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Ahead of the MLB trade deadline, here’s where the Yankees stand
Yankees general manager Brian Cashman is almost always aggressive when he believes in his team.
Moving ‘Casey and Diana’ plumbs the messy layers of hope
Nick Green’s dramatization of Princess Diana’s visit to an AIDS hospice is darkly funny and life-affirming, onstage at American Players Theatre through Sept. 24.
Comcast Announces Plans to Separate Media and Technology Businesses Into Two Leading Public Companies
Comcast Corporation (Nasdaq: CMCSA) today announced its intention to separate into two independent publicly traded companies through a tax-free spin-off of N...
Rural Fosston moves forward in its quest to relinquish control of local hospital from Essentia Health
A northwestern Minnesota community is seeking to regain local control of its hospital, arguing Essentia Health has failed to meet local health care needs. A recent court ruling allows Fosston to take its case to arbitration.
PPDS Brings 'Limitless' TV Entertainment To Historic 5 Star Bellevue Syrene Hotel With Philips MediaSuite
PPDS, the exclusive global provider of Philips Professional Displays, has announced that its Philips MediaSuite TV range has been chosen to deliver seamless access to a virtually limitless world of | Delivering modern luxuries to the 18th century hotel in Sorrento, Philips MediaSuite TVs with cast built in are now bringing seamless access to millions of movies, TV shows, games, and streaming apps to guests at one of Italy's most prestigious and exquisite hospitality destinations.
SG Americas Securities LLC Sells 866,473 Shares of Caesars Entertainment, Inc. $CZR
SG Americas Securities LLC trimmed its position in shares of Caesars Entertainment, Inc. (NASDAQ:CZR - Free Report) by 78.9% during the 1st quarter, according to its most recent 13F filing with the Securities and Exchange Commission (SEC). The firm owned 231,290 shares of the company's stock after
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 […]
The last, best hope for the Colorado GOP
If the Colorado Republican Party desires to retain any relevancy, let alone wrest back any of the levers of political control in the state, it needs to elect Barb Kirkmeyer in the June 30 primary. To be sure, Kirkmeyer would be a solid candidate for governor in any case, whether or not she shared the […]
Los Angeles Venezuelans collect aid after deadly earthquake as business owner searches for missing parents
Full Arepas, on Seventh Street near Hill Street, is accepting donations through Tuesday for people affected by the deadly earthquakes that struck northern Venezuela last week. Owner Kelly Montano said her parents are missing near Caracas.
Life Science Reagent Market Forecast Points Higher Toward 2035, Driven by Biopharma Scale-Up and Cell Therapy Expansion
World life science reagent market forecast 2026-2035: CAGR 6-8%, index 2035=185. Bioprocessing, cell therapy, and QC drive growth. Key players: Thermo Fisher, Merck, Danaher.
Minivan crashes into vacant Benson business
WOWT 6 News 10 p.m. Sunday newscast
Reports: Diomande agrees PSG move from Leipzig
Ivory Coast forward Yan Diomande has decided to leave RB Leipzig for Paris Saint-Germain, according to media reports. Broadcasters Sky and RMC, as well as transfer specialist Fabrizio Romano, reported on Sunday that the 19-year-old has agreed a five-year contract with the French Champions League winners.
Jodie Sweetin praises “Better Call Saul ”actor cast as dad in “Full House ”pilot, but Bob Saget was always 'first choice'
Saget was engaged to cohost CBS' "The Morning Program" when he got the call for "Full House," which led to his absence in the original pilot.
Jodie Sweetin praises 'Better Call Saul' actor first cast as 'Full House' dad, but Bob Saget was No. 1 choice
Bob Saget nearly missed the chance to play Danny Tanner on 'Full House,' and though he was casting's 'first choice,' Jodie Sweetin says this 'Better Call Saul' star was 'very sweet' in the original pilot.
Wife and 2 children of Argentine soccer star discovered dead after earthquakes in Venezuela
Argentine soccer star Lucas Trejo lost his wife, Yanina Maranella, and their two children, Aarón and Ainhoa, in the powerful pair of earthquakes that ravaged Venezuela on June 24.
