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Woman says popular oil change business left her engine in the backseat
“What they pulled out of my car looks like something from a sci-fi movie.”
FDA panel on peptides will include experts who promote the unproven chemicals favored by RFK Jr.
The Food and Drug Administration is meeting next month to consider easing restrictions on several peptides, a group of unapproved drugs popular with followers of Robert F. Kennedy Jr.
WhatsApp Now Lets You Reserve a Username
Popular messaging app WhatsApp is now allowing users to reserve usernames ahead of plans to launch username-based messaging. Right now, WhatsApp uses a person's phone number as an identifier, but usernames will allow people to interact without having to exchange personal information. Username reservations are rolling out starting this week, and not all users will have access to the reservation system right away. WhatsApp is sending a notification when a username can be reserved.
Netflix and Superheroes Are Having a Rough Stretch on Streaming....
(Welcome to my weekly streaming ratings report, the single best guide to what’s popular in streaming TV and what isn’t. I’m the Entertainment Strategy Guy, a former streaming executive who now analyzes business strategy in the entertainment industry. If you were forwarded this email, please subscribe to get these insights each week.) I have a quick prediction before we start today’s article: You might see this data in future news articles. Not my specific charts or analysis, but the core trend I’ve been monitoring—Netflix is having a lackluster Q2—will become inescapable. Often, folks want to know “What does the data say?” Well, that’s what it says. I haven’t seen this analysis hit the trades really yet, but I have a feeling some other outlets are going to start making this case soon. Remember, you read it here first. You probably have read about the problems facing superhero films at the box office this weekend. Well, this week, I explore whether superheroes are dying on TV as well! And the data says: definitely maybe! We have a lot to cover in today’s Streaming Ratings Report, which covers the two weeks of 18-May and 25-May. Today, I’m just looking at TV, like Netflix’s disappointing Q2, superhero shows underwhelming, a few TV shows dropping off the charts, The Pitt finally ending its epic run on the viewership charts (and whether “view counts” change its status as one of the biggest shows of all time), all the flops, bombs and misses, and a whole lot more. Tomorrow, I’ve got a great rundown of the film side of things. Let’s dive right in! (Reminder: The streaming ratings report focuses on the U.S. market and compiles data from Nielsen’s weekly top ten viewership ranks, Luminate’s Top Ten Data, Showlabs, TV Time trend data, Samba TV household viewership, company datecdotes, Netflix hours viewed data, Google Trends, and IMDb to determine the most popular content. While most data points are current, Nielsen’s data covers the weeks of May 18th to May 31st, 2026. You can find a link to my terminology here.) Subscribe Television - Netflix’s Q2 Slump Continues Having analyzed streaming ratings for going on half a decade, I have learned to trust my gut, but I’m always relieved when I can find actual data to back it up. For example, after a string of very popular shows like Stranger Things, Bridgerton, The Lincoln Lawyer and The Night Agent came out, week after week, in January and February, my gut wondered if Netflix had enough new and returning TV shows to sustain them throughout the year. Since then, Netflix’s post-March slate of shows has not impressed me. This week seemed to feature a potential new hit, but then, like a classic Duffer Bros. TV show, there was a twist. I speak of The Boroughs, Netflix’s latest (and last) Duffer Bros. produced show. The pitch is “Stranger Things with older actors”. And it topped the Nielsen charts: With just two weeks of viewership, The Boroughs would have been a top 25 debut show last year: But here’s the twist: Netflix has already cancelled The Boroughs! What happened? Likely a few things. First, the show didn’t do as well globally as it did in the US. As What’s on Netflix showed, it lagged behind several other shows that got cancelled. Second, its completion rate was likely low; after an initial burst of interest, it quickly dropped off on the Samba TV and Luminate charts. Third, the Duffer Bros. left Netflix for Paramount, and that may have factored into Netflix’s decision here. (Though I tend to believe that if a show is doing well, Netflix would have kept greenlighting seasons.) Still, just because I can explain why Netflix may have cancelled this show doesn’t mean I’m justifying it. In particular, as I’ve noted before, Netflix is losing a lot of their bigger shows as they reach their natural ends, and they need to replace those shows. This show had the hallmarks of a big new genre show, and it’s their biggest hit of the last few months (in the US at least), but now it’s done. Netflix’s other show this week—The Four Seasons, the second season of the “hit” show from last year—definitely disappointed. Its sophomore season had about half the viewership of the first, only 12.7 million hours. It also only had a two week run on Samba TV, and its numbers were all down on Luminate too. In other words, even with