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washington — Scientists have found a way to help Alzheimer’s drugs seep inside the brain faster — by temporarily breaching its protective shield.

The novel experiment was a first attempt in just three patients. But in spots in the brain where the new technology took aim, it enhanced removal of Alzheimer’s trademark brain-clogging plaque, researchers reported Wednesday.

“Our goal is to give patients a head start,” by boosting some new Alzheimer’s treatments that take a long time to work, said Dr. Ali Rezai of West Virginia University’s Rockefeller Neuroscience Institute, who led the study.

At issue is what’s called the blood-brain barrier, a protective lining in blood vessels that prevents germs and other damaging substances from leaching into the brain from the bloodstream. But it also can block drugs for Alzheimer’s, tumors and other neurologic diseases, requiring higher doses for longer periods for enough to reach their target inside the brain.

Now scientists are using a technology called focused ultrasound to jiggle temporary openings in that shield. They inject microscopic bubbles into the bloodstream. Next, they beam sound waves through a helmetlike device to a precise brain area. The pulses of energy vibrate the microbubbles, which loosen gaps in the barrier enough for medications to slip in.

Prior small studies have found the technology can safely poke tiny holes that seal up in 48 hours. Now Rezai’s team has gone a step further — administering an Alzheimer’s drug at the same time.

Some new Alzheimer’s drugs, on the market or in the pipeline, promise to modestly slow worsening of the mind-robbing disease. They’re designed to clear away a sticky protein called beta-amyloid that builds up in certain brain regions. But they require IV infusions every few weeks for at least 18 months.

“Why not try to clear the plaques within a few months?” Rezai said, his rationale for the proof-of-concept study.

3 patients, 1 drug, 6 months

His team gave three patients with mild Alzheimer’s monthly doses of one such drug, Aduhelm, for six months. Right after each IV, researchers aimed the focused ultrasound on a specific amyloid-clogged part of each patient’s brain, opening the blood brain-barrier so more of that day’s dose might enter that spot.

PET scans show patients’ amyloid levels before and after the six months of medication. There was about 32% greater plaque reduction in spots where the blood-brain barrier was breached compared to the same region on the brain’s opposite side, researchers reported in the New England Journal of Medicine.

This pilot study is elegant but too tiny to draw any conclusions, cautioned Dr. Eliezer Masliah of the National Institute on Aging.

Still, “it’s very exciting, compelling data,” added Masliah, who wasn’t involved with the research. “It opens the door for more extensive, larger studies, definitely.”

More testing on horizon

Rezai is about to begin another small test of a similar but better proven drug named Leqembi. Eventually, large studies would be needed to tell if combining focused ultrasound with Alzheimer’s drugs makes a real difference for patients.

Masliah said it’s also important to closely check whether speedier plaque reduction might increase the risk of a rare but worrisome side effect of these new drugs — bleeding and swelling in the brain.

Alzheimer’s isn’t the only target. Other researchers are testing if breaching the blood-brain barrier could allow more chemotherapy to reach brain tumors, and ways to target other diseases.
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Washington — Artificial intelligence represents a mixed blessing for the legal field, U.S. Supreme Court Chief Justice John Roberts said in a year-end report published Sunday, urging “caution and humility” as the evolving technology transforms how judges and lawyers go about their work.

Roberts struck an ambivalent tone in his 13-page report. He said AI had potential to increase access to justice for indigent litigants, revolutionize legal research and assist courts in resolving cases more quickly and cheaply while also pointing to privacy concerns and the current technology’s inability to replicate human discretion.

“I predict that human judges will be around for a while,” Roberts wrote. “But with equal confidence I predict that judicial work – particularly at the trial level – will be significantly affected by AI.”

The chief justice’s commentary is his most significant discussion to date of the influence of AI on the law — and coincides with several lower courts contending with how best to adapt to a new technology capable of passing the bar exam but also prone to generating fictitious content, known as “hallucinations.”

Roberts emphasized that “any use of AI requires caution and humility.” He mentioned an instance where AI hallucinations had led lawyers to cite nonexistent cases in court papers, which the chief justice said is “always a bad idea.” Roberts did not elaborate beyond saying the phenomenon “made headlines this year.”  

