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The 'Nail Test': Why This $54 Billion Innovation Is Terrifying Western Auto Executives
BYD says it's fixed yet another major problem with EVs.
Today's hefty Crimson Desert patch includes "beginning of improvements" to keyboard and mouse controls, plus much more
Pearl Abyss has detailed a rather chunky patch for Crimson Desert, after its launch last week was marred by multiple issues and AI controversies.
Science Explains Why You Wake Up at 3 am, and How to Go Back to Sleep
About one in five people have middle-of-the-night insomnia.
Kathy Ireland Accuses Business Managers of Looting Her Fortune
The model-turned-entrepreneur and lifelong Santa Barbara resident claims decades-long deception left her virtually broke.
Small swings, high drama: why UK polls are less volatile than they seem
In what is beginning to look like a fragmented five-party system, small swings carry outsized political consequences
‘Anyone but Labour’ or ‘anyone but Reform’? Clash of animosities likely to define May local elections
While Labour braces for a rout that could see off Starmer, a rising drive to keep out Farage is complicating expectations
What’s at stake for UK in May’s local elections: six key questions
Reform, Plaid Cymru, the SNP and the Greens are all banking on big gains and nationwide repercussions
AI Swarm Attacks Are Coming, Is Your Business Ready?
Leaders need a new cybersecurity playbook for the agentic era, with stronger governance, faster response systems, workforce awareness, and up-to-date security frameworks.
Breaking the Cycle review – meet the charismatic Thai politician striving to change his country’s history
Gripping documentary examines the Future Forward Party’s unprecedented 2019 election result, and its leader’s aim to break Thailand’s repeated military coups
Funding for populist-right ‘media-political complex’ exceeded £170m in five years, research finds
Handful of billionaires gave huge sums in particular to media organisations that boosted rightwing politicians, says Liam Byrne MP
Connections: Sports Edition today: Hints and answers for March 23, 2026, puzzle No. 546
Welcome to Connections: Sports Edition Coach — a spot to gather clues and discuss (and share) scores.
Today's NYT Connections: Sports Edition Hints, Answers for March 23 #546
Here's today's Connections: Sports Edition answer and hints for groups. These clues will help you solve The New York Times' popular puzzle game, Connections: Sports Edition, every day.
Dean for Basic Science Colin Duckett tapped to serve as Boston University Provost
Duckett, executive vice dean for basic and preclinical science, will begin his tenure as chief academic officer at Boston University starting in July.
Simona Martin: Colorado’s data center boom needs public health guardrails
As AI infrastructure expands across the state, lawmakers face a choice about who bears the costs and risks.
Column: Accessing mental health support shouldn’t require a walk across campus
"While well-intentioned universities have developed mental health support systems, they are poorly designed to meet students’ needs."
A promising fatty liver treatment may raise cancer risk
A surprising new study reveals that blocking a supposedly protective enzyme, Caspase-2, could actually backfire—raising the risk of chronic liver damage and cancer over time. Researchers found that without this enzyme, liver cells grow abnormally large and accumulate genetic damage, leading to inflammation, scarring, and eventually tumors, especially with age. While inhibiting Caspase-2 may offer short-term benefits, such as reducing fatty liver disease, the long-term consequences appear dangerous.
This Couple Turned A Facebook Marketplace Side Hustle Into A Seven-Figure Business
When Harrison Gordon and Paige Sandher couldn't find a modular custom sofa that was also affordable, they designed their own. They built a fast-growing business around their idea.
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.
United Airlines Just Issued a Playbook for Any Business Staggered by Skyrocketing Costs
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The trope of ‘choosing pets over people’ is not new
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Crimson Desert admits it used generative AI for "early-stage iteration" and apologises AI images were not replaced before release
Crimson Desert developer Pearl Abyss has responded to claims its latest game used AI to generate images, admitting "2D …
The '80s Car Feature That Would Fit Perfectly In The AI Hellscape Of Today
The '80s car feature that would fit perfectly in the AI hellscape of today is Chrysler's Electronic Voice Alert that gave drivers warnings by speaking to them.
Capcom celebrates Resident Evil's 30th anniversary by promising "even more wonderful experiences" are coming, but doesn't confirm when
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Why Small Process Changes Often Deliver the Biggest Business Results
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Fitchburg Public Library hosts Wisconsin Film Festival preview
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American football takes for ever. In which other sports do you spend most of your time not playing the game?
The long-running series in which readers answer other readers’ questions on subjects ranging from trivial flights of fancy to profound scientific and philosophical concepts
It’s time to take politics out of the Small Business Administration
The White House’s politicization of the agency will have a real-world impact on small business owners in the US
It’s time to take politics out of the Small Business Administration
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This Fresh Take on Sherlock Holmes Is the Best New Show on TV RN
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Natrona County health and food inspections (3/13/26–3/19/26)
CASPER, Wyo. — The Casper-Natrona County Health Department inspects restaurants, grocery stores, convenience stores, mobile food units, commissaries and
Square Enix announces it will integrate Google’s generative AI Gemini into popular online game Dragon Quest X
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UF students celebrate ‘women supporting women’ through new mental health group
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6 Side Hustle Businesses You Can Start With $0
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Give Your Phone a Huge (and Free) Upgrade by Switching to Another Keyboard
Change up the default keyboard in Android and iOS and feel the benefit.
Four truths about covid that have become clouded over time
In the early days, the virus posed a graver threat to people and the health care system, Trump embraced lockdowns he now blasts, and the benefits of vaccines were oversold.
Burcum: UCare collapsed. The Legislature needs to ask why.
"How did UCare, one of Minnesota’s largest health insurers, go from posting record earnings for 2022 to collapsing in 2025?" columnist Jill Burcum writes.
