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INTERVIEW: Knowledge of indigenous peoples can promote harmony with Earth

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INTERVIEW: Knowledge of indigenous peoples can promote harmony with Earth

Dario Jose Mejia Montalvo, Chair of UN Permanent Forum on Indigenous Issues and Leader of the National Indigenous Organization of Colombia.

Many indigenous peoples profess a deep respect for the planet and all forms of life, and an understanding that the health of the Earth goes hand in hand with the wellbeing of humankind.

This knowledge will be shared more widely at the 2023 session of the Permanent Forum on Indigenous Issues (UNPFII), a ten-day event which gives indigenous communities a voice at the UN, with sessions devoted to economic and social development, culture, the environment, education, and health and human rights).

Ahead of the conference, UN News interviewed Darío Mejia Montalvo, an indigenous member  of the Zenú community in the Colombian Caribbean, and president of the Permanent Forum on Indigenous Issues.

UN News: What is the Permanent Forum on Indigenous Issues and why is it important?

Darío Mejia Montalvo: We first have to talk about what the United Nations is. The UN is made up of Member States, most of which are less than two hundred years old.

Many of them imposed their borders and legal systems on the peoples who were there long before the formation of the States.

The United Nations was created without taking these peoples – who have always considered that they have the right to maintain their own ways of life, government, territories, and cultures – into account.

The creation of the Permanent Forum is the largest gathering of peoples in the United Nations System, seeking to discuss global issues that affect all humanity, not just indigenous peoples. It is a historic achievement of these peoples, who were left out of the creation of the UN; it allows their voices to be heard, but there is still a long way to go.

UN News: Why is the Forum focusing its discussions on planetary and human health this year?

Darío Mejía Montalvo: The COVID-19 pandemic was a momentous upheaval for human beings but, for the planet, a living being, it was also a respite from the global pollution.

The UN was created with only one view, that of the Member States. Indigenous peoples are proposing that we go beyond science, beyond economics, and beyond politics, and think of the planet as Mother Earth.

Our knowledge, which goes back thousands of years, is valid, important, and contains innovative solutions.

 

The knowledge of indigenous peoples can support a healthy planet.

UN News: What diagnoses do indigenous people have for addressing the health of the planet?

Darío Mejía Montalvo: There are more than 5,000 indigenous peoples in the world, each with their own worldview, understanding of the current situations, and solutions.

What I think indigenous peoples have in common is their relationship with the land, the basic principles of harmony and balance, where the idea of rights is not based solely around humans, but in nature.

There are multiple diagnoses, that may have elements in common, and can complement the diagnoses of Western science. We are not saying that one kind of knowledge is superior to another; we need to recognize each other and to work together on an equal footing.

This is the approach of indigenous peoples. It is not a position of moral or intellectual superiority, but one of collaboration, dialogue, understanding, and mutual recognition. This is how indigenous peoples can contribute to the fight against the climate crisis.

 

An indigenous Barí woman commits to peace in Colombia after fighting in the FARC guerrilla group.

An indigenous Barí woman commits to peace in Colombia after fighting in the FARC guerrilla group.

UN News: When indigenous leaders defend their rights – especially those who defend environmental rights – they suffer harassment, killings, intimidation, and threats.

Darío Mejía Montalvo: These are really holocausts, tragedies that are invisible to many.

Humanity has become convinced that natural resources are infinite and ever cheaper, and Mother Earth’s resources have been considered commodities. 

For thousands of years, indigenous peoples have resisted the expansion of agricultural and mining frontiers. Every day they defend their territories from mining companies that seek to extract oil, cola and resources that, for many indigenous peoples, are the blood of the planet.

Many people believe that we have to compete with and dominate nature. The desire to control natural resources with legal or illegal companies, or through so-called green bonds or the carbon market is essentially a form of colonialism, which considers indigenous peoples as inferior and incapable and, consequently, justifies their victimization and extermination.

Many States still do not recognize the existence of indigenous peoples and, when they do recognize them, there are considerable difficulties in advancing concrete plans that will allow them to continue defending and living on their lands in dignified conditions.

A group of  Karamojong people in Uganda perform songs to share knowledge about weather and animal health.

A group of Karamojong people in Uganda perform songs to share knowledge about weather and animal health.

