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Were ‘Yellowstone’ Streaming Rights to Blame for ‘Marshals’ Killing Off Monica?
How this might impact Beth and Rip 'Yellowstone' spinoff.
The Rise of Socialism: Washington business owners slam new ‘millionaires tax’
Washington shop owners, talk show radio host Arri Hoffman and a local democratic socialist, Rep. Shaun Scott, discuss the impact of the state’s new “millionaires tax” and how socialist economic policy is impacting local business.
We the People: Truman Library scores with new sports exhibit
The highlights include Lamar Hunt’s ticket to the first game at Arrowhead Stadium, a football signed by Len Dawson and a baseball bat gifted to President Ronald Reagan after the Royals won the 1985 World Series.
Gemma 4 and what makes an open model succeed
Having written a lot of model release blog posts, there’s something much harder about reviewing open models when they drop relative to closed models, especially in 2026. In recent years, there were so few open models, so when Llama 3 was released most people were still doing research on Llama 2 and super happy to get an update. When Qwen 3 was released, the Llama 4 fiasco had just gone down, and a whole research community was emerging to study RL on Qwen 2.5 — it was a no brainer to upgrade. Today, when an open model releases, it’s competing with Qwen 3.5, Kimi K2.5, GLM 5, MiniMax M2.5, GPT-OSS, Arcee Large, Nemotron 3, Olmo 3, and others. The space is populated, but still feels full of hidden opportunity. The potential of open models feels like a dark matter, a potential we know is huge, but few clear recipes and examples for how to unlock it are out there. Agentic AI, OpenClaw, and everything brewing in that space is going to spur mass experimentation in open models to complement the likes of Claude and Codex, not replace them. Especially with open models, the benchmarks at release are an extremely incomplete story. In some ways this is exciting, as new open models have a much higher variance and ability to surprise, but it also points at some structural reasons that make building businesses and great AI experiences around open models harder than the closed alternatives. When a new Claude Opus or GPT drops, spending a few hours with them in my agentic workflows is genuinely a good vibe test. For open models, putting them through this test is a category error. Something else to be said about open models in the era of agents is that they get out of the debate of integration, harnesses, and tools and let us see close to the ground on what exactly is the ability of just a model. Of course, we can’t test some things like search abilities without some tool, but being able to measure exactly the pace of progress of the model alone is a welcome simplification to a systematically opaque AI space. Share The list of factors I’d use to assess a new open-weight model I’m considering investing in includes: Model performance (and size) — how this model performs on benchmarks I care about and how it compares to other models of a similar size. Country of origin — some businesses care deeply about provenance, and if a model was built in China or not. Model license — if a model needs legal approval for use, uptake will be slower at mid-sized and large companies. Tooling at release — many models release with half-broken, or at least substantially slower, implementations in popular software like vLLM, Transformers, SGLANG, etc due to pushing the envelope of architectures or tools. Model fine-tunability — how easy or hard it is to modify the given model to your use-case when you actually try and use it. The core problem is that some of these are immediately available at release, e.g. general performance, license, origin, etc. but others such as tooling take day(s) to week(s) to stabilize, and others are open research questions — with no group systematically monitoring fine-tunability. In the early era of open models, the days of Llama 2 or 3 and Qwen pre v3.5, the architectures were fairly simple and the models tended to work out of the box. Some of this was due to the extremely hard work of the Llama, Qwen, Mistral, etc. developer teams. Some is due to the new models being genuinely harder to work with. When it comes to something like Qwen 3.5 or Nemotron 3, with hybrid models (either gated delta net or mamba layers), the tooling is very rough at release. Things you would expect to “just work” often don’t. I’ve been following this area closely since we released Olmo Hybrid with a similar architecture, and Qwen 3.5 is just starting to work well in the various open-source tools that need to all play nice together for RL research. That’s 1.5 months after the release date! This is just to start really investing more into understanding the behavior of the models. Of course, others started working on these models sooner by investing more engineering resources or relying on partially closed software. The fully open and distributed ecosystem takes a long time to get going on some new models. All of this is lead-in for the most important question for open models — how easy is it to adapt to specific use-cases? This is a different problem for different model sizes. Large MoE open-weight models may be used by entities like Cursor who need complex capabilities in their domain, e.g. Composer 2 trained on Kimi K2.5. Other applications can be built on much smaller models, such as Chroma’s Context-1 model for agentic search, built on GPT-OSS 20B. The question of “which models are fine-tunable” is largely background knowledge known by engineers across the industry. There should be a thriving research area here to support the open ecosystem model. The first step is to understand characteristics of different base and post-trained models to understand what they look like. The second step is to tune pretraining recipes for open models so they’re more flexible. Interconnects AI is a reader-supported publication. Consider becoming a subscriber. Subscribe For The ATOM Project and other Interconnects endeavors, we’ve put in substantial effort to measuring adoption trends in the open ecosystem. Everything takes a long time to unfold after a model is first publicly available — and adaptability is why. What we know for sure now, when Qwen has been going from strength to strength with its releases, is that technical staff across the industry has gotten comfortable working with Qwen models. Countless research methods and datasets were made to work with Qwen. It’ll take patience for any