two successes, the Q2 slump for Netflix looks real: I could add to the list of disappointments: Both Lord of the Files and Man on Fire had short runs on the Nielsen charts. Running Point’s sophomore season also opened to about half its viewership, similar to The Four Seasons. A Good Girl’s Guide to Murder’s second season—see below—didn’t even make any of the three viewership charts I track, unlike the first season. Netflix is absolutely having a dismal second three months of 2026. If this Nielsen data is any indication, and I think it is, I think this will show up in Netflix’s engagement report, and maybe even their financial outcomes. And the rest of June doesn’t look much better. We have two hit shows coming back—Sweet Magnolias, one of their quietest big shows, and Avatar: The Last Airbender, a big hit for them in 2024—but the other big swings are limited series crime thrillers i.e. no future season potential. Like I said above, sometimes when I uncover a juicy nugget like this, other outlets end up writing very similar articles mimicking the data without credit. We’ll see if that happens this time! Share Television - The State of Superhero Shows on Streaming When I first heard the pitch for Spider-Noir—a Sony TV show on Prime Video that binge-released eight episodes first on MGM+ then on Prime Video two days later—I had my doubts. It’s a live-action Spider-Man show set in the 1930s, starring Nicholas Cage, based on a cameo of a character in Spider-Man: Into the Spider-Verse. No, seriously, that’s the pitch. That could either go terrifically well or horribly wrong. Great because, Spider-Man. He’s the biggest superhero we have. I’ve seen tracking numbers that put the new _Spider-Man: Brand New Da_y as the blockbuster of the year and initial pre-sales back that up. And yet this Spider-Noir pitch feels very esoteric. (Also, the eight-episode binge release feels very “Amazon copying Netflix” again.) So what’s the data say? And what does this say about the future of superhero shows?
Alt-rock band Drip Edges hits the stage at Gabe’s
Drip Edges, led by Jeremy Scott, delivers powerful alt-rock influenced by power pop bands like Sugar and the Smithereens, showcasing catchy, dynamic tracks that highlight the lead singer’s dedication to
Peptides are the latest US health craze. But what exactly are they?
While peptides are taking the health and wellness category by storm for various use cases, what exactly are they? Leerink Partners senior research analyst Michael Cherny helps break down what a peptides are, how people are choosing them for personal health and recovery reasons, and who the biggest winners in consumer pharmaceuticals could be if their popularity continues to grow.
Man uses a Game Boy Camera to photograph Jupiter
With a big boost from Mount Wilson Observatory’s powerful Hooker Telescope.
New estimate: Earth has 14 to 20 million insect species
For 40 years, we thought Earth was home to six million insect species. Turns out, it could be three times that.
Monroe County Health Department investigating cluster of cyclosporiasis cases
The Monroe County Health Department is investigating a cluster of cyclosporiasis cases that have popped up in the past week.
Arena, the AI leaderboard everyone uses, is now a $100M business
The startup, which runs a popular free AI leaderboard, launched its commercial service just last September.
Luna the eagle takes a ‘leap of faith’
The 13-week-old eaglet flew to another tree, where his dad Shadow was waiting.
What really happened to Lizzo’s career?
The pop star is back with a new album, a new look and a lot of baggage. People aren’t buying it.
Lizzo slams 'Khia Asylum' meme for 'flopping' pop stars: 'Weapon that targets only women'
Lizzo slammed the 'Khia Asylum' meme often use for 'flopping' pop stars: 'A tool to bully artists,' she said, calling the title itself 'backhanded' for mocking a 'pillar in the Black community.'
Silver Spring business releases 600,000 infected mosquitoes in DC area
In an innovative way to decrease the mosquito population, when one of the male ZAP mosquitoes being released mates with a female, she will no longer be able to produce offspring.
Silver Spring business releases 600,000 infected mosquitoes in DC area
In an innovative way to decrease the mosquito population, when one of the male ZAP mosquitoes being released mates with a female, she will no longer be able to produce offspring.
Star-maker Clive Davis honored at funeral that draws Bruce Springsteen, Dionne Warwick and others
Kenny G played a mournful sax solo to kick off the funeral for music legend Clive Davis. Pop music royalty, including Bruce Springsteen, Barry Manilow, Stevie Wonder and Dionne Warwick,
The Ken-ification of Hungarian Politics
June 29, 2026 | What does Orbán’s defeat reveal about the limits of performative masculinity in populist politics?
Kakao Entertainment Announces Genre-Spanning Lineup
Kakao Entertainment enjoyed a highly successful first half of the year, with its Netflix series “The WONDERfools” and “Boyfriend on Demand” hitting global home runs with their distinctive narratives. Also building on the recently released suspense drama “Notes from the Last Row,” Kakao Entertainment’s genre-spanning 2026 slate features the upcoming action-comedy “A Bona Fide Killer” and the thriller “Mousetrap,” cementing - Read our full Pop Culture on The Outerhaven .
