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Amgen says experimental obesity drug has promising durability

2022-12-03T23:32:16Z

An Amgen sign is seen at the company’s office in South San Francisco, California October 21, 2013 REUTERS/Robert Galbraith

Amgen Inc’s (AMGN.O) experimental obesity drug demonstrated promising durability trends in an early trial, paving the way for a larger mid-stage study early next year, company officials said ahead of a data presentation on Saturday.

The small Phase I trial found that patients maintained their weight loss for 70 days after receiving the highest tested dose of the injected drug, currently known as AMG133.

Amgen shares have gained about 5% since the company said on Nov. 7 that 12 weeks of trial treatment at the highest monthly dose of AMG133 resulted in mean weight loss of 14.5%.

At 150 days after the last dose, maintained weight loss had dropped to 11.2% below original weight at the start of the trial, according to findings detailed at a meeting of World Congress of Insulin Resistance, Diabetes and Cardiovascular Disease in Los Angeles.

Patients treated with AMG133 did have side effects including nausea and vomiting, but most cases were mild and resolved within a couple of days after the first dose, Amgen said.

The U.S. Centers for Disease Control and Prevention estimates that more that 40% of the U.S. population is obese, costing nearly $173 billion annually. It is a primary cause of type 2 diabetes and been linked to heart disease, certain cancers and other health complications such as more severe COVID-19.

The weight loss field has gained renewed medical and investor attention in recent months after diabetes drugs from Eli Lilly and Co and Novo Nordisk (NOVOb.CO), known as semaglutide and tirzepatide, were proven to help obese patients lose weight.

Both of those drugs, which need to be injected every two weeks, are designed to activate GLP-1, a hormone that triggers the feeling of fullness in the body after eating.

Amgen’s AMG133 also targets GLP-1, but has a dual mechanism which aims at the same time to block activity of a gene known as GIP.

The drug was developed from work at Amgen to identify genetic signals associated with lower fat mass and body weight, and also healthy metabolic profiles, explained Saptarsi Haldar, head of cardiovascular metabolic discovery at Amgen.

“Genetics clearly showed in multiple large populations that decreased activity genetically of the GIP receptor gene was associated with lower BMI (body mass index),” he said.

The California-based biotech said it plans to launch a larger mid-stage study of AMG133 early next year, which will enroll a broader range of patients, including those with additional health conditions such as diabetes.

JP Morgan analyst Chris Schott earlier this month said that if all goes well, a Phase III study of AMG133 could begin in 2024, with a launch expected in 2026 or 2027, if approved.

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Putin takes war to new level of “barbarism,“ U.S. diplomat says

2022-12-03T23:32:55Z

Russian President Vladimir Putin chairs a meeting with members of the Security Council via a video link from the Novo-Ogaryovo state residence outside Moscow, Russia December 2, 2022. Sputnik/Mikhail Metzel/Pool via REUTERS

Russian President Vladimir Putin is not sincere about peace talks with Ukraine while he is taking the war to a new level of “barbarism” by trying to turn off the lights of civilians, a top U.S. diplomat said on Saturday.

U.S. Under Secretary for Political Affairs Victoria Nuland met President Volodymyr Zelenskiy and other senior Ukrainian officials in Kyiv to show support at a time when Russia is trying to destroy the country’s energy infrastructure.

“Diplomacy is obviously everyone’s objective but you have to have a willing partner,” she told reporters. “And it’s very clear, whether it’s the energy attacks, whether it’s the rhetoric out of the Kremlin and the general attitude, that Putin is not sincere or ready for that.”

U.S. President Joe Biden said on Thursday he was prepared to speak to Putin if the Russian leader was interested in ending the war. But the idea died quickly when the Kremlin said the West must recognize Moscow’s declared annexation of four Ukrainian regions.

This reaction from Russia, Nuland said, showed “how not serious they are”.

Russia has been carrying out huge attacks on Ukraine’s electricity transmission and heating infrastructure roughly weekly since October, in what Kyiv and its allies say is a deliberate campaign to harm civilians, a war crime.

