but are diverted to three airports—Houston, Atlanta, and DC—for further screening.) Past administrations have used travel notices and stepped-up screening; this goes much further. At first blush, these strict precautions may sound prudent. But this approach could backfire in three ways: Restrictions this blunt give people every reason to hide where they’ve been and whom they’ve been near — making the people we most need to find harder to track, not easier. They also breed a false sense that this is someone else’s problem. But diseases are humbling. They find the small cracks in even the most impenetrable-seeming defenses. Lives lost. There is no treatment for this Ebola strain, which means survival depends heavily on the quality of the health system. We have that system in the States, but we are choosing not to use it for infected Americans. This is unbelievable and infuriating. (See a deeper dive from me here.) The only real way to lower the risk to Americans — and everyone else — is to end the outbreak in the DRC and across the region. What this means for you: If you have travel plans to this region, it’s time to cancel them. This is a high-risk situation in Central Africa, and CDC released a Level 4 Travel Advisory. There is also great uncertainty if and when the Administration will let you back in. To the general public in the U.S., your risk remains very, very low right now. U.S. disease “weather report” Ticks: past peak season? Good news, especially for people in the Northeast and Midwest: tick numbers continue to decline. Though we are at the peak of the season, this unusually early year is trending favorably. Heat-related illnesses in the North Heat risk is certainly not blanketing the entire country yet, but this week it will be moderate in the Midwest and the Southeast. What this means for you: Be sure to check the CDC HeatRisk tool. A red day isn’t the best day for that soccer game for a kid with asthma, and a stretch of orange days is a great time to check on your elderly neighbor. Common colds surging As far as respiratory viruses go, the only thing really going around right now is the common cold. It is higher this year than last year, but should peak very soon before returning this fall. Spotlight: Chemical plants Over the weekend, YLE California covered the serious situation that unfolded around a chemical plant in Orange County, California. Thankfully, the worst-case scenario (a chemical explosion) was mitigated, but only through luck. The health implications in a densely populated area could have been catastrophic. As the situation was winding down, another chemical explosion struck Washington State. This one was fatal. Health officials say the risk to surrounding residents from chemicals in the air and ground remains low, though the community deserves far greater clarity. Clean air and clean water consistently rank as Americans’ top public health concerns — yet when chemical disasters strike, communities are too often met with reassurances rather than transparency and accountability. Residents near the 2023 East Palestine, Ohio train derailment, for example, are still waiting to understand the long-term impact on their health, with few clear answers. What this means for you: Many are wondering if facilities processing potentially dangerous materials are in their neighborhoods. This interactive map allows you to enter your ZIP code and see all facilities monitored by the EPA, including any violations. Good news Ebola vaccines and treatment for the Bundibugyo species are in development. Two vaccine platforms are being explored, at least one of which may be deployable in as little as 2 months. One vaccine is being developed by Oxford, and the other uses the same biotechnology as the FDA-approved Zaire species of Ebola. (It may provide cross-protection, but it’s unclear at this point.) On the treatment side, two promising monoclonal antibody cocktails are likely to be deployed, though doses are limited and logistical hurdles remain significant challenges. Anni over at The Biotech Tea had a great explainer about the Ebola vaccine gap, if you want to read more. [ The Biotech Tea The Ebola vaccine gap, reading vessel damage, & the Makary exit 🗝️ Paid subscribers get the Biotech Term of the Week at $30/year (~$2.50/month). I try to keep it intentionally accessible, but if cost is ever a barrier, send me a message. A few people asked about expensing your subscription, so I put together a short email template… Read more 6 days ago · 10 likes · Annicka Evans, PhD ](https://www.thebiotechtea.com/p/the-ebola-vaccine-gap-reading-vessel?utm_source=substack&utm_campaign=post_embed&utm_medium=web) Polycystic ovary syndrome (PCOS) has been officially renamed polyendocrine metabolic ovarian syndrome (PMOS), following more than a decade of debate and input from roughly 22,000 clinicians, researchers, and patients worldwide. This is good because the old name was medically misleading, leading to patients without visible cysts being dismissed or overlooked entirely. The WHO estimates that 70% of people with the condition remain undiagnosed. A more accurate name should improve recognition, reduce stigma, and ultimately help the millions of people living with this condition get diagnosed and treated sooner. Poll Loading... Bottom line Public health situations are everywhere right now. Staying healthy takes public health professionals and systems working tirelessly behind the scenes and each of us showing up for our neighbors and communities. Love, YLE Big thanks to Ed Nirenberg for staying on top of the Ebola vaccines, Hannah Totte for all the figures, Dr. Craig Spencer for the Ebola insight, and Dr. Matt Willis for covering the chemical situation in CA. Your Local Epidemiologist (YLE) comprises a team of experts, ranging from physicians to immunologists to epidemiologists to nutritionists, working together with one goal: to “Translate” ever-evolving public health science so that people are well-equipped to make evidence-based decisions. YLE suite of newsletters reaches over 475,000 people across more than 132 countries. This newsletter is free to everyone, thanks to the generous support of fellow YLE community members. To support the effort, subscribe or upgrade below: Subscribe
Google Health Premium joins AI Pro as weekly email redesigned
Besides the new mobile app fully rolling out today, Google Health is joining the Google AI Pro subscription.