India’s Yash Raj Films Backs Rusk Media in Vertical Entertainment Push (Exclusive)
IMDb, the world's most popular and authoritative source for movie, TV and celebrity content.
Investor Clive Meanwell on designing biotechs for population health, and AI's role as a catalyst
Clive Meanwell, chairman of investment firm Population Health Partners, was an AI skeptic until recently. Now, he thinks it's a catalyst.
Grand Theft Auto VI Rumored to Offer 60 FPS Mode on PS5/Xbox Series X, But Maybe Not at Launch
One of the reasons Grand Theft Auto VI fans are eager to learn the currently missing details on PS5 Pro enhancements is that the most powerful console available on the market is expected to include a performance mode targeting 60 FPS. However, according to a credible source, there's a decent chance that even the base PlayStation 5 and Microsoft's roughly equivalent Xbox Series X will support 60 FPS in Rockstar's massively anticipated game. The rumor comes from the popular Polish gaming podcast Rock and Borys, which features Remigiusz "Rock" Maciaszek and Borys Nieśpielak. It is the latter who shared in […]
AB Science reports completion of the step 3 of phase 1, evaluating the combination of AB8939 with venetoclax for the treatment of refractory or relapsed AML
PRESS RELEASE AB SCIENCE REPORTS COMPLETION OF THE STEP 3 OF PHASE 1, EVALUATING THE COMBINATION OF AB8939 WITH VENETOCLAX FOR THE TREATMENT OF REFRACTORY OR RELAPSED ACUTE MYELOID LEUKEMIA THE COMBINATION OF AB8939 WITH VENETOCLAX GENERATED A 67% OVERALL RESPONSE RATE (ORR) AND A 100% DISEASE CONTROL RATE (DCR), WITH NO DOSE-LIMITING TOXICITIES (DLT) OBSERVED, IN A POOR-PROGNOSIS POPULATION WITH ADVERSE GENETICS TREATED IN THE SECOND - TO FOURTH-LINE RELAPSED OR REFRACTORY SETTING Paris, June 2
AI scientist company Edison Scientific tapped by team behind Metsera to create new biotechs
Edison Scientific and investment firm Population Health Partners are teaming up to leverage AI agents in drug discovery and development.
Meaningful Outcomes Determine the Winners of the Health AI Race
Global investment in healthcare AI exceeded $18 billion in 2025, yet health systems still lack a shared understanding of the outcomes that investment should deliver. This paper argues that success in the health AI race will be determined not by technological sophistication but by which systems first identify and pursue the outcomes that matter most to patients, professionals and health systems. Without a shared language for defining and measuring what healthcare AI should deliver, systems risk optimizing for what is easiest to count rather than what matters most. This paper provides a framework for ensuring AI investment translates into real value for healthcare systems and the populations they serve.
One of Jackie and Shadow’s chicks accidentally left the nest
Sandy lost her footing and fell down a few branches.
Europe’s Heat Politics
As the continent swelters, some right-wing populists are talking up their support for air-conditioning.
Efzimfotase alfa demonstrated improvements in bone health in treatment-naïve pediatric patients with hypophosphatasia achieving median difference of 1.67 vs placebo in RGI-C Score at week 25 in MULBERRY Phase III trial
Positive results from the MULBERRY Phase III trial showed that efzimfotase alfa (ALXN1850), an investigational enzyme replacement therapy, demonstrated a statistically significant and clinically meaningful improvement in bone health in children (2 to
16 gorgeous images from the 1839 Awards’ Color Photography Contest
All the beautiful shades of our planet and its creatures.
Leo XIV’s second “business” consistory produced few headlines, but that’s by design
On Saturday, Pope Leo XIV brought an end to the second extraordinary consistory of his pontificate. The meeting of cardinals was not very exciting, which might have been the point.
Sen. Warnock was struck that VP Vance ‘wasted no time telling the Pope how to be the Pope.’
Democrats wrestle with race, populism and ideology in clashes with lawmakers of color
The Democratic Party is confronting its long-standing dilemmas over identity and ideology as it wrestles with populist challengers in communities of color.
Democrats Wrestle With Race, Populism and Ideology in Clashes With Lawmakers of Color
WASHINGTON (AP) — After democratic socialist Claire Valdez defeated an establishment-backed candidate in New York's congressional primary last week, her elated supporters quickly turned their attention to a new target. “You're next!” they chanted when an image of House Democratic leader Hakeem ...
Why are airplanes so cold? It’s for your health.
From combating fainting to helping aircraft work efficiently, planes are chilly for a reason.
Popular 9-season sitcom losing its streaming home at end of the summer
The Emmy-award winning series is regarded as as one of the most iconic shows in television history.
