Tag Archives: Uncertainty

Biden hosts Iraqi leader after Iran’s attack on Israel throws Mideast into greater uncertainty – The Associated Press

  1. Biden hosts Iraqi leader after Iran’s attack on Israel throws Mideast into greater uncertainty The Associated Press
  2. Biden to host Iraq’s leader after Iran’s attack on Israel spurs chaos across the Middle East Fox News
  3. Biden hosts Iraqi leader after Iran’s attack on Israel throws Mideast into greater uncertainty WFLA
  4. Analysis: Iran upends decades of shadow warfare in direct attack on Israel as tensions mount at home The Associated Press
  5. Biden says US remains committed to securing ceasefire that will free hostages, prevent conflict from spreading The Times of Israel

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Scepticism, uncertainty, hope: Haitians react to possible Kenya-led mission – Al Jazeera English

  1. Scepticism, uncertainty, hope: Haitians react to possible Kenya-led mission Al Jazeera English
  2. A U.S. delegation visited Kenya about helping Haiti – and was surprised by the response Miami Herald
  3. Haiti expresses skepticism over Kenya’s offer to send police to combat Haiti’s gang violence Fox News
  4. Opinion | Kenya offers Haiti needed help with U.N.-sanctioned peacekeepers The Washington Post
  5. Haitians express skepticism over Kenya’s offer to UN to send police to confront gangs The Associated Press
  6. View Full Coverage on Google News

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Fiji parliament confirms Sitiveni Rabuka as prime minister after days of uncertainty | Fiji

Sitiveni Rabuka has become Fiji’s prime minister after a coalition of parties voted to install him, signalling an end to Frank Bainimarama’s 16 years in power.

The appointment of Rabuka on Saturday ended 10 days of uncertainty after an election delivered a hung parliament. Fiji’s Social Democratic Liberal party (Sodelpa) held the balance of power and on Friday voted to form a coalition with Rabuka’s People’s Alliance and the National Federation party.

The deal was designed to dislodge Fiji First’s Frank Bainimarama, who has led the Pacific archipelago since a 2006 coup.

Saturday’s secret parliamentary vote for prime minister was closer than had been expected, with 28 members of parliament voting for Rabuka while 27 voted in support of Bainimarama. Rabuka’s coalition holds 29 seats in parliament, indicating that one member had broken ranks to vote in favour of the former prime minister.

Rabuka, 74, said he felt “humbled” to be prime minister as he made his way out of parliament to be sworn in by the country’s president.

The military had been deployed on the streets of Suva as Rabuka and Bainimarama raced to cobble together a coalition government following a deadlocked general election.

Citing unsubstantiated reports of ethnic violence, Bainimarama said the military was needed to maintain “law and order”.

But former military commander Rabuka, who served as prime minister between 1992 and 1999, said the government was “sowing fear and chaos” and “trying to set the nation alight along racial lines”.

Many Fijians feared the government’s claims of ethnic violence and subsequent military deployment were a pretext for a “creeping coup”. Fiji has been upended by four coups in the past 35 years.

New Zealand’s prime minister, Jacinda Ardern, congratulated Rabuka on his appointment and said her country looked forward to working with Fiji’s new government to strengthen “our very warm relationship”.

“We strongly value Fiji as a close friend and partner as we progress our shared priorities for the region.”

Ardern said Bainimarama had an “important legacy for Fiji and his role as a regional leader supporting action on regional issues, including climate change”.

Fiji has been pivotal in the South Pacific’s response to increasing competition for influence between China and the United States. Rabuka has said he favours western-style democracy.

At a press conference earlier this month, Sodelpa’s leader said he wanted Fiji’s foreign relations to be closely aligned with Australia, New Zealand and some members of the Pacific Islands Forum.

Reuters and Agence France-Presse contributed to this report

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Inside Twitter as ‘mass exodus’ of staffers throws platform’s future into uncertainty


New York
CNN Business
 — 

Death is in the air on Twitter.

On the platform Thursday evening, where #RIPTwitter was the top trend worldwide, users wrote what they feared might be their last posts, offering apprehensive goodbyes and listing the other (more stable) social media platforms where they can still be found.

They were reacting to the dire news emanating from inside Twitter. Scores of remaining employees at the social media company on Thursday appeared to reject owner Elon Musk’s ultimatum to work “extremely hardcore,” throwing the communications platform into utter disarray and raising serious questions about how much longer it will survive.

A version of this article first appeared in the “Reliable Sources” newsletter. Sign up for the daily digest chronicling the evolving media landscape here.

The death of Twitter would have weighty consequences, given how integral the platform is to global communications. The platform has often been compared to a digital town square. World leaders use Twitter to communicate, journalists use Twitter to newsgather, dissidents in repressive countries use Twitter to organize, celebrities and major brands use Twitter to make important announcements, and the public often uses Twitter to monitor all of it in real-time.

If the platform were to die off, or become unusable because of instability issues, no single space would immediately replace it and communications could become fractured across multiple social media websites, leading to a seismic disruption and slowdown in the flow of information.

Inside the company’s Slack, a mass resignation effectively occurred after Musk’s 5pm deadline for employees to arrive at a decision passed. Hundreds of staffers appear to have called it quits, accepting Musk’s offer to exit in exchange for three months of severance.

Employees flooded the “#social-watercooler” channel with the salute emoji, indicating that they had chosen not to sign Musk’s pledge. A similar series of events unfolded in the Slack channel earlier this month as Musk eliminated roughly 50% of the company’s then 7,500-person workforce.

A former Twitter executive, who recently exited the company, described the situation as a “mass exodus.” Asked about the situation, the former executive said, “Elon is finding out that he can’t bully top senior talent. They have lots of options and won’t put up with his antics.”

“They will struggle just to keep the lights on,” the former executive added.

That assessment was universally shared by the other half dozen current and former employees on Thursday. It was already bad enough after Musk executed mass layoffs at the company earlier this month. So bad that Twitter asked some of the people it had let go to come back just days later. The state-of-play has only become more dire since then.