For instance, Michael Cohen, Donald Trump’s former fixer and lawyer, said in court papers unsealed last week that he mistakenly gave his attorney fake case citations generated by an AI program that made their way into an official court filing. Other instances of lawyers including AI-hallucinated cases in legal briefs have also been documented.  

A federal appeals court in New Orleans last month drew headlines by unveiling what appeared to be the first proposed rule by any of the 13 U.S. appeals courts aimed at regulating the use of generative AI tools like OpenAI’s ChatGPT by lawyers appearing before it.

The proposed rule by the 5th U.S. Circuit Court of Appeals would require lawyers to certify that they either did not rely on artificial intelligence programs to draft briefs or that humans reviewed the accuracy of any text generated by AI in their court filings.
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san francisco, california — Google has agreed to settle a consumer privacy lawsuit seeking at least $5 billion in damages over allegations it tracked the data of users who thought they were browsing the internet privately. 

The object of the lawsuit was the “incognito mode” on Google’s Chrome browser that the plaintiffs said gave users a false sense that what they were surfing online was not being tracked by the Silicon Valley tech firm. 

But internal Google emails brought forward in the lawsuit demonstrated that users using incognito mode were being followed by the search and advertising behemoth for measuring web traffic and selling ads. 

In a court filing, the judge confirmed that lawyers for Google reached a preliminary agreement to settle the class action lawsuit, originally filed in 2020, which claimed that “millions of individuals” had likely been affected.  

Lawyers for the plaintiffs were seeking at least $5,000 for each user it said had been tracked by the firm’s Google Analytics or Ad Manager services even when in the private browsing mode and not logged into their Google account. 

This would have amounted to at least $5 billion, though the settlement amount will likely not reach that figure, and no amount was given for the preliminary settlement between the parties.  

Google and lawyers for the consumers did not respond to an AFP request for comment. 

The settlement came just weeks after Google was denied a request that the case be decided by a judge. A jury trial was set to begin next year. 

The lawsuit, filed in a California court, claimed Google’s practices had infringed on users’ privacy by intentionally deceiving them with the incognito option.  

The original complaint alleged that Google and its employees had been given the “power to learn intimate details about individuals’ lives, interests, and internet usage.” 

“Google has made itself an unaccountable trove of information so detailed and expansive that George Orwell could never have dreamed it,” it added.  

A formal settlement is expected for court approval by February 24, 2024. 

Class action lawsuits have become the main venue to challenge big tech companies on data privacy matters in the United States, which lacks a comprehensive law on the handling of personal data. 

In August, Google paid $23 million to settle a long-running case over giving third-parties access to user search data. 

In 2022, Facebook parent company Meta settled a similar case, agreeing to pay $725 million over the handling of user data. 
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Llay-Llay, Chile — Few players of the online video game Free Fire would know that one of their most ferocious opponents — a lithe, gun-wielding warrior in a short kimono and fang mask — is in reality an 81-year-old grandmother from rural Chile.

From her professional gaming chair at home in a small village, the soft-spoken Maria Elena Arevalo becomes a merciless hunter, mowing down rivals in a game in which tens of millions of players shoot it out to survive on an imaginary remote island.

Wearing an apron over a frilly skirt, Arevalo bears little resemblance to her online alter-ego “Mami Nena” — the nickname she got from her only grandson, Hector Carrasco, 20.

It was Carrasco who introduced Arevalo to the digital world of gaming that has given her a new lease on life after falling into deep loneliness following the death of her husband of 56 years in 2020.

“I didn’t even know what a mouse was,” she told AFP at her home in the town of Llay-Llay in central Chile.

“Afterwards, I got excited. We started to play whenever he [Carrasco] could. I felt better because I didn’t think so much about my late husband anymore.”

At first “I didn’t want to hurt anyone,” she added, but with time, she developed a taste for virtual blood.

Today, Arevalo plays at the “Heroic” level — just one short of the topmost “Grandmaster” level that only 300 players compete in.

She has 4 million followers on TikTok and 650,000 on YouTube, where she shares tips with fellow players.

Last year, she visited Mexico City on an all-expenses-paid trip as a Free Fire ambassador for the game’s anniversary celebrations — her first-ever journey abroad.

“All the kids asked me for autographs. … It was beautiful. The day I die, I’ll take that with me,” she reminisced.