This Fitbit Air rival skips a monthly subscription, and it finally has a launch date
A smart ring company is preparing to launch its Fitbit Air rival, and it will be ditching the subscription model.
Semiconductor decoupling. Powell's politics. Industrializing Ogaden. Free trade and the Magna Carta.
Thank you for opening your Chartbook email. Feliks Topolski, 1907-1989 8th Army’s Front, Italy 1944 Semiconductor decoupling Source: FT One thing that Jerome Powell deeply understood is that chairing the Fed under current conditions is a deeply political job. “Powell has successes and mistakes to his name. But he stands out as having thought more carefully about the Fed’s democratic legitimacy than any chair since Paul Volcker,” said Paul Tucker, a former deputy governor at the Bank of England, referring to the Fed chair who successfully fought the great inflation of the 1970s and early 1980s. … While Powell was at the Treasury in the early 1990s, he watched Alan Greenspan build relationships within the government. That convinced Powell he needed to follow the former Fed chair’s lead and spend more time in Congress than his predecessors Yellen and Bernanke. “The accountability for the Fed runs through Congress,” said Claudia Sahm, a former Fed official who is now chief economist at New Century Advisors. “That’s not just about having people on speed dial — it’s answering questions, explaining policy and getting feedback.” Source: FT Ethiopia’s PM Abiy and Nigerian business tycoon, with Chinese engineering, are driving industrialization in Ogaden/Somali region of Ethiopia. - Michael Masri’s reporting for Africa Report if fascinating. Ethiopia has launched a cluster of large industrial schemes in the Somali region, laying foundation stones for a urea plant and an oil refinery in Gode while opening the first two phases of the Ogaden LNG project. Abiy Ahmed framed the push as part of a broader strategy to link energy, agriculture and industry. “These projects embody more than industrial growth,” he said. “They represent our shared responsibility to harness opportunities, strengthen co-operation and promote peace.” The Gode urea plant, backed by Dangote Group and Ethiopian Investment Holdings (EIH), is designed for 3m tonnes a year. Dangote owns 60%, while EIH holds 40%. Officials say Dangote’s equity totals about $2.5bn, while the state provides land and implementation oversight. Gas from the Calub fields will be piped 108km to the site. Construction is slated for 40 months, with operations targeted for 2028. Ethiopia imports most of its fertiliser, spending more than $1.2bn a year for 1.5m–2m tonnes. Usage was roughly 1.7m tonnes in 2023, almost half of it urea, and demand for 2024–25 is put above 2.4m tonnes. If delivered on time, the Gode plant could cover domestic needs and allow exports to neighbours. Brook Taye, chief executive of EIH, called the venture “a significant milestone in the journey toward industrial self-sufficiency”. Dangote told the groundbreaking crowd that the complex would be integrated with gas supply and a polypropylene unit to support local inputs. He pointed to Ethiopia’s Grand Ethiopian Renaissance Dam (GERD), with a capacity of more than 5,000MW, and noted his group’s cement operations and expansion plans. The Gode refinery is being developed by Golden Concord Group of China. It is designed to process 3.5m tonnes a year of crude and condensate from the Hilala field, with associated storage. Backers say it will ease foreign-exchange pressure from fuel imports and anchor further industrial activity, including a proposed steel smelting site in Dire Dawa. GCL’s chair, Zhu Gongshan, cast the project as “a key step in Ethiopia’s path to energy sovereignty”, underscoring the Beijing–Addis ties. Financing details are still being finalised, but the refinery is central to the government’s energy-security narrative. Source: The Africa Report Dangote’s Ethiopian vision: Dangote began with cement. His crown jewel, Dangote Cement, dominates Nigeria’s market and has 10 operations in other nations in Africa. The formula has been consistent: identify sectors with chronic shortages – cement, fertiliser, sugar – commit massive local investments, and scale up to serve regional demand. Ethiopia was a natural extension of that model. In 2015, Dangote launched the Mugher Cement Plant outside Addis Ababa at a cost of $600m, with an annual capacity of 2.5 million tonnes. The investment gave him a firm foothold in one of Africa’s fastest-growing construction markets. But success came with risks. In May 2018, violent unrest led to the killing of Dangote’s country manager and temporary shutdowns at Mugher. While other investors might have retreated, Dangote doubled down. Today, he is preparing to spend $400m to expand Mugher’s capacity to 5 million tonnes, alongside a new