In fact, Twitter management was in panic mode hours before the deadline passed, people familiar with the matter said, explaining that senior leaders were “scrambling” to convince talent to stay at the company.

Musk himself seemed to finally realize the grim state of affairs, sending an all-staff email relaxing his previously uncompromising anti-remote work position. “Regarding remote work, all that is required for approval is that your manager takes responsibility for ensuring that you are making an excellent contribution,” Musk said in the email.

It didn’t appear to do much good.

Two employees who had decided to reject Musk’s ultimatum on Thursday were quite clear in why they were doing so. “I don’t want to stick around to build a product that’s being poisoned from the inside and out,” one said, adding later that he felt good about making a decision “in line with what I stand for.”

A recently laid off employee who remains in touch with former coworkers said, “People don’t want to sacrifice their mental health and family lives to make the richest man in the world richer.”

And Twitter seemed to grasp the mess on its hands Thursday evening, sending an email to staff notifying them it has once again shuttered all of its offices and suspended employee badge access, presumably to protect its systems and data.

Twitter’s already decimated communications department didn’t respond to requests for comment. But Musk nodded to the situation in a tweet.

“How do you make a small fortune in social media?” Musk asked. “Start out with a large one.”



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How I Learned to Stop Worrying and Love Uncertainty

Like most physicists, I spent much of my career ignoring the majority of quantum mechanics. I was taught the theory in graduate school and applied the mechanics here and there when an interesting problem required it … and that’s about it.

Despite its fearsome reputation, the mathematics of quantum theory is actually rather straightforward. Once you get used to the ins and outs, it’s simpler to solve a wide variety of problems in quantum mechanics than it is in, say, general relativity. And that ease of computation—and the confidence that goes along with wielding the theory—mask most of the deeper issues that hide below the surface.

Deeper issues like the fact that quantum mechanics doesn’t make any sense. Yes, it’s one of the most successful (if not the most successful) theories in all of science. And yes, a typical high school education will give you all the mathematical tools you need to introduce yourself to its inner workings. And yes, for over a century we have failed to come up with an alternative theory of the subatomic universe. Those are all true statements, and yet: Quantum mechanics doesn’t make any sense.

Instead of trying to make sense of the quantum world, let’s use the quantum world to make sense of ours.

The statements that quantum mechanics makes about the subatomic world fly in the face of our natural intuition about the macroscopic world. If I throw a ball at you, you have a decent shot of catching it because you know it will only take a single path. If we make plans for dinner, we don’t need to worry about what the Andromeda Galaxy is doing right now because it’s very far away and thus very unlikely to interfere with our plans. If you see someone walk through your doorway, then you can say with confidence that they did, if fact, walk through your doorway.

And yet all these very reasonable statements break down when we examine the subatomic world. Particles can exist in multiple states at once. They can travel multiple paths at once. Particles can suddenly appear in unexpected places. Particles can maintain a phantom-like connection to each other, known as entanglement, regardless of the distance of their separation. We can’t make confident predictions about the outcomes of experiments, but instead have to rely only on fuzzy probabilities. There are fundamental limits to what we can know.

When I first learned the full extent of quantum weirdness, in school, my brain broke, along with my expectations of how the world works. My first reaction was amazement and wonder at the richness and complexity of the subatomic world. And then … dismay. Heartbreak. Confusion. Torment. A storm of emotions poured over me as I tried, in vain, to go from awestruck wonder to considered understanding.

While my undergraduate and graduate courses on modern physics and quantum mechanics were teaching me these fundamental statements, they didn’t discuss to any significant degree the deep philosophical problems that those statements entail. That kind of reckoning, in my case, didn’t come until over a decade post-Ph.D. As I struggled with the philosophical side of quantum theory, many years after I should have, I discovered to my surprise (and relief) that my struggles were mirrored in the very historical development of the theory itself.

Quantum mechanics is confusing, nonintuitive, and seemingly nonsensical. What I found through my journey is that this confusion and senselessness isn’t a bug, but a feature, and creates a new way to see our everyday life. Instead of interpreting quantum mechanics, I ultimately realized, maybe we should just submit to it—and let quantum mechanics interpret our own lives.

But in order to arrive at this, somewhat unorthodox but ultimately liberating, vantagepoint, I had to journey through the four stages of what I have come to call “quantum grief.”

Stage One: Confusion

The first mystery I encountered, as an undergraduate, of the hidden secrets of the subatomic realm was the bizarre feature of reality called wave-particle duality. In the macroscopic world described by classical physics (the physical view of the world prior to the invention of quantum mechanics) there are two kinds of objects: waves and particles. Particles are generally small, well localized in space, and have a defined, measurable position. If you wanted to, you could point to a particle, and everyone would know that you’re picking out that particle and not another one.

Waves, on the other hand, without a particular place in space, are just kind of … over there, vaguely. It’s much more difficult to point to a wave. Waves also don’t zoom from one place to another, but instead slosh around in complicated patterns.

In this classical view of the world, all fundamental entities are either one or the other. To my undergraduate brain, this simply made sense. But in the quantum view, all objects have properties of both. A single object can sometimes act like a particle or sometimes act like a wave, having wavelike properties in one moment (say, when an electron scatters off of an obstacle, it acts like a wave would) and a particle-like property in another (when that electron finally hits a detection screen, it deposits all its energy in a specific location, much like a particle).

PAGING DOCTORS SCHRÖDINGER AND HEISENBERG: Quantum theory can bring an unexpected peace in the chaos of physics—and the world at large—if we can learn to live our own lives within a quantum framework. Illustration by Zenobillis / Shutterstock.

I had read about this in books as a teenager, but in college I had to confront it head-on in a formal, impossible-to-ignore setting … and it blindsided me. The only response I could conjure was a simple: How?

The wavelike nature of matter doesn’t manifest itself at macroscopic scales, which is why physicists didn’t notice this until they started playing around with subatomic particles at the beginning of the 20th century.

Much like my first taste of the phenomenon, when the early quantum pioneers initially encountered wave-particle duality, their first response was complete and total confusion. What exactly is a wave of matter? How are we supposed to interpret this now-experimentally undeniable aspect of reality?