other model family to get to this point — a patience I’m not sure many open model builders have. This takes us to Gemma 4, Google’s latest open models. Gemma 3 was released more than a year ago, in March of 2025, and is a bit underrated. Gemma 4 comes in 4 sizes for now, with a bigger, MoE model of over 100B total parameters rumored but not released yet. The models we have today come in sizes of ~5B dense, 8B dense, 26B total 4B active MoE, and 31B dense. I’m most excited that they’re finally adopting a standard Apache 2.0 open source license. This’ll massively boost adoption. The standard of better licenses for strong open-weight LLMs was set by mostly Chinese open model labs in the last 1-2 years, and now U.S. companies are following suit. I will personally be so happy if the horrible Llama licenses and Gemma terms of service were an ~18-month transient dynamic of the industry being nervous about releasing strong open models. The Gemma 4 scores look very solid, the small models have incredible benchmark scores (especially in general domains like LMArena) and the 31B model rivals the recent Qwen 3.5 27B, which is the leading member of that class. The ~30B size range is an important one, as it’s accessible both to researchers and to enterprises looking to deploy the model in real use-cases. Where the 7B model scale is the default for tinkering and research, a 30B model is the default for seeing if an open model can unlock substantial value in your specific workflow — a good mix of intelligence, low price, tractability for downstream training, etc. This takes us back to the above adoption criteria I mentioned for open models and the bigger question — do I think Gemma 4 will be an overwhelming success? Previous Gemma models have been plagued by tooling issues and poorer performance when being finetuned. Gemma 4’s success is going to be entirely determined by ease of use, to a point where a 5-10% swing on benchmarks wouldn’t matter at all. It’s strong enough, small enough, with the right license, and from the U.S., so many companies are going to slot it in. I’m cautiously optimistic that Gemma 4 is going to work better here. Winds are shifting for open models built in America. We saw GPT-OSS go through a bumpy launch to become an overwhelming success. There’s a collective energy around the likes of Reflection, Arcee, Nemotron, Gemma, Olmo, and peers that show substantial demand for building new stacks around open models. There’s capital to be spent on AI stacks across the economy by those who want more ownership of everything, including the model. After launching The ATOM Project 240 days ago, the conversation is shifting into the next stage. Summer of 2025 was a crisis moment where the U.S. AI scene realized it can’t wait and figure out open models after building AGI. The two markets will capture different areas and proceed in parallel. Now that more companies in the U.S. are releasing strong models, we need to improve the ecosystem so that these models are easy to use, understand, and build value around. It’s the hard work to build another inflection point in these adoption plots I’ve been updating consistently, but that’s the work to be done. Join me in it. More data coming soon! Here’s a sneak peek:
Caesars Entertainment the Latest to Offer All-Inclusive Packages for Las Vegas Hotels
Caesars Entertainment is offering its guests summer value options with the launch of its Inclusive Summer Package, a bundled hotel experience at Harrah’s L | The package includes accommodations, taxes, resort fees, two meals per day at dining outlets, bottomless drinks, High Roller Observation Wheel tickets and free self-parking.
The health benefits of spicy foods
Spice up your plate: learn how capsaicin in chile peppers may support heart health, reduce inflammation, boost mood, and fit into a balanced diet.
Were ‘Yellowstone’ Streaming Rights to Blame for ‘Marshals’ Killing Off Monica?
How this might impact Beth and Rip 'Yellowstone' spinoff.
Experts dispute US account of deadly Lamerd sports hall strike in Iran
Six weapons experts have contested the US claim that video evidence suggests an Iranian missile could have hit the hall.
Trapanovski question mark as injury ends 'difficult campaign'
Dundee United manager Jim Goodwin has lamented the loss of "one of the best wingers in the league" for the rest of the season, leaving a question mark over the North Macedonia international's future at Tannadice. Goodwin confirmed Kristijan Trapanovski "underwent some surgery" on Wednesday on a knee injury the 26-year-old sustained in last month's Scottish Cup defeat away to Falkirk. Trapanovski, who has two caps for his country, is out of contract this summer having signed a two-year deal when arriving from Shkupi in his homeland in 2024.
A gene mutation may trap the brain in the wrong reality in schizophrenia patients
A newly identified gene mutation may help explain why schizophrenia patients struggle to update their understanding of reality. The mutation disrupts a brain circuit involved in flexible decision-making, causing mice to stick with outdated choices even when conditions change. Researchers pinpointed the issue to a key thalamus–prefrontal cortex pathway. By reactivating this circuit, they were able to restore normal behavior—raising hope for future therapies.
Scientists Discover Why Flu and COVID Hit Older Adults So Hard
A new study reveals that aging lungs may play a major role in why flu and COVID can become so dangerous for older adults. Researchers found that certain lung cells can trigger an exaggerated immune response, creating clusters of inflammatory cells that end up damaging lung tissue instead of protecting it. In experiments, activating this aging-related signal in young mice caused their lungs to behave like older ones, leading to severe illness.
Texas basketball coach laments transfer portal after Iowa State mass exodus
Texas coach Vic Schaefer got emotional discussing Iowa State's Bill Fennelly and his large number of players lost to the transfer portal.
Caesars Entertainment Unveils Inclusive Summer Package, Bringing Big Value to Harrah’s Las Vegas, The LINQ Hotel and Flamingo Las Vegas
LAS VEGAS, April 02, 2026--Caesars Entertainment is offering its guests summer value options with the launch of its Inclusive Summer Package, a bundled hotel experience at Harrah’s Las Vegas, The LINQ Hotel and Flamingo Las Vegas. Guests can book now at caesars.com/las-vegas/hotels/deals/inclusive-summer-package for stays in April 2026 through August 2026.