Earlier this month, Arevalo was named one of Chile’s 100 most important elderly people by the El Mercurio newspaper and the Catholic University for helping break down age stereotypes.

Carrasco is in awe of his famous grandmother.

“It’s totally cool, and I don’t know, I feel like she’s like my best friend and all that,” he said.

‘I’ll keep going’

Three years after starting her Free Fire journey, Arevalo says she no longer feels lonely.

In a nod to her dead husband, a bird named “Benito” in his honor accompanies “Mami Nena” on her campaigns of conquest.

Almost half of people over 80 in Chile declare feeling lonely, according to a recent study, a major mental health risk.

Ever more older people are finding solace in gaming: a Ukrainian team known as “Young Guard” are prolific Counter Strike competitors, while 93-year-old Japanese Hamako Mori — also known by her alias Gamer Grandma — is thought to be the oldest gamer in the world.

For Arevalo, the online campaigns are becoming harder due to worsening scleroderma, a disease that causes a hardening and tightening of the skin.

But she is not planning on slowing down.

“I love doing this. I’ll keep going as far as I can,” she insisted.
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TAIPEI, TAIWAN — Chinese authorities approved 105 new online games this week, bolstering support for the industry just days after proposing regulatory restrictions that sent stocks tumbling.

The National Press and Publication Administration (NPPA) announced approval of the 105 games Monday via WeChat, describing the move as a show of support for “the prosperity and healthy development of the online game industry.

“It was only Friday that those same regulators announced a wide range of proposed guidelines to ban online game companies from offering incentives for daily logins or purchases. Other proposed rules include limiting how much users can recharge and issuing warnings for “irrational consumption behavior.”

The draft rules, which were published as part of efforts to seek public comment on the proposals, caused an immediate, massive blow to the world’s biggest games market, leading to as much as $80 billion in market value being erased from China’s two biggest companies, industry leader Tencent Holdings and NetEase.

After the approval was announced Monday, video game stocks in companies such as NetEase began recovering from Friday’s tumble. China’s state-run CCTV said the approval “strongly demonstrates the clear attitude of the competent authorities to actively support the development of online games,” adding that most game companies are deeply encouraged.

Chinese netizens, however, aren’t optimistic.

“Isn’t it the daily work of the NPPA to [approve games] on a regular basis? Don’t make it look like [you’re doing the industry a favor]” said a commenter named “OldTimeBlues” on YYSTV, a Chinese media platform for online gaming.

Another commenter, named Mizu, described the back-to-back announcements as a proverbial carrot and stick tactic.

“You noticed your kid is [has] a concussion after [you’ve hit] him with a stick,” they said of Friday’s announcement of new guidelines. “Now you are giving him a [treat] to make him feel better.”

Syu Jhen, founder of the policy think tank Hong Kong Zhi Ming Institute, said that the draft rules would affect not only the stock prices of Tencent and NetEase but the entire online gaming industry, even if China’s economy relies on domestic consumption.

Syu said that Beijing’s “one-size-fits-all” regulation of online gaming shows that China’s economic decision-makers do not respect market rules and often resort to moral kidnapping, allowing the social value that officials want to encourage to override principles of economic development and business operations.

A comment on YYSTV said, “Thinking issuing an approval would boost market confidence? It’s completely scratching the surface.”

Chen Chung-hsing, director of the New Economy Policy Research Center at National Dong Hwa University, said that at a time when China’s economy is weak and sluggish, exports and investment can no longer boost China’s economy. China can only rely heavily on domestic consumption. He said if China continues to suppress the domestic online gaming industry, it may have economic consequences and cause public resentment.

“China’s current unemployment rate is so high that some people may need video games to kill time,” he told VOA in a phone interview. In this case, [the rules] are also [a kind of] deprivation. Then, after these people stop playing video games, what will happen? Don’t they think about other ways to express their dissatisfaction? So basically, [playing video games] is also a possible source of power for [social] stability.”

Tseng Wei-feng, an assistant researcher at the Institute of International Relations at National Chengchi University, said the reason why the Chinese government wants to restrict online games is that the games often have a “group-fighting” model, which has become a virtual platform for young people to gather. He said the government worries that players can be united and mobilized in the virtual world.