“Putin has taken this war to a new level of barbarism, taking it into every single Ukrainian home as he tries to turn off the lights and the water and achieve what he couldn’t on the battlefield,” Nuland said.

Russian Foreign Ministry spokeswoman Maria Zakharova was quick to respond.

“It is not for Nuland to teach the world – only the United States and NATO combined destroyed more energy networks than the United States destroyed by itself,” Zakharova said on the Telegram channel, pointing to the 1999 attacks on Serbia.

During the attacks in Serbia, warplanes shut off power to more than 70% of the area, according to NATO.

Nuland also met Andriy Yermak, the head of Zelenskiy’s office, who expressed thanks for the billions of dollars worth of aid Washington has committed to Ukraine.

“Ukraine’s victory, which we are sure of, will be our joint victory,” Zelenskiy’s office quoted him as telling Nuland.

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Dumfries gets kissed as Oranje reach World Cup quarterfinals

DOHA, Qatar (AP) — Louis van Gaal leaned to his left, wrapped his arm around Denzel Dumfries, and planted a kiss on the player’s cheek.

Dumfries probably deserved even more smooches from his coach on Saturday after leading the Netherlands into the World Cup quarterfinals with a goal and two assists in the 3-1 victory over the United States.

“Yesterday, or a day before yesterday, I gave him a big fat kiss,” Van Gaal said at the post-match news conference. “I am going to give him another big fat kiss so everybody can see.”

And so he did.

“There you go,” Van Gaal said, showing his affection for the right back, who plays for Italian club Inter Milan.

Dumfries did it all against the Americans as the Netherlands extended its unbeaten run to 19 games as it pursues an elusive World Cup title.

The Dutch national team carries the burden of probably being best soccer country to never have won the World Cup. The Netherlands has been the runner-up three times — 1974, 1978 and 2010 — and was third in 2014 after losing to Argentina on penalties in the semifinals.

However, the team failed to qualify in 2018, probably providing more motivation this time.

Dumfries scored Oranje’s final goal in the 81st minute on a volley after second-half substitute Haji Wright scored in the 76th to briefly get the Americans back into the match. He also added assists on the other two goals at Khalifa International Stadium — Memphis Depay’s in the 10th, and Daley Blind’s in first-half stoppage time.

“It was a great game and I’m happy I can be important for the team,” said Dumfries, who is named for American actor Denzel Washington.

“I’m proud to have his name,” he said. “I am incredibly proud of Denzel Washington. He is a really strong personality who voices his views and I see that as an example.”

Dumfries said Oranje was “more focused” than it was in lackluster group games — a 1-1 draw with Ecuador and 2-0 victories over Senegal and Qatar.

“We knew that we could play better than we did in the first three matches,” he said.

The United States had more possession of the ball, and more attempts at goal — 16 to 12. But the Dutch dealt with that just fine.

“In Holland we’re used to having the ball, to having possession,” Dumfries said. “This is a different way of playing. I also understand the criticism in Holland because we can play much better with the ball.”

United States goalkeeper Matt Turner and the American defense were under constant pressure handling crosses into the 6-yard box.

“It was like they had a little bit of extra patience and cut the ball back, and we didn’t track well,” Turner said. “I felt like every time they crossed the ball they got a head on it or they got a piece of it.”

Cody Gakpo, who has scored three goals in the tournament, said what Van Gaal has been talking up: The Netherlands can finally win the title, though few think this is one of the nation’s best teams.

“We’ve believed in ourselves from the start and we’ve come here with a goal,” Gakpo said. “And that’s to try and become world champions. We believe in that.”

___

AP World Cup coverage: https://apnews.com/hub/world-cup and https://twitter.com/AP_Sports

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Fan buying famed ‘Goonies’ house in Oregon, listed for $1.7M

ASTORIA, Ore. (AP) — The listing agent for the Victorian home featured in the “The Goonies” film in Astoria, Oregon, said this week the likely new owner is a fan of the classic coming-of-age movie about friendships and treasure hunting, and he promises to preserve and protect the landmark.