I would look at my own face in the mirror. Quantum mechanics taught me that what I saw had some very tiny but very real wave nature. But a wave nature of what? My reflection couldn’t give me an answer.

Physicists like Erwin Schrödinger, working in the first half of the 20th century, argued that at tiny scales matter was literally smeared out over space like a wave. He believed that if we could crack open an atom and look at its bits and pieces, we would see tiny little waves wiggling about. Schrödinger would use this insight to develop a wave-based theory of quantum phenomena that was astoundingly successful in describing a wide variety of otherwise perplexing experimental results.

But Schrödinger was not alone amongst the explorers of the unknown quantum land. Other physicists like Werner Heisenberg, working around the same time, argued that we shouldn’t bother even trying to build up a mental picture of what subatomic particles are up to, and should instead just focus on experimental results. He developed a completely different paradigm for answering quantum problems. His method was based on much more difficult mathematics but was nonetheless equally successful.

Cue heated debate, with Schrödinger snubbing Heisenberg’s approach as nonsense, because what good is a physical theory if it can’t paint a picture of the world, and Heisenberg slamming Schrödinger, saying that subatomic physics is so far beyond the realm of human perception that our normal classical thinking is obsolete.

Stage Two: Orthodoxy

Eventually Schrödinger’s idea fell out of favor, as experiment after experiment revealed that subatomic objects, like electrons, while they had wavelike properties, most definitely did not extend through space. By the 1930s, the initial confusion over the onslaught of experimental evidence and theoretical tools eventually gave way to a sort of quantum orthodoxy.

This mirrored my own experience, beginning in graduate school. Aspects of the quantum world, beginning with wave-particle duality, fly in the face of common sense, logic, and our natural intuitions about the world. But then, just when the confusion reaches a crescendo, and it seems like the feeble human intellect will be swallowed by the quantum tempest, comes sweet conceptual deliverance: a formalism.

The relief I felt when I finally learned the postulates and mathematical framework of quantum mechanics is nearly indescribable. It’s like this wonderful escape hatch, liberating yourself of the mental burden of trying to untangle the Gordian knots of quantum reality, set free to dance through the blissful fields of getting work done.

This confusion and senselessness isn’t a bug, but a feature, and creates a new way to see our everyday life.

In the 1930s, physicists like John von Neumann would take the various initial attempts at quantum mechanics and craft it into a cohesive, rigorous whole. Finally, after decades of study, we had a firm physical theory based on a limited set of founding postulates, a full mathematical language for writing down problems and finding their solutions, and a wide variety of interesting applications to tackle with the theory: the nature of atomic absorption and emission, the building blocks of chemical and nuclear physics, the creation and manipulation fundamental particles, and so much more. We had a physics of the subatomic world.

The interpretation of what the mathematics said about the world slid away from the hopes of Schrödinger and fell firmly into the Heisenberg camp: Don’t worry about the details, and just focus on solving problems. The wavelike nature of particles was demoted into a mere mathematical trick, a way of calculating probabilities rather than an extant property of nature. Other results of the wave-nature of matter, like entanglement or “spooky action at a distance,” were accepted as straightforward facts without any deeper discussion about what that entailed.

Quantum mechanics was weird and made no sense, but it worked, dang it.

And in that work I found safety. I didn’t have to worry about mysterious quantum this-or-that, about what was actually happening, as long as I could keep putting the mathematical pieces together. It felt good to solve problems, to find interesting applications. As a physicist, I developed a new kind of intuition, one not based on growing up a living, thinking, macroscopic creature, but an instinctual grasp of the symbols and machinery of quantum mechanics. I began to intuit which problems were well suited to the theory, and which ones were not. I found myself able to cast meaningful physical questions about the real world into the language of von Neumann—and, amazingly, get an answer, a result that I could test against experiment (as I and my classmates did, in the lab sections of our classes).

I began to believe that I finally—finally—had a firm grip on understanding quantum mechanics.

Stage Three: Rebellion

That is, as long as I didn’t think too hard about what it all means. The siren song of quantum formalism, the raw math, was all too tempting. But follow it too far and you are bound to crash into the sharp unyielding rocks of a deceptively simple question: What does quantum mechanics actually mean?

Schrödinger had his doubts. So did Einstein. So, even, did Heisenberg and Bohr and Dirac and von Neumann and all the other founders of quantum theory. The difference is that Schrödinger and Einstein would go to their graves believing that quantum mechanics was incomplete, while the others held on to the slim comfort that our physical theories had finally taken us to a place that we could not otherwise mentally comprehend … but at least we could get answers and validate against experiment, which was good enough.

The dominant interpretation of quantum mechanics is called the Copenhagen interpretation. If you’ve ever done any reading on the subject, you’ve probably encountered it already. It’s the default assumption of how quantum theory should be viewed, and it’s the default treatment given in a typical physics education, including mine. At its highest level the Copenhagen interpretation instructs us to not sweat the small stuff and just focus on the math. Matter has a wavelike property that maps out probabilities for the outcomes of experiments. When we perform an observation, that wave and all those probabilities snap out of existence, to be replaced with a single result in our apparatus. Aspects like fundamental uncertainty principles and non-local entanglement are simply facets of the full theory.

Quantum mechanics doesn’t make any sense.

How does it all work? Why do the waves snap out of existence upon measurement? How can two distant particles be aware of their entangled partner without exchanging information? What is the state of reality when we’re not observing it? These are all questions that the Copenhagen interpretation ignores, because it says that they’re not important: What matters is results, results, results.

And so I, ever the lifelong student, had to eventually confront the Copenhagen interpretation and its explicit lack of desire to explain anything further. Some physicists are fine with this, choosing to “shut up and calculate” and accept that our puny human brains can’t possibly imagine or envisage what’s happening at the subatomic level. And many I know find a sort of comfort in that.

Other physicists are less fine with this. Thankfully for them, there are plenty of other interpretations to choose from. Some elevate the wavelike nature of matter to a real entity. Some claim that consciousness plays a critical role in the measurement process. Some say that it’s all an illusion of shifting information. There are … more. Dozens of potential interpretations, all selecting some parts of quantum theory to be true and other parts to be mere mathematical artifacts.