“A group of people may attack a city in a certain game, then evolve into a so-called organized force,” he said. “If one day they are dissatisfied with China’s policies, will they all go to the government gate to protest? I think this is an aspect that the Chinese Communist Party has been strictly controlling.”

Some information is from The Associated Press. 
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Jerusalem — Israel’s government agreed to give Intel a $3.2 billion grant for a new $25 billion chip plant it plans to build in southern Israel, both sides said on Tuesday, in what is the largest investment ever by a company in Israel. 

The news comes as Israel remains locked in a war with Palestinian militant group Hamas in the wake of the October 7 Hamas attack on Israel. It also is a big show of support by a major U.S. company and a substantial offer by Israel’s government at a time when Washington has increased pressure on Israel to take further steps to minimize civilian harm in Gaza. 

Shares of Intel, which has a bit less than 10% of its global workforce in Israel, opened up 2.73% at $49.28 on the Nasdaq stock exchange.  

The expansion plan for its Kiryat Gat site, where it has an existing chip plant 42 kilometers (26 miles) from Hamas-controlled Gaza, is an “important part of Intel’s efforts to foster a more resilient global supply chain, alongside the company’s ongoing and planned manufacturing investments in Europe and the United States,” Intel said in a statement. 

Under CEO Pat Gelsinger, Intel has invested billions in building factories across three continents to restore its dominance in chip-making and better compete with rivals AMD, Nvidia and Samsung. The new Israeli plant is the latest investment by the U.S. chipmaker in recent years. 

“Support from the Israel government will … ensure that Israel remains a global center of semiconductor technology and talent,” Intel vice president Daniel Benatar said. 

Intel had previously received around $2 billion over the past 50 years in Israeli grants in other facilities there. 

Ofir Yosefi, deputy director general of Israel’s Investments Authority, said Intel chose a higher grant and tax rate over an offer for a lower grant and lower tax rate. 

He told Reuters the process took months since a grant of such magnitude needed a review and independent analysis that it was economically viable. It was determined Israel would reap much higher fiscal and economic benefits, he added. 

“This investment, at a time when Israel wages war against utter wickedness, a war in which good must defeat evil, is an investment in the right and righteous values that spell progress for humanity,” Finance Minister Bezalel Smotrich said. 

Intel, whose investment will be over five years, will pay a corporate tax rate of 7.5% instead of 5% previously. The normal tax rate is 23%, but under Israel’s law to encourage investment in development areas, companies receive large benefits. 

In Germany, Intel plans to spend more than $33 billion to develop two chip-making plants in Magdeburg, as part of a multibillion-dollar investment drive across Europe to build chip capacity. Berlin has pledged big subsidies to attract Germany’s biggest-ever foreign investment.  

In 2022, Intel said it would invest up to $100 billion to build potentially the world’s largest chip-making complex in the U.S. state of Ohio, and rivals Samsung and Taiwan Semiconductor Manufacturing Company, or TSMC, also have announced big investment plans in the U.S. 

In addition to the grant that amounts to 12.8% of the total investment, the chipmaker also committed to buy $16.6 billion worth of goods and services from Israeli suppliers over the next decade, while the new facility is expected to create several thousand jobs. 

Intel, one of around 500 multinationals in Israel, established a presence there in 1974 and now operates four development and production sites, including its manufacturing plant in Kiryat Gat called Fab 28 that produces Intel 7 technology, or 10 nanometer chips, and employs nearly 12,000 people in the country while indirectly employing 42,000 more. 

At some $9 billion, Intel’s exports account for 5.5% of total high-tech exports. The Centrino chip, which enables the use of WiFi, and its Core processors were developed in Israel. 

Intel, which bought Israeli self-driving auto technologies firm Mobileye for $15.3 billion in 2017, declined to say what technology will be produced at the new Fab 38 plant. Intel says construction has already begun.  

In June, Prime Minister Benjamin Netanyahu said Intel would build a new $25 billion chip plant in Israel, but Intel until now had declined to confirm the investment. 

The Fab 38 plant is due to open in 2028 and operate through 2035. 
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For water managers in drought-stricken regions, accurate forecasts of water availability are critically important. Matt Dibble shows how remote sensing technology is helping in the Rocky Mountains in this edition of LogOn.
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