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Rare success for Alzheimer’s research unlocks hope for future therapies

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A test tube is seen in front of displayed Biogen logo in this illustration taken, December 1, 2021.— Reuters

CHICAGO: The first big breakthrough in 30 years of Alzheimer’s research is providing momentum for clinical trials of “cocktail” treatments targeting the two hallmark proteins associated with the mind-robbing disease, according to interviews with researchers and pharmaceutical executives.

Drugmakers Eisai Co and Biogen reported in September that their therapy lecanemab could slow the progress of the disease by 27% over 18 months compared with a placebo.

The finding validates the theory that clearing the amyloid protein that forms clumps in the brains of Alzheimer’s patients could slow or halt the disease and has strengthened the support from some scientists for simultaneously targeting another notorious protein linked to Alzheimer’s: tau.

Eisai and Biogen are scheduled to present full data from their lecanemab study on Tuesday at the Clinical Trials on Alzheimer’s Disease conference in San Francisco. The US Food and Drug Administration is expected to make a decision by early January on the companies’ application for accelerated approval.

If approved on an accelerated basis, the companies said they would immediately apply for full US regulatory approval which could help secure Medicare coverage.

“I think lecanemab has reinvigorated the idea that now you could do a combination of amyloid (and) tau,” Dr Reisa Sperling, a neurologist and Alzheimer’s researcher at Harvard Medical School, said in an interview.

Tau naturally accumulates in a memory centre of the brain called the medial temporal lobe as people age. A growing body of research suggests that rising levels of amyloid in Alzheimer’s patients act as an accelerant, causing an explosive spread of tau that forms toxic tangles inside brain cells, eventually killing them.

“We’ve been trying to do combination trials for years,” Sperling said. Nearly a decade ago, Alzheimer’s experts met in Washington to discuss testing combined therapies. At the time, “no one would listen,” she said.

Now, however, Sperling and other researchers in the Alzheimer’s Clinical Trials Consortium (ACTC), a research network backed by the National Institute on Aging, say drugmakers are increasingly interested in participating in a study to test tau drugs alone and in combination with anti-amyloid drugs such as lecanemab.

“We’ve been talking to multiple companies about working with us on our proposed platform, which can evaluate multiple drugs, and everybody’s interested,” said Dr Paul Aisen, director of the Alzheimer’s Therapeutic Research Institute at the University of Southern California’s Keck School of Medicine, and a leader with Sperling of the ACTC.

The scientists said they expect an answer on funding by year-end. NIH said it does not discuss grants under review.

More than 6 million Americans have Alzheimer’s, costing the US economy nearly $6 billion a year in direct spending and unpaid caregiving expenses, according to congressional briefing documents. By 2050, Alzheimer’s cases are expected to double to 12.7 million, bringing the total yearly cost to nearly $1 trillion, according to the documents.

Last year, the FDA gave Biogen and Eisai’s drug aducanumab conditional approval even though it failed one of its two late-stage trials. The approval was based on the drug’s ability to remove amyloid from the brain.

Biogen initially priced the drug at $56,000 a year, but the US Centres for Medicare and Medicaid Services said it needed more compelling evidence, and that Medicare would only cover the drug for use in clinical trials.

Lecanemab’s success rests on years of research into the causes of Alzheimer’s as well as advances in measuring amyloid deposits through brain scans and spinal fluids. Trials of tau drugs will aim to build on that progress, using brain scans, spinal fluids and blood tests to better assess the stage of disease, when to intervene and whether the drug is hitting its target. That would allow companies to test drugs even before symptoms emerge.

Nearly a dozen drugmakers, including Roche, Merck & Co, Johnson & Johnson and Eli Lilly and Co, are working on therapies that target tau. At least 16 treatments are being tested in clinical trials, with results expected over the next three years, according to a Reuters review of the clinicaltrials.gov registry.

Merck is testing its MK-2214 therapy aimed at clearing tau in patients in very early stages of the disease in several small trials.

“The understanding of the disease is getting much, much better,” said Jason Uslaner, Merck’s head of discovery neuroscience. The drugmaker has been largely absent from the Alzheimer’s space after the high-profile failure of its drug verubecestat five years ago.