Today's NYT Connections: Sports Edition Hints, Answers for June 28 #643
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.
Caminero to the moon: Rays 4, D-Backs 2
Before you could grab your hot dog, popcorn, and preferred pilsner beverage, the Diamondbacks took a 1-0 lead on a Geraldo Perdomo double, Corbin Carroll single, and a whiff of a tag from catcher Hunter Feduccia. In the bottom half of the first, Junior Caminero hit a thunderous, sky-scraping blast for his sixth homer in […]
Texas Democrats welcome Bernie Sanders and plunge into economic populism
In speeches and conversations throughout the convention, Texas Democrats embraced affordability and anti-corruption themes championed by the Independent senator from Vermont.
Madonna makes rare reveal of 1 major pop diva she was 'jealous' of
"I was like, 'I'll never be as beautiful as Kylie!'" she said.
Madonna makes rare reveal of 1 major pop diva she was 'jealous' of
"I was like, 'I'll never be as beautiful as Kylie!'" she said.
Madonna makes rare reveal of 1 major pop diva she was 'jealous' of
Madonna recently revealed why she was 'jealous' of Kylie Minogue, even though she wore a T-shirt bearing the 'Can't Get You Out of My Head' singer's name to the MTV Music Awards in 2000.
10 Game-Changing Entertainment Venues Designed by Populous
A look at 10 entertainment venues by Populous, spanning esports, concerts, and more, that are redefining audience experiences worldwide.
Scientists finally reveal the shocking truth behind England’s dolphin deaths - Futura-Sciences
A Drastic Decline Along English Shores The dolphin populations along the English coastline have been disappearing at an alarming rate for several decades. Contrary to what many might hope, these aren’t dolphins simply seeking warmer waters elsewhere. The brutal reality is that this is not migration—it’s mass mortality. English researchers...
Ranked: America’s Best-Selling Albums Ever
Michael Jackson may be the king of pop, but in the U.S. he's been outsold by a rock band from Los Angeles.
3 ways you’re working wrong, according to scientists
Stop multitasking.
Country music icons play final show after 6 decades together: ‘What a run we’ve had’
The popular group thanked fans as it took its final bow.
3 foods that seem healthy but may be bad for your heart: cardiologist
A cardiologist said popular "healthy" foods can actually be bad for your heart, since they're highly processed and full of additives like sugar and fat.
Public health alert issued for chicken sold at popular grocery store in the Tri-State area
A public health alert was issued for chicken sold at a popular grocery store chain in the Tri-State area.
iPhone 18 Pro and Pro Max May See $200 Price Increase
Apple's iPhone 18 Pro models could be up to $200 more expensive, according to a prediction from analytics firm IDC. IDC expected Apple to raise iPhone 18 prices, but prior to yesterday's Mac and iPad price hike, the prediction was a $100 increase for the 18 Pro and Pro Max, and a $50 increase for the base models. IDC Senior Director of Data & Analytics Nabila Popal says the magnitude of the Mac and iPad price increase points to even higher iPhone 18 prices.
Bridget and Mike Chiodo on Strong Bond, Health Struggles, Family
Influencer Bridget Bahl and her husband Dr. Mike Chiodo join TODAY’s Jenna Bush Hager and Sheinelle Jones to celebrate Bridget becoming cancer free, open up about their steadfast bond and share an update on their dream of starting a family.
Why do fireflies glow? It’s more than butt goo.
These luminous beetles use light to flirt and fend off predators.