Trump calls likely DC mayor Janeese Lewis George a 'communist' and vows to block her agenda
D.C. mayoral frontrunner Janeese Lewis George faces clash with President Trump over ICE enforcement, policing, cashless bail and sanctuary city policies.
Cedar Crossing Casino to open in 6 months, BBQ restaurant prepares for business boom
CR Midnight Smoker BBQ sits next to the casino construction site. Owner Greg Stoll said business has not slowed during the build.
Katy Perry cancels music festival performance at the last minute: 'They gave me no choice'
Katy Perry apologizes after her Werchter Boutique performance was canceled at the last minute, tells fans 'I am just as unhappy as you are.'
NBC Announces Plans For Special 'Star-Spangled Sunday'
NBC is having a special "Star-Spangled Sunday" broadcast next weekend. Next Sunday is July 5, 2026. It's a very special Fourth of July weekend this year. It's America's 250th birthday. NBC and Peacock will be airing all 15 MLB games on Sunday, July 5. Two games - Mets-Braves and Padres-Dodgers - ...
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
Texas Democrats leave convention united in effort to end GOP's 30-year hold on Texas
Texas Democrats spent their 3-day convention in Corpus Christi rallying party activists, training volunteers and making the case for Democratic policies and candidates across the state ahead of the 2026 midterm elections.
Microbusinesses celebrate New York state’s first cannabis showcase
Five years since the legalization of recreational marijuana in New York state, business owners and growers are still struggling and navigating their way through the complicated legal status and policies surrounding the cannabis industry.
Pennsylvania measles outbreak tops 70 cases as health leaders pledge to get spread ‘under control’
The most recent measles outbreak started in the area of Lebanon and Lancaster counties in late April. Cases now span six counties.
Entertainment Firms Face AI Copyright Uncertainty
Editorial analysis: For AI and ML practitioners, unclear copyright rules raise the legal risk and compliance cost of using generative models in production content pipelines. According to The Economic Times, Indian entertainment firms are investing heavily in AI for content creation, but current copyright law, which is tied to human creativity, may not clearly protect AI-assisted or AI-generated works. The Economic Times reports lawyers warn that, without specific legislation or case law, such works face risks of duplication and misuse, complicating licensing, attribution, and monetization for studios and creators. The article highlights that creators and rights holders in India currently have limited legal recourse under existing statutes, per The Economic Times.
Cassidy, fresh off a blowup with Trump, blasts RFK Jr.’s policies
The GOP senator said a “foundation of lies” had shaped Kennedy's health stances. He also accused Trump of treating Congress as an "appendage."
U.S. Rep. Julia Letlow, endorsed by Trump, wins the GOP primary for Senate in Louisiana
Letlow, who was endorsed by Trump, defeated state Treasurer John Fleming in the two-candidate runoff after they finished ahead of Cassidy in the GOP primary May 16.
How did EBS science show reach Netflix's top 10?
For years, South Korea’s public Educational Broadcasting System has struggled to rival the massive budgets of global streaming originals and star-driven mainstr
GOP Sen. Cassidy seeks to explains RFK Jr. confirmation vote for Health and Human Services
Sen. Bill Cassidy (R-La.) in a Sunday inteview sought to explain his controversial vote to confirm Health and Human Services (HHS) Secretary Robert F. Kennedy Jr., as he said Kennedy is dug in on h…
Long Beach reports first West Nile case
The city of Long Beach has reported California's first human case of West Nile virus this summer, according to health officials.
Trump’s Great American State Fair attendees say they haven’t noticed politics overshadowing the celebration
The gloomy, overcast weather on Saturday didn’t disturb visitors who attended the first weekend of President Donald Trump’s Great American State Fair, an event commemorating America’s 250th anniversar...