So far, only a few trials combine an amyloid-lowering therapy with a drug that targets tau in a “cocktail” approach, similar to those used against cancers and HIV.

Such combinations may improve on the benefit of lowering amyloid alone in people who have symptoms, researchers told Reuters. And when used earlier in the disease, the hope is that they might prevent dementia altogether.

“It may be that you need both — the removal of amyloid that’s driving that biological cascade — and you need to clean up any tau that’s already spreading from one cell to another,” said Dr Adam Boxer, a tau expert at the University of California San Francisco (UCSF) Memory and Aging Center.

But several antibody therapies from Lilly, Biogen and AbbVie that were designed to slow the rate of tau accumulations failed outright last year. A drug from Roche, semorinemab, showed limited effectiveness.

“It took maybe 20 or 30 years before we found a drug that really targeted the right form of amyloid to make a difference,” Boxer said. “It’s still early days.”



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Pakistan seeks support from Bank of China to bring back macroeconomic stability

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Pakistan Tuesday sought support from the Bank of China to bring back the macroeconomic stability, convincing them of an expansion of business relations with Islamabad to deepen the economic and financial relations.

Federal Minister for Finance and Revenue Ishaq Dar held a virtual meeting with Bank of China President Liu Jin at the Finance Division where he briefed the latter about the financial and fiscal conditions inherited by the present government.

According to a statement issued by the Ministry of Finance, Dar shared that it has always been a great pleasure to work with the Bank of China and Pakistan has enjoyed “sound financial dealings” with the bank.

The finance minister also highlighted the recent visit of Prime Minister Shehbaz Sharif to China and talked about the reciprocation of warm sentiments from the Chinese leadership.

Dar, while talking about the long-standing and durable relationships between the government of both countries, shared gratitude to the Bank of China president for continuous support to Pakistan in testing times.

“It was shared that the Bank of China has played a crucial role in extending budgetary support to Pakistan which has played a significant role in easing pressure on the external account and meeting budgetary needs,” the statement mentioned.

Speaking on the occasion, the Bank of China president also highlighted the historical and bilateral ties between both countries and appreciated the Government of Pakistan for taking the necessary measures for easing the lives of the masses in the country.

He also acknowledged the contribution of Pakistan in supporting China during hard times. Liu Jin also commended the ongoing facilitation being provided by the Government of Pakistan on various Chinese projects under the umbrella of the China-Pakistan Economic Corridor (CPEC).

In conclusion, the finance minister thanked the bank’s president for continuous support and assured him of the same support by the present government in deepening the economic, trade and investment cooperation.


— Thumbnail image of Finance Minister Ishaq Dar’s meeting with Bank of China President Liu Jin held on November 29, 2022 at the Finance Division was taken from Twitter/@FinMinistryPak



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Arjun Rampal’s girlfriend Gabriella Demetriades organize birthday party for him on Yacht

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Arjun Rampal was last seen in the film ‘Dhaakad’

Arjun Rampal’s girlfriend Gabriella Demetriades arrange a grand birthday party for him on a yacht.

Both Myra and Gabriella shared inside pictures from the white-themed birthday party. The birthday bash was hosted by Arjun’s girlfriend.

Gabriella shared a series of pictures from the special evening. In the first photo, the two lovebirds posed together for the camera; Arjun dressed in a white outfit while Gabriella wore a pastel green cutout gown.

In the second photo, Arjun enjoys a boat ride with a bunch of his friends. In another picture, he can be seen dancing his heart out on the boat surrounded by a beautiful view.

The caption on the post read: “I’m only throwing parties on yachts from now on. Thank you to all of our loved one for being there.”

See pictures:

As per PinkVilla, she posted a video on Rampal’s birthday which had a montage of their good memories and wrote: “The irony of wishing you on social media is not lost , but for me this is more of an appreciation post . I couldn’t think of a more apt song for one of few humans I’ve met in my life that is the true definition of authentic, I’m inspired each day by your sheer dedication , focus and most of all unflinching nature that you go through life with .”

“There isn’t anyone like you , and that’s because you truly do it your way “ and for that , you should be proud .Happy birthday my love, things are only getting better.”