grinding unit near Addis Ababa. Cement is just one market Dangote is targeting. Ethiopia’s enormous state-controlled sugar industry, long plagued by inefficiency and debt, has struggled for years to reform. Its Omo Kuraz Sugar Development Project, touted as one of the continent’s largest initiatives, continues to face delays and mismanagement. … The most ambitious venture of all is the planned fertiliser production complex in Gode, Somali region. Publicised on 28 August 2025, the Dangote Group and Ethiopian Investment Holdings (EIH) deal plans one of the world’s largest single-site urea manufacturing plants. The project costs an estimated $2.5bn and has an estimated capacity of 3 million metric tonnes annually, a rate that would not only render Ethiopia independent, but even a net exporter of fertiliser. EIH, the state wealth fund of Ethiopia, will hold 40%, while 60% is held by Dangote Group. … For Dangote, Ethiopia is a trifecta: Cement demand is projected to grow by 10% annually, its sugar consumption is growing with rapid urbanisation, and fertiliser demand is all but insatiable, given that farming supports the livelihood of 70% of Ethiopians. Source: The Africa Report The stakes for Abiy are high: For Addis Ababa, the $4bn fertiliser project in Ethiopia’s Somali region is no longer simply a manufacturing investment. It is increasingly being framed as a strategic state project tied to food sovereignty, import substitution and the government’s broader attempt to build economic resilience under mounting fiscal pressure. “Becoming self-sufficient in food is our main agenda,” Abiy says during the visit. “Land is needed; we have it. Water is needed; we have it. Human resources are needed; we have it.” The scale is enormous even by African industrial standards. Once operational, the plant is expected to produce three million metric tonnes of urea annually, potentially making it one of the continent’s largest fertiliser complexes. Ethiopian officials say the project now includes a 110km gas pipeline, a 120MW power plant, a polypropylene packaging facility and a two-million-tonne NPK blending plant. For a government grappling with chronic foreign exchange shortages, ballooning import bills and pressure on agricultural productivity, the numbers matter politically as much as they do economically. The decision to anchor the project in Gode is deliberate. Long viewed as peripheral to Ethiopia’s industrial economy, the Somali region is now being repositioned by the federal government as a future irrigation and agro-industrial corridor. Officials argue that the area’s vast land reserves and access to water could eventually support large-scale commercial farming capable of reshaping Ethiopia’s food economy. The government is simultaneously building housing infrastructure for about 5,000 residents near the plant, while officials project broader industrial expansion along the corridor. Abiy goes further, comparing the long-term revenue potential of the Gode development zone with Ethiopia’s flagship state enterprise. “The investments we are making in this Gode area, combined, will generate high revenue for Ethiopia, at par with Ethiopian Airlines,” he says. Source: The Africa Report Feliks Topolski 1907-1982 Topolski’s Chronicle, ‘Nazi Revival’, Vol. 8, Is. 1-2, 1960 HEY READERS, THANK YOU for opening the Chartbook email. I hope it brightens your day. I enjoy putting out the newsletter, but tbh, what keeps this flow going is the generosity of those readers who clicked the subscription button. Photo by Jakub Dziubak on Unsplash If you are persuaded to click, please consider the annual subscription of $50. It is both better value for you and a much better deal for me, as it involves only one credit card charge. Why feed the payments companies if we don’t have to. Subscribe Grim vision of drone warfare by Sylvie Kaufmann For contributing subscribers only. Subscribe The state of the art in Colbert-studies. Jean-Baptiste Colbert was Louis XIV chief minister from 1661 to 1683 and traditionally seen as an architect of absolutism and mercantilism. Alexander Hamilton later cited him as an inspiration in 1782. Now his legacy is disputed. Daniel Dessert, the chief critic, sees Colbert as the orchestrator not so much of an absolutist state as of an elite cabal. Would be great to have a good English-language review of this important debate. Source: lhistoire Didn’t know that the Magna Carta included free trade provisions Fighting for the right to the beach in Oregon in 1967: Source: Research Gate RAF Station – British and Polish Flags, c. 1940-45, The Ingram Collection Feliks Topolski, 1907-1989 ink and wash If you’ve scrolled this far, you know you want to click: Subscribe
Bond breakout? Big effects of bad data. Immigration and thermostatic politics & dad-chat is coming for dad-books.
