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CRISPR gene-editing therapies need more diverse DNA to realize their full potential – Vox.com

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Medicine has entered a new era in which scientists have the tools to change human genetics directly, creating the potential to treat or even permanently cure diseases by editing a few strands of troublesome DNA. And CRISPR, the gene-editing technology whose creators won the Nobel Prize for Chemistry in 2020, is the face of this new normal.

CRISPRs novel harnessing of bacterial proteins to target disease-carrying genes has reshaped medical research over the past decade. While gene-editing itself has been around for more than 30 years, scientists can use CRISPR to edit genomes faster, cheaper, and more precisely than they could with previous gene-editing methods.

As a result, investigators have gained far more control over where a gene gets inserted and when it gets turned on. That in turn has opened the door to a new class of better gene therapies treatments that modify or replace peoples genes to stop a disease.

Last December, the US Food and Drug Administration approved the first-ever CRISPR-based therapy, designed to treat sickle cell disease. In February, the treatment, called Casgevy, gained approval from the European Commission as well. It joins the dozen or so pre-CRISPR gene therapies that are already available to patients. In early May, the first patients began to receive treatment

But theres a significant impediment to maximizing CRISPRs potential for developing novel therapies: the lack of diversity in genetics research.

For decades, gene therapy has been defined by both its enormous therapeutic potential, and by the limitations imposed by our imprecise knowledge of human genetics. Even as gene-editing methods, including CRISPR, have become more sophisticated over the years, the data in the genetic databases and biobanks that scientists use to find and develop new treatments are still riddled with biases that could exclude communities of color from enjoying the full benefits of innovations like CRISPR. Unless that gap is closed, CRISPRs promise wont be fully fulfilled.

Developing effective gene therapies depends on growing our knowledge of the human genome. Data on genes and their correlation with disease have already changed the way cancer researchers think about how to design drugs, and which patients to match with which drug.

Scientists have long known that certain genetic mutations that disrupt regular cell functions can cause cancer to develop, and they have tailored drugs to neutralize those mutations. Genetic sequencing technology has sped that progress, allowing researchers to analyze the genetics of tumor samples from cancer patients after theyve participated in clinical trials to understand why some individuals respond better than others to a drug.

In a clinical trial of the colorectal cancer drug cetuximab, investigators found retrospectively that tumors with a mutation in the KRAS gene (which helps govern cell growth) did not respond to treatment. As a result, clinicians are now asked to confirm that patients do not have the mutation in the KRAS gene before they prescribe that particular drug. New drugs have been developed to target those mutations in the KRAS gene.

Its a step-by-step process from the discovery of these disease-related genes to the crafting of drugs that neutralize them. With CRISPR now available to them, many researchers believe that they can speed this process up.

The technology is based on and named after a unique feature in the bacterial immune system that the organism uses to defend itself against viruses. CRISPR is found naturally in bacteria: Its short for Clustered Regularly Interspaced Short Palindromic Repeats, and it functions like a mugshot database for bacteria, containing snippets of genetic code from foreign viruses that have tried to invade in the past.

When new infections occur, the bacteria deploys RNA segments that scan for viral DNA that matches the mugshots. Special proteins are then dispatched to chop the virus up and neutralize it.

To develop CRISPR into a biotech platform, this protein-RNA complex was adapted from bacteria and inserted into human and animal cells, where it proved similarly effective at searching for and snipping strands of DNA.

Using CRISPR in humans requires a few adjustments. Scientists have to teach the system to search through human DNA, which means that it will need a different mugshot database than what the bacteria originally needed. Critical to harnessing this natural process is artificial RNA, known as a guide RNA. These guide RNAs are designed to match genes found in humans. In theory, these guide RNAs search for and find a specific DNA sequence associated with a specific disease. The special protein attached to the guide RNA then acts like molecular scissors to cut the problematic gene.

CRISPRs therapeutic potential was evident in the breakthrough sickle cell treatment approved by the FDA late last year. What made sickle cell such an attractive target is not just that it affects around 20 million people or more worldwide, but that it is caused by a mutation in a single gene, which makes it simpler to study than a disease caused by multiple mutations. Sickle cell is one of the most common disorders worldwide that is caused by a mutation in a single gene. It was also the first to be characterized at a genetic level, making it a promising candidate for gene therapy.

In sickle cell disease, a genetic mutation distorts the shape of a persons hemoglobin, which is the protein that helps red blood cells carry and deliver oxygen from the lungs to tissues throughout the body. For people with sickle cell disease, their red blood cells look like sickles instead of the normal discs. As a result, they can get caught in blood vessels, blocking blood flow and causing issues like pain, strokes, infections, and death.

Since the 1990s, clinicians have observed that sickle cell patients with higher levels of fetal hemoglobin tend to live longer. A series of genome-wide association studies from 2008 pointed to the BCL11A gene as a possible target for therapeutics. These association studies establish the relationships between specific genes and diseases, identifying candidates for CRISPR gene editing.

Casgevys new CRISPR-derived treatment targets a gene called BCL11A. Inactivating this gene stops the mutated form of hemoglobin from being made and increases the production of normal non-sickled fetal hemoglobin, which people usually stop making after birth.

Out of the 45 patients who have received Casgevy since the start of the trials, 28 of the 29 eligible patients who have stayed on long enough to have their results analyzed reported that they have been free of severe pain crises. Once the treatment moves out of clinical settings, its exact effects can vary. And if the underlying data set doesnt reflect the diversity of the patient population, the gene therapies derived from them might not work the same for every person.

Sickle cell disease as the first benefactor of CRISPR therapy makes sense because its a relatively simple disorder that has been studied for a long time. The genetic mutation causing it was found in 1956. But ironically, the same population that could benefit most from Casgvey may miss out on the full benefits of future breakthrough treatments.

Scientists developing CRISPR treatments depend on whats known as a reference genome, which is meant to be a composite representation of a normal human genome that can be used to identify genes of interest to target for treating a disease.

However, most of the available reference genomes are representative of white Europeans. Thats a problem because not everybodys DNA is identical: Recent sequencing of African genomes shows that they have 10 percent more DNA than the standard reference genome available to researchers. Researchers have theorized that this is because most modern humans came out of Africa. As populations diverged and reconcentrated, genetic bottlenecks happened, which resulted in a loss of genetic variation compared to the original population.

Most genome-wide association studies are also biased in the same way: They have a lot of data from white people and not a lot from people of color.

So while those studies can help identify genes of importance that could lead to effective treatments for the population whose genes make up the majority of the reference data i.e., white people the same treatments may not work as well for other nonwhite populations.

Broadly, theres been an issue with human genetics research theres been a major under-representation of people of African ancestry, both in the US and elsewhere, said Sarah Tishkoff, professor of genetics and biology at the University of Pennsylvania. Without including these diverse populations, were missing out on that knowledge that could perhaps result in better therapeutics or better diagnostics.

Even in the case of the notorious breast cancer gene BRCA1, where a single gene mutation can have a serious clinical impact and is associated with an increased risk of developing cancer, underlying mutations within the gene tend to differ in people of different ancestries, Tishkoff said.

These differences, whether large or small, can matter. Although the vast majority of human genomes are the same, a small fraction of the letters making up our genes can differ from person to person and from population to population, with potentially significant medical implications. Sometimes during sequencing, genetic variations of unknown significance appear. These variants could be clinically important, but because of the lack of diversity in previous research populations, no one has studied them closely enough to understand their impact.

If all the research is being done in people of predominantly European ancestry, youre only going to find those variants, Tishkoff said.

Those limitations affect scientists up and down the developmental pipeline. For researchers using CRISPR technology in preclinical work, the lack of diversity in the genome databases can make it harder to identify the possible negative effect of such genetic variation on the treatments theyre developing.

Sean Misek, a postdoctoral researcher at the Broad Institute of MIT and Harvard, started developing a project with the goal of investigating the differences in the genetic patterns of tumors from patients of European descent compared to patients of African descent. CRISPR has become a versatile tool. Not only can it be used for treatments, but it can also be used for diagnostics and basic research. He and his colleagues intended to use CRISPR to screen for those differences because it can evaluate the effects of multiple genes at once, as opposed to the traditional method of testing one gene at a time.

We know individuals of different ancestry groups have different overall clinical responses to cancer treatments, Misek said. Individuals of recent African descent, for example, have worse outcomes than individuals of European descent, which is a problem that we were interested in trying to understand more.

What they encountered instead was a roadblock.

When Miseks team tried to design CRISPR guides, they found that their guides matched the genomes in the cells of people with European and East Asian ancestry, whose samples made up most of the reference genome, but not on cells from people of South Asian or African ancestry, who are far less represented in databases. In combination with other data biases in cancer research, the guide RNA mismatch has made it more difficult to investigate the tumor biology of non-European patients.

Genetic variations across ancestry groups not only affect whether CRISPR technology works at all, but they can also lead to unforeseen side effects when the tool makes cuts in places outside of the intended genetic target. Such side effects of off-target gene edits could theoretically include cancer.

A big part of developing CRISPR therapy is trying to figure out if there are off-targets. Where? And if they exist, do they matter? said Daniel Bauer, an attending physician at Dana-Farber/Boston Childrens Cancer and Blood Disorders Center.

To better predict potential off-target edits, Bauer collaborated with Luca Pinello, associate professor at Massachusetts General Hospital and Harvard Medical School, who had helped develop a tool called CRISPRme that makes projections based on personal and population-level variations in genetics. To test it, they examined the guide RNA being used for sickle cell disease treatment, and found an off-target edit almost exclusively present in cells donated by a patient of African ancestry.

It is currently unclear if this off-target edit detected by the CRISPRme tool has any negative consequences. When the FDA approved the sickle-cell therapy in December 2023, regulators required a post-marketing study to look into off-target effects. Any off-target edits affecting a persons blood should be easily detected in the blood cells, and drawing blood is easier to do than collecting cells from an internal organ, for example.

The genetic variant where the off-target effect occurred can be found in approximately every 1 in 10 people with African ancestry. The fact that we actually were able to find a donor who carried this variant was kind of luck, Bauer said. If the cells we were using were only of European ancestry, it wouldve been even harder to find.

Most of these [off-target] effects probably wont cause any problems, he said. But I think we also have these great technologies, so thats part of our responsibility to look as carefully as we can.

These issues recur again and again as investigators hunt for novel treatments. Katalin Susztak, professor of medicine and genetics at the University of Pennsylvania, thinks one promising candidate for a future CRISPR therapy is a standout gene for kidney disease: APOL1.

Researchers identified the gene when they looked into kidney disease risk in African Americans. While genome-wide association studies turned up thousands of distinct genes increasing risk for people of European ancestry, in African Americans, this single gene was responsible for 3 to 5 times higher risk of kidney disease in patients, said Susztak.

The APOL1 variant is common among African Americans because it protects people from developing African sleeping sickness, which is spread by the Tsetse fly present across much of the continent. This is similar to the story of the sickle cell mutation, which can protect people from malaria.

The variant is maybe only 5,000 years old, so this variant has not arisen in Europe, Asia, or anywhere else. Just in West Africa, Susztak said. But because of the slave trades, West Africans were brought to the United States, so millions of people in the United States have this variant.

The variant also predisposes people to develop cardiovascular disease, high blood pressure, and COVID-related disease, which maybe explains why there was an increased incidence of deaths in African Americans during COVID than in Europeans, Susztak said. APOL1 is potentially a very interesting target [for CRISPR] because the disease association is strong.

A CRISPR treatment for kidney disease is currently being investigated, but using the tool comes with complications. Cutting the APOL1 gene would set off an immune response, Susztak noted, so they will have to somehow prevent undesirable side effects, or find a related, but editable gene, like they did with sickle cell.

An alternative RNA-based strategy utilizing CRISPR is also in the works. DNA needs to be transcribed into a messenger RNA sequence first before it can be turned into proteins. Instead of permanently altering the genome, RNA editing alters the sequence of RNAs, which can then change what proteins are produced. The effects are less permanent, however, lasting for a few months instead of forever which can be advantageous for treating temporary medical conditions.