Sweden and WHO launch new long-term initiative to transform Ukraine’s health system
WHO and the Swedish International Development Cooperation Agency (Sida) have launched a new multi-year cooperation project to support the long-term recovery and transformation of Ukraine’s health system. The new project, “Ukraine’s Health System Transformation Initiative: Strengthening Health Governance, Health Financing and Service Delivery for Long-Term Recovery”, was launched at the Ukraine Recovery Conference 2026 in Gdansk, Poland on 26 June, and will run from June 2026 to 2029. Sweden will contribute approximately US$ 26 million (240 million Swedish krona) to support this project. This contribution forms part of Sweden’s broader support to Ukraine through the Team Europe approach, which brings together the European Union, its Member States, and key partners such as the European Commission’s Directorate-General for Enlargement and Eastern Neighbourhood and Enabel, and WHO as lead health agency, to support Ukraine’s recovery, reform agenda and European integration.“Ukraine’s health recovery cannot be measured only by what is rebuilt, but by whether people can count on the health system when they need it most. The scale of the task is immense, with health reconstruction and modernization needs estimated at US$ 19.4 billion over the next decade. Sweden’s US$ 26 million contribution to Ukraine’s Health System Transformation Initiative is a timely investment in the institutions, financing and services that will support Ukraine’s long-term recovery and European integration. WHO remains a trusted partner of the Government of Ukraine in advancing this process. I am deeply grateful to Sweden for its consistent support and partnership,” said Dr Hans Henri P. Kluge, WHO Regional Director for Europe. More than 4 years of war have placed unprecedented pressure on Ukraine’s health system, creating 3 interconnected challenges. The first is responding to the immediate consequences of the war and the urgent health needs of the population. The second is recovering and modernizing health services today. The third is continuing reforms and aligning the health system with European standards in the context of Ukraine’s future accession to the European Union. The war has led to large-scale population displacement, an increasing need for trauma care and rehabilitation, and shortages of health workers. High out-of-pocket payments in Ukraine make access to health services more difficult. Around 46% of total health expenditure is paid directly by individuals, placing a significant financial burden on many households and underscoring the need for reforms in health financing. Older people, persons with disabilities, women, children and veterans continue to face the greatest difficulties in accessing health services. “Ukraine is demonstrating that health system transformation can continue even during war. Ukraine is also continuing to align its health system with European norms and standards. WHO is committed to supporting Ukraine on this journey. We provide technical support, help coordinate partners’ efforts and support the institutional changes needed to strengthen the system. We are grateful to Sweden for its support. Through this partnership, we can help Ukraine build a more resilient, accessible and people-centred health system,” said Dr Jarno Habicht, WHO Representative in Ukraine. About the Health System Transformation InitiativeThe new initiative will support Ukraine through 3 interconnected areas: strengthening governance and coordination of health sector reforms through more inclusive coordination platforms and structured policy dialogue; transforming service delivery by reinforcing a primary health care-centred model that integrates family medicine, nursing and midwifery; and improving financial sustainability by supporting reforms that ensure the long-term viability of the national health system and reduce out-of-pocket payments for households. Overall, these reforms are expected to make the health system more coherent and easier to navigate, improve the quality and continuity of care, and ensure more equitable access to services, particularly for those who need them most. They will also support Ukraine’s progress towards a more modern health system aligned with European standards. “We are convinced that long-term recovery is not possible without strong, high-quality, person-centred health services that are accessible to everyone. Our partnership with WHO is designed to support deep and lasting systemic changes. Investments in human capital especially autonomous midwives, whose role for maternal, newborn and adolescent sexual and reproductive health cannot be understated, stronger governance, digital transformation and the financial sustainability of the health system are investments in Ukraine’s future. We are proud to support this process,” said Malin Perhult, the Head of the Ukraine Unit at Sida. Focus throughout implementation will be given to the most vulnerable population groups, including older people, women and children, and persons with disabilities, who have been affected by the war and face greater health-care needs. The initiative will be implemented in close cooperation with the Ministry of Health of Ukraine, the National Health Service of Ukraine, the Public Health Centre of Ukraine, regional authorities and international partners. This project will help Ukraine move towards a system where everyone can access the health care they need. It will strengthen primary care, make the health finance system more stable and predictable, and reduce the out-of-pocket costs that Ukrainians face when using health services. As a result, the Ukrainian health system will become more aligned with European standards and more sustainable in the long run.
Is Mega Skarmory good for Pokémon GO Raids?
Super Mega Skarmory Raid Day brings one of the new Legends: Z-A Mega Evolutions to Pokémon GO, and gives the undeniably cool Skarmory a new lease of life in the Raids meta. A popular / type from Gen 2, Skarmory has been a staple in the Little and Great League formats, but has never made […]
Salpointe flag football QB named MaxPreps Freshman of the Year
It is the first year that MaxPreps is putting together an All-American team as the sport continues to gain popularity.