The 1896 home with sweeping views of the Columbia River flowing into the Pacific Ocean was listed in November with an asking price of nearly $1.7 million.

Jordan Miller of John L. Scott Real Estate said the sale is expected to close in mid January, The Oregonian/OregonLive reported. The new owner, a self-described serial entrepreneur, will make his name known at that time, Miller said.

Since the movie came to theaters in 1985, fans have flocked to the home in northwestern Oregon’s historic port of Astoria. The city celebrates Goonies Day on June 7, the film’s release date, and welcomes thousands of people for the event.

An offer was accepted six days after the house was listed, according to public record.

“After the word spread that the property was for sale, we received multiple offers, at asking price and higher, and we have a full backup offer,” Miller said.

Seller Sandi Preston is passing along movie memorabilia she has collected or has been given, and some of the furniture in the home, restored to its original 1896 style, may also be sold to the buyer, according to Miller.

Preston was known to be largely welcoming to visitors. But she lived in the house and the constant crowds were a strain that prompted her at times to close it to foot traffic.

After the film’s 30th anniversary drew about 1,500 daily visitors in 2015, Preston posted “no trespassing” signs prohibiting tourists from walking up to the property. She reopened it to the public in August.

Based on a story by Steven Spielberg, the film features a group of friends fighting to protect their homes from an expanding country club and threats of foreclosure. In the process, they discover an old treasure map that leads them on an adventure and allows them to save their “Goon Docks” neighborhood.

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Herschel Walker runs and hides

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It’s the last few days of the Georgia special election. And as we move closer to D-day, a certain vampire is losing his mind. Walker is desperately pleading for money. I suppose it’s only natural for the pretend cop to be freaking out. Senator Warnock has been eviscerating Walker in campaign ads, and voters have been showing up for early voting.

Mr. Walker also appears to have put in place a new rule as it relates to reporters. And that rule is: stay away. It’s being reported that Walker will not let journalists within 20 feet of him. I suppose I can’t blame him, really. After all, they might just have questions that Walker cannot answer. So far, Walker has demonstrated an inability to answer most questions.

And one of Walker’s ex-girlfriends has come forward to say Walker attacked her while in a state of complete rage. So no, these last few days have not smiled upon Walker. And he could still win. This is an article to warn you — that we can’t get complacent.

Republicans are turning out too. And they’re making calls. How do I know this? Because I’ve read the stories of some of them. They are door-knocking. They are doggedly working hard — just as we are.


So that means we must work harder. No matter how much we think we may have in the bag — we do not. Every vote matters. It is indeed possible this race could come down to a mere hundred votes or less. Remember, Georgia only recently became a swing state. Remember how close it will be.

So please — let’s use these last few days to donate, phone bank, tweet, door knock, send postcards, and basically push ourselves to do whatever we possibly can to capture that 51st seat. Lots of people are counting on us. Let’s not let them down.

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Layout of house where Idaho killings took place explained

(NewsNation) — The house where four University of Idaho students were stabbed to death was a tri-level, six-bedroom, three-bathroom house with at least one accessible back door, according to photos analyzed by NewsNation.

The six bedrooms and three bathrooms were spread out across three floors, with two bedrooms and one bathroom on each floor. Victims were found on the second and third floors, according to police.

The father of one of the victims, Kaylee Goncalves, said she and Madison Mogen were found dead in the same bed. Ethan Chapin and Xana Kernodle were also killed in the attack nearly three weeks ago.

The killings have shaken the community of Moscow, Idaho, and left other university students on edge. Many left early for Thanksgiving break, and few returned to campus earlier this week when classes resumed.

Police have not yet identified any suspects, nor have they located a murder weapon. Two other people who were inside the house at the time of the killings have not been publicly identified, though police have eliminated them as suspects.

A total of six people were on the lease, but Moscow police do not believe the person on the lease was there at the time of the stabbings. Chapin did not live at the house, but was dating Kernodle, who was roommates with Goncalves and Mogen.

The crime scene was active again on Friday with what appeared to be investigators. Two men in a Ford pickup truck were seen entering and later exiting the house.

