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Saturday, December 16, 2023

SARS-CoV-2 Virologic Rebound With Paxlovid

 

https://doi.org/10.7326/M23-1756

Abstract

Background:

Data are conflicting regarding an association between treatment of acute COVID-19 with nirmatrelvir–ritonavir (N-R) and virologic rebound (VR).

Objective:

To compare the frequency of VR in patients with and without N-R treatment for acute COVID-19.

Design:

Observational cohort study.

Setting:

Multicenter health care system in Boston, Massachusetts.

Participants:

Ambulatory adults with acute COVID-19 with and without use of N-R.

Intervention:

Receipt of 5 days of N-R treatment versus no COVID-19 therapy.

Measurements:

The primary outcome was VR, defined as either a positive SARS-CoV-2 viral culture result after a prior negative result or 2 consecutive viral loads above 4.0 log10 copies/mL that were also at least 1.0 log10 copies/mL higher than a prior viral load below 4.0 log10 copies/mL.

Results:

Compared with untreated persons (n = 55), those taking N-R (n = 72) were older, received more COVID-19 vaccinations, and more commonly had immunosuppression. Fifteen participants (20.8%) taking N-R had VR versus 1 (1.8%) who was untreated (absolute difference, 19.0 percentage points [95% CI, 9.0 to 29.0 percentage points]; P = 0.001). All persons with VR had a positive viral culture result after a prior negative result. In multivariable models, only N-R use was associated with VR (adjusted odds ratio, 10.02 [CI, 1.13 to 88.74]; P = 0.038). Virologic rebound was more common among those who started therapy within 2 days of symptom onset (26.3%) than among those who started 2 or more days after symptom onset (0%) (P = 0.030). Among participants receiving N-R, those who had VR had prolonged shedding of replication-competent virus compared with those who did not have VR (median, 14 vs. 3 days). Eight of 16 participants (50% [CI, 25% to 75%]) with VR also reported symptom rebound; 2 were completely asymptomatic. No post-VR resistance mutations were detected.

Limitations:

Observational study design with differences between the treated and untreated groups; positive viral culture result was used as a surrogate marker for risk for ongoing viral transmission.

Conclusion:

Virologic rebound occurred in approximately 1 in 5 people taking N-R, often without symptom rebound, and was associated with shedding of replication-competent virus.

Primary Funding Source:

National Institutes of Health.

https://www.acpjournals.org/doi/10.7326/M23-1756

US court orders new FTC review of Illumina's Grail deal

 A U.S. appeals court on Friday struck down a Federal Trade Commission order against Illumina's purchase of cancer diagnostic test maker Grail, a former subsidiary, saying the agency had applied a wrong legal standard.

The New Orleans-based panel of the 5th U.S. Circuit Court of Appeals issued a 34-page order that will require the FTC to reconsider the deal.

The three-judge panel said the agency had substantial evidence to show the deal would lessen competition as companies seek to bring to market a blood test to detect many kinds of cancer.

An FTC spokesperson said the panel's opinion was "an important victory for antitrust enforcement because it clearly recognizes how vertical mergers can threaten competition."

But the panel also said the FTC failed to properly consider Illumina's pledge to continue selling its DNA sequencing services to other firms. Illumina has offered to sign contracts to supply any of Grail's rivals and to not raise prices.

"We are reviewing the decision," Illumina said in a comment issued after the ruling.

The court rebuffed Illumina's argument that the FTC unconstitutionally exercised its powers.

"Illumina's constitutional challenges to the FTC's authority are foreclosed by binding Supreme Court precedent," it wrote.

The FTC spokesperson added that the court's decision marked "a pivotal moment for those who want to protect open, competitive markets, and a huge win for consumers in the modern economy."

San Diego-based Illumina had filed the appeal in June after the FTC demanded that it divest Grail, saying that the agency had denied it due process.

Grail, valued at $7.1 billion under Illumina's deal, is seeking to market a powerful test to diagnose many kinds of cancer from a single blood test, known as a liquid biopsy.

The FTC is concerned that Illumina, the dominant provider of DNA sequencing of tumors and cancer cells that help match patients with the best treatment option, might raise prices or refuse to sell to Grail's rivals.