Second Measles Case of 2026 Confirmed by Wyoming Department of Health
The Wyoming Department of Health (WDH) has confirmed a case of measles in an unvaccinated adult from Teton County. Measles is a highly contagious infection that can cause severe illness. The public may have been exposed to measles at the following locations and times: Cafe Court Pizzeria and Ranch House Restaurant, Colter Bay Village, Grand […]
Natrona County health and food inspections (6/19/26–6/25/26)
CASPER, Wyo. — The Casper-Natrona County Health Department inspects restaurants, grocery stores, convenience stores, mobile food units, commissaries and
Bill Cassidy accuses Trump of treating Congress as ‘merely an appendage’
Out-going Louisiana senator’s rebuke over Iran war is rare instance of a Republican politician standing up to Trump
Cassidy accuses RFK Jr. of building public health "upon a foundation of lies"
On anniversary of disastrous debate, Biden rallies Democrats at a casino
President Joe Biden spent the second anniversary of his disastrous debate performance at a Maryland casino, giving the keynote speech at an annual fundraiser for Maryland Democrats.
Usher makes the case for R&B in stadiums
LOS ANGELES — As Usher prepares to launch a stadium tour with Chris Brown, he says the criticism and legal troubles surrounding the singer never factored into his decision to
Conor Sen: This demographic cliff is reshaping universities. Cities are next
An undergraduate enrollment shortfall at Syracuse University is the latest sign that long-forecast demographic pressures are taking their toll on large and well-known institutions, too. Syracuse laid blame on the
SG Americas Securities LLC Has $8.39 Million Holdings in Flutter Entertainment PLC $FLUT
SG Americas Securities LLC lessened its holdings in Flutter Entertainment PLC (NYSE:FLUT - Free Report) by 85.8% during the first quarter, according to the company in its most recent Form 13F filing with the Securities & Exchange Commission. The fund owned 82,269 shares of the company's stock a
Lingering distrust, low vaccine rates threaten containment of Lancaster measles outbreak
LANCASTER, Pa. — A growing distrust of health professionals seems to be undermining their efforts in central and southeastern Pennsylvania to stop...
Inside country legend Alan Jackson\'s triumphant finale concert
Country music legend Alan Jackson has ended his touring career. On Saturday night, he performed his final show at Nashville's Nissan Stadium. The event, titled “Last Call: One More for
Trump gets the complete domination he wanted in Louisiana
Rep. Julia Letlow, his preferred candidate, won the GOP runoff for his longtime rival Bill Cassidy’s Senate seat.
Arizona health officials investigate suspected pneumonic plague case
Health officials in Yavapai County are looking into a suspected case of pneumonic plague.
Trump-backed Rep. Julia Letlow wins Louisiana Senate primary runoff
Letlow defeated state Treasurer John Fleming in the GOP runoff, NBC News projects. Incumbent Sen. Bill Cassidy did not make the runoff.
Team USA Basketball Showcase celebrates youth sports
The Team USA Basketball Showcase tipped off on Saturday featuring community, camaraderie, and a continuing commitment to youth sports.
Private Selection chicken breast product target of health alert
The U.S. Department of Agriculture wants people who may have purchased a variety of Private Selection raw boneless chicken breasts to check their freezers or refrigerators in case they still have them.
Private Selection chicken breast product target of health alert
The U.S. Department of Agriculture wants people who may have purchased a variety of Private Selection raw boneless chicken breasts to check their freezers or refrigerators in case they still have them.
Trump-backed Julia Letlow faces John Fleming in Louisiana GOP Senate runoff
U.S. Rep. Julia Letlow, who was endorsed by Trump, and state Treasurer John Fleming are competing in the runoff. The two finished ahead of Sen. Bill Cassidy in the May 16 primary after Trump denounced the two-term senator, who voted to convict him following his 2021 impeachment.
Arizona health officials investigate suspected pneumonic plague case
Yavapai County Community Health Services said Friday that a county resident is thought to have contracted the infection.