Thank you for opening your Chartbook email. Anna Airy, A Shell Forge at a National Projectile Factory, Hackney Marshes, London, 1918 Bond breakout - John Authers Across the developed markets, bond markets are staging a slow-motion car wreck. Looking at the drastic moves in the US, Japan, the UK and France, Barclays’ Ajay Rajadhyaksha commented: “Last week, long bonds broke. Not in one country. In all of them. Simultaneously. Four countries. Four different political systems. Four different central banks. But the same trade — “get me out of duration!”” Each country has its own contributing political problems, but the uniformity of the shift out of long-term bonds with high duration makes clear that something broader is afoot. For Rajadhyaksha, it is “simple and uncomfortable.” The developed world “has too much debt, too little fiscal discipline, and no political appetite for fixing either.” If there’s a trigger, it has been the Iran war and the resulting shock to oil supply. Source: Bloomberg G7 countries are now borrowing at rates that were enjoyed by EM in the early 2020s For contributing subscribers only. Subscribe Trade between China and Russia has grown in recent years For contributing subscribers only. Subscribe Big effects of bad data A decade ago nearly nine in ten Americans, when approached, agreed to fill out the Current Population Survey, which is administered to about 60,000 households each month and asks about, among other things, employment. Fewer than seven in ten do so now (see chart 1). For the Consumer Expenditure Survey, which tries to capture 3,700 households monthly, the response rate is down from 68% to 40%. … When the information becomes less reliable, investment decisions get more difficult to make. Some may be delayed, creating a potential drag on the economy. A new working paper by Nicholas Bloom of Stanford University, Erica Groshen, former head of the Bureau of Labour Statistics (BLS) now at Cornell University, and Duncan Hobbs and Michael Strain of the American Enterprise Institute, a think-tank, hazards an estimate. Preserving trust in “the integrity and quality of official statistics”, the authors claim, generates economic benefits of about $25 for every $1 spent on the BLS, the agency with an annual budget of $700m that is responsible for many of these data. To arrive at their conclusion the quartet analysed an ignoble episode in the BLS’s recent history. On August 1st 2025 Donald Trump sacked Erika McEntarfer, appointed as the agency’s commissioner by his predecessor, Joe Biden. The president alleged, without evidence, that the BLS’s steep downward revision to recent jobs numbers had been “RIGGED in order to make the Republicans, and ME, look bad”. In fact, it was the wanton dismissal that looked bad in the eyes of many observers. In the following seven days there was a 50% leap, relative to the week before, in the average value of the index of Economic Policy Uncertainty (EPU), which tracks the number of articles mentioning such uncertainty that are published daily in American newspapers. This was a discernible jump even when compared to the chaos caused by Mr Trump’s trade war in April 2025 and his real one in Iran in the past two months (see chart 2). Based on Mr Bloom’s earlier study with other colleagues of the EPU’s impact on business investment, industrial production and employment, the authors estimate that the jump reduced American GDP by over $100bn (0.3%) and non-farm payrolls by 168,000 (0.1%). Source: The Economist Immigration and thermostatic politics (Sarah O’Connor in the FT) A strange thing happened a year and a half ago. No sooner had Americans elected Donald Trump as president on an explicitly anti-immigration platform than US public opinion began to swing much more favourably towards immigration. … to political scientists who study “thermostatic” politics, this development is no surprise at all. Public opinion often moves against the prevailing party, especially if they are perceived to have gone “too far” in one direction. The phenomenon was first explored in the 1990s with reference to fiscal policy, but in recent years it has been particularly evident in the realm of immigration policy. While these swings in opinion polls can make it seem as if people don’t know their own minds, they can be a useful democratic check on governments by sending bright flashing warning lights when policies stray too far from the public’s comfort zone. The problem comes when politicians misinterpret those signals. When people tell pollsters they want less immigration, or think it is bad for the country overall (or the converse), they are often expressing an opinion about how things appear to be going in that moment relative to their preferences, rather than a deep shift in their underlying views. According to Alexander Kustov, a political scientist, most Americans’ views are quite stable and moderate: they support immigration that is controlled and in the national interest, and oppose flows that are disorderly or under-enforced. In the US, he argues the Trump administration over-interpreted dissatisfaction with high immigration under Joe Biden, and implemented policies that went too far for many voters. “People don’t necessarily change their idea about their ideal immigration policy, but they can react to what the government is currently doing,” he told me. “A lot of people are not happy with what the Trump administration are doing — right now we’re not talking about border enforcement, we’re talking about people not just getting harassed, but killed.” But similarly, he added, pro-immigration advocates would be making a mistake to interpret the recent, more favourable swing towards immigration as a deep-seated ideological shift in attitudes. The recent history of UK immigration policy offers another cautionary tale. After the 2016 Brexit referendum, public concern about immigration fell. This was partly because net migration statistics declined, but also because people felt a sense of catharsis and control, says Sunder Katwala, director of British Future, a think-tank. By 2019, the public ranked immigration as only the ninth biggest issue of concern, according to Ipsos polling. But when the Conservative