And it may turn out that gene therapy is simply not the right approach to the problem. Sometimes, a more conventional approach still works best. Susztak said that a small molecule drug developed by Vertex which works similarly to most drugs except special classes like gene therapies or biologics to inhibit the function of the APOL1 protein has enjoyed positive results in early clinical trials.

Even with these limitations, more CRISPR treatments are coming down the pike.

As of early last year, more than 200 people have been treated with experimental CRISPR therapies for cancers, blood disorders, infections, and more. In the developmental pipeline is a CRISPR-based therapeutic from Intellia Therapeutics that treats transthyretin amyloidosis, a rare condition affecting the function of the heart tissues and nerves. The drug has performed well in early trials and is now recruiting participants for a Phase III study. Another CRISPR drug from Intellia for hereditary angioedema, a condition that causes severe swelling throughout the body, is slated to enter Phase III later this year.

As the CRISPR boom continues, some research groups are slowly improving the diversity of their genetic sources.

The All of Us program from the National Institutes of Health, which aims to find the biological, environmental, and lifestyle factors that contribute to health, has analyzed 245,000 genomes to date, over 40 percent of which came from participants who were not of European ancestry. They found new genetic markers for diabetes that have never been identified before.

Then theres the Human Pangenome project, which aims to create a reference genome that captures more global diversity. The first draft of its proposal was released last May. Another project called the PAGE study, funded by the National Human Genome Research Institute and the National Institute on Minority Health and Health Disparities, is working to include more ancestrally diverse populations in genome-wide association studies.

But at the current pace, experts predict that it will take years to reach parity in our genetic databases. And the scientific community must also build trust with the communities its trying to help. The US has a murky history with medical ethics, especially around race. Take the Tuskegee experiment that charted the progression of syphilis in Black American men while hiding the true purpose of the study from the participants and withholding their ability to seek treatment when it became available, or the controversy over Henrietta Lacks cervical cells, which were taken and used in research without her consent. Those are just two prominent historical abuses that have eroded trust between minority communities and the countrys medical system, Tishkoff said. That history has made it more difficult to collect samples from marginalized communities and add them to these critical data sets.

Where the research is being done, where the clinical trials are being held, as well as whos doing the research, can all have an impact on which patients participate. The Human Genetics & Genomics Workforce Survey Report published by the American Society of Human Genetics in 2022 found that 67 percent of the genomic workforce identified as white. Add in the financial burden of developing new treatments when using a reference genome, or a pre-made biobank from past efforts to collect and organize a large volume of biological samples, saves time and costs. In the race to bring CRISPR treatments to market, those shortcuts offered valuable efficiency to drug makers.

What this means is that the first-generation of CRISPR therapeutics might therefore be blunter instruments than they might otherwise be. However, if improvements can be made to make sure the source genomes reflect a wider range of people, Pinello believes that later generations of CRISPR will be more personalized and therefore more effective for more people.

Finding the genes and making drugs that work is, of course, momentous but ultimately, thats only half the battle. The other worry physicians like Susztak have is whether patients will be able to afford and access these innovative treatments.

There is still an overwhelming racial disparity in clinical trial enrollment. Studies have found that people of color are more likely to suffer from chronic illness and underuse medications like insulin compared to their white counterparts. Gene therapies easily rack up price tags in the millions, and insurance companies, including the Centers for Medicare and Medicaid Services, are still trying to figure out how to pay for them.

Because its the pharmaceutical industry, if they dont turn around profit, if they cannot test the drug, or if people are unwilling to take it, then this inequity is going to be worsened, said Susztak. We are essentially going to be creating something that makes things worse even though we are trying to help.

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CRISPR gene-editing therapies need more diverse DNA to realize their full potential - Vox.com

Road to safer self-driving cars is paved with deep learning – ISRAEL21c

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Safer and more reliable autonomous systems, such as self-driving vehicles, may be possible thanks to a new understanding of deep learning, a type of artificial intelligence (AI) that mimics the way humans learn and process information.

The study, conducted at Bar-Ilan University and published in the Physica A journal, highlights the interplay between AI confidence levels and decision-making processes.

Understanding the confidence levels of AI systems allows us to develop applications that prioritize safety and reliability, explained Ella Koresh, an undergraduate student who contributed to the research.

For instance, in the context of autonomous vehicles, when confidence in identifying a road sign is exceptionally high, the system can autonomously make decisions. However, in scenarios where confidence levels are lower, the system prompts for human intervention, ensuring cautious and informed decision-making.

According to the researchers, deep learning architectures can achieve higher confidence levels for a substantial portion of inputs, while maintaining an overall average confidence.

Put more simply: deep learning AI can be more certain about a lot of things without sacrificing overall reliability.

The ability to bolster the confidence levels of AI systems establishes a new benchmark for AI performance and safety and could be applicable across a spectrum of fields, from AI-driven writing and image classification to pivotal decision-making processes in healthcare and autonomous vehicles.

In addition to Koresh, the study was authored by Yuval Meir, Ofek Tevet, Yarden Tzach and Prof. Ido Kanter from the department of physics at Bar-Ilan and the universitys brain research center.

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Road to safer self-driving cars is paved with deep learning - ISRAEL21c

Neoliberal economics: The road to freedom or authoritarianism? – NPR

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Neoliberal economics: The road to freedom or authoritarianism? : Planet Money Nobel-winning economist Joseph Stiglitz's new book argues the road to tyranny is paved not by too much, but by too little government.

In the early 1930s, Austrian economist Friedrich Hayek, then based at the London School of Economics, jotted off a memo to the school's director, William Beveridge. At the time, the Great Depression was wreaking havoc around the world. And the ideals of classical liberalism, like democracy and free-market capitalism, were under assault. Witnessing the rise of fascist parties around Europe, Beveridge, like many others in his day, had argued fascism was the ultimate expression of a failed capitalist system. Absolutely not, argued Hayek in his memo. Fascism, with its rejection of liberal democracy and embrace of government power, actually had its roots in socialist ideas and policies.

What began as the germ of an idea in a memo became a magazine article and then, in 1944, a book, which Hayek titled The Road To Serfdom. When Hayek shopped the publication rights of the book in the United States, three commercial publishing houses rejected it. They didn't see its potential. Hayek settled for an academic publishing house: The University of Chicago Press.

The Road To Serfdom became a smashing success. Not only did it sell hundreds of thousands of copies, it blew wind into the sails of a flagging conservative movement, which had struggled to captivate the hearts and minds of mainstream America after the Great Depression.

Hayek argued that the ballooning welfare state, characterized by policies like those of the New Deal, handed too much power and control to the central government, robbing people of autonomy over their economic lives, hurting the economy, and paving the road to tyranny. He argued that freedom and prosperity could only be achieved by embracing the free market.

80 years later, economist Joseph Stiglitz who like Hayek, won a Nobel Prize in economics has a new book out with a response to Hayek and his generations of followers. "A major theme of my book is that Hayek got it 180 degrees wrong," Stiglitz told Planet Money in an interview last week. In fact, the very title of Stiglitz's book is a counterpunch to The Road to Serfdom. It's called The Road To Freedom.

Like in the 1930s, when Hayek began working on his book, populism is now exploding around the world. And Stiglitz fears some countries may be careening towards "a 21st century version of fascism." But contrary to the classic argument made by Hayek, Stiglitz says, this rise in authoritarianism "comes not in the countries where the government is doing too much, but where the government is doing too little to protect individuals against unemployment, the stresses of adaptation to globalization, to technical change, to the stresses of migration."

For a long time, conservative politicians sold lower taxes, fewer regulations, and smaller government as integral to enhancing freedom. But, Stiglitz argues, this conception of freedom is all wrong and, even worse, it has paved the way to a dangerous political era that threatens our real freedom.

For Hayek and later Milton Friedman and a whole host of other conservatives and libertarians who were inspired by Hayek's work freedom largely meant freedom from government.

Stiglitz opposes this narrow way of thinking about freedom. In his book, he offers a much different conception of freedom, which he writes is really about, using jargon from economics, "a person's opportunity set the set of options she has available."

Freedom, in other words, is "really what you're free to do," Stiglitz says. "Somebody who is at the point of starvation doesn't really have much freedom. He does what he has to do to survive." By giving that person more resources, Stiglitz says, he becomes more free. He has more options in life. In this sense, Stiglitz argues, the government can step in and give citizens more freedom by, for example, levying taxes to fund programs that eliminate poverty or help people get jobs.

Even more, Stiglitz argues, policymakers should be wary that policies that expand the freedom of some people may come at the cost of the freedom for many more people. He begins his book by quoting the Oxford philosopher Isaiah Berlin: "Freedom for the wolves has often meant death to the sheep." He uses this metaphor to criticize policies like financial deregulation, which, he says, gave more freedom to banks at the expense of the freedom of ordinary Americans.

Stiglitz goes well beyond an effort to reclaim the concept of freedom for progressives. Much of his book is aimed at bulldozing away any legitimacy for "neoliberalism" an increasingly popular term for the free-market ideology that swept America and much of the world in the 1980s and 1990s.

"Neoliberalism's crimes include freeing financial markets to precipitate the largest financial crisis in three-quarters of a century; freeing trade to accelerate deindustrialization [by, for example, gutting American manufacturing]; and freeing corporations to exploit consumers, workers, and the environment alike," Stiglitz writes. "This form of capitalism does not enhance freedom in our society. Instead, it has led to the freedom of a few at the expense of the many. Freedom for the wolves; death for the sheep."

As a member and then president of the Council of Economic Advisors in the Clinton White House, Stiglitz had a prominent seat at the table when neoliberal ideas spread beyond their traditional stronghold in the Republican Party and began being pushed by Democrats. President Bill Clinton promoted a range of free-market policies, including signing the North American Free Trade Act (NAFTA), supporting China in its bid to join the World Trade Organization, and deregulating the telecommunications and financial industries.

Stiglitz says that, behind closed doors, he fought tooth and nail against many of these policies. He notes, for example, he was successful at staving off financial deregulation that is, until he left office in 1997. Clinton didn't sign financial deregulation into law until 1999.

"I strongly opposed deregulation of finance, in part because I understood that 'freeing' the financial sector would make us all less free in the end," Stiglitz writes in his book. He blames financial deregulation for contributing to the 2008 financial crisis.

After serving in the Clinton Administration, Stiglitz again battled creeping neoliberalism, this time on a global scale as the chief economist of The World Bank. There he fought against policies like the liberalization of capital markets, which allowed global investors to more freely move money to and from poor countries. He blamed this policy for creating financial volatility and contributing to economic crises around the world.

Of course, there are many who disagree with Stiglitz's take on neoliberalism and the need for strong government involvement in the economy. They may believe the government is too dumb or corrupt to do a good job regulating the market and engineering a more prosperous and freer society. Countries like Argentina and Venezuela, where generations of left-wing leaders have pursued interventionist policies, have seen a host of economic problems, including runaway inflation and dismal economic growth.

Many economists still believe in the virtues of free-market capitalism. For example, in a new book titled The Capitalist Manifesto: Why The Global Free Market Will Save The World, Swedish author Johan Norberg argues that free-market capitalism has lifted millions and millions of people out of poverty, fostered incredible technological innovations, and brought down prices on all sorts of goods and services. Turning against it, Norberg warns, will only hurt growth, lower our living standards, and devastate many, especially the world's poor.

Now is the time, Stiglitz argues, for the United States and other nations to abandon neoliberalism and embrace a new form of "progressive capitalism," where the government plays a bigger role in managing the economy, fighting climate change, breaking up monopolies, and eradicating poverty, inequality, and joblessness.

"If we continue down this path you might say the road to serfdom we will lose some freedom because it's leading to more populism," Stiglitz says. "This populism is an authoritarian kind of populism and is a real threat to the sustaining of democracy and even, really, a market economy that actually functions."

While Stiglitz spends much of his book criticizing Republicans, many Republicans these days are more receptive to the idea that the free market is failing America and that we need greater government intervention. Senator Josh Hawley (R-Missouri), for example, has been vocal against monopolies and has sponsored various bills to break them up. Last year, Senator Marco Rubio (R-Florida) published a book, Decades of Decadence, which explicitly blasts neoliberalism, especially free-trade deals, for hurting American workers. Rubio now supports "industrial policy" handing the federal government more power to shape and grow strategic American industries (For more on industrial policy, listen to this Indicator episode). In a recent op-ed in The Washington Post, Rubio says "industrial policy" used to be dirty words in his political circle, but now he believes the federal government must play an active role in revitalizing American manufacturing.