Scouting Future Saints: Washington wide receiver Denzel Boston
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We are living in a period of political anti-intellectualism. But in pop culture, clever is the new cool
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The Business of Football: How many players do you need to win a World Cup anyway?
The English FA and the Premier League are having another row, as the club vs country debate rages on in English football
Connections: Sports Edition today: Hints and answers for March 22, 2026, puzzle No. 545
Welcome to Connections: Sports Edition Coach — a spot to gather clues and discuss (and share) scores.
New Research Shows the 6 Skills You Need to Master Anything
Scientists explain why some of us benefit more than others from expert guidance.
Today's NYT Connections: Sports Edition Hints, Answers for March 22 #545
Here's today's Connections: Sports Edition answer and hints for groups. These clues will help you solve The New York Times' popular puzzle game, Connections: Sports Edition, every day.
Amanda Peet Shares Breast Cancer Diagnosis
Amanda Peet detailed her recent breast cancer diagnosis in a new essay, sharing that her health battle coincided with both of her parents' final months in hospice care.
Arkansas vs High Point live updates: March Madness Round 2 game highlights, how to watch
We're running out of Cinderellas. Will the slipper still fit for High Point? Arkansas and Darius Acuff Jr. will have something to say about that.
Uber's Advertising Business May Be Bigger Than Investors Think
Uber is best known for moving people and delivering food. However, something small but potentially profitable is growing at the company.
Surprise! Minecraft Dungeons 2 is coming later this year
Surprise! Minecraft Dungeons 2 is coming to PC via Xbox and Steam, PS5, Nintendo Switch and Switch 2, and Xbox Series a…
Top business aviation banker talks debt, profits, JetGate, EBITDAR
Jefferies' Nick Fazioli on why Wall Street loves private jets, non-GAAP financial metrics and why past results don't preclude more investment
Wrexham’s Hollywood owners’ Sky Sports’ watchalong criticised by Swansea CEO
Sky offered an alternative commentary with Wrexhman owners Ryan Reynolds and Rob Mac alongside regular presenter David Prutton.
Not all business owners: How Business for Good is building a new voice in San Diego
Business for Good, a network of San Diego business leaders, advocates for progressive causes in the region.
Apple M5 MacBook Pro and Air Review: When the Neo Isn’t Enough
Apple’s new laptops and high-end display fit the bill for the company’s most demanding customers.
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Doulas can improve health outcomes for women and babies. Insurers are taking notice.
While more Medicaid patients and even some on private plans have gained doula coverage in recent years, United is the first major insurer to begin rolling out the benefit nationwide.
Here's How You Can Watch Sports With a VPN
A VPN can enhance your sports streaming by unblocking regional matches, circumventing geographical limitations or bypassing throttling restrictions.
Small Business Tech News: Google Maps Gets A Big AI Upgrade
AI takes over Google Maps, TikTok is helping small businesses advertise, AI hacking is better than humans.
11 Free AI Courses That Can Help You Start a Business
Several companies, including Anthropic, OpenAI, and Google, offer free online courses to help you learn AI.
The Science Behind the $19 Million Colostrum Craze: Miracle Cure or Marketing Myth?
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Ole Miss eyes May decision on VaughtHemingway entertainment district partner
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Minnesota Blue Cross CEO steps down from Sutter Health board over conflict of interest
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Big changes ahead for State Health Plan as trustees work to lower costs
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Department of Health retracts claim sunbeds are as dangerous as smoking
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From Project Hail Mary to Saturday Night Live UK: your complete entertainment guide to the week ahead
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Israel deliberately targeting medical facilities in south Lebanon, say health workers
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Connections: Sports Edition today: Hints and answers for March 21, 2026, puzzle No. 544
Welcome to Connections: Sports Edition Coach — a spot to gather clues and discuss (and share) scores.
What Buffy's Nicholas Brendon Said About His Congenital Heart Defect, Cauda Equina Syndrome Before Death
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What I’m seeing at Astros camp: Brice Matthews’ OF bid, Cam Smith’s mindset, more medical changes
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Readers Write: The size of the Legislature, Markwayne Mullin, voter ID, science fiction
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Today's NYT Connections: Sports Edition Hints, Answers for March 21 #544
Here's today's Connections: Sports Edition answer and hints for groups. These clues will help you solve The New York Times' popular puzzle game, Connections: Sports Edition, every day.
Bangor Mall furniture store sold to out-of-state business
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The Best Early Amazon Big Spring Sale Apple Deals We've Found So Far
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Maternal and Infant Health in State Rural Health Transformation Proposals Set Promising Priorities in an Uncertain Landscape
Visit the post for more.
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Sports writer and photographer win Quill awards for work for Guardian Australia
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The R.I.-based pharmacy giant also owns health insurer Aetna and pharmacy benefit manager Caremark, allowing it to control how medications are priced, prescribed, and dispensed
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MSU Museum panel teaches about AI, politics and misinformation
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Group, which also owns Dove and Hellmann’s, will focus more on personal care products if deal agreed
Allegheny County health board considers fracking impacts
There are 225 active wells located on 30 well pads in Allegheny County, according to data from the Pennsylvania Department of Environmental Protection analyzed by the non-profit Fractracker Alliance.
How Muslim Businesses in New York Prepare to Celebrate Eid
From Fordham to Bay Ridge to Hollis, Muslim businesses get ready for Eid al-Fitr, the exultant celebration marking the end of the holy month of Ramadan.
Rising toll: Are NC sports betting protections enough?
With two years of legalized sports betting in the books, public health advocates, researchers and counselors suggest changes.
Researcher: Addressing runaway college sports spending in Virginia
This whole college sports enterprise is business development that is being financed by student subsidies, and frequently ever higher student loan debt. As a society, do we do this for any other fo…