Overnight fire destroys business district in Butler, New Jersey
Families and businesses are picking up the pieces in Butler on Thursday after flames ripped through the business district along Main Street.
New Electronics Manufacturing Business Comes to Alamosa County with Support from Rural Jump-Start Program - by Ark Valley Voice Staff
This week, Governor Jared Polis and the Business Funding and Incentives (BF&I) division of the Colorado Office of Economic Development and
Stars, Stripes & Slams: Professional wrestling coming to Great Allentown Fair
Organizers say tickets for The Great Allentown Fair’s Stars, Stripes & Slams go on sale to the public at 10 a.m. Friday, April 10.
Sporting KC to play Colorado Springs Switchbacks in U.S. Open Cup Round of 32
Sporting Kansas City will begin the club’s participation in the 2026 Lamar Hunt U.S. Open Cup in the Round of 32 on the road at USL Championship opponents Colorado Springs Switchbacks on Tuesday, April 14. U.S. Soccer conducted the U.S. Open Cup Round of 32 and Round of 16 draw
Flamengo open talks with Dybala
Paulo Dybala’s future remains uncertain, with several options emerging as the player prepares to end his tenure with Roma after four seasons. After surgery in early March, “La Joya” is currently...
Meet the new directors of GLAM, PULSE, and the Ginzton Lab
Three interdisciplinary research labs anchored in the physical sciences have new faculty directors – each a longtime member of the community they’ll now lead.
Doctors blamed her symptoms on motherhood. She actually had mold illness.
Kate Ames spent years battling chronic symptoms like fatigue and joint pain. She later learned there was mold in her home that was making her sick.
Scaloni laments Italy’s 2026 World Cup miss: “It hurts Argentina—our brother nation won’t be there”
Argentina manager Lionel Scaloni has said the absence of Italy from the 2026 World Cup makes him sad.Italy missed out on qualification to this summer's tournament after losing to Bosnia and Herzegovin...
'A considerable gamble' at 'a fragile moment'
Only Tottenham would respond to the current bin fire at the club by turning to a famously incendiary manager to put out the flames. After tens of thousands of supporters lined the streets in an act of unity, the Tottenham board split the fanbase by appointing Roberto de Zerbi. The Italian, known for his high-pressing, attacking football, arrives with a reputation that has already prompted concern from supporter groups and the Tottenham Hotspur Supporters' Trust.
Lamont, Democrats split on Connecticut Option health plan
House Speaker Matt Ritter, D-Hartford, said establishing any new health insurance plan “would be a tall order.”
Solanco surprise: Golden Mules upset Lampeter-Strasburg in Section Two baseball opener
To anyone who thought the Section Two baseball race belonged to Lampeter-Strasburg, Solanco offered a second opinion. The Golden Mules pulled off an early-season surprise.
Denmark’s unique political model is in crisis – I blame the boomerang effect
Voters rejected rule from the centre in last month’s election – but could end up with another centrist government, says Rune Lykkeberg, editor-in-chief of the Danish newspaper Information
High school sports top 9 performances from the final day of March
Close the book on March. These nine high school athletes made sure it ended with an exclamation point. Here are the top performers from Tuesday.
2025-26 CBS Sports All-America teams: College basketball's best and most talented players
Duke's Cameron Boozer, Michigan's Yaxel Lendeborg, BYU's AJ Dybantsa and Arkansas' Darius Acuff Jr. were unanimous first-team selections
Niecey Shaw has the latest in entertainment headlines
Keep up with Niecey Shaw, middays on Classix 1029
Disney accidentally creates an original movie that shakes the entertainment industry
This article is SATIRE. Quotes, attributions and facts are fictional. LOS ALAMITOS, Calif. — Over the past few years, Disney has come out with a multitude of new, inspiring and out-of-the-box movies. According to Disney, the new animated film that is in the works follows a hamster named Demi that loves food. The plot known...
Scientists found a baby dinosaur hidden in rock and it is surprisingly cute
Scientists uncovered a rare baby dinosaur in South Korea and named it Doolysaurus after a famous cartoon character. Using cutting-edge CT scans, they discovered hidden bones—including a skull—inside rock much faster than traditional methods. The young dinosaur, possibly fluffy and lamb-like, even had stomach stones that reveal it ate a mix of plants and small animals. The discovery suggests many more dinosaurs may still be hidden in Korea’s rocks.
Hands-on: Anker's new Nano Power Strip will be a perfect fit in your desk setup
Today, Anker is releasing its new Nano Power Strip, initially unveiled at CES 2026. It clamps onto the side of...
Car slams into Redlands business, one injured
The victim was hospitalized with non-life-threatening injuries.
Surprising study shows Alzheimer's may start in the body instead of the brain, a discovery that turns medical science upside down
Alzheimer’s disease may begin outside the brain, with inflammation in organs like the skin, lungs, and gut decades before symptoms appear.
Night With A Nerd Is Back April 16 At Bradbury Science Museum
LANL NEWS RELEASE The Universe is bursting with activity with hundreds of cosmic explosions occurring every second. These explosions provide astronomers a window into the universe, studying everyth…
Running local models on Macs gets faster with Ollama's MLX support
Apple Silicon Macs get a performance boost thanks to better unified memory usage.