We asked Stiglitz whether the growing bipartisan consensus that the government needs to play a bigger role in the economy gives him any hope that his vision may actually come into being. Stiglitz, a staunch Democrat, began by criticizing Republicans, including for pushing the unsubstantiated claim that the 2020 presidential election was stolen.

"But," Stiglitz continued, "when I read, say, Marco Rubio's views about industrial policy, I sometimes think he may have cribbed it from some of the things that I've written," he says with a laugh. "And so there is hope that on a lot of these issues, there is an understanding that neoliberalism failed it's so obvious to me and that we have to have new policies, like industrial policies, like more competition to stop Big Tech. I do think we're moving in that direction in a bipartisan way."

By the way, Joseph Stiglitz and I had a wide-ranging conversation about freedom, economics, neoliberalism, and his views on the world's problems. We covered a whole lot more than what I could fit in this newsletter. We will be releasing an audio version of this interview to Planet Money+ subscribers soon. You can subscribe here.

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Neoliberal economics: The road to freedom or authoritarianism? - NPR

Srinivasan on Open Letters, Protests, Free Speech, and Academic Freedom – Daily Nous – Daily Nous

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Amia Srinivasans specialty, it seems to me, is making sense of moral ambivalence: detecting, dissecting, and sometimes defending its reasonability, even in the face of unavoidable and urgent decisions.

[Knot by Anni Albers]

It begins with the matter of signing open letters:

An open letter is an unloved thing. Written by committee and in haste, it is a monument to compromise: a minimal statement to which all signatories can agree, or worse a maximal statement that no signatory fully believes. Some academics have a general policy against signing them. I discovered that was true of some of my Oxford colleagues last year, when I drafted and circulated an open letter condemning Israels attack on Gaza and calling for a ceasefire. Some, like those who are in precarious employment or whose immigration status isnt settled, have good reasons for adopting such a policy. Others understandably dont want to put their name to something that doesnt perfectly represent their views, especially when it might be read as a declaration of faith. I always cringe at the self-importance of the genre: though open letters can sometimes exert influence, stiffly worded exhortations hardly suffice to stop states, militaries, bombs. And yet, a no open letters policy can serve as a convenient excuse when one is hesitant to stand up for ones political principles.

Srinivasan has signed several open letters about Gaza, and recently signed an open letter committing her to an academic and cultural boycott of Columbia University, owing to how it handled student protestors. Then:

In April I was asked to sign a letter opposing the University of Cambridges investigation into Nathan Cofnas, a Leverhulme early career fellow in philosophy. A self-described race realist, Cofnas has written widely in defence of abhorrently racist particularly anti-Black views, invoking what he claims are the findings of the science of heredity.

She shares her many reservations about signing the open letter, but also her reason for ultimately signing it:

Do we think that students should be able to trigger investigations into academics on the grounds that their extramural speech makes them feel unsafe? Do we want to fuel the rights sense of grievance towards the university, when their minority presence within it is owed to the robust correlation between education and political liberalism, not some Marxist plot? Do we want to empower university administrators to fire academics on the grounds that they are attracting negative publicity? Do we think there is any guarantee that a further strengthened institutional power will only be wielded against those whose views and politics we abhor? If we say yes, what picture of power theirs and ours does that presume?

But thats not the end of the discussion, for theres the question of whether her taking a principled stand is her also being a sucker for her political opponents:

free speech and academic freedom are, for many on the right, ideological notions, weapons to be wielded against the left and the institutions it is (falsely) believed to control, the university most of all [and] the free-speech brigade has found justifications for the draconian repression of student protest.

Theres also the question of the extent to which the free speech brigade understands how academic freedom and freedom of speech come apart, or how even different considerations in favor of free speech might be in tension with each other:

After signing the letter criticising the investigation into Cofnas, I was written to by someone from the Committee for Academic Freedom, which bills itself as a non-partisan group of academics from across the political spectrum. He asked me whether I might consider signing up to theCAFs three principles. I looked them up: I. Staff and students atUKuniversities should be free, within the limits of the law, to express any opinion without fear of reprisal. II. Staff and students atUKuniversities should not be compelled to express any opinion against their belief or conscience. III.UKuniversities should not promote as a matter of official policy any political agenda or affiliate themselves with organisations promoting such agendas. I thought about it for a bit. Im on board with PrincipleII, so long as we dont think that asking staff and students to use someones correct pronouns is akin to demanding they swear a loyalty oath. Principle I is problematic, because it doesnt register that academic freedom essentially involves viewpoint-based discrimination that indeed the whole point of academic freedom is to protect academics rights to exercise their expert judgment in hiring, peer review, promotion, examining, conferring degrees and so on. And PrincipleIIIwould prevent universities from condemning, say, Israels systematic destruction of universities and schools in Gaza, which I think as educational institutions they are entitled to do.

Discussion welcome, but read the whole thing first.

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Srinivasan on Open Letters, Protests, Free Speech, and Academic Freedom - Daily Nous - Daily Nous

Liberty Hospital, University of Kansas Health System finalize partnership – KSHB 41 Kansas City News

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KANSAS CITY, Mo. Liberty Hospital and the University of Kansas Health System announced details Wednesday of a new partnership in which UKHS will operate Liberty Hospital.

The announcement came after the Liberty Hospital District Board of Directors unanimously approved a definitive agreement in a meeting early Wednesday.

Under the agreement, UKHS will make $300 million of investment in Liberty Hospital over a 12-year period. The investments include technology, facilities and recruitment of staff.

The agreement outlines UKHS as the new operator of Liberty Hospital through the New Liberty Hospital Corporation. The Liberty Hospital District will continue to be responsible for the maintenance of assets.

"Patients will continue to receive the same care, from the same physicians and the same providers," Liberty Hospital CEO Raghu Adiga said in a press conference Wednesday announcing the agreement.

The two organizations started initial discussions about the partnership in May 2023, reaching a letter of intent to complete due diligence later in 2023.

"As Liberty and the Northland continue to grow, it is important patients can get the necessary care close to home," said Tammy Peterman, MS, RN, FAAN, and President of the Kansas City Division of UKHS. "This agreement will not only allow us to treat more patients overall but also offer access to those with the most complex care needs at 39th and Rainbow and other locations."

Peterman said KU Cancer Center services will be available to Liberty Hospital patients. She added Liberty Hospital employees will become employees of UKHS and retention of employed Liberty Hospital physicians and maintenance of open medical staff for many services.

"As the region's largest locally headquartered health system, we are committed to ensuring patients and their families in our region have access to the highest quality care close to home," said University of Kansas Health System President and CEO Bob Page. "As a health system, we put patients first in every decision we make.

"We are excited to have the leaders, physicians, nurses, other care providers and employees of Liberty Hospital join our health system and look forward to serving even more people in our region and beyond."

News of the proposed partnership initially drew concern from Missouri legislators, including Missouri Sen. Greg Razer (D-Jackson County).

Adiga said Wednesday hospital officials have "spent a lot of time" with legislators to inform them of the hospital's plans.

"We don't anticipate any legislative hurdles to this partnership," Adiga said.

KU's Page said UKHS officials reviewed Kansas laws and said they are "confident we're on solid ground."

The agreement is set to be finalized on July 1.

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Liberty Hospital, University of Kansas Health System finalize partnership - KSHB 41 Kansas City News

Liberty back to take second shot at title – Brooklyn Daily Eagle

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Liberty coach Sandy Brondello has her team back and reloaded for another run at the franchise's first-ever WNBA title. AP Photo by Frank Franklin II

The buzzer sounded at Barclays Center just before Jonquel Jones final attempt at extending the WNBA Finals last October.

Courtney Vandersloot missed everything on a potential game-winning jumper just over a second earlier.

WNBA Most Valuable Player Breanna Stewart made only three of her 17 field-goal attempts in the Game 4 heartbreaker.

The New York Liberty had a lot to lament this offseason after coming within a single shot of forcing a fifth and decisive game against the reigning two-time champion Las Vegas Aces.

The hard-to-swallow 70-69 defeat before another record-setting crowd at Barclays brought with it some doubt whether Jones, the 2021 WNBA MVP, and Stewart, who earned her second league award last season, would be back for another run at it.

Also, Vandersloot, a surefire Hall of Fame point guard, had a decision to make regarding whether shed continue playing in the best womens basketball league in the world after 13 brilliant seasons.

But they all agreed, along with current and former All-Stars Sabrina Ionescu and Betnijah Laney-Hamilton, to reboot the quest for this franchises first-ever championship.

That journey officially began Sunday when New York players reunited on the corner of Atlantic and Flatbush to finish off what they started in 2023.

The Superteam is back to complete some unfinished business.

We know what happened last year and the fact we didnt achieve our goal will motivate us, but its not what were thinking about the entire season, reigning WNBA MVP Breanna Stewart revealed.

Liberty general manager Jonathan Kolb, who earned WNBA Executive of the Year honors for bringing Jones, Stewart and Vandersloot to Brooklyn, didnt stay put with the roster that earned the Liberty the most wins in franchise history and their first Finals appearance since 2002.

After re-signing Stewart and Jones, he brought in a trio of free agents, Kennedy Burke, Leonie Fiebich and Ivana Dojki, each of whom has international and WNBA experience.

Kolb, alongside head coach Sandy Brondello, also infused the roster with fresh talent in last months draft.

The Liberty selected guard Marquesha Davis from the University of Mississippi with the 11th overall pick, and added second-rounders Esmery Martinez and Jessika Carter at forward and center, respectively.

Tonight was a success for the future of the New York Liberty. Welcoming Marquesha, Esmery, Jessika, and Kaitlyn to the organization further expands our breadth of young talent for 2024 and beyond as we strategically pursue perennial contention, Kolb said at the Brooklyn Academy of Music.

We are excited to add this versatile group, both in the immediate and future, with unique skillsets that fit our style of play here in New York, added Brondello.

New talent aside, the Liberty will rely most heavily on the players that brought them to the brink of a title last year, as well as veteran returnees Kayla Thornton and Nyara Sabally.

But unlike last May, there isnt an air of mystery as to how well this then-newly formed group would perform.

I know at this time last year I was meeting Courtney as a teammate for the first time, Ionescu told the Associated Press.

Having one year under our belt, training camp feels different. Weve been able to grow so much as a group and having a returning starting five helps so much that were building from last year.

Whether theyve built something that will result in our boroughs first championship parade down Flatbush Avenue since 1955 is yet to be determined.

However, knowing a team that came so close last year against a reigning dynasty from Sin City should bring Brooklynites out in droves to Barclays, where the Liberty set team and league records for attendance last summer.

Stewart, a two-time WNBA champion in Seattle, is chomping at the bit to run it back in 2024.

Im really excited to get things going with a new and old group and build the chemistry, she noted. Now most of us have a year under our belt, what are we going to do bigger on and off the court?

They cant do something bigger than last year until October at the earliest.

But the drive for Title I begins May 14 in Washington, D.C., with the teams regular-season opener.

The Liberty will open the home portion of their schedule May 18 vs. first overall pick Caitlin Clark and the Indiana Fever.

April 30 | John Torenli, Sports Editor

April 25 | John Torenli, Sports Editor

April 24 | John Torenli, Sports Editor

April 23 | John Torenli, Sports Editor

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Liberty back to take second shot at title - Brooklyn Daily Eagle

Ascension health care system retracts nationwidebut not in Indy Indianapolis Business Journal – Indianapolis Business Journal

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The six-story Women & Childrens Tower under construction on the hospitals West 86th Street campus will feature both private neonatal intensive care unit rooms and pediatric intensive care unit rooms. (IBJ photo/Eric Learned)

In the past five years, the nations largest Catholic health system, Ascension, has unloaded more than a dozen hospitals across the country, from New York to Alabama, as it restructures amid a growing tide of red ink.

In Indiana alone, it shut a critical-access hospital in Bedford, closed 11 immediate-care walk-in centers in central Indiana and shut down or repurposed five small neighborhood hospitals.

And theres no sign the sell-off is over.