The agency filed a complaint aimed at stopping the deal in March 2021, but lost before an FTC administrative law judge. The case went back to FTC commissioners, who reinstated the case. Illumina then took it to an appeals court.

Despite the fight with the FTC, and a similar battle in Europe, Illumina closed the acquisition of Grail in mid-2021.

Europe has since proposed measures for Illumina to unwind its acquisition of Grail. Illumina is arguing it does no business in Europe and therefore the EU competition enforcer has no jurisdiction.

https://news.yahoo.com/us-court-strikes-down-ftc-000725752.html

Vaping grows fastest among UK groceries in 2023

 Vaping products were the fastest growing category in UK grocery for the second year running in 2023, while sales of cigarettes, cigars and loose tobacco fell sharply, industry data showed.

Britain's government in October proposed banning younger generations from ever buying cigarettes and Prime Minister Rishi Sunak said it also needed to act on youth vaping.

And on Thursday the World Health Organization (WHO) urged governments to treat e-cigarettes in a similar way to tobacco and ban all flavours, threatening the bets tobacco companies have made on smoking alternatives.

Vaping products saw growth in value sales in Britain of 897.4 million pounds ($1.15 billion) in 2023, according to the data published on Saturday by market researcher NIQ and The Grocer.

The Lost Mary brand, owned by Chinese vaping firm Heaven Gifts, was the UK's fastest growing product with sales up by 310.6 million pounds on the previous year, the data showed.

NIQ said vaping products also saw growth on a volume basis, or the amount people bought, while sales of cigarettes and cigars and loose tobacco were down 849.1 million pounds and 393.1 million pounds respectively on a sales value basis.

Another growth area was in sales of sport and energy drinks, which rose 390.1 million pounds, boosted by the viral success of Prime Hydration, the brand fronted by YouTubers KSI and Logan Paul and distributed by Congo Brands.

Some of the fastest growing grocery categories in 2023 were as a result of inflation, NIQ said, with value sales of milk, cheese, fresh meat and poultry increasing significantly but masking volume declines.

It said sales of bagged snacks, chocolate and sweet biscuits also declined on a volume basis.

Meat-free products were in marked decline, down 34.8 million pounds on a value basis and also down on a volume basis.

NIQ also noted that own label sales increased 12.8% as shoppers sought value by trading down from branded items, which are generally more expensive.

https://news.yahoo.com/vaping-grows-fastest-among-uk-000614612.html

Meet Ashley, the first AI political campaign caller

 “Are you familiar with Shamaine Daniels and her campaign for Congress?”

This political campaign call is from Ashley – a new artificial intelligence volunteer.

She's part of a new era of political campaigning being ushered in by generative AI.

But some warn tools like Ashley could make disinformation in American politics worse.

Democrat Shamaine Daniels is running for Congress in Pennsylvania.

Last year, Daniels lost to Trump-aligned Republican Scott Perry.

This time around, she's looking for help from Ashley — who can speak 20 languages — to reach more voters.

"You know, when I was initially approached about thinking about this, you know, my first thought was one of the things that we are very poor at is reaching diverse populations."

"The goal for me in using this tool is to expand those who can participate in the campaigning process."

Ashley’s creator is a startup called Civox.

It says she’s the first political phone banker powered by generative AI.

And that this tech is going to scale – fast.

CEO Ilya Mouzykantskii says his firm plans mainly to work with Democrats.

"Each call is unique before a number is called. There is a set of data that the campaign already knows about the person they're calling. Sometimes that can be as basic as a first name and last name. Or sometimes it can be a lot more detailed than that. And based on that information, we are able to have conversations that are customized to the recipient, and that's done on the fly."

Some are worried.

In May, OpenAI CEO Sam Altman testified in Congress that he was “nervous” about generative AI’s ability to compromise election integrity through “one-on-one interactive disinformation.”

Others say this tech could worsen disinformation in the polarized landscape of American politics that’s already battling "deepfakes”….

…realistic but fabricated videos and images created using AI algorithms.

The federal communications and election commissions are looking into AI…

but so far there are no rules that directly apply to Ashley's work.