For some physicists dissatisfied with the aloofness of the Copenhagen interpretation, they find refuge in these alternative interpretations.

I did not. The interpretations of quantum mechanics try to make sense out of the nonsense by applying a layer of rationality on top of the bare mathematics of the theory—a bedtime story to help us sleep at night when we can’t stop thinking about how strange the subatomic world is. I myself tried to find salvation in interpretations, years after learning the theory itself in graduate school, hopping from paper to paper like a neophyte trying out different religions.

Ultimately, I couldn’t find any interpretations that were satisfying. The classic Copenhagen left a sour taste in my mouth for its refusal to paint a picture of subatomic processes—I believe that humanity is smarter and cleverer than Heisenberg gave us credit for. But the other interpretations have their own shortcomings. For example, if you follow the logic of making the wave-nature real, you end up with parallel universes constantly splitting into existence … with no further explanation of how that’s supposed to work. And so on and so on. For every interpretation, there are some attractive features to it, and some parts of its own theory that it fails to explain.

Stage Four: Acceptance

So what was I to do if none of the interpretations seemed to satisfy that deeper craving to live in an understandable universe? One answer is to retreat back to the safety of the Copenhagen interpretation, finding solace in the mathematics and giving up on the dream of visualizing subatomic processes. Another is to dig deep into one of the alternative interpretations, believing that with enough work and enough cleverness, I could overcome their shortcomings and build a coherent, consistent, complete model of the universe.

There is another way, one that I found after years of frustration, and that is to completely subsume myself into the weird and wonderful quantum world, embracing the ultimate lessons of the theory. We have tried for over a hundred years to force an interpretation on the theory, to no avail. So perhaps that’s nature trying to tell us something: that no interpretations are available to us.

The experimentally verified reality of quantum mechanics is, indeed, that classical thinking, based on our intuitions of the macroscopic world, is inadequate to describe every aspect of the cosmos. And trying to create an interpretation and insist that it’s the correct one—even the Copenhagen interpretation—is precisely the trap of classical, binary, yes/no thinking that the subatomic world is trying to tell us to avoid.

Here’s the mental model I eventually settled on, after years of apathy and antipathy: Instead of trying to make sense of the quantum world, let’s use the quantum world to make sense of ours. Thinking about quantum behavior seems absurd, but that’s only because we live and breathe in a classical world. So what if we tried to live in a fully quantum one, even in our everyday lives?

When I released myself from interpretation, I found the freedom to see the fundamental lessons of quantum mechanics: probabilities, uncertainties, non-locality, entanglements, and so much more, and apply those lessons to my life.

For example, I could begin to live my life truly accepting the uncertainty of the future, setting goals and visions without the burden of concrete expectations. I could acknowledge that my actions had influence across the globe, with even small gestures of kindness or charity making an impact. I accepted that I can’t know everything as well as I wish I could. I stopped myself from falling into binary, either/or choices, allowing situations, choices, and even people to be more complex than that. As I continued to put these thoughts into daily practice, I found that Schrödinger, Heisenberg, and the rest sounded less and less like physicists and more and more like therapists (indeed, nothing I had learned was a new revelation to mental health professionals). These were useful lessons that enriched and informed my daily life: Through a quantum lens, I found happiness, contentment, satisfaction, and a better sense of my own humanity.

It wasn’t easy—and it still isn’t. I still feel the occasionally classical tug to insist on an interpretation, or to finally get to the bottom of all this quantum nonsense. Every day I have to wake up and resist those temptations and remind myself that the quantum world—the real world—is so much more rich and vibrant and wonderful than that.

Paul M. Sutter is a research professor in astrophysics at the Institute for Advanced Computational Science at Stony Brook University and a guest researcher at the Flatiron Institute in New York City. He is the author of Your Place in the Universe: Understanding our Big, Messy Existence.

Lead image: Mentalmind / Shutterstock




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Relyvrio: ALS drug gets FDA approval despite uncertainty about effectiveness



CNN
 — 

A new treatment for amyotrophic lateral sclerosis, or ALS, has been approved by the US Food and Drug Administration.

The FDA announced approval of Relyvrio, developed by Amylyx Pharmaceuticals, on Thursday. The oral medication can be taken as a standalone therapy or with other treatments, according to the company, and it has been shown to slow disease progression.

But there’s still some uncertainty about the drug’s efficacy: Amylyx’s submission for approval is based on data from a small Phase 2 trial, and the FDA’s own advisory committee initially voted this spring that the data didn’t show that the drug was effective, before changing its opinion this month.

“There are limitations to these findings that result in a degree of residual uncertainty about the evidence of effectiveness that exceeds that which might typically remain following a conclusion that substantial evidence of effectiveness has been demonstrated,” says an FDA summary memorandum on the approval. But “given the serious and life-threatening nature of ALS and the substantial unmet need, this level of uncertainty is acceptable in this instance.”

The approval is the first in the US for Amylyx, CEOs Josh Cohen and Justin Klee said in a statement, and “is an exciting milestone” for the ALS community.

“Amylyx’ goal is that every person who is eligible for Relyvrio will have access as quickly and efficiently as possible as we know people with ALS and their families have no time to wait,” they said. “While Amylyx is working on launching Relyvrio, healthcare professionals will be able to write prescriptions for Relyvrio immediately by enrolling their patients into our comprehensive support program that we are implementing.”

Patients and some advocacy groups had urged the FDA to approve the drug, as there are limited treatments available for ALS, and the agency granted priority review in December.

ALS, also known as Lou Gehrig’s disease, affects as many as 30,000 people in the United States. It’s a neurodegenerative disease that causes muscles to weaken, eventually affecting the ability to speak, swallow, move and breathe.

“ALS is a horrific disease: rapidly fatal and really debilitating during the period from initial symptoms to death. FDA has approved a couple of treatments, but they are minimally effective and certainly not a cure. And so, there’s a vast unmet need in this disease area, which FDA has acknowledged,” said Holly Fernandez Lynch, an assistant professor of medical ethics and health policy at the University of Pennsylvania.