Ascension continues selling spree, said a headline last month in Beckers Hospital Review, a trade news site, which added that the St. Louis-based system has more deals in the pipeline.

Ascension hastens exit out of Michigan, said a headline in Crains Detroit this month, after the health care system sold three hospitals in the northern part of the state to a large health system affiliated with the University of Michigan and set up a joint venture with another large system in the Detroit area.

Ascension, trying to dig itself out from a $3billion operating loss in fiscal year 2023, has not limited its sell-off to hospitals. It has also sold its interest in laboratory operations and a health insurance group.

So does Ascension plan to close or sell more Indiana assets?

In an unusual move for a national hospital system amid a major restructuring, Ascension disclosed part of its plans. It is not considering offloading or closing any more Indiana operations, an Ascension corporate spokeswoman told IBJ in an email.

The changes to our footprint in other parts of our national ministry are designed to ensure sustainable and favorable options for those communities, the email said. There are no plans to make any such changes to our Indiana ministry.

Several health care consultants said they would be shocked if Ascension sold a large number of properties in Indiana or exited the state altogether, as it has done elsewhere.

I wouldnt just be surprised. I would be totally aghast, said Ed Abel, retired director of health care practice at Indianapolis-based Blue & Co., an accounting and consulting firm. I would just say its never going to happen.

Thats because Indiana is one of the systems most profitable operations, delivering $192million in net income for the system for the fiscal year ending June 30, 2022, the most recent Indiana figures available. The same year, the system as a whole lost $879million from operations.

Translation: Indiana is a moneymaker for Ascension, helping it to fund a huge system that otherwise would be posting much larger losses.

So any further cost-cutting in Indiana would be relatively minor, some experts say.

In general, large health systems are constantly tweaking their portfolios, said David Blish, director of health care consulting for Katz Sapper & Miller, an Indianapolis-based accounting and consulting firm. I doubt Indiana Ascension will contract at a significant scale.

Ascension pointed to its flagship campus on West 86th Street, where construction continues on $325million worth of improvements, including a new brain and spine center, a new womens and childrens tower, and a new parking garage.

The company said the investments will help the companys operations here, known as Ascension St. Vincent Indiana, a premier destination for care in the Midwest.

Separately, Ascension St. Vincent this week issued invitations for a public celebration marking the 50th anniversary of the companys West 86th Street hospital. It said the event will take place 2-4 p.m. April 28 on top of the parking garage at the corner of Harcourt Drive and Katie Knox Drive.

The 50th anniversary of our 86th Street location gives us the opportunity to honor all of those who contributed to making the hospital what it is today as well as look forward to the future of health care, the invitation said.

The event will mark the 1974 move, when staff of St. Vincent and the U.S. Army Reserves transferred 102 patients from the hospitals Fall Creek campus (now part of Ivy Tech Community College) to a new campus on the northwest side of Indianapolis, which was then largely fields and forest.

Twenty-five years later, in 1999, Ascension bought St. Vincent for an undisclosed amount.

That marked the end of more than a century of independent ownership, since four nuns from the Daughters of Charity religious order arrived in Indianapolis in 1881 at the invitation of Catholic Bishop Francis Chatard and set up St. Vincent Infirmary in a house near Vermont and East streets.

Within a few years, the infirmary grew to 50 beds and changed its named to St. Vincent Hospital. It relocated twice before the move to West 86th Street. After decades of expansion, that campus now fills the better part of 20 square blocks between West 86th and West 79th streets.

Ascension said the six-story Women & Childrens Tower going up on the south side of the campus is designed to address the high level of maternal and infant mortality in Indianapolis. It will feature 109 private neonatal intensive care unit rooms along with an expanded pediatric intensive care unit. The tower is scheduled to be completed this year.

The four-story Brain and Spine Hospital is rising at the front of the campus and will include operating rooms, an intensive care unit, an intensive care step-down unit, and a residency training program. Ascension said it expects construction to be completed early next year.

The new projects, announced in 2021, represent one of the largest capital investments in decades for Ascension Indiana. It also gave the strong suggestion that the corporate parent was committed to the Indianapolis flagship, a major anchor on the busy West 86th Street commercial corridor.

So why is Ascension building here while unloading hospitals elsewhere and exiting some states altogether?

In many cases, the answer seems to be that Ascension is leaving where it cannot take advantage of a wide system of community hospitals in coordination with a top-tier hospital to handle complex cases.

In modern health care, hospital systems increasingly want a network of hospitals that can act as feeders for the major hospital in a large metropolitan area. And if they are a small player in a market that is dominated by a huge competitor, they have less chance to fill beds, negotiate favorable insurance plans and make money.

In Minnesota, the world-famous Mayo Clinic dominates the market with net patient revenue of $3.32billion in 2022far ahead of second place University of Minnesota Medical Center, which pulled in $1.68billion.

Who is ever going to beat the Mayo Clinic there? Abel said. Yes, theres a lot of competition up there. But theres a lot that have dropped out and said, Were never going to be as good as those guys.

Central Indiana has no single dominant player. Instead, there are four or five large players and a few dozen small players, mostly in the suburbs. And each system has a different claim to fame.

In the nine-county metropolitan area, Ascension St. Vincent has the most staffed beds, with 1,995, ahead of Indiana University Health (1,514), Community Health Network (1,124), Franciscan Health Network (563) and Eskenazi Health (333), according to IBJ research. (Those figures are from 2022, the most recent year available.)

Yet in the same year, Indiana University Health pulled in far more revenue across its statewide system, $8.1billion, than Ascension St. Vincent ($3.7billion) and Community Health ($3.1billion).

Statewide, Ascension owns 19 hospitals from Anderson to Brazil, including facilities in Carmel, Fishers, Indianapolis, Anderson and Kokomo.

In addition to being a large player, Ascension St. Vincent is performing well financially in central Indiana and has no reason to start offloading assets, Abel said.

Indiana is what I would call an aircraft carrier for Ascension, he said. They have a huge presence here, and theyre proud of it.

And Ascensions corporate leadership clearly has a soft spot for Indiana. The companys CEO, Joseph Impicciche, was raised in Crawfordsville and earned his bachelors at Wabash College. He went on to earn a law degree and a master of health administration degree from Indiana University. He practiced for more than a decade at Indianapolis law firm Hall Render Killian Heath & Lyman, which specializes in health care law.

Ascension declined to make Impicciche or any other senior leader available for an interview with IBJ.

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Ascension health care system retracts nationwidebut not in Indy Indianapolis Business Journal - Indianapolis Business Journal

Man had rare Covid infection that lasted 613 days, showed extensive mutations – South China Morning Post

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Researchers from the Netherlands have reported an extremely long Covid-19 infection in a man who died last year and warn of the emergence of more dangerous variants of the coronavirus.

The elderly man, who was immunocompromised due to previous illnesses, was admitted to a hospital in Amsterdam in February 2022 with a Covid-19 infection, according to a statement.

He was continuously positive for the coronavirus until his death in October 2023 for a total of 613 days.

Other cases of very long infections in people whose immune systems were unable to adequately fight the virus have previously been reported.

01:29

Like drinking milk tea: China launches worlds first inhalable Covid vaccine

Like drinking milk tea: China launches worlds first inhalable Covid vaccine

The researchers led by Magda Vergouwe from the University of Amsterdam plan to present the results at a congress of the European Society for Clinical Microbiology and Infectious Diseases in Barcelona on April 27-30.

The case is also interesting for researchers because the coronavirus can change particularly strongly in such long-term infected people. This harbours the risk of variants of the virus emerging that can more easily overcome the immune systems of healthy people.

The researchers in the Netherlands repeatedly took samples from the man to analyse the genetic material of the coronavirus. They found a total of more than 50 mutations compared to the Omicron variant BA.1 that was circulating at the time, including those that would allow the virus to evade the immune defence.

Just 21 days after the man had received a certain anti-coronavirus drug, the virus also developed signs of resistance to it.

German with comically large number of Covid jabs 217 had no side effects

The man eventually died from a flare-up of one of his previous illnesses. As far as is known, he had not infected anyone with his mutated version of the coronavirus, also known under its scientific name Sars-CoV-2.

This case highlights the risk of new immune-evasive Sars-CoV-2 variants emerging in immunocompromised patients, the researchers are quoted as saying in the press release.

The extensive development of the virus in a single patient could lead to the emergence of unique variants, they warn.

It is important to closely monitor the evolution of the coronavirus in immunocompromised individuals. There is a risk that variants could emerge and spread in society that are less susceptible to the immune systems of healthy people, they added

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Man had rare Covid infection that lasted 613 days, showed extensive mutations - South China Morning Post

Man dies after 613-day COVID-19 infection that underwent 50 mutations – Scripps News

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A new reportby Dutch scientists revealed a very peculiar case: On Feb. 2022, a 72-year-old man with a compromised immune system was admitted to Amsterdam University Medical Center with aCOVID-19infection. The virus in his body proceeded to evolve over the course of 613 days, leading to a highly mutated variant that ultimately killed him.

According to the study, the man, whose identity was not disclosed, suffered from a blood disorder. Despite receiving multiple doses of the SARS-CoV-2 vaccine, his compromised immune system made him unable to generate a detectable antibody response, allowing the virus to continue to evolve into a "novel immune-evasive variant" that had mutated over 50 times. The man died from his underlying blood disorder after fighting COVID for nearly two years, the scientists from the University of Amsterdams Centre for Experimental and Molecular Medicine stated.

This case underscores the risk of persistent SARS-CoV-2 infections in immunocompromised individuals as unique SARS-CoV-2 viral variants may emerge due to extensive intra-host evolution," the study authors stated ina press release. "We emphasize the importance of continuing genomic surveillance of SARS-CoV-2 evolution in immunocompromised individuals with persistent infections given the potential public health threat of possibly introducing viral escape variants into the community.

While the study notes there have been cases in which people have tested positive for COVID-19 for hundreds of days, this case is the longest reported by far. Furthermore, researchers say the rare variant found in this patient hasn't been reported in anyone else, but emphasize the need for more study to protect the public from potential new variants.

The researchers say they plan to further present this study at the European Society of Clinical Microbiology and Infectious Diseases Global Congress in Barcelona, Spain, startingthis weekend.

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Man dies after 613-day COVID-19 infection that underwent 50 mutations - Scripps News

The Longest Case of COVID-19 Lasted 613 Days – Healthnews.com

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For most, COVID-19 symptoms last for a few weeks before passing. New research from the Netherlands finds a patient suffered from the respiratory virus for nearly two years before his death.

A Dutch man with a poor immune system lived with a high-mutated novel variant of COVID-19 for 613 days, according to the University of Amsterdams Centre for Experimental and Molecular Medicine (CEMM). The case is known as the longest bout of COVID-19.

Healthy patients diagnosed with COVID-19 typically recover from mild cases of the virus within a few weeks. However, immunocompromised individuals may develop a persistent infection with increased adverse effects that can evolve such as the Omicron variant, which originated in a patient with a weakened immune system.

A European Society of Clinical Microbiology and Infectious Diseases release says the study led by Magda Vergouwe of the CEMM describes a male patient who was admitted to the Amsterdam University Medical Center in February 2022 due to COVID-19. He was infected with the Omicron SARS-CoV-2 variant BA.1.17.

The patient suffered from myelodysplastic and myeloproliferative overlap syndrome due to a stem cell transplant. In myelodysplastic diseases, immature blood cells in bone barrow do not mature and become healthy blood cells. Meanwhile, myeloproliferative diseases result in a total number of blood cells slow increasing.

This case underscores the risk of persistent SARS-CoV-2 infections in immunocompromised individuals as unique SARS-CoV-2 viral variants may emerge due to extensive intra-host evolution, study authors said. We emphasise the importance of continuing genomic surveillance of SARS-CoV-2 evolution in immunocompromised individuals with persistent infections given the potential public health threat of possibly introducing viral escape variants into the community.

The 72-year-old patient had previously received multiple COVID-19 vaccinations. He was treated with multiple antibody medications without any response and within 21 days, the man developed a mutation that resisted sotrovimab, one of the antibody medications. In the full genome sequencing of the virus that persisted for 613 days, researchers uncovered it had undergone 50 genetic code mutations.

