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Assenagon Asset Management S.A. Decreases Stock Holdings in Live Nation Entertainment, Inc. $LYV
Assenagon Asset Management S.A. lessened its stake in Live Nation Entertainment, Inc. (NYSE:LYV - Free Report) by 77.4% in the 1st quarter, according to the company in its most recent Form 13F filing with the SEC. The fund owned 74,497 shares of the company's stock after selling 254,802 shares duri
Greens examining how party decides policy as membership triples under Zack Polanski
Exclusive: Concerns in-person vote system is giving bigger say to organised fringe activists who can attend conference
Two years after their last debate, Biden jabs at Trump: ‘What a loser’
As he rallied Maryland Democrats at a state party fundraiser Saturday night, former President Joe Biden decried the actions of the man who succeeded him in the White House, painting him as vain and corrupt.
Report: Rockets have been linked to Lakers' Marcus Smart
The Rockets reportedly have interest in signing Marcus Smart away from the Lakers if he declines his player option for next season.
Tony Brown, trailblazing journalist, TV talk show, dies at 93
"Tony Brown’s Journal," which ran on PBS for nearly four decades, provided a national platform for frank discussions on race, politics, and culture.
Hurricanes Acquire Rights to John Carlson
It had been a long day. Some teams were using all of their allotted time, even in the later rounds to make their draft decisions. Then came Carolina, and time had expired while the world waited for them to make pick number 192 in the Draft. What happened? Eric Tulsky and company smacked everyone in […]
Black Hills Renaissance Fair draws crowds for weekend of medieval entertainment
The kickoff of the Renaissance Festival started on Saturday
MS Comic Con 2026: cosplayers, celebrities and fans unite to celebrate beloved characters
Attendees decked out in costumes and homemade props from their favorite TV shows and movies gathered at the Mississippi Trade Mart for Comic Con 2026
Gunnar gives back: O's shortstop surprises local kid with specialized cleats
BALTIMORE -- The story of 11-year-old Declan Lefevre’s youth baseball career is inspirational. When Declan was about 4 years old, a doctor noticed his legs were different lengths. And it wasn’t something he would grow out of, either, which is something his parents -- father Jeff Lefevre and mother Nichole
Man with same name as U.S. Sen. Dan Sullivan is eligible for Alaska's primary ballot, judge rules
The judge ruled that the division’s decision to exclude Dan J. Sullivan because his candidacy was not “in good faith” was not based on the Constitution, Alaska law or the division’s own regulations.
Starz Entertainment (STRZ) Stock Sees Fair Value Lift After Q1 Analyst Target Increases
Price targets for Starz Entertainment have shifted as the analyst fair value estimate moved from US$19.38 to US$28.50, putting a higher reference point in focus for investors tracking the stock. Recent Street research has turned more constructive after the Q1 report, with several firms lifting price targets and updating models to reflect how they now view execution risks and valuation support. In the sections that follow, you will see how to interpret these changing targets and what they...
ABC7 reporter goes viral after declaring she doesn’t want to know anything about Bosnia
An ABC7 Los Angeles reporter has gone viral ahead of the United States’ World Cup round of 32 matchup with Bosnia and Herzegovina next Wednesday in Santa Clara, and not for the right reasons Reporter Abigail Velez, wrapping a live shot from Long Beach following the UMSNT’s group-stage loss to Türkiye, announced proudly that she…
3 million Americans have dropped Obamacare health coverage over past year, after Republicans let federal subsidies expire
KFF expects the total number of people in the government healthcare program to continue to decline throughout the year, potentially to a low of about 17.5 million from 19.2 million now.
Is Tencent Music Entertainment Group (TME) A Bargain Following Its Sharp Pullback?
Tencent Music Entertainment Group (TME) has drawn fresh attention after recent trading left the stock down about 9% over the past month and about 11% over the past 3 months, which has sharpened the focus on its current valuation. See our latest analysis for Tencent Music Entertainment Group. At a recent share price of $8.39, Tencent Music Entertainment Group has posted a year to date share price decline of about 53% and a 1 year total shareholder return decline of about 55%. However, the 3...