UN News: What do you expect this year from the session of the Permanent Forum on Indigenous Issues?

Darío Mejía Montalvo: The answer is always the same: to be heard on an equal footing, and recognized for the contributions we can make to major global discussions.

We hope that there will be a little more sensitivity, humility on the part of the Member States to recognise that, as societies, we are not on the right track, that the solutions to crises proposed so far have proved insufficient, if not contradictory. And we expect a little more coherence, so that commitments and declarations are converted into concrete actions.

The United Nations is the centre of global debate, and it should take indigenous cultures into account.

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Countdown to SpaceX Starship Flight Test Launch (Update: Launch Cancelled)

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Countdown to SpaceX Starship Flight Test Launch (Update: Launch Cancelled)

UPDATE: The launch test was switched to the so-called “wet dress rehearsal” (WDR) sequence which is meant to assess the system’s state and whether it is safe to be launched. The launch was cancelled 10 seconds before the planned launch due to pressurization concerns. SpaceX will reattempt the launch no sooner than after 48 hours. This time is needed to recycle the fuel in the rocket’s tanks.

The new SpaceX Starship flight test is being targeted for today, April 17 at 8:00 a.m. CT. This will be the first orbital flight test using a fully integrated Starship and Super Heavy rocket, which is set to be launched from Starbase in Texas.

SpaceX Starship rocket ready for its launch. Image credit: SpaceX

The Starship rocket encompasses a complete reusable transportation system that is designed to offer the capabilities of a human crew transportation to Earth orbit.

The rocket will also be able to deliver cargo to space and is also expected to become one of the vessels capable of reaching the Moon, Mars, and even traveling beyond these distant locations of the Solar System.

https://www.youtube.com/watch?v=L5QXreqOrTA

This new flight test will be used to collect important data about the technical performance of the Starship rocket itself, as well as all associated ground-based flight support systems. The ultimate aim is to improve the probability of successful orbital flights in the future.

Until now, SpaceX has already completed several sub-orbital flight tests using the upper stage of Starship. The company has proven that the vehicle can perform a precisely controlled flight, including re-orienting itself and re-lighting its engines to position itself in a vertical position for landing on the ground.

The rocket is measured 119 meters (390 ft) tall. Its launch and catch tower is the tallest in the world, reaching the height of 146 meters (500 ft).

During the upcoming test, SpaceX will not attempt a vertical landing of Starship, and it also will not attempt to catch the Super Heavy booster using the launch and catch tower.

A live webcast of the flight test will begin ~45 minutes before liftoff. The company notes that this schedule is dynamic and can be changed at any moment.


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A New Approach to Software Development: Top Trends to Rule the Industry in 2023

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A New Approach to Software Development: Top Trends to Rule the Industry in 2023

9 Upcoming Technology Trends to Revolutionize Your Business in 2023

The software development industry is constantly in flux, with new trends emerging and older ones fading away. But how will the landscape change in 2023? What are the top trends that will be ruling the software development industry by then? In this article, we’ll take a deep dive into some of these upcoming trends to give you an idea of where the future may be heading. From AI-driven automation to cloud computing and more, get ready for a glimpse into what’s coming down the pipeline!

Coding, software development, team meeting – illustrative photo. Image credit: Austin Distel

9 Software Development Trends to Know in 2023

1. AI-Driven Automation

AI-driven automation is one of the most exciting aspects of software development in 2023. With more advanced machine learning and natural language processing capabilities, developers will be able to automate more complex tasks with greater accuracy and efficiency than ever before. This could enable businesses to save time and money while still delivering high-quality software.

Besides, such automation could also open up the possibility of creating user-friendly and customized software solutions, increasing the efficiency of software development processes and making it easier for developers to quickly create custom applications tailored to their clients’ specific needs.

2. Cloud Computing 

Cloud computing has been gaining traction in recent years, and it’s expected to become even more popular in 2023. With cloud computing, businesses can access data and applications from anywhere, anytime. It enables them to scale quickly and provide more efficient customer services. 

Additionally, cloud-based software development is becoming increasingly popular due to its ability to reduce the costs of developing customized applications for specific clients. Cloud-based software development also allows developers to deploy applications faster and integrate them with other software solutions. 