Ahead of the FDA decision, Lynch told CNN that she would be “shocked” if the drug did not get approved because the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee made a shift in its opinion of the drug at a meeting this month, voting 7-2 in favor of approval.

In November, Amylyx submitted a drug application to the FDA for the medication, then called AMX0035, as an oral ALS treatment, seeking approval based on a Phase 2 trial that included 137 people with ALS who received either the drug or a placebo for 24 weeks. The study was funded in part by a grant from the ALS Ice Bucket Challenge, the viral social media campaign that started in 2014 involving people dumping buckets of ice water over themselves to raise awareness and money around ALS.

The trial also showed that the drug was generally well-tolerated, but there was a greater frequency of gastrointestinal events in the group getting the medication. Amylyx is now continuing to study its safety and efficacy in a Phase 3 trial.

In March, the Peripheral and Central Nervous System Drugs Advisory Committee voted 6-4 that a single Phase 2 trial did not establish the conclusion that the drug is effective in treating ALS.

“In terms of establishing the conclusion that it’s effective, we were asked to look for substantial evidence with persuasiveness and robustness and I think this one trial doesn’t quite meet that bar,” Dr. Kenneth Fischbeck, one of the committee members and an investigator at the National Institutes of Health, said at the March meeting. Fischbeck added that he has cared for ALS patients.

One key difference between the FDA advisory committee’s March and September meetings is that in the later meeting, Amylyx indicated that if the drug was approved but its Phase 3 trial results fail to confirm the drug’s benefits, the company would consider withdrawing the drug from the market, Lynch said. She added, however, that the company didn’t say specifically what it would view as a failure.

“So at the vote, the advisory committee members switched, and most of them said, ‘Yes, we are now convinced that this product should be approved.’ And when they were asked why they changed their minds, some of them said, ‘Well, the company said they would withdraw,’ ” she said. “And they were also convinced by patients’ testimonies that they very much want to try this drug.”

But overall, the FDA’s approval was based on Phase 2 trial data, which, Lynch said, may send a message to other pharmaceutical companies that they don’t need robust Phase 3 trial data to get products on the market.

Lynch said that although she understands why people with ALS want access to this promising drug, she has concerns that such a message could open the door more broadly to the approval of medications that have not been proved to work. The FDA could later withdraw those products if needed, she said, but doing so without voluntary company agreement is “a huge pain” and often requires a very lengthy process.

As for Relyvrio, some ALS advocacy groups – including the ALS Association – have been rooting for its approval for several months. After the FDA advisory committee meeting in March, when the panel initially voted against the drug, Calaneet Balas, president and CEO of the ALS Association, said in a statement that “FDA has a choice to make – whether it will approve a drug that has been proven safe that will help people living with ALS today, or whether it will delay approval and require more evidence while more people with ALS die.”

“We cannot allow perfection to stand in the way of real progress toward turning ALS from a fatal disease into a livable one. The FDA’s own ALS Guidance acknowledges that people with ALS are willing to accept greater risk for the possibility of some benefit,” Balas said. “People with ALS and their loved ones deserve better and the FDA has the tools to accomplish this with urgency.”

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Putin’s Nuclear Threats Meant to ‘Manipulate’ Uncertainty

  • Putin’s recent nuclear threats have prompted a range of responses from key players in the war.
  • One expert told Insider that Putin likely hoped to cause confusion and uncertainty with his warning.
  • Still, analysts say the risk of nuclear warfare remains low, despite Putin’s escalation.

Russian President Vladimir Putin’s thinly-veiled nuclear threat last week has set the world on edge — accomplishing exactly what he hoped it would, according to experts. 

Despite the brazen escalation, experts and analysts alike have said in recent days that the threat of nuclear war remains minimal.

“There are a bunch more steps he would take to convince the world of his seriousness and put pressure on Ukraine and the West before using nuclear weapons,” said Paul D’Anieri, a political science professor at the University of California, Riverside and the author of “Ukraine and Russia: From Civilized Divorce to Uncivil War.”

But that doesn’t mean Putin won’t invoke his nuclear arsenal to sow fear in the meantime. 

Putin likely has little desire to risk World War III seven months into Russia’s war in Ukraine. But his televised threat last week certainly calls to mind the country’s trove of more than 5,000 nuclear warheads and its cache of rockets, missiles, and artillery shells.

Putin intensified his nuclear threats in a speech last week during which he announced a partial mobilization order, conscripting hundreds of thousands of reservists in a move he hopes will give his depleted army a triumphant boost on the battlefield. But experts say the call-up in conjunction with the nuclear threat has also narrowed the range of acceptable outcomes that Russia could reasonably consider a victory.  

“The conscription has turned this war into a war that Putin can’t really afford to lose,” D’Anieri told Insider. “That fact increases the likelihood that he would do something really drastic like use nuclear weapons.”

Putin’s threat raises the stakes for several key players in the conflict.

Ukraine has always had the most to lose in this war, and the renewed threat of nuclear warfare only further reinforces what’s at stake for the country.

Despite experts’ assessment that the likelihood of an impending Russian nuclear display is slim, Ukraine offered an alarmist appraisal of the danger this week.

In an interview with The Guardian, Vadum Skibitsky, a deputy head of Ukraine’s military intelligence, put the probability of Russia hitting Ukraine with a tactical nuclear weapon at “very high.”

“They will likely target places along the frontlines with lots of [army] personal and equipment (sic),” he told the outlet. “In order to stop them we need not just more anti-aircraft systems, but anti-rocket systems.

The military official offered no evidence for his claims and officials in his organization have repeatedly spread baseless theories. But Ukraine may have good cause to be alarmist, as many analysts believe Putin’s nuclear invocation is also an attempt to manipulate the US into limiting its support for Ukraine.

“Putin is now upping the ante and he’s counting on the fact that we won’t go to nuclear war for Ukraine which will get the West to tell Ukraine to negotiate a solution that is basically a Russian victory,” D’Anieri said.