John Basl at Northeastern University says that’s a problem.

"They just pollute or can pollute our information ecosystem. And it's not just that we don't have the tools to fight that, people aren't quite prepared. Like we see this all the time when people go to use ChatGPT for something and then are surprised when it hallucinates or makes up something that's not quite true."

Civox says it welcomes regulation.

And that it intentionally makes Ashley sound like a bot and disclose that it's AI – despite not being legally required to do so.

https://news.yahoo.com/meet-ashley-first-ai-political-010108486.html

How F-16 fighter jets could reshape Ukraine's aerial battlefield

 As U.S.-made F-16 fighter jets for Ukraine arrive at training centres in the United States and Europe, Kyiv’s allies hope the modern aircraft can push Russian planes farther from the frontlines, target radar transmitters more effectively and hunt down more cruise missiles.

Commander in Chief of the Ukrainian Armed Forces Valery Zaluzhnyi said in November that F-16s will be "less helpful" now than they would have been a year ago because Russia has had time to improve its air defences.

But they will help address a problem that has persisted from the start of the invasion in February 2022: Russia’s more modern combat aircraft have been difficult for Ukraine’s military to counter with its own aging fighters.

(This is the text version of a multimedia graphic. Please click here for the interactive version: )

Reuters examined technical documents and spoke to eight military experts, including former F-16 trainers and pilots, about the jets’ capabilities, limitations and the impact they could have on the war in Ukraine.

Western military officials and experts say adding F-16s to Ukraine’s fleet will not abruptly change the course of the war. Training pilots and support crews takes time, surface-to-air missiles remain a major threat, and the jets are not designed for Ukraine's damaged and sometimes makeshift runways.

But they are an improvement on the closest equivalent Ukraine has - the Soviet-designed MiG-29 - and, in the long run, will help Kyiv integrate with Western military allies and break away from reliance on ageing hardware built by its enemy.

“It locks Ukraine onto a technological path that NATO is currently on,” said Robert Farley, a professor at the University of Kentucky who specializes in military affairs and airpower. “What Ukraine has now is a dead end; It’s not going anywhere. If you want to have an air force in 10 years, it’s going to have to be F-16s or something similar.”

THE IMPACT

The fighters will replace Ukraine’s strained and thinning fleet of MiG-29s, Su-24s and Su-25s, jets that came of age in the depths of the Cold War.

Ukraine has found novel ways to integrate Western weapons onto those aircraft. F-16s will allow Ukraine’s military to squeeze more performance out of such systems, said Brynn Tannehill, a former U.S. Navy pilot who helped train U.S. Air Force F-16 pilots.

One example is the AIM-120 Advanced Medium-Range Air-to-Air Missile (AMRAAM), which Ukraine uses in a ground-launched anti-air role now, and which will soon be provided for air-to-air use.

The AMRAAM C and D models heading to Ukraine can attack targets beyond visual range, but more important they are “fire and forget”: if the pilot has to break radar-lock with a target, the missile’s onboard radar will guide it. Even if there are no dogfights over the front lines, Ukrainian pilots can hunt down cruise missiles more effectively.

MULTIROLE

More than 4,600 F-16s have been manufactured and sold to more than two dozen countries in many different configurations. Lockheed Martin declined to comment on the specific capabilities of the aircraft being sent to Ukraine.

Since it was introduced in the late 1970s, the F-16 has been upgraded to perform many missions. By the Gulf War in 1990, F-16s were flying regular ground-attack missions with missiles, bombs and anti-radar weapons.

Although the MiG-29 can do some rudimentary air-to-ground missions, it’s not made for the task, said Peter Layton, a visiting fellow at the Griffith Asia Institute and former Royal Australian Air Force officer.

“They both started out as a lightweight day fighter, but because Western concepts evolved… (the F-16) gradually evolved into a multirole fighter capable of doing more advanced air defence missions as well as ground attack,” Layton said.