The ESCMID Global release says study authors note there must be a balance between protecting the masses from new variants and providing care for these terminally ill patients. Also, scientists emphasize while there is an increased chance of novel variants in those with weakened immune systems, it is not the case for each patient.

The duration of SARS-CoV-2 infection in this described case is extreme, but prolonged infections in immunocompromised patients are much more common compared to the general community. Further work by our team includes describing a cohort of prolonged infections in immunocompromised patients from our hospital with infection durations varying between 1 month and 2 years.

The complete research of this unique COVID-19 case will be presented at the ESCMID Global Congress in Barcelona which runs from April 27-30.

The U.S. Centers for Disease Control and Prevention (CDC) updated its COVID-19 guidelines in March, no longer recommending isolation following a positive test. Those who are infected should wear a high-quality mask or respirator when around others, monitor symptoms, and contact a healthcare provider for possible treatments. The CDC reported 6,406 COVID-19 hospitalizations last week, a 13.8% drop.

However, COVID-19 can still be a threat to those with weak immune systems like the 72-year-old Dutch man. The CDC highlights those who are immunocompromised have lesser defenses against infections. Those six months and older who are moderately to severely immunocompromised are recommended to receive at least one dose of the updated 2023-24 COVID-19 vaccine.

The CDC says people with weakened immune symptoms may reach out to their healthcare provider for possible antiviral medications. Recovering from COVID-19 for immunocompromised patients may take longer than the normal few weeks

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The Longest Case of COVID-19 Lasted 613 Days - Healthnews.com

Toxic: How the search for the origins of COVID-19 turned politically poisonous – El Paso Inc.

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BEIJING (AP) The hunt for the origins of COVID-19 has gone dark in China, the victim of political infighting after a series of stalled and thwarted attempts to find the source of the virus that killed millions and paralyzed the world for months.

The Chinese government froze meaningful domestic and international efforts to trace the virus from the first weeks of the outbreak, despite statements supporting open scientific inquiry, an Associated Press investigation found. That pattern continues to this day, with labs closed, collaborations shattered, foreign scientists forced out and Chinese researchers barred from leaving the country.

The investigation drew on thousands of pages of undisclosed emails and documents and dozens of interviews that showed the freeze began far earlier than previously known and involved political and scientific infighting in China as much as international finger-pointing.

As early as Jan. 6, 2020, health officials in Beijing closed the lab of a Chinese scientist who sequenced the virus and barred researchers from working with him.

Scientists warn the willful blindness over coronavirus origins leaves the world vulnerable to another outbreak, potentially undermining pandemic treaty talks coordinated by the World Health Organization set to culminate in May.

At the heart of the question is whether the virus jumped from an animal or came from a laboratory accident. A U.S. intelligence analysis says there is insufficient evidence to prove either theory, but the debate has further tainted relations between the U.S. and China.

Unlike in the U.S., there is virtually no public debate in China about whether the virus came from nature or from a lab leak. In fact, there is little public discussion at all about the source of the disease, first detected in the central city of Wuhan.

Crucial initial efforts were hampered by bureaucrats in Wuhan trying to avoid blame who misled the central government; the central government, which muzzled Chinese scientists and subjected visiting WHO officials to stage-managed tours; and the U.N. health agency itself, which may have compromised early opportunities to gather critical information in hopes that by placating China, scientists could gain more access, according to internal materials obtained by AP.

In a faxed statement, China's Foreign Ministry defended Chinas handling of research into the origins, saying the country is open and transparent, shared data and research, and made the greatest contribution to global origins research. The National Health Commission, China's top medical authority, said the country invested huge manpower, material and financial resources and has not stopped looking for the origins of the coronavirus.

It could have played out differently, as shown by the outbreak of SARS, a genetic relative of COVID-19, nearly 20 years ago. China initially hid infections then, but WHO complained swiftly and publicly. Ultimately, Beijing fired officials and made reforms. The U.N. agency soon found SARS likely jumped to humans from civet cats in southern China and international scientists later collaborated with their Chinese counterparts to pin down bats as SARS natural reservoir.

But different leaders of both China and WHO, Chinas quest for control of its researchers, and global tensions have all led to silence when it comes to searching for COVID-19s origins. Governments in Asia are pressuring scientists not to look for the virus for fear it could be traced inside their borders.

Even without those complications, experts say identifying how outbreaks begin is incredibly challenging and that its rare to know with certainty how some viruses begin spreading.

Its disturbing how quickly the search for the origins of (COVID-19) escalated into politics, said Mark Woolhouse, a University of Edinburgh outbreak expert. Now this question may never be definitively answered.

Secrecy clouds the beginning of the outbreak. Even the date when Chinese authorities first started searching for the origins is unclear.

The first publicly known search for the virus took place on Dec. 31, 2019, when Chinese Center for Disease Control scientists visited the Wuhan market where many early COVID-19 cases surfaced.

However, WHO officials heard of an earlier inspection of the market on Dec. 25, 2019, according to a recording of a confidential WHO meeting provided to AP by an attendee. Such a probe has never been mentioned publicly by either Chinese authorities or WHO.

In the recording, WHOs top animal virus expert, Peter Ben Embarek, mentioned the earlier date, describing it as an interesting detail. He told colleagues that officials were looking at what was on sale in the market, whether all the vendors have licenses (and) if there was any illegal (wildlife) trade happening in the market.

A colleague asked Ben Embarek, who is no longer with WHO, if that seemed unusual. He responded that it was not routine, and that the Chinese must have had some reason to investigate the market. Well try to figure out what happened and why they did that.

Ben Embarek declined to comment. Another WHO staffer at the Geneva meeting in late January 2020 confirmed Ben Embareks comments.

The Associated Press could not confirm the search independently. It remains a mystery if it took place, what inspectors discovered, or whether they sampled live animals that might point to how COVID-19 emerged.

A Dec. 25, 2019, inspection would have come when Wuhan authorities were aware of the mysterious disease. The day before, a local doctor sent a sample from an ill market vendor to get sequenced that turned out to contain COVID-19. Chatter about the unknown pneumonia was spreading in Wuhans medical circles, according to one doctor and a relative of another who declined to be identified, fearing repercussions.

A scientist in China when the outbreak occurred said they heard of a Dec. 25 inspection from collaborating virologists in the country. They declined to be named out of fear of retribution.

WHO said in an email that it was not aware of the Dec. 25 investigation. It is not included in the U.N. health agencys official COVID-19 timeline.

When health officials from Beijing arrived in Wuhan on Dec. 31, they decided to disinfect the market before collecting samples, destroying critical information about the virus. Gao Fu, head of the China CDC, mentioned it to an American collaborator.

His complaint when I met him was that all the animals were gone, said Columbia University epidemiologist Ian Lipkin.

Robert Garry, who studies viruses at Tulane University, said a Dec. 25 probe would be hugely significant, given what is known about the virus and its spread.

Being able to swab it directly from the animal itself would be pretty convincing and nobody would be arguing about the origins of COVID-19, he said.

But perhaps local officials simply feared for their jobs, with memories of firings after the 2003 SARS outbreak still vivid, said Ray Yip, the founding head of the U.S. Centers for Disease Control and Prevention outpost in China.

They were trying to save their skin, hide the evidence, Yip said.

The Wuhan government did not respond to a faxed request for comment.

Another early victim was Zhang Yongzhen, the first scientist to publish a sequence of the virus. A day after he wrote a memo urging health authorities to action, Chinas top health official ordered Zhangs lab closed.

They used their official power against me and our colleagues, Zhang wrote in an email provided to AP by Edward Holmes, an Australian virologist.

On Jan. 20, 2020, a WHO delegation arrived in Wuhan for a two-day mission. China did not approve a visit to the market, but they stopped by a China CDC lab to examine infection prevention and controlprocedures, according to an internal WHO travel report. WHOs then-China representative, Dr. Gauden Galea, told colleagues in a private meeting that inquiries about COVID-19s origins went unanswered.

There are a few cadres who have performed poorly, President Xi Jinping said in unusually harsh comments in February. Some dare not take responsibility, wait timidly for orders from above, and dont move without being pushed.

The government opened investigations into top health officials, according to two former and current China CDC staff and three others familiar with the matter. Health officials were encouraged to report colleagues who mishandled the outbreak to Communist Party disciplinary bodies, according to two of the people.

Some people both inside and outside China speculated about a laboratory leak. Those suspicious included right-wing American politicians, but also researchers close to WHO.

The focus turned to the Wuhan Institute of Virology, a high-level lab that experimented with some of the worlds most dangerous viruses.

In early February 2020, some of the Wests leading scientists, headed by Dr. Jeremy Farrar, then at Britains Wellcome Trust, and Dr. Anthony Fauci, then director of the U.S. National Institutes of Health, banded together to assess the origins of the virus in calls, a Slack channel and emails.

They drafted a paper suggesting a natural evolution, but even among themselves, they could not agree on the likeliest scenario. Some were alarmed by features they thought might indicate tinkering.

There have (been) suggestions that the virus escaped from the Wuhan lab, Holmes, the Australian virologist, who believed the virus originated in nature, wrote in a Feb. 7, 2020, email. I do a lot of work in China, and I can (assure) you that a lot of people there believe they are being lied to.

American scientists close to researchers at the Wuhan Institute of Virology warned counterparts there to prepare.

James DeLuc, head of a Texas lab, emailed his Wuhan colleague on Feb. 9, 2020, saying hed already been approached by U.S. officials. Clearly addressing this will be essential, with any kind of documentation you might have, he wrote.

The Chinese government was conducting its own secret investigation into the Wuhan Institute. Gao, the head of the China CDC, and another Chinese health expert revealed its existence in interviews months and years later. Both said the investigation found no evidence of wrongdoing, which Holmes, the Australian virologist, also heard from another contact in China. But Gao said even he hadn't seen further details, and some experts suspect they may never be released.

WHO started negotiations with China for a second visit with the virus origins in mind, but it was Chinas Foreign Ministry that decided the terms.

Scientists were sidelined and politicians took control. China refused a visa for Ben Embarek, then WHOs top animal virus expert. The itinerary dropped nearly all items linked to an origins search, according to draft agendas for the trip obtained by the AP. And Gao, the China CDC head who is also a respected scientist tasked with investigating the origins, was left off the schedule.

Instead, Liang Wannian, a politician in the Communist Party hierarchy, took charge of the international delegation. Liang is an epidemiologist close to top Chinese officials and China's Foreign Ministry who is widely seen as pushing the party line, not science-backed policies, according to nine people familiar with the situation who declined to be identified to speak on a sensitive subject.

Most of the WHO delegation was not allowed to go to Wuhan, which was under lockdown. The few who did learned little. They again had no access to the Wuhan Institute of Virology or the wildlife market and obtained only scant details about China CDC efforts to trace the coronavirus there.

On the train, Liang lobbied the visiting WHO scientists to praise Chinas health response in their public report. Dr. Bruce Aylward, a senior adviser to WHO Director-General Tedros Adhanom Ghebreyesus, saw it as the best way to meet Chinas need for a strong assessment of its response.

The new section was so flattering that colleagues emailed Aylward to suggest he dial it back a bit.

It is remarkable how much knowledge about a new virus has been gained in such a short time, read the final report, which was reviewed by Chinas top health official before it went to Tedros.

As criticism of China grew, the Chinese government deflected blame. Instead of firing health officials, they declared their virus response a success and closed investigations into the officials with few job losses.

There were no real reforms, because doing reforms means admitting fault, said a public health expert in contact with Chinese health officials who asked not to be identified because of the sensitivity of the matter.

In late February 2020, the internationally respected doctor Zhong Nanshan appeared at a news conference and said that the epidemic first appeared in China, but it did not necessarily originate in China.

Chinese officials told WHO that blood tests on lab workers at the Wuhan Institute of Virology were negative, suggesting they hadnt been previously infected with bat coronaviruses. But when WHO pressed for an independent audit, Chinese officials balked and demanded WHO investigate the U.S. and other countries as well.

By the time WHO led a third visit to Wuhan in January 2021, a year into the pandemic, the atmosphere was toxic.