A county coroner’s preliminary report determined that Chapin, 20; Mogen, 21; Kernodle, 20; and Goncalves, 21, all died from stab wounds and were likely asleep at the time of their murders.

Police will not share which victims were found where inside the rental home. Pictures from inside, analyzed by NewsNation, seem to show there are two bedrooms on the first floor with a bathroom in the middle. The second floor also appears to have two bedrooms, another bathroom and a kitchen. On the third floor, there are two bedrooms and another bathroom. According to investigators, the murders happened on the second and third floors of the home.

There are two sliding glass doors on the home: one on the second floor that can be accessed from the ground level outside, and one on the third floor that connects to a deck only accessible from inside the home.

Family members spoke at a vigil Wednesday night, where emotions ran high.

“The circumstances that bring us here tonight, they’re terrible. The hardest part: We cannot change the outcome,” said Stacy Chapin, Ethan’s mother.

“These girls were absolutely beautiful. They had been friends since sixth grade,” Steve Goncalves said of his daughter and her lifelong best friend, Mogen. 

NewsNation has been covering this story from the beginning and will continue its investigation in a special hour on Sunday. National correspondent Brian Entin will host “Special Report: Idaho Murder Mystery” at 9 p.m. ET on Dec. 4 on NewsNation. Here’s how you can watch.

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Australia defender Souttar takes on the greats at World Cup

AL RAYYAN, Qatar (AP) — From a World Cup -threatening knee injury to marking Lionel Messi and Kylian Mbappe at soccer’s biggest tournament, it’s been a wild ride for Australia defender Harry Souttar.

Now, after a 2-1 loss to Argentina on Saturday and elimination from the World Cup, it’s back to the grind of English soccer’s second division for the Stoke defender.

Souttar, however, has experienced one pinch-yourself moment after another in Qatar and leaves with stories that will last a lifetime. Like the moment he left arguably the greatest player ever in a heap on the turf at Ahmad Bin Ali Stadium.

In a total mismatch, the 6-foot-6 (1.98-meter) Souttar crashed through the 5-7 (1.69-meter) Messi in the 41st minute.

Shortly before that collision, the Argentina great had scored by sweeping a shot between Souttar’s legs — one of the most embarrassing moves that can happen to a professional soccer player.

So maybe that was payback.

Not that Souttar needed to beat himself up too much about that moment. It was, after all, Lionel Messi, the seven-time Ballon d’Or winner, playing his 1,000th game for his country and scoring his ninth World Cup goal to move one ahead of Diego Maradona and one behind Argentina’s record-holder in the tournament, Gabriel Batistuta.

That Souttar was even on the same field as Messi was an achievement in itself. Especially after recovering from a ruptured ACL, which he injured in a World Cup qualifier against Saudi Arabia in Sydney last November.

His road to Qatar was long, arduous and at times lonely as he worked individually in the gym at Stoke’s training ground, watching his teammates out on the field doing what he couldn’t.

It was almost a year to the day that he made his comeback, on Nov. 8 in a 2-0 win over Luton.

Hardly ideal preparation before heading into a World Cup, let alone coming up against two of the best players on the planet.

In Australia’s opening Group D game, the team faced Mbappe and defending champion France. Mbappe scored in the 4-2 victory, but Souttar and the Aussies recovered to secure a spot in the knockout round for only the second time in its history after reaching the round of 16 in 2006.

That set up a date with Messi, which is where Australia’s story ends.

For Souttar, however, his brush with the greatest will live forever.

___

James Robson is at https://twitter.com/jamesalanrobson

___

AP World Cup coverage: https://apnews.com/hub/world-cup and https://twitter.com/AP_Sports

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Built to disappear: World Cup stadium 974

DOHA, Qatar (AP) — Of the seven stadiums Qatar built for the World Cup, one will disappear after the tournament.

That’s what the games’ organizers have said about Stadium 974 in Doha — a port-side structure with more than 40,000 seats partially built from recycled shipping containers and steel.