government liberalised visa routes for students and care workers between 2019 and 2022, that helped net migration to surge. And so, too, did public concern. Today’s Labour government has implemented another sharply restrictive turn in immigration policy. As Kustov and researcher Caitlyn Yates argue, thermostatic public opinion should be a useful check on politicians. Instead it seems to have helped to magnify the pendulum swing in the UK. The government over-interprets and overreacts to a change in public opinion, which reacts in turn, prompting a sudden swing the other way. Source: Financial Times HEY READERS, THANK YOU for opening the Chartbook email. I hope it brightens your day. I enjoy putting out the newsletter, but tbh, what keeps this flow going is the generosity of those readers who clicked the subscription button. If you are persuaded to click, please consider the annual subscription of $50. It is both better value for you and a much better deal for me, as it involves only one credit card charge. Why feed the payments companies if we don’t have to. Subscribe Anna Airy, Shop for Machining 15-Inch Shells: Singer Manufacturing Company, Clydebank, Glasgow, 1918 Racing for a vaccine … we have been here before! The deadly Ebola outbreak in two African countries driven by a virus species with no vaccine has triggered an urgent search for a potential jab, in a test of troubled global efforts to avert threats posed by emerging diseases. A World Health Organization advisory group is due to would meet on Tuesday to recommend candidate jabs to prioritise for clinical trials, the global health body said. It will assess data including an analysis by the Coalition for Epidemic Preparedness Innovations (Cepi), which was set up after failures in the international response to a previous Ebola crisis. The latest Ebola outbreak in Democratic Republic of Congo and Uganda has infected hundreds of people and killed more than 80, health authorities say. Cepi’s reaction will be a crucial indicator of its progress towards its wider goal of producing vaccines for pandemic threats in just 100 days, despite steep cuts to international health funding. “If there was ever a time that we could show the world why Cepi is needed and show the world why the 100-day mission is needed, it’s now,” Nicole Lurie, the organisation’s executive director for preparedness and response, told the FT. “We’re happy to accept that responsibility, but obviously we need help from partners — particularly financial help in the long run.” DR Congo and Uganda would make the final decision on whether to press ahead with any vaccine candidates endorsed for clinical trials by the WHO experts, the global health body said. “Other ethical and community acceptability issues will be considered,” said the WHO, which declared the latest outbreak a public health emergency of international concern on Sunday. “This will be important to make sure that the trial, if it happens, will be adequately communicated to the population.” Lurie said Cepi had provided information from a survey of research teams and companies working on drugs that might be effective against the Bundibugyo virus behind the outbreak. The organisation hoped soon to announce partners in the quest for a jab, she added, although she declined to give a timescale for when one might be developed. Cepi’s Nicole Laurie said global health bodies were ‘getting some live-fire drills’ with hantavirus and the latest Ebola outbreak. The hunt for a vaccine should be helped by scientific advances including the use of artificial intelligence to find drugs active against viruses, Lurie said. Existing jabs against the Zaire Ebola virus responsible for many previous outbreaks might provide a basis for tackling the Bundibugyo species, she added. “We’ll see how far and how fast we can get,” Lurie said, adding that Cepi had done preliminary work recently on a possible jab for the rat-borne hantavirus responsible for a recent fatal outbreak on a cruise ship. “Both with hantavirus and now with Ebola, [we] are getting some live-fire drills.” Source: Michael Peel in the Financial Times Dad-chat is coming for dad-books. (By Pamela Paul and Jeffrey A. Trachtenberg in the WSJ) They were the go-to gifts for Father’s Day: a book about some little-known chapter of World War II, the sweeping narrative of a shipwreck, perhaps the latest presidential biography. These days, dad books are a dying breed. Nonfiction book sales have been in decline for the past four years, and are now the most challenged segment of the print book market. Publishers say certain types of books still fare well—including celebrity memoirs and religious titles. But in recent years, print sales in such categories as biography, current affairs and business and economics—what publishers refer to as “serious nonfiction” and which tend to resonate especially with men—have fallen considerably. Sales of nonfiction print titles were down nearly 8% through May 9 this year, and sales of books about politics and current affairs were down 19%, according to book tracker Circana BookScan. Publishing has long been subject to cyclical changes, with trends in format and genre taking over bookshelves in grand sweeps. (Remember the adult coloring-book craze? Or the stratospheric rise of romantasy?) But many in publishing believe the decline in serious nonfiction is more existential. “The trend couldn’t be clearer,” said Jonathan Karp, the former chief executive of Simon & Schuster and publisher of the new Simon Six imprint. “This is a sea change and people should wake up and realize we’re living in a new world.” One culprit for the shift: a new media diet for fans of more serious nonfiction. … Sixty-two percent of men and 54% of women consumed a podcast in the prior month, according to a recent survey by Edison Research at SSRS, up from 46% and 39%, respectively, in 2023. “When we have internal meetings to talk about this problem, it always comes around to podcasts,” said Jonathan Burnham, president and publisher of the Harper Group at HarperCollins Publishers. “The man who wants to read American history is now tuning into one of the many good podcasts about history that lends the quiet attention to a serious subject he’s looking for. It makes the idea of sitting down with a 700-page Ron Chernow book less appealing. You’ve scratched that itch.” Source: Wall Street Journal Remarkable report by Novara from the nationalist rally in London in mid May. Anna Airy, Leopard Moth and Plums, 1915 If you’ve scrolled this far, you know you want to click: Subscribe