Liang, the Chinese health official in charge of the first two WHO visits, continued to promote the questionable theory that the virus was shipped into China on frozen food. He suppressed information suggesting it could have come from animals at the Wuhan market, organizing market workers to tell WHO experts no live wildlife was sold and cutting recent photos of wildlife at the market from the final report. There was heavy political scrutiny, with numerous Chinese officials who werent scientists or health officers present at meetings.

Despite a lack of direct access, the WHO team concluded that a lab leak was extremely unlikely. So it came as an infuriating surprise to Chinese officials when, months later, WHO chief Tedros said all origins hypotheses, including the lab leak theory, remained on the table.

China told WHO any future missions to find COVID-19 origins should be elsewhere, according to a letter obtained by AP. Since then, global cooperation on the issue has ground to a halt; an independent group convened by WHO to investigate the origins of COVID-19 in 2021 has been stymied by the lack of cooperation from China and other issues.

Chinese scientists are still under heavy pressure, according to 10 researchers and healthofficials. Researchers who published papers on the coronavirus ran into trouble with Chinese authorities. Others were barred from travel abroad for conferences and WHO meetings. Gao, the China CDC director, was investigated after U.S. President Joe Biden ordered a review of COVID-19 data, and again after giving interviews on the virus origins.

New evidence is treated with suspicion. In March 2023, scientists announced that genetic material collected from the market showed raccoon dog DNA mixed with COVID-19 in early 2020, data that WHO said should have been publicly shared years before. The findings were posted, then removed by Chinese researchers with little explanation.

The head of the China CDC Institute of Viral Disease was forced to retire over the release of the market data, according to a former China CDC official who declined to be named to speak on a sensitive topic.

It has to do with the origins, so theyre still worried, the former official said. If you try and get to the bottom of it, what if it turns out to be from China?

Other scientists note that any animal from which the virus may have originally jumped has long since disappeared.

There was a chance for China to cooperate with WHO and do some animal sampling studies that might have answered the question, said Tulane Universitys Garry. The trail to find the source has now gone cold.

Cheng reported from Geneva.

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Toxic: How the search for the origins of COVID-19 turned politically poisonous - El Paso Inc.

SpaceX leads the crusade against the NLRB as its head calls major employers ‘lawbreakers’ – Fortune

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In a galaxy not so far away, the National Labor Relations Board (NLRB) strikes back. The independent federal agency, which safeguards the rights of employees and investigates violations of the National Labor Relations Act, is taking on a legion of billion-dollar corporations.

SpaceX, Starbucks, Amazon, and Trader Joes have all taken swipes at the NLRB as of late. SpaceX has led the charge with an I know you are but what am I approach to allegations of union-busting by claiming the agency is unconstitutional.

Jennifer Abruzzo, acting general counsel of the NLRB as appointed by President Joe Biden, isnt standing down to these corporate entities, and called out their legal tactics during a panel hosted by the Roosevelt Institute last week.

A growing number of deep-pocket, low-road employers are jumping on the bandwagon, seeking preliminary injunctions in courts, solely to slow [us] down or prevent us from engaging in our enforcement actions against them because they have the money to do so, she said.

These legal tactics are distractions to divert attention away from the fact that they are actually lawbreakers who need to be held accountable in a timely manner, she added.

Abruzzo described a back-and-forth thats not unlike a David and Goliath story, if Goliath was simply trying to run out the clock and leave David high and dry.

The NLRB isnt deterred, though, despite limited resources and a deluge of unfair labor practice filings amid heightened strike activity. There is no way were going to succumb, Abruzzo said, adding that the board will continue to call out companies where it sees fiteven among challenges to its very existence.

The main challenger of the NLRB, SpaceX, began its campaign against the federal branch earlier this year. Just one day after the NLRB issued a complaint against the astronautics company on Jan. 3, SpaceX sued the board in the Southern District of Texas, asserting that the institutions structure was unconstitutional. A judge subsequently opened the SpaceX hearing in March, with a case expected to be heard starting in May.

Amazon, Starbucks and Trader Joes followed suit in the companys crusade against the almost 90-year-old institution, Abruzzo said Friday. These esoteric legal arguments came about, why? Because we dared to issue a complaint against SpaceX after it unlawfully fired eight workers for speaking up about their workplace concerns, she said.

SpaceXs pushback and suing of the organization seems much more an ideological debate than how most employers handle it, Matthew Bodie, a labor law professor at the University of Minnesota who was a previous field attorney at the NLRB, told Fortunes Jessica Mathews this past March. It just seems like more of a crusade, almost, than a rational economic response to litigation.

While SpaceX is leading the charge, other large employers have eagerly taken up the same argument. Trader Joes argued that the board, in its current form, shouldnt exist during a hearing in January over alleged unfair treatment of workers at its Hadley, Mass., storeits first in the nation to unionize.

The National Labor Relations Act as interpreted and/or applied in this matter, including but not limited to the structure and organization of the the National Labor Relations Act Board and the Agencys administrative law judges is unconstitutional, Trader Joes attorney, Christopher Murphy, said in January, according to a transcript first obtained by HuffPost.

Im certainly not going to be ruling on my own constitutionality anytime soon, quipped Administrative Law Judge Charles Muhl. Youll have to take that up with the Board and with the federal courts.

Trader Joesanother of the companies taking aim at the NLRBtold Fortune the company has not filed or joined any lawsuit that challenges the constitutionality of the NLRBs administrative law judge system or seeks to dismantle any aspect of the NLRB. It added that its statement during the January hearing was an affirmative defense, which was not an argument; it was an opportunity to preserve all of our legal rights under the law.

Amazon raised a similar argument in a case regarding the only Amazon warehouse to successfully unionize, in Staten Island, N.Y. Starbucks did the same in a post-hearing brief about some of its stores. Starbucks, however, has now distanced itself from Elon Musks raging brainchild. Starbucks has not joined a lawsuit against the NLRB questioning its constitutionality or initiated similar litigation against the NLRB, the company told Fortune, linking to a statement. As of March, the coffee conglomerate has 741 open or settled NLRB cases, according to the Economic Policy Institutealthough the coffee chain recently reversed itself and pledged to negotiate with its unionized workers.

Amazon did not respond to Fortunes request for comment.

Legalese aside, these major employers have been part of the ranks of companies answering charges of labor complaints by pointing the finger back at the NLRB. Whether or not they have called the NLRB unconstitutional or simply implied it, these employers are joining the Republican-backed charge against one of the only federal safeguards of workers rights.

But these corporate titans crusade isnt meeting meek soldiers. We are not going to stop despite these challenges, said Abruzzo, noting that the NLRB is the only federal agency guarding the rights of workers to unionize. During a time of workers discontent, billion-dollar companies are seemingly attempting to make one of the few checks to their power go broke.

It seems to me they would rather spend their money initiating court litigation rather than improving their workers lives and their own workplace operations, said Abruzzo. She added the main goal is to divert our scarce resources away from protecting workers rights to organize and to fight for recognition and respect for the value that they add to their employers operations. And that is not going to happen.

The NLRB isnt just twiddling its thumbs until it gets its day in court; rather, it appears to be fueled more than ever to tackle these companies and workplace violations.But Abruzzo conceded the companies efforts to draw attention to the NLRB are having an effect.

Frankly, that strategy is working, she said. Theres a lot of public reporting about the challenges as opposed to the law breaking.

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SpaceX leads the crusade against the NLRB as its head calls major employers 'lawbreakers' - Fortune

Can psychedelics treat people with a severe brain injury? – National Geographic

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Ultimately, the logic driving these scientific initiatives is the correlation that exists between brain complexity and conscious level. But correlation is not causation, and its possible that the rise in complexity seen when under the influence of psychedelics is actually pointing to brain activity unrelated to growing conscious awareness, says Anil Seth, professor of computational neuroscience at the University of Sussex, and investigator on the 2017 study.

For example, it could be capturing the multi-sensorial richness of their experience during the trip, the random firing of neurons, or unwanted, reflexive bodily movements.

Theres many missing knowledge gaps, says Seth.

Still, the results led scientists to wonder: could psychedelics ability to boost complexity levels be used to awaken patients with disorders of consciousness?

For David, there was only one way to find out.

On August 25, 2023, exactly 336 days following Sarahs tragic accident, David, who is based in Colorado where psychedelic mushrooms are decriminalized, obtained a tincture of distilled liquid psilocybin. He had already given Sarah low and moderate doses of the drug over the course of several months and it had a remarkable" affect in her bodily movements.

This time, however, he would go all in, using the equivalent of 2.5 gramsa dose high enough to provoke a powerful psychedelic experience and which is often used in clinical trials for therapeutic purposes. At this dose, both Gosseries and Carhart-Harris said an awakening was theoretically possible.

The legalities of what David was about to do were unclear. Colorados decriminalization of certain psychedelics in 2022 means that psilocybin is easy to access and magic mushrooms can be grown and consumed. But whether David was crossing a line by giving Sarah the drug, when she could not consent, was not obvious.

David felt that if there was even a slim chance that psychedelics could awaken Sarah, he would take the risk.

Sarah sat in her wheelchair and wore a helmet-like headset with cables sprouting out of the back of her head, feeding into a laptop. The headset, a commercial-grade piece of equipment called a WAVi, measured the electrical activity from her brain and was going to be recorded and analyzed by Frank Palermo, medical director of the Colorado-based company, WAVi Co., which focuses on medical equipment manufacturing. Palermo also describes himself as a physiatrist specializing in neurorehabilitation, as he does in a video of him posted on Neurologic Life, a company that markets medical devices, including WAVi.

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Can psychedelics treat people with a severe brain injury? - National Geographic

Judicial watchdog wants metro Atlanta judge off the bench – The Atlanta Journal Constitution

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Douglas Countys probate judge should be removed from office in response to a host of ethics charges, a panel of the Georgia Judicial Qualifications Commission has said in a report.

Christina Peterson, who became a probate judge in an uncontested November 2020 election, has been fighting the ethics charges since they were filed by the director of the states judicial watchdog in July 2021. At one point, Peterson faced 50 separate charges accusing her of violating the Georgia Code of Judicial Conduct, but 20 have been withdrawn or dismissed.

Peterson, a University of Georgia School of Law graduate who practiced as an attorney for several years before taking the bench, was accused of inappropriate social media posts, unnecessarily jailing and fining a woman who sought to amend her marriage license and letting wedding participants into Douglas Countys courthouse after hours without permission. She was also abusive toward a fellow judge and other county officials, obstructed access to public records and had improper contact with a litigant, among other things, the judicial commission alleged.

(Petersons) actions demonstrate a troubling pattern of ineptitude and misconduct, the panel wrote in a 54-page report Sunday. She is not fit to serve.

The Georgia Supreme Court will decide whether Peterson remains on the bench.

Petersons attorney, Lester Tate, said they reject the panels recommendation and look forward to arguing the case before the court.

Throughout the ethics case, Peterson has said that she has faced unfair criticism as the first Black probate judge in Douglas County. During a trial before the commission panel last year, Peterson admitted to making mistakes in her first year as a judge while learning the ropes and said she was trying to do better.

Peterson acknowledged that it was harsh of her to jail and fine the woman who sought, without an attorney, to amend her marriage license in 2021. She also expressed regret about sending an April 2021 email to David Emerson, who at the time was the chief judge of the Douglas County Superior Court, questioning his judicial authority and competency, records show.

The commission, which is tasked with investigating complaints of judicial misconduct, has twice sought Petersons suspension. Both requests were denied by the state Supreme Court.

In its report, the panel said Peterson had been disingenuous, if not outright dishonest, during the investigation process. It said her testimony during last years trial was untruthful and evasive.

This persistent unwillingness to apply to herself the rules that apply to everyone else is deeply troubling, the panel said. Moreover, she has demonstrated a steadfast unwillingness to accept moral accountability in nearly all the episodes of misconduct.

Given Petersons stance that the ethics case against her has been unfair, biased and intentionally obstructive to her career, no sanction less than removal from office will have a meaningful impact, the panel said.

(Petersons) actions in the courtroom and outside it demonstrate a consistent and persistent pattern of misconduct comprised of intemperance, judicial incompetence, and danger to the rights of litigants, it said. And so she must go.