Lamar Odom's kids detail decision to skip his wedding to Khloé Kardashian: 'I never even met her'
Lamar Odom's kids LJ and Destiny detail their decision to skip their father's wedding to Khloé Kardashian in the Netflix documentary 'Untold: The Death & Life of Lamar Odom.'
Inspector general's report says human error, not political motive, to blame for release of Mikie Sherrill's military records
The inspector general for the National Archives concluded human error, not political motivations, was to blame for the release of New Jersey Gov. Mikie Sherrill's military records last year.
Charlie Kirk highway got vetoed in Arizona. Elected officials are citing politics
There will be no Charlie Kirk highway in his home state of Arizona. The reason: politics. Exactly whose politics is to blame has become a point of debate.
Fiesta Sports Foundation Completes Sixth Annual Kindness Arizona Week, Recognized with Official Proclamation from Gov. Katie Hobbs
In honor of the sixth annual Fiesta Sports Foundation Kindness Arizona initiative, Governor Katie Hobbs officially proclaimed the week of March 23-27, 2026 "Kindness Arizona Week," recognizing the Foundation's sixth year of statewide community service. Over five days, Fiesta Sports Foundation Board of Directors, Yellow Jackets, Ambassadors, staff and volunteers completed eight service projects and events, delivering acts of kindness and community impact across the Valley, Tucson and Rio Verde.
Ollama Now Runs Faster on Macs Thanks to Apple's MLX Framework
Ollama, the popular app for running AI models locally on a computer, has released an update that takes advantage of Apple's own machine learning framework, MLX. The result is a hefty speed boost on Macs with Apple silicon. According to Ollama, the new version processes prompts around 1.6 times faster (prefill speed) and nearly doubles the speed at which it generates responses (decode speed).
The surprising health benefits of everyday herbs
These leafy greens are loaded with flavor and nutrients—and studies show that even small doses are filled with compounds that reduce inflammation and even protect against cancer.
Lone Star Politics: March 29, 2026
Lone Star Politics is reporting from the Conservative Political Action Conference in Grapevine. NBC 5’s Phil Prazan and Gromer Jeffers with the Dallas Morning News discuss how President Trump has changed CPAC and new school vouchers excluding Islamic Schools. Plus, interviews with the candidates running for Texas Attorney General.
THE WEEK OF MARCH 30, 2026
- NASA revises lunar plans - Trump clamps down on federal contractor DEI - DOE Office of Science heads discuss reorg and facilities
This week on The V: Faith, politics and unfinished business
Panel examines faith in campaigns, Tuberville lawsuit, IVF debate and legislative priorities as Alabama's legislative session nears its end.
'Angel Dad' slams politicians for migrant crime and sanctuary policies
'Angel Dad' Joe Abraham condemns politicians and sanctuary policies amid rising instances of migrant crime on 'Sunday Night in America.'
Just a few minutes of effort could lower your risk of 8 major diseases
Just a few minutes of getting out of breath each day could dramatically cut your risk of major diseases—including heart disease, dementia, and diabetes. A large study of nearly 100,000 people found that it’s not just how much you move, but how intensely you move that matters. Short bursts of vigorous activity—like rushing for a bus or climbing stairs quickly—were linked to striking reductions in disease risk, especially for inflammatory conditions and brain health.
Denmark’s politics is all a bit chaotic right now – but Danes like it that way
Following last week’s general elections, Danish lawmakers are locked in the routine negotiations that come with forming a coalition government....
Tudor's 44 days in charge
Igor Tudor lost his first four matches as Tottenham boss, including against Arsenal, Fulham and Crystal Palace in the league before a calamitous 5-2 Champions League last 16 first-leg defeat at Atletico Madrid.
Lamar University unveils new doctoral energy management program
Lamar University unveils new doctoral energy program to facilitate advanced academic research in local sector.
Fox News Entertainment Newsletter: David Spade slams Newsom and Bass, Howie Mandel calls out Kelly Ripa
The Fox News Entertainment Newsletter brings you the latest Hollywood headlines, celebrity interviews and stories from Los Angeles and beyond.
Fox News Entertainment Newsletter: David Spade slams Newsom and Bass, Howie Mandel calls out Kelly Ripa
The Fox News Entertainment Newsletter brings you the latest Hollywood headlines, celebrity interviews and stories from Los Angeles and beyond.
Tony Vitello takes blame for Giants' scoreless start, says 'fire and brimstone' speech might have backfired
The rookie MLB manager has seen his team get shut out in back-to-back games to begin the 2026 season
Health boss exit during Lampard Inquiry 'cowardly', say families
Bereaved families have criticised the timing of Paul Scott's departure during the Lampard Inquiry.
Officer fired after fatally shooting man in mental health crisis — as others tried to de-escalate
The mayor of Hartford, Connecticut, has fired a white police officer who fatally shot a Black man in a mental health crisis nine times. Mayor Arunan Arulampalam announced Friday that he terminated...
The Big Business of Carolyn Bessette-Kennedy
How much has ‘Love Story’ increased business for CBK's rumored favorite brands? Turns out, a lot. Ahead, we spoke to J.Crew, Kiehl's, and more about the 'Carolyn Bessette-Kennedy effect.'