World Cup collides with religion, politics in Seattle
Pride Match turns into dramatic game as Iran and Egypt settle for 1-1 draw
Fiorentina agreement for Beltran, but striker resists River Plate
Fiorentina have agreed to sell half of Lucas Beltran to River Plate following the loan at Valencia, but it’s reported the player wants to remain in Europe.The striker spent time in the River Plate a...
HISTORY IN THE MAKING: A RECORD-BREAKING OPENING DAY AT THE PAN AMERICAN ATHLETICS CHAMPIONSHIP MEDELLÍN 2026
The Pan American Athletics Championship delivered everything the Americas had been waiting […]
“RuPaul's Drag Race” star reveals queen dropped out of “All Stars 11 ”cast“ ”before filming (exclusive)
Jasmine Kennedie tells EW which one of her franchise sisters exited before filming — and the queen in question responds!
Caesars Entertainment (CZR) Expands In Maine Online Gaming, Is The Stock Already Fully Valued?
Caesars Entertainment expands digital footprint with Wabanaki Nations partnership Caesars Entertainment (CZR) is extending its partnership with three Wabanaki Nations to include online casino gaming in Maine, targeting a potential 2026 iGaming launch, subject to regulatory approvals. See our latest analysis for Caesars Entertainment. Caesars Entertainment shares have climbed over recent months, with a 90 day share price return of 16.79% and year to date gain of 28.14%. However, the 5 year...
GTA 6 has no plans for a post-launch physical release, "not at launch, and not months later", insists new report
A new report has cast doubt on news that a physical version of Grand Theft Auto 6 will follow the digital release later this year after all.
Mountain lions changed everything in this tiny California preserve
A surprising ecological makeover unfolded when mountain lions began frequenting a small preserve south of San Francisco. Deer activity dropped, plants recovered, and shifts among predators like coyotes, bobcats, and foxes followed. The study shows that powerful “trophic cascades” aren’t limited to remote wilderness—they can happen in small, suburban preserves too.
Florida cases echo Italy’s gangmaster economy
Legal labor systems can still become traps for powerless workers.
After ousting Bill Cassidy, Donald Trump faces fresh test of his sway with GOP voters in Louisiana’s Senate runoff
Louisiana Republican voters already rejected an incumbent senator who was crossways with President Donald Trump. In a primary runoff on Saturday, they’ll decide whether to follow Trump’s lead in choosing a new nominee.
Alito and Kagan’s telling exchange about race and politics
Both sides of the debate in the court’s case on temporary protected status could have used a little more realism.
Letlow, Fleming face off for Cassidy's seat in Louisiana GOP Senate runoff
Politics Unplugged Podcast: Headlines with Stacy Pearson and Marcus Dell’Artino
The Politics Unplugged panel breaks down a possible Arizona special session tied to ESA vouchers, union protections and ballot measures. The discussion centers on whether lawmakers could unwind late-night legislation that angered teachers, police and firefighters. They also examine Gov. Katie Hobbs’ political leverage and why both parties may have reasons to cut a deal. Later, the podcast turns to Trump tax cuts, Democratic Socialists, the White House reflecting pool controversy and the World Cup.
Burglars steal from Grand Forks business, cancer fundraiser
The owner of An Elegant Affair says burglars stole merchandise, cash and donations collected for an employee battling cancer.
But-For Causation and the Essential Business Hurdle: Analyzing the Summary Judgment in RAAM Construction
RAAM Construction Inc v. United States of America, Case No. 2:25-cv-04681-SPG-AJR, 2026 WL 18391 (C.D. Cal. June 23, 2026). The Employee Retention Credit (ERC) codified under Internal Revenue Code Section 3134 remains a significant source of controversy, audits, and high-stakes federal litigation.
Local business celebrates 10 year anniversary with $5,000 in cash prizes up for grabs
It is a celebratory feat for any small business to successfully reach 10 years in operation.To mark their 10 year anniversary, Escape It Grandview will be host
Live Results: Louisiana midterm primary runoffs
Louisiana Republicans will nominate a candidate for U.S. Senate in a primary runoff Saturday, six weeks after denying Republican U.S. Sen. Bill Cassidy a shot at a third term.