Citing construction, downtown Noblesville business will close
The Velvet Plum Vintage & Consignment, a home decor and furniture consignment shop at 894 Logan St. in Noblesville, has announced it will close July 15, citing Embrace Downtown construction as the driving factor. The Embrace Downtown project began earlier this year to provide infrastructure a
Citing construction, downtown Noblesville business will close
The Velvet Plum Vintage & Consignment, a home decor and furniture consignment shop at 894 Logan St. in Noblesville, has announced it will close July 15, citing Embrace Downtown construction as the driving factor. The Embrace Downtown project began earlier this year to provide infrastructure a
Buffalo Bills Make Decision On Honoring O.J. Simpson
As the franchise transitions to a new stadium, officials confirm the legendary running back’s name will be scrubbed from the Wall of Fame, ending a controversial decades-long tribute.
Burcum: Sanford Health got what it wanted. Now comes the moment of truth.
From columnist Jill Burcum: The South Dakota health system has spent a decade trying to crack the Twin Cities health care market. With the North Memorial deal, it now has a chance to prove itself.
The sky is not falling. Americans are getting healthier.
Despite declining obesity and heart disease rates, increasing cancer survival rates, and a record high life expectancy, politicians from both parties are pushing costly and ineffective policies to …
Vanilla Ice: Music brings people together, transcends politics
Rapper Vanilla Ice explains his decision to perform at the America 250 event. He states music is universal and should bring people together, transcending political divides. He emphasizes celebrating the country's 250 years.
Omaha City Council agenda notes for June 30
Items on new apartments, pedestrian safety improvements, and the city’s food truck ordinance in Tuesday’s agenda.
Mets Make Roster Decision After 7th Straight Loss
The New York Mets have made roster decisions before game two against the Phillies.
Your health insurer shouldn’t decide your treatment plan. That’s what your doctor (and possibly AI) should be doing.
With a digital health record, clinicians and AI-driven diagnostic tools would be able to see your full health history — and then make better decisions.
Hurricanes follow Stanley Cup title by looking at how to improve roster
Carolina doesn't have a lot of free-agency decisions after winning the team's first Stanley Cup title in 20 years.
Andy Burnham distanced himself from UK Prime Minister Starmer, but may be stuck with his policies
Burnham, the former mayor of Greater Manchester who was sworn into Parliament hours after Starmer announced his resignation on Monday, will be constrained by the platform the center-left Labour Party was elected on that decisively ended 14 years of Conservative rule in 2024.
Phillies vs Mets Prediction, Picks & Odds for Today's MLB Game
The Phillies have been hot, and our expert MLB predictions expect their winning ways to continue against the lowly Mets.
Eat, Sip, Shop: New businesses bring unique products, services to Bethlehem’s Main Street
Whether you’re shopping for toys, games and puzzles or jewelry, home decor and pet treats and accessories, a variety of new retailers on downtown Bethlehem’s Main Street have you covered.
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...
Bill Maher reveals to JD Vance which political party keeps refusing to face his questions
Bill Maher told Vice President JD Vance on Friday's episode of "Real Time" that many of the Democrats he has supported over the years have declined invitations to appear on his show. (Credit: Real Time with Bill Maher)
"Playhouse For Predator": Epstein Used 'Fake' Science Office As Prison Escape
The Florida Science Foundation was presented as a legitimate organisation focused on supporting research. But a review by The Telegraph of more than 1,000 documents connected to the company painted a different picture.
After decades in the business, a Staten Island owner closes his dream restaurant
After decades building his dream in Annadale—and nearly losing it during COVID—the restaurateur steps back to savor family milestones.
Recent rulings show that SCOTUS has ditched reason for politics
'The flurry of 6-3 decisions shows how SCOTUS has become a political body, not the judicial one the founders of our Constitution sorely aspired to,' writes an L.A. Times reader.
Some paid the ultimate price to enact voting rights. Their survivors see America turning backward
It’s been six decades since the Voting Rights Act was enacted
Prediction market Kalshi sues Illinois over its push to regulate sports bets
Prediction market Kalshi — which offers trades on everything from the World Cup top goalscorers to the winners of the reality show Love Island and the 2028 Democratic primary — sued Illinois on Tuesday over its latest push to regulate sports bets on the platform.
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.
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.
Browns Warned Over Deshaun Watson Decision
The Cleveland Browns can insist that their quarterback competition between Deshaun Watson and Shedeur Sanders will be decided on the field, but the decision will not be made in a vacuum. The post Browns Warned Over Deshaun Watson Decision appeared first on HEAVY.
Walbert Ureña implodes as Angels drop series opener against Athletics
On a night that started with an abrupt front office decision, Los Angeles Angels’ starter Walbert Ureña saw an abrupt end to an outing after a disastrous fifth inning led to a 9-3 loss against the Athletics on Friday.