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Pak vs Eng: Pakistan’s possible playing XI for first Test match

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Pakistan skipper Babar Azam. — Reuters/File

KARACHI: Pakistan will go up against England in the upcoming Test series, scheduled to begin on December 1 (Thursday) in Rawalpindi, with the team management reportedly having finalised the playing XI.

Pakistan skipper Babar Azam and 11 others have been reportedly included in the Test squad. Two Pakistani cricketers will make their Test debuts. 

Fast bowler Haris Rauf and leg spinner Abrar Ahmed are strong contenders to play the Rawalpindi match, while three all-rounders are expected to be included in the squad.

Left-hand spinner Mohammad Nawaz will be playing at his home ground for the first time, while Salman Agha and Faheem Ashraf are also among the expected all-rounders to be included in the team.

Abdullah Shafiq and Imam-ul-Haq are expected to be placed as openers.

The expected squad will include captain Babar Azam, Muhammad Rizwan, Abdullah Shafiq, Imam-ul-Haq, Azhar Ali, and Salman Ali Agha. Other players expected to join the team are Mohammad Nawaz, Faheem Ashraf, Haris Rauf, Naseem Shah, and Abrar Ahmed.



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Clarence Gilyard, the tech genius from

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Clarence Gilyard, the fine arts professor and actor remembered for his standout roles in action films and television series in the 80s and 90s, has died, the University of Nevada, Las Vegas, announced in a statement. Gilyard, who taught film and theater courses at the university, was 66. Details surrounding his death, and what may have caused it, were not disclosed.

“It is with profound sadness that I share this news,” said Dean Nancy J. Usher, of the UNLV College of Fine Arts, in the university’s statement. “His students were deeply inspired by him, as were all who knew him. He had many extraordinary talents and was extremely well-known in the university through his dedication to teaching and his professional accomplishments.”

Promotional portrait of American actor Clarence Gilyard Jr (as James ‘Jimmy’ Trivette), dressed in a pin-stripe suit, for the television series ‘Walker, Texas Ranger,’ .

CBS Photo Archive / Getty Images


Usher added that Gilyard’s “generosity of spirit was boundless,” and noted his willingness to lend a hand to various projects and performances at the school whenever possible.

“We remember Clarence with joy and gratitude for all he contributed to the College of Fine Arts, the UNLV community, and, through his impressive personal achievements, to the world,” the dean said.

Before joining the university staff, Gilyard built a career in Hollywood that spanned several decades. Born on Christmas Eve in 1955 in Moses Lake, Washington, Gilyard’s family moved several times during his childhood due to his father’s position in the U.S. Air Force, and they lived at a number of army bases before settling in a San Bernardino, California, suburb during his adolescent years.  

Gilyard later moved to Los Angeles to pursue acting, and during the early 80s appeared in guest spots on television series such as “Diff’rent Strokes,” “The Facts of Life” and “Riptide.” He is best known for his performances in the popular action films “Top Gun” and “Die Hard,” where he played alongside stars like Tom Cruise and Bruce Willis, respectively, as well as his leading roles in the 90s legal drama series “Matlock” and crime drama “Walker, Texas Ranger.”

He is survived by his wife, Elena Gilyard, and six children.



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Shopper turnout hit record high over Black Friday weekend, retail trade group says

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A customer searches for shoe products inside a Macy’s store during Black Friday sales on November 25, 2022 in Jersey City, New Jersey.

Kena Betancur | Getty Images

A record number of holiday shoppers – 196.7 million – flocked back to stores and hunted for deals from Thanksgiving Day to Cyber Monday, according to a survey by the National Retail Federation, which tracks the figure for in-person and online shopping.

The trade group did not estimate spending over the weekend, but said Tuesday that sales for the overall holiday shopping season are on track to meet its forecast. It anticipates that holiday sales will rise by 6% to 8% from last year to between $942.6 billion and $960.4 billion. Some of that increase will come from nearly four-decade high inflation.

The National Retail Federation defines the holiday season as November 1 through December 31. The sales forecast excludes spending at automobile dealers, gasoline stations and restaurants.

Shoppers spent an average of about $325 on holiday-related purchases over the weekend. That’s higher than last year’s average of $301.