Courtney Veal, the commission director who has led the ethics case against Peterson, said the panels report speaks for itself. Veal said she looks forward to a final ruling by the state Supreme Court.

Peterson and Veal have 20 days to file responses to the panels report. Its unclear when the court will make a decision.

Peterson has qualified for reelection this year as Douglas Countys probate judge. She is being challenged in the Democratic primary in May by Douglasville attorney Valerie Vie. No Republican candidates have qualified in the race.

After becoming a lawyer in 2013, Peterson worked at a private law firm then as a prosecutor in Douglas and Fulton counties, records show. She had no prior experience as a judge.

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Judicial watchdog wants metro Atlanta judge off the bench - The Atlanta Journal Constitution

Ranching of tomorrow: Smooth Ag bringing robotics to ranchers with autonomous Ranch Rover – Graham Leader

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By automating the cattle feeding process the Graham-based company Smooth Ag is looking to bring the innovation of robotics to ranchers through its autonomous Ranch Rover vehicle.

The Ranch Rover was the creation of fourth-generation rancher River McTasney who had the agricultural lifestyle ingrained in his bones at a young age growing up on a 3,000-acre ranch while tending 120 head of cattle.

I went to school at Paint Creek High School, an agriculture community. Most of us kids there grew up working on our own stuff. We have a mechanical skill set from that lifestyle that really equips us with the problem solving skills that I think a lot of people from outside of the rural community may not quite get, McTasney said. ...So that problem solving skill set really helped with this later on down the road.

Following high school, McTasney attended Texas A&M University and graduated in 2018 with a degree in construction management. He worked for a year in College Station in sales for an HVAC company before deciding he wanted a break and moved back to his family ranch.

I was feeding cows and I was like, Theres got to be a better way to do this. ...Being one of the only able-bodied people on the ranch to do other stuff, there was other stuff I needed to get done instead of spending three hours a day in the feed pickup, he said. I started tinkering with different ideas and finally decided that a mobile platform, just like a feed pickup without the driver, was the best way to do it.

McTasney learned to code with the intention of making the dream of the Ranch Rover a reality. Over the next two years he built a conceptual machine on an old pickup truck frame and eventually moved up to the current prototype.

It has a 4,000-pound payload. Its GPS waypoint navigation fused with machine vision, so its completely autonomous. They have the ability to set routes and then with those routes set individual feed missions... and those are on a timer, he said. You can schedule them however you like, you can pick your feed locations (and) pick how much youre going to feed at each of those feed locations.

The rover has data-driven decision making which McTasney said can provide owners information for planning.

Theres a lot of data collection involved as well thats going to be extremely valuable. With computer vision its one of those things that is hard to see, but the way technological advancements are working out right now computer vision is getting amazing, he said. The type of data that were going to be able to directly feed back to the customer based off of that is actually going to be really insane. Its going to be very valuable. So thats just one of the perks of solving a problem directly is we get to put up those various sensors and cameras on this thing and kind of knock out two birds with one stone.

Around a year-and-half ago McTasney connected with representatives from Graham to see if they wanted to be involved with making the city a home base for the project. The site was also something McTasney wanted due to having land close.

We have land in Caddo as well... just East of Breckenridge. I wanted to stay around home because we do have obligations to the ranch. ...Graham is just a great community, too, he said. ...Whenever youre doing something like this, youre really grabbing everything you can to stay motivated and keep doing it and so you really want to be surrounded and supported by a community that believes in success, beliefs in new things. I think Graham did a really good job of displaying that and really got me roped in.

The company has a 4,000 square foot shop located on Rocky Mound Road in Graham and has expanded to a three-man team internally.

The company has $400,000 in the sales pipeline for orders and will be delivering its first vehicle to Oklahoma State University next week. The team has been busy showcasing the rover, most recently at the Texas and Southwestern Association Convention at the end of March.

The response has been incredible. We picked up three more customers there in one day. Thats without having any inventory, which is a really neat thing, he said. These guys know... its going to be a while there. They got about a six month lead time. So that in itself, getting people to sign a letter of intent saying that theyre going to buy one as we produce, thats... a very validated customer and a very convicted customer. So they believe in us, they really like what were doing. This is something they feel can be very useful and beneficial in their operation.

McTasney said the rover is tailoring to the actual needs of cattle ranches which is assisting with the labor shortage. While the company is focused on the Ranch Rover for pasture land for open range cow/calf operations, they plan to address another need with a feedlot machine within the next 18 months.

(Theres) a huge demand in feedlots. Thats a much bigger machine mechanically... so well focus on Ranch Rover, this pasture land model, to grow those sales numbers to continue to prove validation for investors, he said. Well move sometime in the next one-to-two years to building out a much larger machine built specifically for feedlots, which is going to be a real enterprise as this is new technology for them as well. And thats a huge labor burden, compared to the pasture land.

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Ranching of tomorrow: Smooth Ag bringing robotics to ranchers with autonomous Ranch Rover - Graham Leader

Universities build their own ChatGPT-like AI tools – Inside Higher Ed

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When ChatGPT debuted in November 2022, Ravi Pendse knew fast action was needed. While the University of Michigan formed an advisory group to explore ChatGPTs impact on teaching and learning, Pendse, UMichs chief information officer, took it further.

Months later, before the fall 2023 semester, the university launched U-M GPT, a homebuilt generative AI tool that now boasts between 14,000 to 16,000 daily users.

A report is great, but if we could provide tools, that would be even better, Pendse said, noting that Michigan is very concerned about equity. U-M GPT is all free; we wanted to even the playing field.

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The University of Michigan is one of a small number of institutions that have created their own versions of ChatGPT for student and faculty use over the last year. Those include Harvard University, Washington University, the University of California, Irvine and UC San Diego. The effort goes beyond jumping on the artificial intelligence (AI) bandwagonfor the universities, its a way to overcome concerns about equity, privacy and intellectual property rights.

We need to talk about AI for good of course, but lets talk about not creating the next version of the digital divide.

Students can use OpenAIs ChatGPT and similar tools for everything from writing assistance to answering homework questions. The newest version of ChatGPT costs $20 per month, while older versions remain free. The newer models have more up-to-date information, which could give students who can afford it a leg up.

That fee, no matter how small, creates a gap unfair to students, said Tom Andriola, UC Irvines chief digital officer.

Do we think its right, in who we are as an organization, for some students to pay $20 a month to get access to the best [AI] models while others have access to lesser capabilities? Andriola said. Principally, it pushes us on an equity scale where AI has to be for all. We need to talk about AI for good of course, but lets talk about not creating the next version of the digital divide.

UC Irvine publicly announced their own AI chatbotdubbed ZotGPTon Monday. Deployed in various capacities since October 2023, it remains in testing and is only available to staff and faculty. The tool can help them with everything from creating class syllabi to writing code.

Offering their own version of ChatGPT allows faculty and staff to use the technology without the concerns that come with OpenAIs version, Andriola said.

When we saw generative AI, we said, We need to get people learning this as fast as possible, with as many people playing with this that we could, he said. [ZotGPT] lets people overcome privacy concerns, intellectual property concerns, and gives them an opportunity of, How can I use this to be a better version of myself tomorrow?

That issue of intellectual property has been a major concern and a driver behind universities creating their own AI tools. OpenAI has not been transparent in how it trains ChatGPT, leaving many worried about research and potential privacy violations.

Albert Lai, deputy faculty lead for digital transformation at Washington University, spearheaded the launch of WashU GPT last year.

WashUalong with UC Irvine and University of Michiganbuilt their tools using Microsofts Azure platform, which allows users to integrate the work into their institutions applications. The platform uses open source software available for free. In contrast, proprietary platforms like OpenAIs ChatGPT have an upfront fee.

A look at WashU GPT, a version of Washington Universitys own generative AI platform that promises more privacy and IP security than ChatGPT.

Provided/Washington University

There are some downsides when universities train their own models. Because a universitys GPT is based on the research, tests and lectures put in by an institution, it may not be as up-to-date as the commercial ChatGPT.

But thats a price we agreed to pay; we thought about privacy, versus what were willing to give up, Lai said. And we felt the value in maintaining privacy was higher in our community.

To ensure privacy is kept within a universitys GPT, Lai encouraged other institutions to ensure any Microsoft institutional agreements include data protection for IP. UC Irvine and UMichigan also have agreements with Microsoft that any information put into their GPT models will stay within the university and not be publicly available.

Weve developed a platform on top of [Microsofts] foundational models to provide faculty comfort that their IP is protected, Pendse said. Any faculty memberincluding myselfwould be very uncomfortable in putting a lecture and exams in an OpenAI model (such as ChatGPT) because then its out there for the world.

Once you figure out the secret sauce, its pretty straightforward.

It remains to be seen whether more universities will build their own generative AI chatbots.

Consulting firm Ithaka S+R formed a 19-university task force in September dubbed Making AI Generative for Higher Education to further study the use and rise of generative AI. The task force members include Princeton University, Carnegie Mellon University and the University of Chicago.

Lai and others encourage university IT officials to continue experimenting with what is publicly available, which can eventually morph into their own versions of ChatGPT.

I think more places do want to do it and most places havent figured out how to do it yet, he said. But frankly, in my opinion, once you figure out the magic sauce its pretty straightforward.

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Universities build their own ChatGPT-like AI tools - Inside Higher Ed

ChatGPT: student chatbot use ‘increasing loneliness’ – Times Higher Education

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Universities should exercise caution as they outsource more functions to artificial intelligence (AI), according to the authors of a study that links student usage of ChatGPT to loneliness and a reduced sense of belonging.

Australian researchers surveyed 387 university students in different parts of the globe to seek to understand the less understood side effects of the rapid uptake of the OpenAI tool since itslaunch in November 2022.

They found evidence that while AI chatbots designed for information provision may be associated with student performance, when social support, psychological well-being, loneliness and sense of belonging are considered it has a net negative effect on achievement, according to the paper published inStudies in Higher Education.

Alongside ChatGPT which is primarily used by students for help with academic tasks universitieshave adopted a range of chatbotsto help with other processes, including in admissions and student support.

It seems students may be seeking out AI help instead of librarians, student advisers and counsellors, and this means universities have no visibility from a whole-of-student continuity of care perspective, said Joseph Crawford, a senior lecturer in management at the University of Tasmania and one of the authors of the study.

Universities could save money deploying these tools at the expense of students spending time building their social skills and social capital.

The study found that students who reported using ChatGPT more displayed some evidence of feeling socially supported by the AI, explained Dr Crawford, who worked on thepaper with Kelly-Ann Allen and Bianca Pani, both of Monash University, and Michael Cowling, based at Central Queensland University.

But the paper also shows that increased chatbot usage led to human relationships weakening possibly without users even realising.

Those who got their support from friends and family reported reduced loneliness, higher grade performance and were less willing to leave universitythan those who reported being socially supported by the AI.

Dr Crawford said it was still not completely clear whether AI use causes lower performance, or whether students experiencing lower performance turn more often to AI.

But he recommended that universities should find ways to promote peer networks, social opportunities for students and other ways of building social connections as a way of insulatingthem from some of the more negative effects of AI use.

tom.williams@timeshighereducation.com

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ChatGPT: student chatbot use 'increasing loneliness' - Times Higher Education

‘Digital twins’ project will help clean up space junk, repair and decommission spacecrafts – University of California

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Imagine Earth from space: a blue marble, a pristine orb that is our one and only home. But like many other places on the planet itself, this view is littered with the evidence of humans: in the earths orbit floats more than 30,000 individual pieces of space debris larger than 10 cm, according to a 2023 report from the European Space Agency.

A new project led by Ricardo Sanfelice, UC Santa Cruz Professor and Department Chair of Electrical and Computer Engineering, will develop technology for better spacecraft that use complex robotics to clean up space debris, as well as repair, refuel and decommission other spacecraft. A research team will create highly detailed digital twin models of spacecraft that can carry out these complex tasks in space and develop next-generation control algorithms to manipulate those models, enabling experimentation without the costs of testing on the physical system.