Business Lookahead: Gauging the war's impact
STORY: From a worrying drop in stocks to a surge in energy prices from the war in the Middle East to key data on jobs and trade, these are the stories to watch in business and finance in the coming week. ::Look Ahead::War impactThe first quarter is ending with financial markets at the mercy of geopolitics.The Iran war has wiped roughly $7 trillion off global stocks since it erupted.With oil prices up nearly 70% year to date, suddenly interest rates are heading up, rather than down, and energy-hungry AI does not look like such a slam-dunk anymore.Meanwhile, gold has plunged 16% after being nearly unstoppable since the start of 2025.We’ll see whether markets roll on or rollover as the second quarter begins.::Job growth in focusThe U.S. jobs report for March comes out Friday.It will offer a crucial view into the economy's health as investors gauge fallout from the energy price surge.Monthly payrolls are seen rising by 48,000, according to a Reuters poll. February's surprisingly weak report caught Wall Street off guard, showing nonfarm payrolls fell by 92,000 while the unemployment rate increased to 4.4%.Uncertainty over the Iran war is also clouding the economic forecasts for the Federal Reserve, with Wall Street pulling back on expectations for U.S. interest rate cuts this year as the oil price surge fuels concerns about rising inflation.Other U.S. data in the coming week includes retail sales for February and reports on manufacturing and services activity.::Chip checkSouth Korea releases its trade data for March on Wednesday.It will provide an early indicator of how the global economy is holding up in the face of the war and the resulting shock to energy prices. Korea's export-heavy economy is a bellwether for global trade and one of the first to report data from the previous month.Its manufacturing fortunes are of even greater interest than usual, not just because of its dependence on Middle Eastern energy imports, but also because its world-leading DRAM chips are of critical importance to the AI sector and currently in short supply too. ::Inflation assessmentAnd flash euro zone inflation for March is due on Tuesday. After long hovering around the 2% mark, higher energy prices are now expected to push headline inflation up, as they did in 2022. The question is, how large and sustained any jump in inflation might be.Early data is not painting a pretty picture. Private sector growth in the euro zone slowed sharply in March, with input costs rising to their highest in more than three years and supply chains being significantly disrupted.Money markets are now heavily pricing in a rate hike which was almost unthinkable before the Iran war.
To Comment or Not to Comment: Stars Wrestle With Politics on Red Carpet
It used to be that celebrities landed in hot water when they dared speak out about politics. Nowadays, they're getting slammed when they don't.
Why is laughter contagious? Blame your brain.
The science behind that uncontrollable giggle.
FSU College of Social Science launches three new degree programs
Florida State is expanding its career-focused curriculum, turning popular certificate tracks into full Bachelor of Science programs by fall 2026.
Sony Announces Price Rises for PS5, PS5 Pro, and PlayStation Portal, Blames 'Continued Pressures in the Global Economic Landscape'
Sony has announced price rises for PS5, PS5 Pro, and PlayStation Portal, blaming “continued pressures in the global economic landscape.”
Scientists find gut bacteria inject proteins that control your immune system
Gut bacteria aren’t just passive passengers—they can actively send proteins straight into our cells. Using microscopic injection systems, even harmless microbes can influence immune responses and metabolic pathways. Researchers found these interactions may play a role in inflammatory diseases like Crohn’s. It’s a major shift in how scientists understand the microbiome’s power over human health.
Marina and bar owner remains hopeful after Key Bridge collapse impacted business
It was two years ago that the Key Bridge collapsed in seconds after being slammed into by the Dali cargo ship.It was one of those moments those in Maryland reme
CSU Extension offers Ag Business Management workshop
Learn to create an enterprise analysis for alfalfa, barley, potatoes, quinoa, cow calf and forage cover crops
Cocaine-fueled sharks are on the prowl in the Caribbean — scientists blame partying tourists
This puts the "white" in "Great White."
Slow roll! Islam Makhachev not fighting until August
Islam Makhachev won’t be fighting over International Fight Week, according to UFC CEO Dana White. Makhachev’s manager was on TMZ Sports yesterday discussing the No. 1 pound for pound fighter and welterweight champion’s next move. He implied a July fight was ‘a done deal,’ but that’s apparently not the case. White came out on social […]
‘Congress is the villain’: Ex-Trump adviser slams shutdown blame game
The Most Overlooked Sign of Chronic Inflammation, Per a Holistic Health Doctor
Dr. Taz Bhatia reveals the physical changes you don't want to ignore and how to treat them.
After teaming up with Sony Music Publishing to acquire Miranda Lambert catalog, Domain Capital closes $768M
SMP Nashville and Domain teamed up to acquire Miranda Lambert catalog in January…
Jaguars President Mark Lamping & Mayor Donna Deegan Unveil Jaguars' New Business Headquarters
Jaguars President Mark Lamping and Jacksonville Mayor Donna Deegan speak to the media to provide a detailed overview of the Jaguars' new business headquarters. They discuss the vast improvements to the office space as well as the other businesses that wil
Jaguars President Mark Lamping on Impact of New Business Headquarters in Downtown Jacksonville
Jaguars President Mark Lamping meets with the media following the grand opening of One Tower Court: The Jaguars' new business headquarters.