NRF CEO Matt Shay said the weekend’s biggest takeaways are that Americans are eager to shop in-person again and that they’re hungry for big bargains. More than 122.7 million people visited brick-and-mortar stores over the weekend, a jump of 17% from 2021.

As inflation hits Americans’ wallets, he said, promotions have become a important motivator.

“Consumers are out shopping, but they’re out shopping when they see deals and when they get the promotions that meet what it is they’re looking for, and so you can get them engaged, but you’ve got to deliver value and price,” he said on a call with reporters.

Retailers have nevertheless been cautious about their holiday outlooks, particularly as families feel the pinch of inflation. Walmart has spoken about customers skipping over discretionary items and trading down to cheaper proteins like hot dogs and peanut butter. Target cut its forecast for the holiday quarter. And Best Buy said customers have had a higher interest in shopping during sales events.

So far, though, industry-watchers have reported a strong start to the shopping season. Figures from Adobe Analytics showed that online spending hit record highs on key days during the holiday shopping weekend. Black Friday sales hit $9.12 billion and Cyber Monday sales hit $11.3 billion, according to the company, which tracks sales on retailers’ websites.

On average, consumers said in the NRF survey that they are about halfway done with holiday shopping. That means retailers can expect more purchases in the weeks ahead, Shay said.

NRF said Tuesday that its tally of shoppers over the holiday weekend topped last year’s turnout of 179 million during the same period last year. The group, which began tracking the figure in 2017, had forecast a turnout of 166.3 million for this year.

A bigger turnout and record spending this holiday season could be a result of a variety of factors. It could indicate that consumers are willing to buy − but only if items are on deep discount. It could also signal a return to the pre-pandemic timetable of holiday shopping, with people concentrating their gift-buying around Black Friday and in the final sprint before Christmas Day.

Or it could portend a more challenging 2023. If Americans are funding shopping spree by slashing savings rates and tallying up big balances on credit cards or through ‘Buy Now Pay Later,’ that could leave them with less to spend in the months ahead.

The National Retail Federation, a major trade group, has taken a bullish stance on consumer spending — saying a strong job market has encouraged Americans to keep spending.

Shay also shook off concerns about a recession on Tuesday, but acknowledged another risk for retailers: the threat of a railway strike. While retailers may have most of their holiday merchandise, he said a work stoppage could be a blow to consumer confidence.

“We think that the holiday season would be the worst possible time,” he said.



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Bird flu: Free range turkey supplies hit by bird flu

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About 600,000 birds have been culled or have died in the UK’s worst avian flu outbreak.



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Katie Price shares cryptic post after Carl Woods ‘cheating’ scandal

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Katie Price’s recent post has grabbed everyone’s attention and has left her fan wondering.

It comes after Katie’s fiancé Carl Woods made a bombshell claim in a video last week that their two-year relationship was over.

The 44-year-old former glamour model turned to a photo-video sharing platform to share various quotes, including one about becoming a “new woman.”

It read: “When a woman is consistently spoken to softly & treated gently, she becomes a new woman.

“You’re helping her heal her nervous system, you’re helping her heal generational trauma, you’re allowing feminine energy to flourish, you’re helping her to remember who she is.”

Katie once referred to Carl, 34, as her “rock” and the pair were planning to marry and had even been trying for a baby.


They seemed loved up just days before the cheating claims, having just returned from a luxury trip to Thailand together.

The pair then appeared to be back on after they were seen kissing and holding hands in public.

The couple were seen sharing an intimate moment just days after Katie was said to have split from the car dealer.



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Analysis | Supreme Court Should Separate Sleazy Lobbying from the Criminal Kind

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Comment

The US Supreme Court heard oral argument Monday in the most important case you’ve never heard of. Although Percoco v. United States has generated few headlines, its reach could alter the way businesses deal with regulators and legislators.

The case arises from the 2018 conviction of one Joseph Percoco, who took a break from his job in Governor Andrew Cuomo’s office to run Cuomo’s reelection campaign. During his time away, a company having trouble with state labor regulators offered him $35,000 if he could, let us say, make the problems disappear. Percoco placed a few calls to key officials, the regulators backed off, and the company was happy. And Percoco then returned to his senior role in state government after Cuomo won his new term.