3. Custom Software Development

Custom software development is one of the most important trends that will be dominating in 2023. With custom software, businesses can create unique applications tailored to their specific needs and preferences. Such custom applications make it easier for companies to differentiate themselves from their competitors and increase their customer base. 

Custom development also helps businesses save time, as they don’t have to rely on generic software solutions that may not fit their exact requirements. With custom software development, companies can create unique applications that provide the best user experience and maximum efficiency.

4. Security

With more connected devices and data worldwide, security will be a top priority in 2023. As a result, companies must ensure that their software solutions are secure and can effectively protect their customers’ data.

New technologies such as blockchain, encryption, and authentication protocols will become increasingly important to ensure software applications remain secure against potential threats. Additionally, companies must have robust disaster recovery plans in place to quickly recover from data breaches and other security incidents.

5. Internet of Things (IoT) 

The Internet of Things (IoT) will be a key trend in 2023 as more businesses want to leverage connected devices to create more innovative services and solutions. With the help of IoT, companies can gather real-time data from their customers’ devices, allowing them to provide more personalized and efficient services.

In addition, the IoT will create new opportunities for developers, who will be able to make more secure and interconnected applications. This could open up possibilities such as automated homes, smart farms, and intelligent transportation systems.

6. DevOps 

DevOps is an approach to software development that focuses on collaboration between developers and operations teams. DevOps helps businesses quickly develop and deploy software solutions by automating processes and streamlining team communication. 

In 2023, DevOps will become even more popular as organizations look to increase their efficiency and reduce the costs associated with developing and maintaining applications. Additionally, DevOps can help companies remain agile in an ever-changing digital landscape by allowing them to adapt to new trends and technologies. 

7. AR and VR

Augmented reality (AR) and virtual reality (VR) will continue to be significant trends in 2023. As businesses look to create more interactive and engaging user experiences, they are increasingly turning towards these technologies. 

For example, AR can be used to provide customers with a more immersive shopping experience, while VR can help train employees in a cost-effective manner. Additionally, both AR and VR can be used to create more entertaining and engaging content for customers. 

8. Low-Code/No-Code Development 

Low-code/no-code development will continue to grow in popularity as organizations look for faster and more cost-effective solutions. Low-code/no-code allows businesses to develop applications quickly without having to write code, thereby reducing the costs associated with developing custom software solutions.

This approach also makes it easier for non-technical people to create applications, allowing them to focus on other aspects of their business. In 2023, many companies are expected to leverage low-code/no-code development to increase efficiency and reduce costs. 

9. 5G

5G networks are expected to become widespread in 2023, allowing faster data speeds and more reliable connections. This technology could enable companies to build more secure and efficient applications as it will provide them with access to higher-quality data.

Additionally, 5G could help businesses reduce their reliance on cloud services by enabling them to store and process data locally. This could open up new possibilities for businesses regarding scalability and performance. 

Final Thoughts

The digital landscape is constantly evolving, and businesses need to stay up-to-date with the latest trends. By keeping an eye on these emerging technologies, companies can ensure they remain competitive and prepare themselves for the future. 

Thus, by embracing these nine technology trends, businesses can take advantage of the opportunities they provide and remain at the forefront of digital innovation. So, keep an eye out for these trends and start planning now for the future of your business. 


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How to make self-folding surgical tools

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How to make self-folding surgical tools

For minimally invasive surgery, the instruments used must be small. ETH Zurich researchers have now developed a method to transport large devices through a narrow catheter. This expands the possibilities for designing minimally invasive surgical tools.

A camel cannot go through the eye of a needle. But researchers at ETH Zurich have now achieved something that – figuratively speaking – comes quite close. They have developed a new approach to minimally invasive surgical instruments, thanks to which large objects can be brought into the body through a narrow catheter.

This works as follows: The researchers disassemble such devices into individual parts and then slide them through the catheter in a row, like a string of pearls. At the end of the catheter, the parts assemble themselves into a predefined shape thanks to built-in magnets.

In its research, the team – led by ETH doctoral student Hongri Gu, now a postdoc at the University of Konstanz – was primarily concerned with demonstrating the many possibilities of this new approach. Using 3D printing, the scientists also constructed an endoscopic grasper in a relatively simple way. Moreover, they showed that the new approach makes assembling an endoscope head consisting of three parts possible.