It's Xbox's turn (again), as console prices keep going up
Microsoft announced a price hike for the Xbox Series consoles today, the third in little over a year. Effective August 1, the Xbox Series S, which launched in 2020 for $300, will cost $500 in the U.S. The Xbox Series X, which launched in 2020 at $500, will go for $800. This follows a round of PlayStation 5 price increases from Sony this spring, and a slow-motion increase for Nintendo’s Switch 2, which will kick in in the U.S. in September. (Mind you, there were also eight video game industry price hikes in six months of 2025). The chart up top shows the sudden ascent of console prices over the past year, a sudden surge in an already unusual hardware generation. Prices had been flat for years, now “up” is the new “flat.” Game console prices used to go down across the length of a console generation, but not this time around. Microsoft’s explanation for the new price hike today: We hoped another price increase would not be necessary, and we have spent the last several months working with suppliers on options. Unfortunately, console storage and memory prices have increased by more than 2.5x and we expect another doubling by the fall of 2027. The entire consumer electronics industry is struggling with the current components crisis, but the effects are particularly hard on consoles. Unlike phones, computers, speakers, and other consumer devices, consoles are typically not sold at a profit, but instead for less than they cost to make. This is an issue well beyond game consoles. Apple announced price hikes on its computers and tablets today as well. Game File is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber. Subscribe Item 2: Brutal Bungie cuts Bungie laid off “most” of its Destiny development team and some developers who worked on Marathon, the newest game from the struggling Sony-owned studio. A WARN notice issued by Sony to Washington State, where Bungie is based, tallied cuts impacting 292 workers, effective next month. That’s strictly for Bungie/Sony jobs in Washington and wouldn’t account for any elsewhere. The video I clipped below shows the redacted list of Bungie cuts filed to Washington State officials. As you’ll see, I had to scroll for a while… In a note emailed to PlayStation workers and published online, PlayStation game studios chief Hermen Hulst offered the following explanation for these latest cuts at Bungie: This is painful news, especially for talented colleagues whose roles have been eliminated. This decision was made only after extensive discussion and careful consideration, and I want to provide some context on how we arrived here. Over the past several months, together with Bungie leadership, we reviewed the studio’s long-term direction, development priorities, resource needs, and role within our broader portfolio strategy. We explored multiple alternatives before concluding that a reduction was necessary to align the studio’s resources with its current priorities and long-term goals. In 2022, Sony bought Bungie for $3.7 billion. The studio’s marquee game, the multiplayer live service shooter Destiny 2 was losing popularity at the time. Its next game Marathon, released earlier this year, has been well-reviewed but had a slow start. Bungie is renowned for making great shooter games, and Destiny fans have mourned the wind-down of Destiny 2. They’ve also expressed bewilderment over reports that Destiny 3 is not, per Bloomberg, immediately in the cards.
Behavioral Healthcare Close to Home: SRMC Services Available in Sandoval County
Sandoval County spans more than 3,000 square miles with a population of 160,000 residents. As one of New Mexico’s fastest growing counties, it’s crucial the people who live there have access to high quality healthcare, including behavioral health...
Health officials: State's first West Nile virus-positive mosquito of the year found in Berkshires
“With warmer weather and summer officially beginning this week, it is the time of year when we typically begin detecting West Nile virus in mosquito populations,” a public health official said.
Making Our Own Luck
We are cross-posting a piece that former NIH official Kris Willis wrote for Macroscience. Kris is now the President and Founder of the Woodley Park Institute, for which I’m a board member. Picking winners or hedging bets? Federal science agencies have long wrestled with the question of how to ensure their billions of dollars of grants and contracts result in maximum benefits for Americans. On the surface, it might seem that a goal-oriented, interventionist style of management would be the best policy: prioritize our most pressing problems and distribute funding accordingly.This top-down strategy creates a unique hazard, though: bad choices can send resources in the wrong direction, resulting in slow progress that impedes the delivery of tangible benefits to citizens. Moreover, if decision makers pursue an applied advance when the underlying scientific principles remain poorly understood, they risk costly failures and a loss of support for the research enterprise at large. Examples include Nixon’s 1971 War on Cancer, undertaken on the premise that a cure could be achieved in less than a decade, the drive to build an operational commercial fusion plant by the mid-1990s, and the National Plan to Address Alzheimer’s Disease, which failed to produce the effective treatments and prevention strategies promised by 2025. The contrasting laissez-faire approach is to hedge your bets. If the path to an advance is impossible to predict, then the wisest choice might be to distribute funding to as widely as possible. The main risk of this strategy is that spreading funding thinly may limit the resources available to the most promising research, resulting in the same negative outcomes as the interventionist approach: limited support for the most promising topics, slow progress, and delayed returns. In reality, at science agencies like the National Science Foundation and National Institutes of Health, program managers navigate between these two extremes, setting some funds aside to target high-priority areas and using the rest to cover the widest possible range of meritorious proposals. This middle path seems like the most rational way to proceed, but it still requires making choices. How much should be set aside for high priority topics? What should those topics be? How should we define merit? Expert opinion can provide a helpful guide, but leading experts can have remarkably different opinions about what matters and what should be