Sure, sounds a wee bit grafty. But the question the justices agreed to consider isn’t whether Percoco is a shining example of ethical probity. The question is whether he violated a federal statute aimed at punishing public officials who take bribes. The jury found he did, and the US Court of Appeals for the Second Circuit rejected his defense that the law didn’t apply to him because when he took the money and placed the calls he was, technically, a private citizen.

The Second Circuit’s opinion makes fun reading. The text abounds with references to “The Sopranos” and schemes to “keep the ziti flowing.” But the relevant issue isn’t whether Percoco was a sleazy character who hatched sleazy plans. The relevant issue is whether those sleazy plans violated a murky 1988 congressional amendment that prohibits participation in “a scheme or artifice to deprive another of the intangible right of honest services” — what’s become known as “honest services fraud.”

This vague and obscure amendment has long been a boon to prosecutors precisely because of its vagueness and obscurity. As the legal scholar Albert W. Altschuler points out, the 1988 law “enabled lower federal court judges, like the priests of ancient Delphi, to explicate language ordinary mortals could not understand.” But writing language ordinary mortals can’t understand and adding it to the criminal code isn’t good for democracy or for the law.

For example, prosecutors argue that the prohibition should cover all those who “function” as employees, even when they hold no official position. The Second Circuit agreed. In its opinion affirming Percoco’s conviction, the court concluded that the law provides no basis to distinguish a “formal” from a “functional” government employee. The judges wrote that the law is broad enough to cover all those individuals “who are relied on by the government and who in fact control some aspect of government business.”

Percoco argues that this language is so broad that it could apply to a huge number of people, including lobbyists. To show the influence top lobbyists have, Percoco’s brief cites a 2012 study which found that lobbyists whose key Senators leave office lose a whopping $182,000 in annual revenue.

The Justice Department rejects the analogy, arguing that none of these well-connected lobbyists function, even informally, as public officials. That would be reasonable, except that the test for who functions as a public official is so murky — a major factor is whether government employees feel obliged to treat the lobbyist’s requests as commands.  There are plenty of lobbyists so powerful that the lowliest bureaucrat trembles to cross them.

Consider the very real case of a legislator convicted under the statute after voting the way a lobbyist urged. In upholding the conviction, the US Court of Appeals for the Third Circuit explained that even though entertaining legislators was part of the job, here the lobbyist — who was also convicted — had entertained the legislator too lavishly. How much is too much? Read the court’s guidance for yourself:

[A] lobbyist does not commit honest services fraud … if his ‘intent was limited to the cultivation of business or political friendship.’ He commits those violations ‘only if instead or in addition, there is an intent to cause the recipient to alter her official acts.’

This guidance fails to guide. It seems to say that a lobbyist is innocent as long as the lobbyist doesn’t lobby.

This is Percoco’s point, and it’s a good one. Whatever one thinks of his conduct, the way the lower courts have construed the statute leaves prosecutors far more leeway than Congress likely intended. Critics who call the case a classic example of prosecutorial overreach aren’t entirely wrong. 

The true problem isn’t the prosecutors but the statute itself. Put Percoco aside and think instead about the rest of us. A minimum democratic fairness demands that crimes be spelled out with crystalline clarity. When we interact with the government that serves us, we should not be left to guess whether we’re breaking the law.

More From Bloomberg Opinion:

• To Defeat Trump, Stop Calling Him a Loser: David A. Hopkins

• Where Abortion Will Be on the Ballot in 2024: Julianna Goldman

• New Trump Special Prosecutor Won’t Be the Mueller Sequel: Noah Feldman

This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.

Stephen L. Carter is a Bloomberg Opinion columnist. A professor of law at Yale University, he is author, most recently, of “Invisible: The Story of the Black Woman Lawyer Who Took Down America’s Most Powerful Mobster.”

More stories like this are available on bloomberg.com/opinion



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Musk ending Twitter COVID-19 misinfo policy infuriates liberals: ‘Dangerously amplifying lies’

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Liberals on Twitter raged over the fact that Twitter under Elon Musk removed its COVID-19 “misleading information protocol in recent days, a protocol that resulted in the suspension of 11,000 users that have posted pandemic information.”