Sanfelice and his research team have been awarded $2.5 million from the Air Force Office of Scientific Research (AFOSR) Space University Research Initiative (SURI) for this three-year project. Co-principal investigators include UC Santa Cruz Professor of Applied Mathematics Daniele Venturi, UT Austin Professor of Aerospace Engineering Karen Wilcox, and University of Michigan Professor of Aerospace Engineering Ilya Kolmanovsk; and the team will collaborate with government and industry partners including the Air Force Research Lab Space Vehicles Directorate, The University of Arizona, Raytheon Technologies, Trusted Space, Inc., and Orbital Outpost X.

A digital twin is a computer model of a physical system, designed to perfectly mimic the properties of the real-world object, including all of the instruments, computers, sensors, surrounding environment, and anything else the system might include. Digital twins enable researchers to conduct experiments and run analysis in the digital world, testing what concepts might work in the real world to determine if they are worth building and manufacturing.

Unlike more traditional simulations, digital twins often incorporate machine learning that allows the system to improve itself through experimentations, providing valuable iteration to build a more accurate and detailed system.

Digital twins can be useful in a range of engineering disciplines, but are particularly relevant for aerospace engineering where the costs associated with building the real systems are so high.

You can accelerate your production, you can reduce time and costs and risk of spacecraft design because spacecraft technology is very expensive and requires a lot of certification and regulation before they can go into space, Sanfelice said. Rather than performing those experiments which take a lot of time in the real world, with a digital twin you can do conceptual analysis and initial validation in the computer environment. This same logic extends to other complex and costly systems its all about scale and reduction of production time, cost, and risk while maintaining system performance and safety.

Digital twins are also especially useful for aerospace engineering because they allow engineers to test complex scenarios and so-called corner cases, situations where multiple parameters are at their extreme, within the realm of the computer. Highly complex and extreme situations are more likely to occur in the harsh conditions of space, and cant be fully replicated for experimentation back on Earth.

The models will enable the researchers to deeply examine what is necessary to carry out the highly complex tasks of clearing up space debris and using a spacecraft to refuel, repair, or demission other spacecraft. Such tasks could include a situation where a robotic arm on one spacecraft is trained to grab another spacecraft that is malfunctioning and tumbling through space, potentially damaging one or both of the systems. The researchers need to teach the computers to handle the tumbling and steering, developing optimization-based techniques to quickly compute and solve unexpected problems as they arise while also allowing for possible human intervention.

Sanfelice and his Hybrid Systems Lab will focus on developing the control algorithms that allow for experimentation on the spacecraft digital twins. The digital twin models need to be so complex to fully encapsulate the physics and computing variables of the real-world systems they represent, and this in turn requires new methods to control the models that go beyond the current state-of-the-art.

I have this massive detailed model of my system, it keeps updating as the system evolves and I run experiments can I write an algorithm that makes the digital twin do what I want it to do, and as a consequence hopefully the real physical system will do the same? Sanfelice said.

Sanfelices work will center around developing model predictive control algorithms, a type of optimization-based control scheme, to control the digital twins, of which Wilcox will lead the creation. Sanfelices lab develops robotic manipulators for grasping and other tasks performed by robotics, which require hybrid control schemes to enable the robotic fingers to be able to transition between conditions of contact and no contact with the object they are manipulating.

While the model predictive control techniques they develop for this project will be highly relevant to aerospace applications, Sanfelice believes there is an opportunity to expand to other complex application areas and develop more advanced basic science for digital twins and their control.

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'Digital twins' project will help clean up space junk, repair and decommission spacecrafts - University of California

Dave Murrow (AeroEngr BS’84) | Ann and H.J. Smead Aerospace Engineering Sciences – University of Colorado Boulder

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Dave Murrow retired in 2023, capping a 36-year career serving the space exploration community. In retirement, he sits on NASAs Planetary Science Advisory committee, works with the Colorado state economic development office, and has established a consulting business, Space Connections.

Murrows most recent professional role was as the leader of Lockheed Martins Deep Space Exploration Business Development team. He worked with executives, communicators, and program execution teams to develop a multi-mission, 7-year backlog in the DSE market segment. He served in similar roles for the Lockheed Martin Human Spaceflight Advanced Programs team and for the Ball Aerospace Space Science and Exploration team.

At Lockheed Martin, he worked towards an expansive vision of exploration by designing human missions to the Moon, Mars, and asteroids. At Ball, he expanded the companys NASA footprint through pursuit of NASA science, technology, and human exploration missions.

Murrow joined industry after 13 years with the Jet Propulsion Laboratory, where he began as an orbit determination analyst for the Galileo mission to Jupiter and served as the Cassini Mission Systems Engineer. Beckoned by Mars, he participated in the contract award, flight system development of the twin Mars '98 spacecraft. Adding the Stardust mission to Mars Climate Orbiter and Mars Polar lander, he managed the successful 3-peat launch campaign between December 1998 and February 1999.

His JPL role followed aerospace engineering degrees at the University of Texas at Austin (MS 87), and the University of Colorado Boulder (BS 84, Honors). In Austin, he worked at the Universitys Center for Space Research, supporting high precision Earth gravity field development for the Topex mission. In 2003, Murrow inaugurated a graduate semester class in Interplanetary Mission Design in CU Boulder Aerospace. Over the last decade, he has also lectured on Launch Vehicles for CU Boulders unique Space Minor program.

A native of Boulder, Colorado, Dave now lives in Highlands Ranch with his wife, and has two grown daughters. He spends his free time traveling, reading, skiing, and hiking in the mountains.

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Dave Murrow (AeroEngr BS'84) | Ann and H.J. Smead Aerospace Engineering Sciences - University of Colorado Boulder

Sharing Innovations in Psoriasis Biologics and Uplifting Women in Dermatology – Dermatology Times

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I'm going to walk the team through the head-to-head clinical trial data, but also the real-world data because the reality is a drug may perform beautifully in a controlled clinical trial setting, but the real world is messy, so that drug may not perform in the same way. I'm going to guide the attendees on which drugs offer the best durability of response over time. Spoiler alert: the IL-23's have really held up not only from an efficacy standpoint, but also from a safety standpoint over time, said Mona Shahriari, MD, FAAD, in an interview with Dermatology Times at the 2024 American Academy of Dermatology (AAD) Annual Meeting in San Diego, California.

Shahriari, an assistant clinical professor of dermatology at the Yale School of Medicine and the associate director of clinical trials at CCD Research in Connecticut, presented pearls from her AAD session, Comparative Efficacy and Relative Ranking of Psoriasis Biologics Using Real-world and Clinical Trial Data. Shahriari reviewed the efficacy of various biologics and systemics for psoriasis in both clinical trials and real-world examples. Shahriari also reviewed the efficacy of biosimilars and their success.

At AAD, Shahriari also participated in a panel during Bristol Myers Squibbs Women Connection Forum. Shahriari spoke alongside Latanya Benjamin, MD, FAAD, FAAP; Alexandra Golant, MD, FAAD; and Jenny Murase, MD, FAAD, to share their personal and professional journeys, as well as advice for women in dermatology.

If there's something that you want, it's okay to ask. I think a lot of times as women, we assume that certain opportunities are given to us based on our credentials, people look at our CV, people look at everything that we've done. But that's not always the case. Sometimes people don't even know that you're interested in activity. I learned that if there was something I was interested in, if I just asked and said, Hey, I just want to throw my name in the hat for XYZ opportunity that's coming up, they've actually looked at me more carefully, and I've been able to partake in that opportunity, said Shahriari when sharing her advice for women wanting to advance in dermatology.

Transcript

Mona Shahriari, MD, FAAD: Hi, my name is Mona Shahriari. I'm an assistant clinical professor of dermatology at Yale University and the associate director of clinical trials at CCD research.

Dermatology Times: What pearls are you sharing during your session, "Comparative efficacy and relative ranking of psoriasis biologics using real-world and clinical data?"

Shahriari: At this year's American Academy of Dermatology meeting, I'm going to be doing a talk that looks at the comparative effectiveness of different biologics and systemics for plaque psoriasis, not only in clinical trial data, but also in real-world data, because we have a busy toolbox of medications. And sometimes, it's tough to know which drug do I reach for first, and if that fails, which drug do I reach for a second? I'm going to really walk the team through the head-to-head clinical trial data, but also the real-world data, because the reality is a drug may perform beautifully in a controlled clinical trial setting, but the real world is messy, so that drug may not perform in the same way. I'm going to guide the attendees on which drugs offer the best durability of response over time. Spoiler alert the IL-23's have really held up not only from an efficacy standpoint, but from a safety standpoint over time. And interestingly, some of our biosimilars have proven to be just as good as our originator drugs. So,we'll walk through the nitty gritty of those details.

Dermatology Times: What other topics or sessions are you looking forward to at AAD?

Shahriari: Well, I have to say the late breaker session is always my absolute favorite. I make sure not to miss that because being on the cutting edge of clinical trials and dermatology research, I want to make sure I'm offering my patients the most innovative treatment for their skin disease. So that is a session I do not miss because I want to make sure I know what the rest of 2024 is going to look like. But also, the JAK Inhibitors: A New Frontier, that was a new session that hit the space last year, heavily attended, and JAK inhibitors are revolutionizing how we treat so many different diseases within dermatology. I really want to see what else is out there on the horizon, and how we can bring this amazing therapy to our patients.

Dermatology Times: What is the significance of the Bristol Myers Squibb Women's Forum Panel that you participated in?

Shahriari: Well, I really think this is a landmark connection form that they put together, because the reality is as women not only in dermatology, but also as career women out there, there are definitely some disparities that go on, whether it's related to pay, whether it's related to promotion, or really just getting your name out there and exposure. And really, the purpose of this woman's connection forum is to not only help us gain connections with other women leaders within the field, and have those friendships develop and networking opportunities develop, but also to hear about the struggles of other women. Sometimes when you normalize it, and you have somebody who you look up to tell you, "You know what, I went through the same challenges. And this is how I overcame them." It can really help you feel closer to those individuals. But also, you realize everybody's human, everyone's going to face challenges, and what can you do to overcome those challenges and not let them get you down?

Dermatology Times: What advice do you have for other women in dermatology?

Shahriari: I really think the 2 main pieces of advice I have is to find a good mentorship network. And I'm calling it a network and not a mentor because in different stages of your life and different aspects of your career, you're going to need different people. And that mentor might be a female, that mentor might be a male. You want to find different individuals to include in that network of yours so you'll have individuals to go through. But also, one other piece of advice I have is if there's something that you want, it's okay to ask. I think a lot of times as women, we assume that certain opportunities are given to us based on our credentials, people look at our CV, people look at everything that we've done. But that's not always the case. Sometimes people don't even know that you're interested in an activity. And I really learned that if there was something I was interested in, if I just asked and said, "Hey, I just want to throw my name in the hat for XYZ opportunity that's coming up, "they've actually looked at me more carefully, and I've been able to partake in that opportunity. So that was one of the simplest pieces of advice I got once upon a time. And it's really done well for me.

Dermatology Times: What positive changes have you seen in dermatology?

Shahriari: I think one thing I've noticed is historically, as a specialty, we used to prescribe a lot of topical agents for our patients. But we've had an explosion of oral and injectable medications for the treatment of various diseases. And I've been really pleased to find a lot of my colleagues jumping on the bandwagon to offer patients some of these newer therapies because sometimes as dermatologists we do want to see more safety data, we do want to see more efficacy data. But I think the value of these newer generation medications, not only from an efficacy standpoint, but also from a safety standpoint is becoming more evident. So, to see my colleagues jump on the bandwagon and offer these to the patients is really going to make a difference for our patients for years and years to come.

One other piece that I've seen is there's been a lot of emphasis on diversity within clinical trials and really allowing for our patients with skin of color to be at the forefront of many activities that we do within dermatology. Because the reality is that historically a lot of our patients with skin of color, they were not in our clinical trials. And when these individuals went to dermatology offices, they were either not getting appropriate treatment, or they were being undertreated. misdiagnosed. And many of my contemporaries and colleagues just didn't feel comfortable caring for these individuals, but as the population of the United States diversifies, and those people who are a minority today become more of the majority, I love that within dermatology, we are prioritizing the needs of these individuals so that we can take care of all of our patients across all skin tones moving forward.

[Transcript lightly edited for space and clarity.]

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Sharing Innovations in Psoriasis Biologics and Uplifting Women in Dermatology - Dermatology Times