Qatar says the stadium will be fully dismantled after the World Cup and could be shipped to countries that need the infrastructure. Outside experts have praised the design, but say more needs to be known about what happens to the stadium after the event.

“Designing for disassembly is one of the main principles of sustainable building,” said Karim Elgendy, an associate fellow at the London-based Chatham House think tank who previously worked as a climate consultant for the World Cup.

“It allows for the natural restoration of a building site or its reuse for another function,” he said, adding that a number of factors need to considered “before we call a building sustainable.”

Buildings are responsible for nearly 40% of the world’s energy-related carbon emissions. Of that, about 10% comes from “embodied” carbon or the greenhouse gas emissions related to the construction, maintenance and demolition of buildings.

Qatar has faced international criticism for its treatment of low-paid migrant workers who built over $200 billion worth of stadiums, metro lines and other infrastructure for the World Cup. Qatar says the criticism ignores labor reforms enacted in recent years.

Stadium 974, named after Qatar’s international dialing code and the number of containers used to build the stadium, is the only venue that Qatar constructed for the World Cup that isn’t air-conditioned. During a match Friday in which Switzerland defeated Serbia, the air was noticeably more humid and hot than in other venues.

The stadium is hosting only evening matches, when temperatures are cooler.

Fenwick Iribarren Architects, which designed Stadium 974 and two other World Cup stadiums, says the idea was to avoid building a “white elephant,” a stadium that is left unused or underused after the tournament ends, as happened following previous World Cups in South Africa, Brazil and Russia.

Qatar says it has developed plans for the other six stadiums after the games are over. Many will have a number of seats removed.

The multi-colored shipping containers are used as building blocks for Stadium 974 and also to house facilities such as restrooms in the interior of the structure. Like giant Lego blocks, the bright red, yellow and blue corrugated steel boxes appear suspended between layers of steel. The design gives the stadium an industrial feel.

Qatar has not detailed where the dismounted stadium will go after the tournament or even when it will be taken down. Organizers have said the stadium could be repurposed to build a venue of the same size elsewhere or multiple smaller stadiums.

Where its components go matters because of the emissions implicated by shipping them thousands of kilometers away.

Carbon Market Watch, an environmental watchdog group that investigated Qatar’s World Cup sustainability plans, said whether Stadium 974 has a lower carbon footprint than a permanent one comes down to “how many times, and how far, the stadium is transported and reassembled.”

FIFA and Qatar acknowledge that in a report estimating the stadium’s emissions. If the stadium is reused only once, they estimate its emissions would be lower than a permanent one as long as it is shipped fewer than 7,000 kilometers (about 4,350 miles) away.

If it’s repurposed more than once, it could be shipped farther and still be less polluting than a permanent venue, they said, because of how energy-intensive building multiple new stadiums is.

Qatar’s Supreme Committee for Delivery and Legacy, the organizing committee for the World Cup, did not respond to a request for more information about plans after the tournament.

The report also didn’t factor in operational emissions — or those produced from running a building — once the stadium is repurposed because standards vary in different countries, FIFA and Qatar said.

“The energy required for dismantling and shipping the building components will obviously need to be estimated,” Elgendy said, “but it is unlikely to outweigh the carbon embodied in the building materials.”

For now, the stadium’s design isn’t lost on spectators. On any game night, fans entering and leaving the stadium take selfies against its modern, industrial facade. The temporary stadium is hosting seven games in total — with the final one on Monday between Brazil and South Korea.

Jhonarel Miñoza, a 42-year-old Qatari resident originally from the Philippines, said she and her sister wanted to see a game in each of the seven stadiums.

Miñoza, an administrative officer who has lived in Qatar for five years, said she had heard about Stadium 974′s unconventional design before the game she attended on Friday.

“I was really eager to know how they built it,” Miñoza said. “When I came inside here, I was just checking how they did that.”

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AP World Cup coverage: https://apnews.com/hub/world-cup and https://twitter.com/AP_Sport

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Pentagon chief: US faces pivotal years in countering China

SIMI VALLEY, Calif. (AP) — The U.S. is at a pivotal point with China and will need military strength to ensure that American values, not Beijing’s, set global norms in the 21st century, Defense Secretary Lloyd Austin said Saturday.