The F-16 can carry more weapons than the MiG-29, Su-27 and Su-25, and roughly as much as Ukraine’s tactical bomber, the Su-24. The versions being sent to Ukraine most likely have an upgraded version of the AN/APG-66 radar, said Kelly Grieco, a senior fellow at the Stimson Center. It can keep tabs on targets on the air and ground, with an air-to-air range past 100km.

Russian aircraft can spot Ukraine’s MiG-29s “much further away than the Ukrainians can spot Russian aircraft,” Grieco said. The more powerful F-16 radars will reduce the radar disadvantage but “will not close it,” she said.

F-16s, and Western aircraft in general, tend to be more pilot-friendly, with intuitive controls and displays that allow fliers to keep their heads up, Tannehill added, calling MiG-29 and Su-27 cockpits “hopelessly out of date”.

THE CHALLENGES

MiG-29s, and many Soviet-era fighter designs, were meant to operate in poor runway conditions, and have shutters that drop down over their air intakes to prevent the engines from sucking in debris when the plane is on the ground. The F-16’s underslung intake does not have such protections, and it is not meant to operate in austere conditions, Grieco said.

“The F-16 is kind of a precious aircraft, it’s fragile,” she said. “It’s an aircraft that needs a long runway, and the runway is really smooth. But they’re in an environment where (Ukrainian pilots) have been doing distributed operations. … This is not an aircraft that can do that.”

To compensate, Ukrainian forces must perform careful sweeps of runway surfaces, a challenging proposition in the midst of a war.

Training enough pilots and support crew to operate the new fleet will take many months.

Eight pilots and 65 support personnel are in the first stages of learning how to operate the F-16 in Denmark; others are in Arizona and southeastern Romanian town of Fetesti.

Although the exact number of aircraft has not been disclosed, it is expected to be in the dozens, experts said.

For inexperienced pilots, the first step is familiarization with the new aircraft on the ground and in a classroom. Those elements, plus simulator time, will last about three weeks, said Layton, who transitioned from P-3B maritime patrol aircraft to F-111 bombers during his career. The next step is to ease into flying over the next month.

After basic daytime flying has met instructors’ expectations, students would move into night-time, bad weather and instrument flying, which “is a lot more technical”.

Air combat would come next, with six to eight weeks of instruction. Air-to-ground training would last another two months, he said. After basic instruction, U.S. and NATO pilots spend months learning how to carry out more specialized missions.

“It’s not enough just to train them to do the basics if you want to get the most out of those aircraft. You’re going to have to train them to do the complex stuff,” Tannehill said, such as coordinating with ground units or flying multi-aircraft missions.

Even for experienced pilots, learning new systems can be tough, Grieco said.

“If you talk to fighter pilots, they talk about muscle memory: ‘I have to be able to do something where I don’t think, where’s the button?’ she said. “These are people who have split seconds to make decisions.”

Language could be an issue for fliers without much English experience. “Several” pilots and dozens of maintenance personnel are getting language instruction before training in the United States, the Pentagon has said.

Spare parts, manuals and supplies for the F-16s should be plentiful, and the jet is still in production, Farley said. Only about 1,600 MiG-29s were ever produced, and the aircraft are on their way out even in Russia, according to a Royal United Service Institute (RUSI) report in 2020.

Well-trained maintenance crews are crucial, as keeping F-16s in the fight will require regular work—perhaps more than usual if they are operating in difficult conditions.

Soren Sorenson, a former Danish F-16 pilot, said maintenance needs would mean each aircraft would be flyable 25%-50% of the time. Layton estimated that each jet would require about 20 maintenance hours between flights, and that on a daily basis, about 25 of every 40 would be ready to fly.

THE WEAPONS

In 2022, the United States began supplying Ukraine with AGM-88 High-speed Anti-Radiation Missiles (HARM), a weapon designed to home in on and destroy enemy radar systems. Introduced in the 1980s, it was never meant to be used with anything other than Western aircraft. But by attaching a U.S. weapons pylon to a Ukrainian pylon, the missile was made to work.

It made a quick impact, catching Russian radar operators off guard and forcing them, for the first time in the war, to be careful about when and where they operated, Tannehill said. But the HARMs had to be programmed on the ground to fly to certain coordinates. If there was nothing to lock onto when they arrived, the missiles landed harmlessly.