prioritized. Moreover, experts and administrators alike can be risk averse, giving an edge to high-profile, well-established concepts. What’s really needed is a data-driven framework to help guide decision-making, one that doesn’t simply repackage prestige or incumbency. Recognizing breakthroughs years in advance Many breakthroughs fail to attract funding or recognition at the earliest stages of development. Katalin Karikó, for example, spent years struggling to win grants for work on mRNA that would eventually win her and Drew Weissman a Nobel Prize. Similar stories can be told about Jim Allison’s groundbreaking studies leading to the development of cancer immunotherapy, Stan Pruisner’s demonstration that prions can self-replicate without DNA, or Robin Warren and Barry Marshall’s proof that Helicobacter pylori, not stress, causes ulcers. Yet at some point, the scientific community recognizes and responds to transformative breakthroughs like these. How does that change happen? And what if science funders could identify the areas that are on the cusp of a breakthrough? Those questions led my collaborators and me to study how scientists responded to past breakthroughs. Based on patterns in that data, we developed a means of predicting future breakthroughs, using biomedicine as a proof of concept. It’s worth taking a moment to describe how our approach works. Briefly, our prediction process begins by grouping the 18 million or so peer-reviewed papers in PubMed, the authoritative database of biomedical research, into roughly 50,000 unique topics. A small subset of these topics are so widely acclaimed as breakthroughs that they have been recognized with a major prize like a Nobel or a Lasker Award. We theorized that studying the development of these outliers over time, especially before they gained acclaim, was the key to identifying future instances of them. After defining topics, we chose 21 representative breakthroughs and asked what they looked like before they won prestigious prizes. To answer that question, we re-ran our topic-mapping algorithm repeatedly, winding back the clock one year each time, stringing together the years to follow the progress of each field as it grew and advanced. We found that in each case, the years leading up to a discovery followed a pattern: a burst of papers on a new, rapidly evolving topic, many of which quickly became influential. These characteristics—the percent of papers that are new, the percentage of papers that are brought in from other topics, and the influence of each individual paper—can all be measured separately for any given topic. Together, they act as a predictive signal that is detectable an average of five years before a transformative discovery is made, and up to thirty years before the discovery receives a major prize. Scanning the current research landscape for topics that display this signal allows us to predict what work will likely produce a future breakthrough. Each year we analyzed includes four or five signals, a number that appears to have remained constant across a twenty year time frame. In their classic work on the sociology of science, Bruno Latour and Steve Woolgar established that the desire to participate in a major discovery is an important motivator for scientists as they consider whether they should take up (or abandon) a research problem. Although further work is needed, the simplest explanation for our results is that this behavior is widespread enough to detect at scale. A foundational advance, or something like it, draws the attention of scientists and causes them to change the direction of their research. They vote with their feet, staking their own reputation and careers by publishing on and citing the new idea. That upswell of interest is the foundation of our breakthrough signal. What kind of research does our model identify as a breakthrough? After building a model based on the patterns in our 21 preselected breakthroughs, we tested it by identifying all early signals of discovery from 1994 through 1997. Of the 18 signals we found in that time period, 17 can be traced forward in time to a breakthrough. Examples include super-resolution fluorescence microscopy (see the image above), the directed evolution of proteins and enzymes (Chemistry Nobel, 2018), and sequencing the human genome (National Medal of Science, 2008). The discovery of the role of leptin signaling in obesity is a particularly interesting case study. Around 1950, scientists noticed the existence of a type of lab mouse that suffered from a unique inherited form of obesity. When given the freedom to choose their own diet, these mice ate more than normal and preferred food that was high in fat. Researchers had few clues as to why the animals overate; early experiments pointed to the existence of a soluble ob factor found circulating in the bloodstream that regulated appetite, but its identity was unknown. In 1994, Jeffrey Friedman and colleagues identified and sequenced the ob gene, noting that the protein it encoded appeared to fit the profile of a circulating factor. A year later, a trio of high-profile publications demonstrated that ob was a hormone that regulated body weight and fat deposition by regulating appetite. One of these was co-authored by Friedman, who christened it leptin from the ancient Greek word for thin. Using our model, the data from 1996 make it clear this advance would become a breakthrough. Scientists had flocked to study the biology of the new hormone, generating the flurry of new papers and citations required to produce a signal. One of these demonstrated that serum leptin concentrations reflected the amount of adipose tissue in the human body, providing clinical validation of the earlier mouse studies. Before the identification of leptin, scientists were unable to point to a specific molecule that controlled appetite and adiposity, so that it was impossible to rule out non-physiological causes of obesity; its characterization fundamentally changed our concept of weight gain. In 2010, Friedman and fellow pioneer Douglas Coleman were awarded a Lasker for the discovery. Our work also identifies breakthroughs in clinical practice and behavioral and social sciences, even though these areas are less likely to draw the attention of major prize committees. One example that falls into this category is the introduction of endovascular aneurysm repair, a minimally invasive surgical procedure for the treatment of abdominal aortic aneurysm, a leading cause of death among Americans over the age of 65. Relative to the previous standard of care, it