Peters, Bergman lead Michigan delegation in calling on Small Business Administration to approve disaster declaration
WASHINGTON, DC — U.S. Senator Gary Peters (D-MI), Ranking Member of the Homeland Security and Governmental Affairs Committee, led members of the Michigan Congressional Delegation in urging the Small Business Administration (SBA) to support Michigan Governor Gretchen Whitmer’s request for an administrative disaster declaration following the severe thunderstorms, tornadoes, high winds, large hail and torrential […]
Testing gives science-based data for Fairmont lakes
FAIRMONT— A partnership between the city of Fairmont and Minnesota State University-Mankato will result in comprehensive scientific data on the Fairmont Chain of Lakes. The $25,000 contract started on April 1 and will go through Dec. 31 of this year. Fairmont’s Water Resources Coordinator, Hannah Neusch, acknowledged that while the water treatment plant in Fairmont […]
Communism is greatest threat to the U.S., Trump says
The president equated the democratic socialists who won primaries in New York this week with communism and the decline of nations
‘It’s a bad time to be a normal’: House Republican on current political environment
Rep. Dusty Johnson (R-S.D.) reacts to President Trump's decision to cancel the signing of the bipartisan housing affordability bill. Rep. Johnson also discusses the president’s Iran strategy and the current political environment.
CDFW News | Monterey Bay Northern Anchovy and Pacific Sardine Commercial Take Restrictions and Recreational Advisory in Place Due to Public Health Hazard
State health agencies determined that northern anchovy and Pacific sardine recently sampled from Monterey Bay contained elevated levels of domoic acid and recommended a commercial fishery restriction and recreational health advisory in the bay for the take of anchovy and sardine for human consumption in the area.
Congress subpoenas Leon Black during interview about Jeffrey Epstein
The House Oversight Committee issued subpoenas to billionaire Leon Black after he declined to answer questions about non-disclosure agreements.
Sports Intelligence Project explores high-end decision making in multifaceted industry
A new co-curricular offering tasks students with combining data, AI and the human element of athletics.
Kroenke Sports & Entertainment deemed most valuable sports empire
The Jones family ($17.6B) and Harris Blitzer Sports & Entertainment ($16.91B) followed KS&E in the CNBC rankings.
“The Cheaper the Better,” Says Valve About its Steam Machine Pricing, but Don’t Expect a Price Decrease “Any Time Soon”
"The cheaper the better" is Valve's official line for how it would like to price the Steam Machine, but don't expect it to happen soon.
Disagreements between Supreme Court justices bubble into public view as major rulings loom
The Supreme Court is handing down major opinions at a rapid clip, but even with some of the biggest decisions yet to come there are signs of tension between the justices.
Rangers trade Brett Berard to Canadiens for William Trudeau: Sources
The deal marked the first trade between Rangers team president Chris Drury and his predecessor, the Canadiens' Jeff Gorton.
After 80 Years, Mathematicians Give Famed ‘Erdős Method’ an Upgrade
Decades ago, Paul Erdős used randomness to illuminate the vast and weird world of networks. Now mathematicians are making his technique even more powerful.
Cody Johnson’s country music is only getting bigger. On ‘Banks of the Trinity,’ he’ll take you home
Texas born and bred country star Cody Johnson is seeing a surge in new fans after two decades in the industry.
Warren Buffett Bought A Business For $1.7B ‘Over The Phone Without Ever Meeting The People There’ Using The ‘Most Valuable Skill’ He Learned
Buying a company for $1.7 billion without meeting management sounds like the kind of decision that would keep lawyers busy for months. Warren Buffett did it over the phone. Speaking at the University of Nebraska-Lincoln in 2003, Berkshire Hathaway Chair...
Has VAR become a lottery at the World Cup?
After a week of strange decisions many supporters have been left scratching their heads with VAR.
Weather drives cowherd size, not broken markets
Data shows weather, not broken markets, drives cowherd decisions. Producers cite grazing concerns and drought as top barriers to expansion.
Taylor Launches New Bachelor's Degree in AI and Machine Learning
Taylor University is launching a Bachelor of Science in Artificial Intelligence and Machine Learning, building on four decades of AI expertise.
What Happens to Your Liver When You Drink Green Tea Every Day
What does green tea do for your liver? Learn how it may affect fat buildup, inflammation, and liver enzymes, plus risks and benefits.