A blatant nuclear reminder, Putin hopes, might scare the West into ramping down or discontinuing its aid to Ukraine, experts posited — aid that has helped Ukraine stage a series of recent victories.

“The beauty for him I think, is he believes he could nuke Ukraine and nobody in the West would want to nuke Russia in retaliation,” D’Anieri said. 

Ukraine, meanwhile, has a motivation to play up the danger of nuclear war in an effort to curry even more support from the country’s Western allies who have nuclear weapons of their own. 

Russian Yars ballistic nuclear missiles on mobile launchers roll through Red Square during the Victory Day military parade rehearsals on May 6, 2018 in Moscow, Russia.

Mikhail Svetlov/Getty Images



The world is closely watching. 

Putin has repeatedly hinted at Russia’s massive arsenal of nuclear power since the war began, but his most recent threat has prompted a more reactive response on the international stage.

President Joe Biden and other White House officials have publicly condemned the Russian president’s comments and privately warned the Kremlin of dire consequences should the country break the global non-use standard of nuclear weapons that has been in place since 1945.

In addition to issuing its own warnings to Russia, the US is also aiming to bring the global community into the fold of nuclear worry. Politico reported this week that there are increasing calls within and outside of the Biden administration to urge China and India — two Moscow allies with their own access to nuclear weapons — to reign in Putin’s threats.

Meanwhile, US officials are reportedly following signs that Russia has changed the location of its nukes or their alert status, with no signs of such activity as of Thursday. 

Putin’s threats have undoubtedly done exactly what he hoped they would, D’Anieri said, which is stoke fear and confusion.

“I think what Putin in a way is trying to do, and probably succeeding in doing, is manipulating uncertainty so people in the West are now more worried about what might happen than he is,” he said.

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Saturn Ring Mystery Possibly Solved After Four Centuries of Uncertainty

Saturn isn’t the only ringed planet in our solar system, but its girdle of ice and dust is by far the most spectacular. And a new study gives a fresh explanation of how and when Saturn’s rings formed, offering a solution to a mystery that has stymied astronomers ever since Galileo held up his telescope and first observed the planet in 1610.

The rings formed 100 million to 200 million years ago when one of Saturn’s moons, thrown off course by another moon, veered too close to the planet and was ripped to pieces by its gravitational forces, the study suggests. Rubble from the hypothetical moon, which the researchers dubbed Chrysalis, continued to orbit Saturn and over time flattened into the disk of particles seen today, according to the findings, which were published Thursday in the journal Science.

The rings are just 30 feet thick in places but span a diameter of about 170,000 miles. Jupiter, Uranus and Neptune also have rings, but they are smaller, darker and fainter.

For many years, scientists believed Saturn’s rings formed more than 4 billion years ago, but recent observations called that idea into question.



Photo:

NASA, ESA, A. Simon, M.H. Wong, OPAL Team

The new research represents “a completely new scenario that may solve the age of the rings for good,” said Dr.

Maryame El Moutamid,

a Cornell University astronomer who wrote an editorial accompanying the study but wasn’t involved in it.

In addition to explaining how and when the rings might have formed, the missing-moon scenario offers an explanation for Saturn’s puzzling tilt. Like Earth but unlike Jupiter—the planet in our solar system it most resembles—Saturn rotates at a significant angle with respect to the plane in which it orbits the sun.

“It ties together two puzzles that had previously been treated as separate,” Dr.

Francis Nimmo,

a professor of planetary science at the University of California, Santa Cruz, and a co-author of the study, said of the scenario. “It turns out that you can explain both in a single story.”

For many years, scientists believed Saturn’s rings formed more than 4 billion years ago, when the young planet’s strong gravitational field captured passing comets and asteroids and slowly flattened them into rings. But observations by three National Aeronautics and Space Administration missions—Voyager 1 and 2 in the 1980s and Cassini between 2004 and 2017—called that idea into question. The observations revealed that the rings’ mass and composition were much younger than previously believed.

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“If they’re not old, they must be a result of a breakup of a body, like a large comet or a moon later on,” Dr.

Jack Wisdom,

professor of planetary science at the Massachusetts Institute of Technology and lead author of the new research, said of the rings. But figuring out just what sort of object—and exactly how it broke up to form the rings—proved to be a difficult puzzle.

The solution came when the research team’s analysis of Cassini data upended long-held ideas about the complex relationships between Saturn, its moons and the nearby planet Neptune. Scientists had thought that Saturn and Neptune were in resonance, meaning they were gravitationally interacting. But the analysis showed that had been true but no longer was, suggesting that a small moon must have disrupted the resonance when gravitational forces exerted by another moon, Titan, sent it spiraling toward Saturn.

Not everyone is convinced that the question of Saturn’s rings and its tilt has been put to rest.

Jack Lissauer, a planetary scientist at NASA’s Ames Research Center in California’s Silicon Valley, said the new scenario “has a lot of things going for it” but that it is hard to verify the complex series of celestial events it is based upon. Dr. Lissauer wasn’t involved in the research.

The science community needs to spend time reviewing the new research, said Matthew Tiscareno, a planetary-rings researcher at the SETI Institute in Mountain View, Calif., who wasn’t involved in the study. But Dr. Tiscareno called the missing-moon scenario “an exciting new idea that likely gets us closer to solving several intertwined mysteries at Saturn.”

Write to Aylin Woodward at Aylin.Woodward@wsj.com

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Uncertainty remains after Sri Lankan president offers to resign

COLOMBO, Sri Lanka — Political parties in Sri Lanka met Sunday morning, facing intense pressure to quickly form an interim government after the country’s president and prime minister agreed to step down following fierce anti-government protests.

No fresh protests were reported in Colombo but people thronged the president’s home seized by protesters the previous day, picnicking in the gardens and swimming in the pool.

Nuwan Bopege, a volunteer associated with the protest movement, told The Post the protesters will occupy the homes of the two leaders until they formally resign.

Tens of thousands of people flooded the streets of Colombo this weekend to demand President Gotabaya Rajapaksa’s ouster over disastrous economic policies that have driven the country to collapse.