Health Alert: Worldwide Caution – Updated Public Health Arrival Restrictions and Enhanced Ebola Screening – May 22, 2026 - U.S. Embassy & Consulate in Thailand
Health Alert: Worldwide Caution – Updated Public Health Arrival Restrictions and Enhanced Ebola Screening – May 22, 2026 Event: U.S.-bound American citizens and lawful permanent residents (LPRs) who have been present in the Democratic Republic of the Congo, Uganda, or South Sudan within 21 days of arrival in the United States must only enter through the following airports for enhanced screening: Washington Dulles International Airport (IAD) for flights after 11:59 PM on May 21, 2026 Hartfield-Jackson Atlanta International Airport (ATL) for flights after 11:59 PM on May 22, 2026 George Bush Intercontinental Airport, (IAH), Houston, for flights departing after 11:59 PM on May 26, 2026 The U.S. Centers for Disease Control and Prevention (CDC) and the Department of Homeland Security’s (DHS) Customs and Border Protection (CBP) will apply enhanced public health screening at IAD in response to the Ebola outbreak. This requirement applies to all passengers, including U.S. citizens and LPRs, who were present in those countries. Please be prepared for flight changes or cancellations. Actions to take: Read the Modification of List of Designated Airports Regarding Arrival Restrictions Review the U.S. Centers for Disease Control and Prevention (CDC) information on what travelers need to know about returning to the United States from DRC, Uganda, and South Sudan. Read the Department of Homeland Security Alert on Enhanced Ebola Screening. Review Consular Information for Americans Regarding the Ebola Outbreak. If you are planning to travel to the United States, contact your airline to confirm your flight and route. You may also contact the State Department – Consular Affairs: Phone: +1-888-407-4747 or +1-202-501-4444 Enroll in the Smart Traveler Enrollment Program (STEP) to receive safety and security updates. If you are a registered user, you can manage your subscriptions by clicking the link below. Guest subscribers cannot manage subscriptions but can create a Login.gov account to manage future subscriptions. Manage Your Subscriptions
Sony’s other PS Plus plans are going up in price too.
When it announced price hikes this week, Sony focused on the cheapest Essential tier. As we suspected though, now the new prices are live, Extra and Premium have gone up too. Extra now starts at $16.99 per month, while Premium is $19.99. [Link: Sony is raising short-subscription prices for PlayStation Plus | https://www.theverge.com/games/932430/sony-playstation-plus-subscription-price-raise | The Verge]
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[Dear DSOS readers – this article is the latest in our “Shaky Political Science” series. In our 38 page report, “Shaky political ‘science’ misses mark on ranked choice voting,” released in early December, we examined over 40 studies focused on ranked choice voting. We found that many of these studies suffered from puzzling research methodologies, poorly constructed surveys, unrealistic simulated elections, cherry picked data, and faulty analyses that often were contradicted by results from real-world elections (a link to our full paper is here). Here are links to the first three articles in our series: the first one summarizing the overall results of our report, the second one analyzing a study co-authored by University of Minnesota academic Larry Jacobs, which was one of the most error-prone of all the research we reviewed in our report, and a third article showing an admirable example of two political scientists holding two other political scientists accountable for their flawed, sloppy research]. In this fourth article in our “Shaky Political Science” series, we shine a spotlight on seven studies that were web-hosted and funded by New America’s Political Reform Program and its Electoral Reform Research Group (the ERRG is an ad hoc committee headed by New America’s Political Reform Program and joined by the American Enterprise Institute, the Unite America Institute and Stanford University’s Center on Democracy, Development, and the Rule of Law). This research consortium has been led by Lee Drutman, senior fellow with New America’s Political Reform Program. These seven studies are simply not credible from any objective standard about how political “science” is supposed to illuminate our understanding of either ranked choice voting or politics in general. The feature that six of these seven studies have in common is that they all used surveys – artificial, simulated elections -- to attempt to say something cogent or interesting about ranked choice voting (RCV) elections. None of them used real world data from actual RCV elections – either the 1000+ elections in the US or the many thousands of elections from places like Australia, Ireland and elsewhere where RCV has been used for 100 years. While a few of these studies conclude with some mixed positives about RCV, our analysis here is content neutral. The idea that, with a political reform like RCV, you can ask respondents in a mock, artificial election to vote with that method, with only the barest of explanation about how RCV works or its likely impacts (i.e. no spoiler candidates, majority winners, voters liberated to pick their favorite candidates, coalition-building), and then ask them their thoughts/reactions about voting in that system, with fake candidates and no real campaigning, no real exposure to an actual election or actual candidates, rests on some very puzzling assumptions. The findings of these seven studies actually are contradicted by the findings from many other studies based on real-world RCV elections. These New America studies also failed to list the real-world RCV studies in their own citations, instead including those studies that reinforced their