Glyphosate: A story of science, risk, and nuance
In the summer of 2014, a California groundskeeper named Dewayne Johnson started noticing patches of raw, weeping skin spreading across his body. He had spent years applying Roundup, Monsanto’s glyphosate-based herbicide, for a school district, sometimes drenched in it when equipment malfunctioned. By 2014, he had a diagnosis: non-Hodgkin’s lymphoma. In 2018, a jury awarded him $289 million in damages, later reduced on appeal. Tens of thousands of lawsuits followed. The story hasn’t quieted down. It’s all over the internet, swinging between “this will kill you, buy organic” and “relax, you’re fear-mongering.” Some of that recent chatter stems from an Executive Order protecting glyphosate and its production, which set off intense infighting within the MAHA movement. Some of it reflects a deeper truth: Americans genuinely care about harmful chemicals in their environment (see poll below). And the conversation isn’t going anywhere, with a Supreme Court case involving Monsanto set for this April. Glyphosate (the active ingredient in Roundup) is one of the most widely used herbicides in the world. But does glyphosate cause cancer? And how much exposure is actually risky? With so much mistrust in institutions and corporations (and some genuine conflicts of interest), making sense of the actual scientific evidence is genuinely hard. Here is a translation of what the scientific evidence actually says. Does glyphosate cause harm? Glyphosate is an herbicide that kills most plants it contacts rather than targeting specific species. It works by blocking an enzyme pathway (EPSPS) that plants and many microorganisms need to produce essential amino acids. Without those amino acids, the plant can’t grow and dies. Glyphosate was first developed by Monsanto in the 1970s and became ubiquitous after the company introduced “Roundup Ready” crops in the 1990s. In 2024, Bayer removed glyphosate from residential Roundup-branded products due to litigation pressure. But today it is still the most widely used herbicide in the world. Farmers also discovered they could spray it directly on crops like oats, lentils, beans, and peas just before harvest to dry them out faster and make harvesting easier. Because of its widespread use, it’s obviously really important to understand if it’s harmful to humans. The key principle: The dose makes the poison The most important concept in toxicology is that “the dose makes the poison.” Sixteenth-century physician Paracelsus articulated what remains the foundational principle of toxicology: sola dosis facit venenum. Water will kill you if you drink enough of it. Aspirin saves lives at 81 milligrams and causes internal bleeding at higher chronic doses. So, at what dose is glyphosate poisonous? The LD50 in rats (the dose that kills half the test animals) is around 5,600 mg/kg body weight. Table salt is roughly 3,000 mg/kg. By that classic measure, glyphosate is less acutely toxic than salt. But some people are exposed to a lot of glyphosate through their work. And among the general public, there are many questions about low-dose, cumulative exposure from multiple sources over long periods. Does glyphosate cause health problems? Cancer Correlation maps are striking, with one analysis finding that 60% of counties that spray the most glyphosate have non-Hodgkin’s lymphoma rates above the national average. But correlation alone doesn’t establish cause, which is why animal and human studies matter. In animals: Rat studies are typically what most fear is rooted in, but most people don’t know the study details on the dosage given to rats. A pooled analysis of the 13 most rigorous rat studies found evidence that very high doses, around 55,000 times greater than typical food residue exposure, can cause certain cancers. In humans: One of the strongest studies followed 55,000 herbicide users over 20 years and found no overall increased cancer risk. There was one signal: among those with the highest use, rates of acute myeloid leukemia (AML) appeared elevated. A broader meta-analysis of 18 human studies also found no overall cancer risk, though a separate meta-analysis focused specifically on non-Hodgkin lymphoma found that people with high cumulative glyphosate exposure faced a 41% higher relative risk compared to those with low or no exposure. These human studies are observational studies (randomized controlled trials would be unethical), and meta-analyses are only as reliable as the studies they pool. But the story seems consistent: at very high exposure levels, there may be some cancer risk. But that’s about as far as the science currently takes us. Emerging research: gut and reproductive health Gut: Because glyphosate targets a pathway that exists in some gut bacteria, scientists have questioned whether it could affect the microbiome. In mice, a 2023 University of Iowa study found that glyphosate altered gut bacterial composition and raised markers of intestinal inflammation. A 2024 systematic review found similar patterns: disrupted gut bacteria and problems with the mucus layer that protects the intestinal wall in mice. Whether this translates to humans is an open question. The human gut is highly variable and resistant, and we don't yet have strong studies confirming the same effects in people. Reproductive health: Animal studies have found that glyphosate-based herbicides can interfere with reproductive hormones, including disrupting egg cell development in mice and reducing the number of eggs available in sheep’s ovaries. However, the doses used in these experiments were high, so it’s not yet clear whether the same effects would occur in humans. On the human side, a 2021 pilot study led by Mount Sinai researchers tested urine samples from pregnant women across the U.S. and found glyphosate in 95% of them. The study also found a possible connection between higher glyphosate exposure during pregnancy and a subtle physical difference measured in female newborns. That said, some connections weren’t statistically reliable and this was a small study. The researchers themselves said more and larger studies are needed before drawing firm conclusions. What do regulators say about glyphosate safety? In 2015, the International Agency for Research on Cancer (IARC), part of the World Health Organization, classified glyphosate as "probably carcinogenic to humans" (Group 2A). The classification is worth taking seriously. But, there’s an important distinction: IARC classifies hazard, meaning the