On Saturday, angry crowds stormed the presidential residence and office, and celebrated their victory by diving into the swimming pool and lounging on his bed. By nighttime Rajapaksa had conveyed his decision to resign on July 13 to the parliamentary speaker. He had moved out of his home a day ahead of the protests, and his whereabouts remain unknown.

Prime Minister Ranil Wickremesinghe too offered to resign to quell growing unrest, but his offer did not placate irate protesters who set his home ablaze.

The announcements of the resignation offers marked a major win for the protesters but plunged the island nation into political turmoil over what happens next.

Sri Lankan president to resign next week, says Parliament speaker, after protesters storm residence

“This was a failed president and a failed government,” said Faiszer Musthapha, a member of an opposition party that previously allied with Rajapaksa.

He said the long-suffering people of the country had taken control. “It was the might of the people on show,” he said.

“It is a historic moment,” said Harini Amarasuriya, an opposition member of Parliament, “where a true citizen’s struggle ended the rule of an unpopular and untrustworthy government.”

At an all-party meeting Saturday night, lawmakers decided to form an interim government until elections can take place. Discussions are underway to appoint a prime minister before the resignation of the president on Wednesday.

“We can now move into a more acceptable long-term trajectory for the country and for the international community,” said Eran Wickremerathne, a leader of the main opposition party.

The Senate Foreign Relations Committee, in a tweet, said President Rajapaksa had lost the confidence of the Sri Lankan people. “Now, all parties must work together with the international community for a new government that respects the democratic and economic aspirations and upholds human rights the Sri Lankan people deserve,” the tweet said.

What to know about the upheaval in Sri Lanka

The European Union in a statement urged political parties to “focus on a peaceful, democratic and orderly transition” to return to normalcy.

Even as the opposition tries to build consensus on next steps, the situation remains volatile as people’s patience has run out and with no quick fixes available.

In May, similar large-scale protests led to the resignation of Rajapaksa’s older brother Mahinda as prime minister and other family members. But the president hung on, appointing a former prime minister to head a new government.

The anger over continued economic distress spilled over again, this time in greater force. Recent weeks have been marked by severe fuel shortages, lengthy power cuts and skyrocketing food prices. The extraordinary circumstances forced authorities to shut down schools and offices and ask government workers to grow food in backyards.

The signs of acute distress are apparent everywhere — in the miles-long lines at gas stations, where it can take up to three days to reach the front, and the desperate attempts by asylum seekers to reach Australia by sea.

Far from Ukraine, Sri Lanka is the epicenter of a global crisis

Experts say Sri Lanka is experiencing stagflation – a period marked by slow growth and high unemployment accompanied by rising prices. The current negative growth could touch minus 4-6 percent later this year, some forecasts suggest, worse than the Covid hit to the economy in 2020. The Russian invasion of Ukraine that has sent global fuel and food prices soaring has exacerbated the country’s woes.

Sri Lanka has been in bailout talks with international lenders, but continuing political instability threatens to jeopardize that process.

Manjuka Fernandopulle, a lawyer specializing in debt restructuring, said creditors would like to deal with a government that is “credible and legitimate” and can “deliver on the promised reform.”

Local media reported that the International Monetary Fund said it hopes for an early resolution so that talks may resume on a bailout package. Ganeshan Wignaraja, an economist at ODI, a U.K.-based global affairs think tank who has been involved in the IMF discussions described the economic situation as “hugely challenging.”

The first step forward for Sri Lanka is the IMF program, Wignaraja said, which will include “higher taxes, raising interest rates to stabilize inflation and cutting down on public subsidies like electricity and power.”

“Step two is economic reforms [such as] lowering barriers to foreign investors,” he said. “My biggest fear is this could be a lost decade and all the gain made in poverty reduction could be reversed.”

Aid groups say nearly a quarter of the country’s 22 million residents are in need of food assistance. Many have resorted to eating less or skipping meals altogether. Countries like India and Australia have sent humanitarian aid such as food and medicines.

Now with the imminent ouster of the president, many Sri Lankans are hopeful of things turning around.

Namal Ratnayake, 40, was part of the protesting crowd that marched toward the president’s office. The last few months had been devastating for the a wedding photographer, with income drying up and no fuel to get around for assignments.

“We had to oust these corrupt people who have brought us down to our knees,” Ratnayake said. “My demand is that we have honest and educated people appointed from the present parliament to take us out of this immediate mess.”

At the presidential residence, celebrations by the jubilant crowd continued.

Visuals from local media showed a stream of visitors walking through an imposing stairway at the president’s home. Announcements were made to not steal or harm the property. Some collected trash and cleaned up debris.

In a large conference room, people enacted a discussion with the IMF while a young man played the Rajapaksa campaign song on the president’s piano to loud cheers.

Masih reported from New Delhi.



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Making sense of the uncertainty with Madrona’s Tim Porter – GeekWire

Tim Porter, Madrona Venture Group managing director. (Madrona Photo / GeekWire Illustration)

What the heck is going on in the economy, and how will the market gyrations impact startups and venture capital? The backdrop for these questions is dynamic and complex right now.

To help make sense of this turbulent environment, we invited Tim Porter to join us on the GeekWire Podcast. He’s a Madrona Venture Group managing director who has invested in early-stage technology startups at the Seattle-based venture capital firm for the past 15 years, focusing on cloud, AI and enterprise software companies.

Listen below, and continue reading for our notes from the discussion.

It seems a little grim out there. What are you seeing?

  • These last few years have been an absolute roller-coaster, for the world, the tech market, and in the startup market, as well.
  • In some ways, what’s happening now is a return to historical normalcy rather than a “sky is falling” scenario. There’s been a compression of multiples from unsustainably high levels last year. Companies are now focused a little bit more on efficiency, not just growth at all cost.
  • At the same time, the world has gone through so much trauma (pandemic, wars, supply chain issues, energy shocks, inflation), and those have a real impact on businesses and individual consumers.
  • It is going to be harder to fundraise in the near term. Investors have largely pressed the pause button right now. Startups need to think about extending their runway, rebalancing the trade-off between efficiency and growth. Growing a little bit less, but being a lot more efficient.
  • Companies aren’t hiring as aggressively, but there aren’t widespread hiring freezes or layoffs.
  • In many cases, demand from end customers is still strong. Companies have been hitting their Q1 targets, and Q2 is looking strong.
  • All that said, there’s an overall sense of caution, and a recognition that there’s a need to preserve capital.