How Science and Music Blurred Politics One Day Back Home
What to expect when you talk and play music to people you grew up with but have not seen for decades and have different political views from you. Turns out it was fabulous.
How Science and Music Blurred Politics One Day Back Home
What to expect when you talk and play music to people you grew up with but have not seen for decades and have different political views from you. Turns out it was fabulous.
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.
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.
Ben Wood, longtime three-dot columnist known as ‘Mr. Show Business,’ dies at 94
Ben Wood, a multifaceted copy editor, food and entertainment writer, and three-dot columnist for the Honolulu Star-Bulletin and Honolulu Star-Advertiser for almost 50 years, died June 19 after several years of declining health. He was 94.
After Supreme Court’s TPS decision, more than a million immigrants face scramble to stay in US
Until Thursday, hundreds of thousands of Haitians were legally living and working in the United States, along with thousands of Syrians. Now, they’re in legal limbo.
In governor's race, voters face stark choice on immigrant healthcare
California’s next governor will face tough decisions on a highly controversial piece of healthcare policy: what to do about health coverage for the more than 1.4 million low-income residents without legal status.
'It's business': 2027 5-star CB on choosing Texas over Texas A&M
2027 5-star CB John Meredith "loves A&M to death" but made a reported business decision in choosing the Texas Longhorns.
Cabo Verde Is a Breakout Star of the World Cup. So Is the Family-Owned Business That Designed Its Jerseys
After more than three decades manufacturing apparel, Capelli Sport co-founder and CEO George Altirs found his company’s biggest billboard yet—3,500 miles away from his midtown Manhattan office.
Sweden: European Social Rights Committee calls for an end to Sweden’s two-tier healthcare system
Amnesty International welcomes a landmark decision by the European Committee of Social Rights finding that Sweden breached the right to health without discrimination.
How Perizaad Zorabian Left Bollywood And Turned Her Family's Poultry Business Into A Rs 120 Crore Enterprise
Perizaad Zorabian was at the peak of her career when she decided to quit acting and turned her focus to her family's poultry business
Former Illinois forward Ben Humrichous signs contract with Nets
Heading to Brooklyn.
CRAWFORD | Kenny Klein, beloved longtime Louisville sports information director, dies at 66
Klein's career spanned nearly four decades and helped shape the public face of Cardinals athletics through some of its greatest triumphs and most difficult crises.
iHeart-broken: Listeners react to mass layoffs at local sports radio station
iHeart lays off radio hosts at three of its four stations in Des Moines.
Astros Share Hunter Brown Decision Ahead of Tigers Series
A key roster situation develops as the season continues.
Billionaire tax, affordable housing: See the measures on California's November ballot
California voters will decide on 14 statewide policy proposals come November, from the controversial billionaire tax to an $11 billion affordable housing bond.
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.
JD Vance says Nixon’s Watergate scandal would be ‘12-hour news story’ today
Vice-president declares admiration for 37th president and claims Nixon and Trump targeted by ‘deep state’ forces
Baxter Health Heart and Vascular Clinic Welcomes Brandi Watson, APRN
Baxter Health is proud to welcome Brandi Watson, APRN, to the Baxter Health Heart and Vascular Clinic. Watson joined the team on May 15 and is currently accepting new patients. Watson brings more than 25 years of experience caring for some of the most critically ill patients. Much of her career has been spent in intensive care settings, where she learned to make fast, high-stakes decisions for patients whose lives depended on getting the right care at the right moment. That kind of experience, which is gained through years at the bedside, is exactly what heart and vascular patients need from a provider.
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.
Distrust In Science Isn't New: We Mistook Silence For Trust
Distrust in medicine and science isn't a new crisis. Drawing on decades in communities, a physician explains the real source and how we earn trust.
Sports with Sam: FIFA Fan Fest kicks off at Olympic Park: U.S. vs.Turkey
Winter Sports Club to raise Olympian banners July 3 at Olympian Hall
The Steamboat Springs Winter Sports Club will raise banners to the rafters of Olympian Hall at Howelsen Hill to honor the area’s most recent Olympians. The event will take place from 4-5:30 p.m. on July...
Neuroimaging utilization in emergency departments has increased year-over-year for a decade
Researchers believe their new data could be used to better inform staffing coverage in modern radiology departments.
Tennessee court temporarily blocks state health officials from sharing undocumented ill children’s information
The “state cannot go forward with the policy” until the judge makes a final decision, said the head of the Tennessee Justice Center.
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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