potential to cause harm under some conditions. It does not assess risk, which accounts for actual exposure levels and the real-world probability of harm. The U.S. EPA, the European Food Safety Authority, Health Canada, and regulatory agencies in Australia and Japan have all concluded that glyphosate is “unlikely to be carcinogenic to humans” at realistic exposure levels. They’re asking a different question: given how much of this people actually encounter, what is the probability of harm? Your actual exposure is what determines your actual risk. What does glyphosate mean for your daily life? At the grocery store: Food residues are small. The EPA’s acceptable daily intake is 1.75 mg/kg of body weight per day. To hit that threshold from oatmeal alone, a 150-pound adult would need to eat roughly 50 pounds of oats every day. But this calculation addresses only one pathway (food), and we don’t yet have robust tools to measure people’s actual total exposure. If reducing exposure matters to you, organic certification prohibits synthetic herbicides, and organic oat products generally test at lower or undetectable levels. Either way, a diet rich in whole grains, conventional or organic, is far better for your health than one that omits them out of fear of residues. On the farm: Occupational exposure is orders of magnitude higher than consumer exposure. Farmers and farm workers who mix, load, and apply glyphosate-based herbicides, especially without protective equipment, face meaningfully different risk profiles. Proper PPE isn’t optional. Integrated weed management strategies that rotate chemical modes of action are also worth taking seriously, both for health and for long-term effectiveness. If you live near a farm: Spray drift is real. Concentrations near field edges can spike during and after application, particularly on windy days. This is an area where I think public health could really step up and empower rural communities with buffer zones, rather than placing the onus on individuals. But for now, knowing your local agricultural calendar and keeping windows closed during application are the first steps. Bottom line Dewayne Johnson was exposed to glyphosate at levels most people will never encounter, and a jury decided he deserved compensation. That outcome is not evidence that the oatmeal in your pantry is dangerous. But it is a reminder that the dose, the context, and the person doing the exposing all matter enormously. Glyphosate is a chemical tool with benefits, trade-offs, and genuine open scientific questions. Learning to hold that complexity without collapsing into panic or dismissal is, honestly, one of the most useful and hardest things to do in navigating modern health science. Love, YLE Your Local Epidemiologist (YLE) is founded and operated by Dr. Katelyn Jetelina, MPH PhD—an epidemiologist, wife, and mom of two little girls. Hannah Totte, MPH, is an epidemiologist and YLE Community Manager. YLE reaches more than 425,000 people in over 132 countries with one goal: “Translate” the ever-evolving public health science so that people will be well-equipped to make evidence-based decisions. 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
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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!]
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Salamander Migration Has New Citizen Science Component
Each spring, blue-spotted salamanders emerge from their underground burrows at Presque Isle Park in Marquette and venture across the road to lay their eggs. Northern Michigan University students have been involved in conservation, data collection and public education efforts for this annual event, but this year, the general public is invited to play a more active role in salamander migration research. Northern Michigan University Biology Department Head Jill Leonard encourages community members to participate in the Marquette Citizen Science Project.
We disagreed on politics. We agreed on wine. That was enough.
At the Virginia Governor’s Cup Gala in Richmond earlier this month, a very dapper gentleman approached me and introduced himself. In his light-colored suit and bowtie, he looked very Southern in a classical sense, the sort of Virginia Gentleman you used to see south of the Rappahannock as recently as my college days. “I’m a longtime reader and fan of your writing, if not your politics,” he said. His comment was the proverbial iron fist in a velvet glove, simultaneously conveying praise and disapproval while establishing boundaries. Man, I wish we still discoursed like this instead of shouting bromides and insults to try and “own” our opponents with a funny meme and a furrowed brow. Subscribe “Well, we’ll always have wine to share together,” I said, and thanked him for his kind words. We clinked glasses, exchanged pleasantries about the delicious gold medal-winning wines being poured that evening, and went our separate ways. Our exchange reminded me that more unites us than divides us. Wine brings people together to share a meal and a few hours of joy despite our differences.1 That’s why I refer to the wine community — including readers and consumers — rather than the wine industry. Together, we are so much more than production, distribution and sales statistics. A few minutes later the evening’s awards ceremony began. Applause grew as the 12 winemakers who made the top-scoring wines for the Governor’s Case took the stage, including a loud cheer for Jonathan Wheeler of Trump Winery and his 2018 Blanc de Noir sparkling wine. All the winemakers on stage had reason to be proud, Wheeler perhaps more so. Trump Winery was the only winery to win six gold medals in the competition this year. (Wineries are limited to six entries.) Two of Wheeler’s ciders also won gold medals in a separate competition. When you cover the labels and take the sour taste of politics off your palate, the wines are pretty darn good.2 Then Gov. Abigail Spanberger, newly elected Democrat and Virginia’s first female governor, was introduced to great applause to announce which of the 12 wines had won the Governor’s Cup. She spoke for a few minutes about the importance of wine to Virginia’s economy and tourism and the international acclaim Virginia wine has received. Just two weeks earlier, she gave the Democrats’ response to Trump’s State of the Union speech, but this night wasn’t about politics. That didn’t stop several people in the crowd from speculating on the irony should she have to present the trophy