It seems like a bit of a strange downturn. It’s not so much a business or customer reset; it’s simply a market and valuation reset. Is that an accurate assumption?

  • “I don’t want to say there’s zero impact in some of these end markets, but that’s largely been the case.”
  • The forward revenue multiple for the top 25 fastest-growing public SaaS companies was a median of 52 at the peak on Nov. 15. Now it’s a median of eight. And so you have seen a valuation reset.
  • Public companies are beating earnings expectations but tempering their forecasts due to issues including the impact of foreign exchange rates. (See Salesforce and Microsoft.)
  • For hardware companies, there is also a direct impact from supply chain challenges. (See Valve’s Steam Deck dock delay.) Consumer spending has become more muted as stimulus has worked its way through the economy.
  • “So I don’t want to say that there’s absolutely nothing to be concerned about around inflation and the overall economy. But I would say that most of the core trends we’re investing against — digital transformation, the move to the cloud, machine learning, the impacts of software — those all seem to be very durable.”
  • Looking ahead, people seem to be in a wait-and-see mode, not slamming on the brakes, but also not putting the gas pedal to the floor as in the past couple of years.

We’ve had COVID and a war and all these supply chain issues, inflation. Entrepreneurs must be feeling like they can’t catch a break. It’s exhausting and taking a psychological toll. How are you coaching entrepreneurs to get through this?

  • It has been wild. All the uncertainty and challenges of COVID in 2020, then the best fundraising market in history in 2021, the biggest run on tech valuations that we’d seen in 20 years. Now things are coming home to roost with inflation and broader global issues.
  • Yet founders are resilient and optimistic. Some of the best companies were created in past downturns. For Madrona, examples from the 2007-2009 era include Smartsheet, Apptio, and Extrahop.
  • “We want to partner with founders who want to build something meaningful and sustainable for the long term. Cycles are going to go up, and they’re going to go down. … And so you just have to respond, put your head down and keep building.”
  • “We try to always have a view of, every dollar demands a return. And if you see an opportunity, yes, be aggressive and invest against it. But don’t just pour money on something because money is available.”
  • That type of efficient growth mindset is what people are focused on right now.

Let’s say you’re an entrepreneur at the end of your Series A financing round, and going out for your Series B. What’s your advice for that entrepreneur?

Madrona is still figuring this out right now with several factors in mind.

  • Very late-stage private markets are essentially closed right now.
  • Up until three weeks ago, the very early stage market (pre-seed and seed investing) was cranking along. We saw a lot of early stage deals continuing to get done at robust prices. In the last three weeks, that market has started to slow.
  • In the Web3 world, the meltdown of Terra and Luna has contributed to a slowdown.
  • At the same time, the bar for startups to show progress in their metrics has been raised, with a greater focus on capital efficiency. Valuations are less than what entrepreneurs previously anticipated as a result.

So the advice is, if you don’t need to raise, don’t. Instead, extend your runway to achieve more with your existing capital. If you need to raise now, then consider a smaller round, and readjust your thoughts about valuation. Play for the long run, think about how you can make your pie bigger down the road, don’t just focus on dilution now.

We’re seeing hiring cutbacks from small companies to big ones. What are you seeing as it relates to hiring? Is this an opportunity for earlier stage companies to grab talent?

  • It does seem like an opportunity. Just as in the funding markets, there’s a cascading impact in the talent market that starts with later-stage companies and trickles down to earlier-stage companies. It takes a while.
  • The competition for talent has just been intense in Seattle in recent years, certainly on the technical and engineering side, but also on sales and marketing.
  • “It still is pretty competitive from what I’m seeing. But I think it’s going to ease, and get a little bit more normalized here in the back half of the year and into next year.”

It’s another example of this being a strange downturn — all these macroeconomic issues and yet hiring is still keeping up and customers are still coming. How much of this is groupthink versus reality?

  • One popular observation is that the technology market moves swiftly from greed to fear. When it moves to fear, all these things build on each other.
  • One truism through many cycles is that when a downturn is coming, you never want to react too late.
  • However, things haven’t just completely stopped. There is opportunity to build. It really depends on your business, runway, and end market.
  • The move toward efficiency is real and needed. You don’t want to go into pure survival mode, but you also don’t want to ignore the warning signs and burn through your money.
  • Tim hasn’t yet seen any down rounds (where the valuation was lower in a new round than it was previously). However, there was a deal where the price was adjust down in real time, through a collaborative discussion between the investors and founders.

Does a downturn like this change your investment focus?

  • “It largely does not. We are trying to invest in trends that we think are decade-plus-long trends, and invest really early for companies that can build over the long term. And so that hasn’t changed at all.”
  • Madrona’s pace of investing has also stayed relatively steady.
  • One thing that slows things down is price discovery, determining how to value companies. So there will probably be a slower pace of follow-on rounds vs. the prior year. New investments might slow, but to a lesser degree.

Is there something specific about this downturn that concerns you the most?

“I think it’s whether inflation and a broader slowing in the world economy will turn this into a much longer downturn or recession. How long will this last? The longer it lasts, the more I think you will see markets having to pull back. … Will it turn into a full-on recession? I’m not sure. And we’re hoping not. But that’s the question.”

How concerned are you on a scale of 1-10, with 1 being no concern, and 10 being massive devastation?

Seven. “I think it’s going to be a harder fundraising market for some time here. And I think that there are some broader issues around inflation and the economy. I don’t think it’s a 10. I don’t think it’s as bad as in the Great Recession in 2008. But I also think you have to show appropriate caution and be really focused on efficiency, and really understanding the forward indicators of your business to see how things are going to continue to respond.”

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