conclusions. The seven studies featured in this article were chosen because they form a cohesive cohort which precisely illustrates one of the main points of our research paper, namely that using surveys, i.e. artificial elections, or mathematical/theoretical models, instead of real-world data, is in fact “shaky political science.” Below are summaries of our analysis of five of the seven New America studies. You can read our complete analysis of all seven studies at our paper, “Shaky political ‘science’ misses mark on ranked choice voting.” Choosing to “Vote As Usual” by Andre Blais, Carolina Plescia, and Semra Sevi. New America. (Blais et al., 2021). This study, web-hosted and funded by New America’s Political Reform Program and its Electoral Reform Research Group, used two surveys in which respondents completed ballots for simulated elections using plurality, approval, RCV and point (Score) voting. In both cases the authors provided the respondents with only minimal explanation of each method. For example, the entire explanation for RCV was “For this vote, rank the candidates from your first to your last choice (you do not need to rank them all). This is called the ranked vote.” That’s it. The study did not provide any context or explanation to survey respondents about why she/he might want to rank multiple candidates. Participants were not even told that ballots would be tabulated using an “instant” runoff, not to mention any description of RCVs ability to eliminate the spoiler effect or liberate voters to rank their favorite candidates without fear of helping the “greater evil” candidate to win. That’s like taking an iPhone back in time to 1970 and asking someone if they like it better than their rotary phone without explaining how it works. Their first survey targeted states that held 2020 Super Tuesday Democratic primaries and used the real candidates’ names in the survey; the second survey used fictitious candidates. In other words, they surveyed respondents who had only ever participated in plurality elections, had no history or background with using RCV or any of the other methods, had no clue about its likely impacts, and did not communicate how the alternative methods would be counted, and then asked them: “How satisfied are you with using each system?” Predictably, the winner was plurality elections, the system used for president, Congress, gubernatorial and state legislative elections – in other words, the method they have been using, year after year, all their voting lives. With so little explanation of RCV and its impacts, this study is simply not credible in discovering anything useful about real-world RCV elections. It merely shows that a basic voter education campaign is needed when adopting a new election system. Additionally, the result contradicts many other post-election surveys following real RCV elections, asking opinions from voters who had just participated in a RCV election, that showed a great deal of satisfaction with RCV (see details on that in Studies 22-25 in our paper, as well as the four studies cited in the review for Study 28). Share Other studies on “satisfaction” and “understanding” make similar mistakes, in terms of basing their surveys on inadequate explanation to respondents and lack of education about context. How could any survey ever hope to measure accurately, in essence simulate a real-world election, without actual campaigning candidates, the media writing about those candidates, organizations endorsing candidates and voters being inundated with crucial information? More than anything, what these “studies” based on surveys show is that if you ask voters about something they don’t know very much about, and fail to adequately educate them, their responses will unsurprisingly reflect their confusion. Equally puzzling is that New America’s Electoral Reform Research Group, headed by political scientist Lee Drutman, found this to be a credible enough study that they not only published it but highlighted it in Drutman’s own discussion of research related to ranked choice voting. This pattern was repeated in study after study featured by New America’s Electoral Reform Research Group. For example in Ranked-Choice Voting and Political Expression: Voter Guides Narrow the Gap between Informed and Uninformed Citizens by Cheryl Boudreau, Jonathan Colner, and Scott MacKenzie, the researchers based their analysis on a survey which found that respondents who were asked to vote in a simulated RCV election, with minimal explanation of RCV or how it works, displayed less evidence of being informed about how to use RCV effectively, with the least informed voters ranking fewer candidates. As pointed out under the study above, in a real election voters are informed by a wide variety of methods, including public education by the election administration, by interested political groups, the media, and the candidates themselves who benefit from voters being aware of how to vote in the new system. In Support for Ranked-Choice Voting across Race and Partisanship by Joseph Anthony, David C. Kimball, Jack Santucci and Jamil Scott, the researchers used respondents from different parties and races voting in simulated plurality and RCV elections, who indicated their satisfaction with each voting method. Instead of using real world election results, the authors fell back on the easy, armchair and less reliable academic research methodology of making up mock elections. As with the other studies, little explanation was given of how RCV works or what its implications might be (electing majority winners or eliminating spoilers, for example). Unsurprisingly, this study found that respondents were not very satisfied with RCV. However, when the authors added an explanation that RCV has a tendency to elect more women and people of color, they found that this greater explanation increased the preference for RCV. The more voters were familiar with it, and the more they understood potential positive impacts – surprise! -- the more they were open to switching away from the status quo. Of note, the results from this study are thoroughly contradicted by a number of other studies whose data was obtained from real RCV elections with real