With the F-16, “you can dynamically program them in flight. The HARM, you can use the full potential because you can change the instructions,” she said.

F-16s also allow Ukraine to upgrade its air-to-air capabilities, Layton said. Ukraine’s radar-guided air-to-air missile inventory is centred on the R-27 model - introduced in the early 1980s. It uses “semi-active radar” guidance, in which the launch aircraft’s sensors guide it to the target.

By contrast, the fire-and-forget AMRAAM and its longer range - the U.S. Air Force lists it as “more than 20 miles” and Ukraine air force spokesperson Yuriy Ihnat said it could hit targets 160km away - may mean Russian aircraft can no longer shoot at Ukrainian planes with impunity.

THE FUTURE

Ihnat said he did not expect the jets to operate in Ukraine until 2024.

“We will not win the war immediately, but the F-16 is capable of changing the course of events,” he said in August.

Russia has warned against delivering F-16s to Ukraine, with its ambassador to Denmark saying in August that doing so would be “an escalation of the conflict”.

The most important effects, Tannehill said, would be evident not in months, but in years.

“The F-16s are probably going to be necessary to continue to have a viable air force going forward,” she said. “It’s preparing for a future with NATO, it’s modernizing… it’s an infusion of fresh airframes. And that’s going to be important."

https://news.yahoo.com/f-16-fighter-jets-could-060202293.html

US & UK Warships Down At Least 14 Houthi Drones In Red Sea

 Capping off a week which saw daily attacks and threats on commercial shipping in the Red Sea, US and coalition warships have once again intervened against inbound Houthi projectiles.

US Central Command announced Saturday that its guided-missile destroyer shot down 14 drones launched by the Houthis in a fresh attack.

A British warship was also involved in staving off attacks, with UK defence secretary Grant Shapps stating: "Overnight, HMS Diamond shot down a suspected attack drone which was targeting merchant shipping in the Red Sea. One Sea Viper missile was fired and successfully destroyed the target."

"The ship recently arrived in the region to bolster international efforts to maintain maritime security," he added.

"The recent spate of illegal attacks represent a direct threat to international commerce and maritime security in the Red Sea. The UK remains committed to repelling these attacks to protect the free flow of global trade.”

Friday saw two Liberia-flagged vessels suffer missile and drone damage. Currently, the USS Eisenhower aircraft carrier is getting closer to the Middle East while traversing the Mediterranean, after earlier this month and last being in the Persian Gulf. 

The latest US statement detailed the following incident: "In the early morning hours of 16 December the US Arliegh Burke-class guided-missile destroyer USS Carney (DDG 64), operating in the Red Sea, successfully engaged 14 unmanned aerial systems launched as a drone wave from Houthi-controlled areas of Yemen," according to CENTCOM.

"The UAS were assessed to be one-way attack drones and were shot down with no damage to ships in the area or reported injuries. Regional Red Sea partners were alerted to the threat," it added.

Germany-based Hapag-Lloyd has joined Denmark's Maersk liner in halting all its Red Sea container ship traffic until at least Monday, following a Houthi attack on one of its vessels. "Hapag-Lloyd is interrupting all container ship traffic across the Red Sea until Monday," Hapag-Lloyd confirmed in a statement.

Via AP

Iran is meanwhile warning against a Western naval coalition in the Red Sea. But already US and other warships have increased their presence in regional waters, with the US Navy especially directly engaging Houthi projectiles. The incidents are becoming more frequent, even daily. The Western coalition and Houthis are headed for a likely major showdown.

https://www.zerohedge.com/geopolitical/us-uk-warships-downs-least-14-houthi-drones-red-sea

The travesty verdict against Rudy Giuliani and the left’s lawfare against lawyers

 A mother and daughter duo sued Rudy Giuliani in Georgia, alleging that he had defamed them in connection with the Fulton County vote county. They just received a $148,000,000 verdict (and yes, that’s the right number of zeroes). But all is not as it seems, and the story is a reminder of the multi-level lawfare being practiced against conservatives, especially Trump supporters.