Factory Entertainment Announces Three More STAR TREK Collectibles, Including Gold-Pressed Latinum Bars
Factory Entertainment today unveiled three more STAR TREK replicas, including bars of gold-pressed latinum and Eline’s necklace from “The Inner Light”
Downtown Largo could become an open-container entertainment district
Downtown Largo could allow open-container drinking, outdoor entertainment and live music under a proposed entertainment district.
Value of Things: A look at the hot seat
Is Nick Caserio on the hot seat if the offensive line fails again
As Pa. measles outbreak worsens, state health official issue strong call to action: 'We are not just sitting back and watching this virus spread'
LANCASTER, Pa. — State Health Secretary Debra Bogen on Friday issued a strong call to action in the wake of a measles outbreak not seen in Pennsylvania...
'The Bear' ending explained – Jeremy Allen White, cast unpack finale
Warning: This story contains spoilers from the Season 5 finale of “The Bear,” now streaming on Hulu. Clear the plates and pack the linens – “The Bear” has served its
Friday Morning Politics: As Goes New York...?
Lisa Kashinsky talks about the national implications of New York's Democratic primary results.
Pennsylvania’s Health Secretary unveils plan to combat measles outbreaks
LANCASTER COUNTY, Pa. (WHTM) — Pennsylvania’s Health Secretary Dr. Debra Bogen was in Lancaster County on Friday, giving an update about the measles outbreak in the state, with most of …
Bunnie Xo says she told ‘so many girls’ to DM Jelly Roll amid divorce: 'Good luck with that'
Bunnie Xo said that she told 'so many girls' to DM Jelly Roll amid their divorce. The country star filed for divorce from the podcaster in May after nearly 10 years of marriage.
Morocco jails 29, including politicians and sports figures, in drug trial
Casablanca court delivers landmark verdict in 'Escobar of the Sahara' case: up to 12 years for top figures.
AI Is Already Reshaping US Politics at Every Level
From data center backlash to boundless cash from tech billionaires and concerns about deepfaked campaign ads, AI is everywhere in the 2026 US elections.
Dragon's Dogma 2: Dark Arisen: What We Learned In Capcom's Showcase
Kento Kinoshita, Dragon's Dogma: Dark Arisen's original director, is returning for Dragon's Dogma 2: Dark Arisen
Strictly Business Cannes Lions: Deloitte, AWS, Sony Execs on AI and Tech Adoption
Variety Strictly Business Podcast Live presented by AWS & Deloitte featured Deloitte's Michelle McGuire, AWS's Ruba Borno, and Sony Pictures Entertainment's Pete Wood.
Strictly Business Cannes Lions: Deloitte, AWS, Sony Execs on AI and Tech Adoption
Variety Strictly Business Podcast Live presented by AWS & Deloitte featured Deloitte's Michelle McGuire, AWS's Ruba Borno, and Sony Pictures Entertainment's Pete Wood.
Athlete of the Year finalist: Penn Manor standout provided the power for Comets in 3 sports
Anneli Starry didn’t know what she had in Joelle Kroesen. The Penn Manor girls lacrosse coach labeled the then-freshman as a swing — an athlete who is rostered on two
How PENN’s US$360 Million Aurora Resort Shift At PENN Entertainment (PENN) Has Changed Its Investment Story
PENN Entertainment has opened the US$360 million Hollywood Casino and Hotel Aurora, replacing its former Fox River riverboat with a 388,500-square-foot, 24/7 land-based resort featuring over 1,000 slots, 50 table games, a sportsbook, 226-room hotel, spa, event center, and extensive dining options. The Aurora project, which created around 700 permanent roles and mirrors PENN’s broader shift into higher-amenity land-based properties, highlights how the company is reinvesting heavily to refresh...
Case Studies From Ireland: Making Sustainability Good Business
From Kinisla to Strong Roots, these food companies are making the business case for sustainable practices.