reduces in-hospital mortality by almost four-fold. In 2017, Timothy Chuter received the American College of Surgeons’ prestigious Jacobsen Innovation award for his multiple refinements to the technique. Another under-recognized breakthrough identified by our model is the development of standardized survey instruments to assess the quality of life for HIV+ patients. The antiretroviral cocktails introduced in the mid-1990s reduced AIDS mortality, but treatment came with serious side effects. The new evaluations showed that patients whose disease progressed had worse physical functioning than Americans with other chronic diseases, while those who were asymptomatic maintained a health-related quality of life on par with the overall US population. This evidence made it possible for patients and activists to argue that even in the absence of a total cure, and in spite of the side effects, alleviation of symptoms was a worthwhile priority for clinicians. My colleagues and I have failed to identify any significant recognition for the physicians and health policy experts who pioneered this advance, although in 2016, researchers called for the World Health Organization to set targets for good health-related quality of life as part of its framework to end the AIDS pandemic. From forecasting to funding How should science funders use our predictions? Any serious discussion of what we should do with this new capability needs to begin with an understanding of its limitations. We can’t (and shouldn’t) invest all of our resources in the small number of topics predicted to produce breakthroughs. Innovative new fields are born from existing ones; they rarely arise de novo. If funders don’t maintain a diverse portfolio, the breakthroughs of tomorrow will have no antecedents. Think of this as eating the seed corn, or killing the goose that lays the golden egg. There are also multiple goals of funding beyond basic scientific discovery, including translating discoveries into clinical practice, developing new technologies, supporting economic development, and training new scientists. The investments needed to accomplish these goals are likely different from those required to support emerging breakthroughs. Finally, we must be aware that we may not capture every instance of a breakthrough. The concept is fuzzy, and not every significant discovery is recognized with a major award. Further, breakthroughs are rare, meaning that our dataset is, by necessity, small. This makes formal estimates of accuracy challenging. Although our overall success rate appears to be high, any one signal may turn out to be a false positive. We found one apparent example: the development of the third generation COX-2 inhibitors, Vioxx and Celebrex, which were much celebrated in the early 2000s as effective but non-addictive pain relievers, meets all the algorithmic criteria of a breakthrough. Five years after it received FDA approval, researchers demonstrated that Vioxx was associated with serious cardiovascular complications, and the manufacturer voluntarily pulled the drug from the market. Celebrex remains available, although like other NSAIDs, it carries an FDA warning for increased cardiovascular risk. Decision makers who were overly focused on the breakthrough potential of this research might have wasted substantial resources nurturing an area that ultimately proved to be a failure—but so would those who relied on expert opinion at the time. That said, the potential benefits of funding the next mRNA vaccine or cancer immunotherapy years earlier than we might have are large. When we can’t assume the outcome of an action, it’s worth conducting an experiment. Can targeted support for areas that are poised to produce a breakthrough increase the return on scientific investment without cannibalizing future advances? With the necessary administrative infrastructure in place, conducting this experiment would be straightforward. First, identify all the breakthrough signals between 2018 and 2023, select half at random, and commit to a decade of investment. For biomedicine, a six year window should yield about 30 topics with the potential to produce a breakthrough. Providing strong support to half of these might be accomplished for $300 million a year. That’s roughly half of the recent annual budget of the NIH Common Fund or around 20% of the fiscal year 2025 budget for ARPA-H. After five years, then again at ten, compare to see which group — the one that was actively managed, or the control — produced more breakthroughs, and on what timescale. Although we used biomedicine as an example, the same experiment could just as well be run for physics, materials science, or any other discipline. Any attempt to undertake such an experiment should keep three points top of mind. First, we can predict the topic of future breakthroughs, but the people and vision for how to move the work forward are still important. In practice, this means success requires active program managers with the expertise to develop the science and the authority to do so, including by recruiting investigators. Second, we would be wise to learn from the failures of past attempts to fund transformative research. High among these are funding modestly repackaged work, confusing the genuinely novel with the merely unfamiliar, and relying too much on incumbent investigators. All of these risks can be mitigated by thoroughly and intelligently integrating high quality data into portfolio management. Finally, we need to have patience. Even with strong funding support, producing a breakthrough takes time. If supporting breakthroughs is the best way to nurture the birth of new fields, we also need to accurately describe and properly manage the other two stages, so that we invest wisely throughout the productive lifetime of ideas and divest once they reach the point of diminishing returns. We would benefit from more study of all of these phases, especially the transition from one to another. More research could answer questions like: When does a breakthrough become an established field? How do the availability of funding, the size and characteristics of the available workforce, and the accumulation of evidence that disagrees with prevailing models affect a field’s decline? Exactly how do old ideas give birth to new ones, and can we speed up the process? The more we understand about the dynamics of scientific progress, the better we can maximize the odds that our curiosity leads to results. I’d call that finding a way to make our own luck.
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