The headlines are screamers: The jury awarded one plaintiff $16,171,000 in compensatory damages and the other $16,998,000 in compensatory damages. In addition, the jury ordered that Giuliani pay each plaintiff $20,000,000 for intentional infliction of emotional distress and pay an additional $75,000,000 to both as punitive damages. The grand total is $148,169,000. These verdicts aren’t meant to punish someone; they are meant to destroy him.

But as I said, all is not as it seems. You see, Giuliani’s case was never actually tried before a jury. No jury saw the videos of the plaintiffs or even heard their or Giuliani’s testimony before, during, or after a full trial.

Instead, Judge Beryl Howell, an Obama appointee, sanctioned Giuliani for failing to produce documents…and she used the harshest sanction available to a judge, which is an automatic verdict against the party who failed in his or her discovery obligations. What this means is that the only thing “tried” was the plaintiffs’ claims about their suffering due to the wrongdoing that Howell mandated had taken place.

In thirty years of practicing law, I never saw a judge apply that sanction, no matter how egregious a party’s conduct was. Judges (rightly) will do anything to avoid having a party to a case lose the chance to have due process determine who should prevail.

But here’s something even worse. It turns out that Giuliani couldn’t comply with significant parts (or all?) of the discovery request because the material demanded wasn’t in his care, custody, or control (those are legal terms of art). And why wasn’t it in his care, custody, or control? Because the FBI confiscated much of it.

The fact that Giuliani never had his case actually tried also means that all the recent headlines about Giuliani refusing to testify in his trial (see here and here, for example) are misleading. They imply that Giuliani refused to testify in his own defense on the substantive charges. In fact, he was already barred from doing so. All that he could do would be to sit in court and listen to the plaintiffs explain why they were entitled to almost $150,000,000 in damages.

Giuliani also said that he was having a hard time paying his attorneys, which affected his ability to respond to discovery, and that possibility leads to a different issue. There is a possibility that his attorneys messed up. I am not saying that they did. It’s just something that can happen.

The point about attorneys messing up is an important one because attorneys matter tremendously. The average person cannot navigate through the judicial system without help. It’s simply too complicated. Moreover, as my Criminal Law professor said, when students asked him why someone who is even obviously guilty deserves an attorney, no one should have to face the awesome power of the government without a friend at his side.

Shakespeare understood how important lawyers are. People love quoting the line from Henry VI, Part 2, in which he wrote “The first thing we do, let’s kill all the lawyers.” However, the line was spoken by one of Shakespeare’s villains, who viewed lawyers as a bulwark of law and order, something he wished to destroy.

John Adams understood that, too, for he took the highly unpopular stand of defending the British soldiers charged in the Boston Massacre. As he famously said in his summation, “Facts are stubborn things; and whatever may be our wishes, our inclinations, or the dictates of our passions, they cannot alter the state of facts and evidence.”

Bad lawyers are a plague. Good lawyers are the first line of defense in a stable, sane, functional society. And that brings me to a less visible side of the lawfare Democrats and other leftists are waging against conservatives, and that’s the war on lawyers.

In Georgia, the Fulton County D.A., Fani Willis, indicted Trump’s attorneys for daring to make legal arguments that there was election fraud. One of them, John Eastman, was also subject to FBI, DOJ, and congressional investigations, criminally referred to the DOJ, became the subject of a California State Bar investigation, and lost his job. In Arizona, Kari Lake’s attorneys face “discipline” for supporting her election challenges.

Lawyers are trained to make the most aggressive arguments possible to support their clients’ cases. If their arguments are bad, they lose. However, if their arguments are colorable—if there is a coherent legal argument that can be made on the facts—that should be where it ends.

But as Shakespeare’s villain understood, when you want to overthrow the government, “First thing we do, let’s kill all the lawyers.” And in modern America, killing lawyers means subjecting them to professional, economic, and even criminal sanctions.

Democrats have effectively weaponized January 6, and this kind of lawfare will not stop unless it is turned against them. Conservatives don’t like to sue and prosecute. They should start learning how.

https://www.americanthinker.com/blog/2023/12/the_travesty_verdict_against_rudy_giuliani_and_the_lefts_lawfare_against_lawyers.html