voters. Those studies show a great deal of satisfaction with RCV. More “fake election” research An interesting wrinkle on this “research by fake elections” approach, which only served to illustrate how unreliable such “research” can become, was taken in Ranked-Choice Voting, Runoff, and Democracy: Insights from Maine and Other U.S. States by Joseph Cerrone and Cynthia McClintock_,_ also web-hosted and funded by New America’s ERRG. It gets high marks for creativity, but an eye-roll for thinking this could possibly add anything meaningful to our understanding of real world RCV elections. This study tried to determine whether RCV, plurality or two-round runoff elections provided greater voter satisfaction and acceptance of election results. To determine that, the authors conducted a survey asking if voters were satisfied with a fictional newspaper report of an election, with three different versions given to respondents – plurality, runoff and RCV, with variations of Republican/Democrat winners and variations of “come-from-behind” winners,” i.e. candidates not initially in first place but who win the “runoff.” Again, a minimal explanation of RCV or how it works was given, and the survey showed that respondents had the greatest unfamiliarity with RCV than the other methods. The unsurprising result? Respondents were much more satisfied with “come-from-behind” victories in a traditional two-round runoff election than in RCV, even though RCV is also a runoff system but with a single round of counting. Interestingly, the dissatisfaction with RCV disappeared for those who were more familiar with RCV. In fact, among those respondents who were “very familiar” with RCV, they were equally satisfied with RCV, runoff and plurality. Surprise, surprise. Again, what this study revealed, more than anything, is not only the inadequacy of the explanation for RCV given by the authors of this study, but the failure of the research format itself, thinking that such an artificial mock election could somehow simulate what actually happens in the real world in a real RCV election. Those four studies reviewed above are fitting examples of inadequate and shaky political “science.” Other studies reviewed in our paper from the New America/Electoral Reform Research Group cohort which also used mock elections included: Ranked-Choice Voting is an Acquired Taste by Joseph Anthony and David C. Kimball. New America. (Anthony et al., 2021). Ranked-Choice Voting is No Refuge for Extreme Candidates by Melissa Baker. New America. (Baker, 2021). Also included in this New America cohort is Does Ranked-Choice Voting Reduce Racial Polarization? by Yuki Atsusaka and Theodore Landsman, which actually did use real-world election results data but applied an odd and unconventional methodology to the data which relied on shaky assumptions and non-real-world scenarios that were too divorced from reality. To determine levels of “racially polarized voting,” the researchers imagined “ethnic parties,” by which they mean political parties for each ethnic group, which was especially odd since the election data they were using came from nonpartisan RCV races. But then they made an even odder assumption, namely that since race and ethnic characteristics of studied voters were not available, the authors tried to infer that information based on who voters selected and the racial make-up of voters in each district. This amounted to little more than vague and ambiguous guesswork dressed up with a bunch of mathematical equations used to give it a veneer of scientific appearance. Indeed, it seemed to assume racial polarization in order to prove racial polarization. Based on this questionable methodology, the authors concluded that RCV doesn’t reduce racial polarization. But the premise of this study missed an obvious reality: since RCV incentivizes more candidates to run and can result in more diverse fields of candidates, one would expect more racially-polarized voting in voters’ top rankings, not less, because more voters would have someone on that ballot who represents their racial or ethnic identity and more freedom to vote for their real first choice. By encouraging more diverse candidates and eliminating the spoiler effect, RCV facilitates voting for a favorite candidate of your own race and then selecting a second choice with the best likelihood of winning. The real measure is what voters do with their additional rankings – do they consider other candidates and vote “for the best of the rest”? This study didn’t tell us anything useful about that. But readily available data shows this is common in real RCV elections, and candidates act on this knowledge by engaging with voters outside their racial group. So the authors of this study failed to consider or account for what actually happens in real-world elections, and their conclusions are tainted by this failure. New America has contributed a great deal over the past 2.5 decades to our understanding of many policy areas, including politics and political reform (full disclosure: Steven Hill, one of the authors of this article and of the “Shaky Political Science” research paper and series, is a former senior fellow and former director of New America’s political reform program, 2005-2010). So it was especially disappointing that New America funded and published such a large batch of dubious studies about ranked choice voting. The stated praiseworthy goal of its Electoral Reform Research Group was to inspire new academic research about ranked choice voting that would shed light and help the public better understand the impacts of RCV. Instead, the ERRG research did just the opposite. It produced dubious research that created more confusion and misinformation. In so doing, New America’s political reform program contributed to “shaky political science.” Steven Hill and Paul Haughey Share Upgrade to $5 subscription Thanks for reading DemocracySOS, a reader-supported digital portal for the pro-democracy movement. Subscribe for only $5 per month to receive full benefits and to support our work. Subscribe
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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. 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