Ex-Trump adviser John Bolton expected to plead guilty in classified information case
Bolton to plead guilty charges that he unlawfully retained sensitive national security information in agreement that includes $2.25m fine
Nevada takes step toward becoming corporate litigation hub with business court pilot program
The Clark County District Court this week announced it has restructured its departments to include a dedicated business court. The restructuring is expected to bring down case adjudication times, and it could help an ongoing effort to transform Nevada into a premier destination for corporate litigation. Judges Maria Gall and Joe Hardy–Departments 9 and 15, […]
Supreme Court rules in weedkiller cancer case
Dems want to unmask Eli Lilly's obesity drug user, a new genome-editing tool raises ethics questions, and more health news
Samsung will soon start charging to access its smart home API
Regular users could get caught by Samsung’s new $4.99 monthly charge for individual developers.
Accel Entertainment (ACEL) Expands Louisiana Gaming Footprint Through Truck Stop Casino Acquisition
Accel Entertainment, Inc. (NYSE:ACEL) ranks among the best sin stocks to buy for recession protection. On June 3, Accel Entertainment, Inc. (NYSE:ACEL) strengthened its Louisiana business with the acquisition of Rice Palace Truck Stop Casino in Crowley, adding a high-volume gaming venue that expands the company’s route-based gaming network in another of its strongest growth […]
Cascades doubles down on business case for sustainability
The fiber specialist laid its path forward in a 2026-2030 sustainability plan. It’s emphasizing supplier vetting and its capacity to assist customers with their sustainability goals as it continues to strive for widely recyclable packaging.
Lancaster County public sales: June 26, 2026
Witman Auctioneers Inc., of Manheim, conducted a public auction of real estate June 11 for the Dorothy McVey estate at 22 Sleepy Hollow Road, Nottingham. A two-bedroom mobile home on
Karl Stefanovic Speaks Out on Nine Exit After Tommy Robinson Scandal
The 'Today' host declares himself 'free' in a YouTube statement after Nine ends his contract following a deleted Tommy Robinson podcast episode.
NC Democrats demand lower utility costs + budget talks drag on as deadline nears
Read our Under the Dome newsletter and listen to our Under the Dome podcast to stay up to date on #ncpol.
Trump foe John Bolton is set to plead guilty. Here’s why the case didn’t fall apart
As several criminal investigations into President Donald Trump’s foes continue to flail, federal prosecutors are now ushering one of his biggest critics to a conviction.
Trump likely to ‘lose’ on birthright citizenship case, political analyst says
Fox News senior political analyst Juan Williams discusses the Supreme Court set to issue a ruling on birthright citizenship on ‘Special Report.’
Blue state leaders erupt after Supreme Court’s decision ending TPS protections for Haitians, Syrians
Supreme Court rules 6-3 in favor of Trump administration in two key immigration cases on Temporary Protected Status and asylum, drawing opposition from blue state Democrats.
DC Wrap: Supreme Courts rules on immigration and gun cases
A look at the day's biggest stories in national politics
Business Council deliberations continue with four bill drafts
Lawmakers on the Joint Appropriations Committee spent another day diving through the Wyoming Business Council’s dealings. This time, they also reviewed draft bills that would influence how the council operates.
Santa Ana Star Casino Hotel launches app, unveils July entertainment lineup
Santa Ana Star Casino Hotel offers comedy, entertainment, perks, and more. In July, the casino has a lineup of comedians and other entertainment. July Entertainment Lineup June 26, 27 – Carme…
PAHO mobilizes emergency health response following earthquakes in Venezuela
Caracas, Venezuela/Washington, D.C., 25 June 2026 (PAHO) – The Pan American Health Organization (PAHO) has activated its emergency response mechanisms to support the health response in Venezuela following two magnitude 7.5 earthquakes that struck the country on June 24.
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.
PANAM SPORTS AND THE CANADIAN COACHES ASSOCIATION LAUNCH A CERTIFICATION PROGRAM FOR COACHES IN THE AMERICAS
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