to Trump Winery. In the end, Valley Road Vineyards was displayed on the screen behind Spanberger as the winning winery. Blue Bee Cidery in Richmond took top honors for that category. The crowd cheered a female governor presenting the state’s highest trophy to a female winemaker and then resumed the evening’s festivities, united by their mutual love of wine. A whiff of politics couldn’t dim the cheer of celebration and a community united by its love of wine. In Memoriam: Michel Rolland The global wine community lost a giant March 20, with the passing of Michel Rolland. He was 78. Rolland was the original “flying winemaker,” a globe-trotting consultant who helped Bordeaux regain its mojo in the 1970s and then shaped the rise of Napa Valley cult Cabernet as consultant to Simi, Harlan, Newton, Screaming Eagle, Araujo, Dalle Valle and other wineries. He was instrumental in Argentina’s rise to prominence and even had his own winery, Clos de los Siete, in a partnership with other wine families. Rolland’s career arc paralleled that of Robert Parker, the world’s most influential critic. Parker championed many of the wines Rolland consulted on, helping build his reputation and demand for his services. It also made him a target for Parker’s critics. As W. Blake Gray wrote on Wine-Searcher in his excellent tribute to Rolland: Rolland created the type of wines Parker loved: rich body, plenty of fruit, soft tannins. He sometimes faced the accusation of creating a generic international style of red wine, where the great wines he made in Argentina were indistinguishable from the great wines he made in France. Rolland chafed at that critique, as did many of his fans. He was credited with championing green harvesting and leaf pulling, as well as careful selection of grapes in the winery, practices we nearly universally think of today for high-quality winemaking. “Michel was an incredible innovator who changed how wine was made and how grapes were grown,” Napa Valley winemaker Aaron Pott wrote on Facebook. “His work has transformed the wine trade. He created new ways of looking at wine, tasting wine, evaluating ripeness and quality. … This was not just a man with a ‘style’ that he imposed on vineyards but a man that understood how to make great wine from great sites.” Rolland started his consulting company in 1973 in Libourne, in Bordeaux, with his wife, Dany. Both had graduated the year before from Bordeaux’s Institute d’Oenologie. The couple sold their majority share in the business in 2020, according to Wine Spectator. Over his career, Rolland reportedly worked with more than 100 wineries in 20 countries. He even made it to Virginia, where he consulted for Kluge Estate in the mid-2000s. (Kluge Estate is now Trump Winery.) Reader feedback, please! Last week, I did my first WineLine Live! with Dr. Laura Catena of Catena Zapata winery in Argentina. We enjoyed a fascinating discussion about her efforts to preserve the genetic heritage of old vineyards in Mendoza. I conceived of WineLine Live! for paid subscribers, as a thank you for your financial support. And while only a few people joined live, the video now has more views than I have paid subscribers, so I guess that’s pretty good. Even so, I’m considering opening future installments to anyone on Substack to reach a broader audience. So my questions to you: Should these be public? And what format do you prefer? Live gives a chat feature with the potential for viewers to interact with me and the guest, while a video post would just be that. Another alternative is a podcast, which would just be audio, without video of my chins. Please let me know in the comments. Leave a comment In the Glass A few wines I’ve enjoyed recently: Bonny Doon Vineyard Take Me to Your Liter, Le Cigare Volant, Red Wine of the Earth. 2023, Central Coast, CA. Blend of Grenache, Syrah Cinsaut and Petite Sirah. Delightful wine with expressive red fruit flavors, casual drinking. Doon lovers of a certain age will remember Randall Grahm’s Big House Red; this is more in that style than his original Le Cigare Volant, modeled after Chateauneuf du Pape. The liter bottle makes it an even better value. I see this online at about $15. Great value. Albert Bichot Bourgogne Pinot Noir Origines 2023. 13% - Textbook pinot noir and an excellent, affordable entry (regional) Burgundy. Wine Enthusiast Top 100 Wines of 2025. $24 at Total Wine & More. Loma Larga Pinot Noir 2021 “Coastal Cool Climate Wine”, Valle de Casablanca, Chile. An older sample, showing beautifully. Spicy and fruit forward. I’m seeing widely varied pricing online, from $18-$32. At the lower end, it’s a terrific value. 13.5% Dr. Loosen Riesling Dry 2016, Mosel, Germany. Found this “in the stack.” And it stacked up well, shedding some of its youthful acidity for opulent Riesling character, including a hint of the mineral oil older Riesling often features. A great value, as I’m seeing it as low as $14 online. 12% abv. Red Tail Ridge Blau Franc Blend 2024, Sans Oak, Finger Lakes. 13.4% abv. The name is a neat portmanteau of Blaufrankisch and Cabernet Franc, thus Blau Franc. The blend is 50-50, no oak involved. The Blau dominates on the palate, with the spicy caraway seed (think New York deli rye bread). The Franc adds body. The result is juicy, energetic and joyful. Sokol Blosser Estate Rosé of Pinot Noir 2025, Dundee Hills, Willamette Valley, Oregon. This first rosé of 2025 was a welcome respite to our cold, snowy winter here in the Mid-Atlantic. Oh man, I needed this! Bright and energetic, exuberant even, it perks up the mood and goes down fast. 13%. Certified B Corp. Ingredient and nutrition labeling, and in a modest way that doesn’t occupy a lot of label space. (Since it’s not required, presumably there are no minimum font size requirements.) More wineries should follow this example. Dave McIntyre's WineLine is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber. Subscribe Thanks for reading Dave McIntyre's WineLine! This post is public so feel free to share it. Share 1 Some restraint may be required. 2 Especially the bubblies.
Scientists say NAD+ could slow aging and fight Alzheimer’s and Parkinson’s
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Khloé Kardashian Recalls How Her Divorce from Lamar Odom Made Her ‘Obsessed’ with Leading a Healthy Lifestyle
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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. 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.
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