Austin’s speech at the Reagan National Defense Forum capped a week in which the Pentagon was squarely focused on China’s rise and what that might mean for America’s position in the world.

On Monday it released an annual China security report that warned Beijing would likely have 1,500 nuclear warheads by 2035, with no clarity on how China would seek to use them.

On Friday in a dramatic nighttime rollout, Austin was on hand as the public got its first glimpse of the military’s newest, highly classified nuclear stealth bomber, the B-21 Raider, which is being designed to best the quickly growing cyber, space and nuclear capabilities of Beijing.

China “is the only country with both the will and, increasingly, the power to reshape its region and the international order to suit its authoritarian preferences,” Austin said Saturday. “So let me be clear: We will not let that happen.”

The Pentagon is also concerned about Russia and remains committed to arming Ukraine while avoiding escalating that conflict into a U.S. war with Moscow, he said at the forum, held at the Ronald Reagan Presidential Library.

“We will not be dragged into Putin’s war,” Austin said.

“These next few years will set the terms of our competition with the People’s Republic of China. They will shape the future of security in Europe,” Austin said. “And they will determine whether our children and grandchildren inherit an open world of rules and rights — or whether they face emboldened autocrats who seek to dominate by force and fear.”

Still, between the two nuclear power threats, China remains the greater risk, Austin said.

To meet that rise, “we’re aligning our budget as never before to the China challenge,” Austin said. “In our imperfect world, deterrence does come through strength.”

The bomber is part of a major nuclear triad overhaul underway that the Congressional Budget Office has estimated will cost $1.2 trillion through 2046.

It includes the Raider serving as the backbone of the future air leg of the triad, but it also requires modernizing the nation’s silo-launched nuclear intercontinental ballistic missiles and its nuclear submarine fleet.

The Defense Department has the largest discretionary budget of all the federal agencies, and it may receive up to $847 billion in the 2023 budget if Congress passes the current funding bill before this legislative session ends.

However, defense advocates argue it is still not enough to modernize and keep up with China because much of that spending goes to military personnel. The CBO estimates that about one-quarter of the defense budget is spent on personnel costs such as salaries, health care and retirement accounts.

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St. Edward’s Crown moved out of tower ahead of coronation

LONDON (AP) — St. Edward’s Crown, the centerpiece of the Crown Jewels viewed by millions of people every year at the Tower of London, has been moved to an undisclosed location for modification in preparation for the coronation of King Charles III next year.

The move was kept secret for security reasons until the operation was complete, Buckingham Palace said in a statement Saturday. The palace provided no details and didn’t say where the modification work would take place.

Charles will be crowned on May 6 at Westminster Abbey in a ceremony that will embrace the past but look to the modern world after the 70-year reign of the late Queen Elizabeth II. The Imperial State Crown will also be used during the service.

Versions of St. Edward’s Crown are believed to have been used by monarchs since the 11th century.

The current crown was made for Charles II in 1661, as a replacement for the original, which was melted down in 1649 after the House of Commons abolished the monarchy and declared a commonwealth during the English Civil War. The original was thought to date back to Edward the Confessor, who reigned in 1042-1066.

The crown includes a 2.23-kilogram (4.91-pound) solid gold frame — set with rubies, amethysts, sapphires, garnets, topazes and tourmalines — a purple velvet cap and ermine band. It was worn by Elizabeth during her coronation in 1953.

Charles will be crowned in a solemn religious ceremony conducted by Justin Welby, the archbishop of Canterbury, the palace said in a statement. Camilla, the queen consort, will be crowned alongside her husband.

The palace is planning the coronation, known as Operation Golden Orb, as Charles and his heir, Prince William, seek to demonstrate that the monarchy is still relevant in modern, multi-cultural Britain.

While there was widespread respect for Elizabeth, as demonstrated by the tens of thousands of people who waited hours to file past her coffin, there is no guarantee that reverence will transfer to Charles.