Critics reacted to the news, claiming “dangerous” users are being welcomed onto platform with the end of such policies. 

The decision appears to follow Musk’s appeal to protecting free speech on the platform, as well as his plans to grant “amnesty” to accounts banned prior to his acquisition of the platform. 

TWITTER ERUPTS AFTER ELON MUSK MOCKS CNN WITH CHYRON ABOUT THREATS TO FREE SPEECH 

Elon Musk has wasted little time making his mark on Twitter since he took over last month.

On Tuesday, Fox Business quoted Twitter’s official announcement ending the policy, which stated, “Effective November 23, 2022, Twitter is no longer enforcing the COVID-19 misleading information policy.” 

The piece stated, “Additionally, the COVID-19 policy is no longer listed on Twitter’s, “How we address misinformation on Twitter” explainer, and the URL for the misinformation policy now redirects to Twitter’s Help Center.”

The previous policy, enacted in March 2020, announced that Twitter posts going against “authoritative sources” on COVID-19 would be removed. As such, over 11,000 Twitter accounts have been suspended in the last two years for violating the policy. 

Media spotted the change in policy several days after it went into effect. CNN reported on it Tuesday morning, with a piece headlined, “Twitter said it will no longer enforce its longstanding Covid misinformation policy, yet another sign of how Elon Musk plans to transform the social media company he bought a month ago.”

MSNBC’S CHRIS HAYES FRETS HIS ‘WORST FEARS’ HAVE BEEN REALIZED SINCE MUSK ACQUIRED TWITTER

A nurse prepares to administer a COVID vaccine.

A nurse prepares to administer a COVID vaccine.
(REUTERS/Ronen Zvulun/File Photo)

Prominent liberals on Twitter expressed shock and dismay over reports of the reversal. 

Hollywood screenwriter Randi Mayem Singer shared the CNN report, commenting, “What kind of S*** headline is this, @CNN? How about ‘Dangerously amplifying lies that may cost lives…’?”

BBC freelance reporter Euan MacDonald commented on the serious nature of the change, tweeting, “This is an international health issue.”

CNN anchor Brianna Keilar tweeted about the policy change, writing, “Twitter is no longer enforcing its Covid misinformation policy that was once hailed by the Surgeon General as an example of what companies should do to combat misinformation.”

Epidemiologist Dr. Eric Feigl-Ding appeared distressed over the reversal, tweeting, “Bad news—it seems @Twitter just updated its misleading info policy that #COVID19 misinformation will no longer be enforced. The 11k accounts that were suspended under the old policy will soon be restored. Stay folks—do NOT cede the town square to them!”

Liberal Georgetown professor Don Moynihan tweeted that Musk will be held accountable for this spreading of “misinformation.” He wrote, “It’s easy to snipe from the sidelines, but Musk is now the dog that caught the car. Grand proclamations about free speech won’t cut it. The costs of his decision (e.g. on allowing misinformation) and hypocrisies (potential tensions with China) will be scrutinized.”

Tesla and SpaceX Chief Executive Officer Elon Musk speaks at the SATELLITE Conference and Exhibition in Washington. A Delaware judge is hearing arguments, Tuesday, Sept. 27, 2022 over the exchange of information by lawyers in Twitter's lawsuit seeking to force billionaire Elon Musk to carry through with his $44 billion acquisition of the social media giant. 

Tesla and SpaceX Chief Executive Officer Elon Musk speaks at the SATELLITE Conference and Exhibition in Washington. A Delaware judge is hearing arguments, Tuesday, Sept. 27, 2022 over the exchange of information by lawyers in Twitter’s lawsuit seeking to force billionaire Elon Musk to carry through with his $44 billion acquisition of the social media giant. 
(AP Photo/Susan Walsh, File)

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Liberal influencer Brendan Nyhan sarcastically responded to Keilar’s tweet on the news, asking, “What could go wrong?”

And liberal author Robert Swartwood tweeted sarcastically about the news as well, asking, “Gee, I wonder why advertisers are fleeing Twitter?”



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