For their prototypes, the researchers combined soft, elastic segments with rigid segments, into which the tiny magnets are incorporated. This design method also allows an endoscope head to perform movements with very tight radii and angles that aren’t feasible with today’s endoscopes. This increased mobility broadens the possibilities when designing devices for minimally invasive surgery on organs such as the intestine or the stomach. The scientists published their demonstration study on the journal external pageNature Communications.

Source: ETH Zurich


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Ukrainian fighter jet pilot: Our MiG-29s can be improved while we wait for better options

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Ukrainian fighter jet pilot: Our MiG-29s can be improved while we wait for better options

Transferring Western combat aircraft to Ukraine and training pilots to operate new machines will take time, but Ukraine needs to make the best use of what it has to protect its sky right now, says military pilot Vadym Voroshilov.

Polish Mikoyan Mig-29 – illustrative photo. Image credit: Peter Gronemann via Flickr, CC BY-NC-ND 2.0

Ukraine puts a lot of effort into communication with its allies about the possibility to upgrade its heavily aged military jet fleet. But meanwhile, other things can be done, too. For example, Vadym mentions that old MiG-29s can be upgraded, and this could provide a short-term boost to their combat capabilities.

“While we are waiting for the moment of transfer of fighter jets, we have to work with what we have,” the pilot said.

He also explained that there are two specific areas where Ukraine could improve the operation of its aircraft and aviation equipment.

The first logical step would be to upgrade the available fire control and flight control systems. For example, fighter pilots need their planes to support outboard fuel tanks and newer guns. The pilot is certain that many useful modifications to existing avionics systems could be done by Ukrainian engineers.

The second step is to improve the existing weapons that are carried onboard. For example, fighter jets could be equipped with extended-range air-to-air missiles. These weapons could be bought or acquired through military aid mechanisms from NATO countries.

“There are such missiles on the market specifically for the MiG-29, they are being sold, I will not announce the names. I believe that we also really need them to improve the efficiency of work on these aircraft. I believe that during the year of the war, the Air Force withstood, showed its effectiveness despite the technical and quantitative superiority of the enemy, closed the sky of Ukraine,” Vadym Voroshilov explained.

In October 2022, Vadim Voroshilov received a serious injury while fighting Shahed-136 drones during a large-scale attack, after explosion debris hit the cockpit of his MiG-29 aircraft, causing a fire. But the pilot managed to eject. His treatment lasted four months, but now he is piloting a fighter jet once again.

Vadim Voroshilov is a military pilot. He has been awarded the official title of the hero of Ukraine.

Full interview can be watched below:


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Ukraine included Xiaomi in the list of companies sponsoring the war

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Xiaomi products are not banned from sale in Ukraine yet. The Chinese company – one of the largest global suppliers of smartphones – is categorically against the accusations.

Xiaomi office building in Beijing – illustrative photo. Image credit: Jon Russell via Flickr, CC BY-SA 2.0

Ukrainian National Agency for Prevention of Corruption (NAPC) has recently included Xiaomi in the list of companies sponsoring the war in Ukraine.

“The company not only continued its work in Russia after a full-scale invasion, but still remains the leader in sales of smartphones in the terrorist state,” stated the press service of the NACP. It also said that sales of Xiaomi products in the Russian market increased by 39% in mid-2022, after the start of the invasion of Ukraine.

The official answer from Xiaomi was published on Twitter. Here, the company said it denies any involvement in sponsoring the Russian military. “Xiaomi does not support any military action, but fully supports world peace,” the message said, adding that its desire is “to make the lives of people in the world better thanks to innovative technologies.”

Ukrainian NCAP reacted to this message by posting a photo of Russian president Vladimir Putin holding a smartphone, with a quote where he said that he is grateful to Xiaomi for “having a right to access to their communication tools”.

Will Xiaomi smartphones be banned in Ukraine?

The decision of NCAP does not mean an immediate ban on Xiaomi’s products. Such trade limitation can be done only if the President, the Cabinet of Ministers, the National Bank, or the Security Service of Ukraine submit such a proposal to the National Security and Defense Council. Then, the council’s duty would be to analyze this proposal and decide whether to proceed with such a course of action or not.

As the Ukrainian news portal Focus noted, the National Agency for the Prevention of Corruption does not have the power to impose trade bans. Instead, its decisions are of an advisory kind – through them, the institution informs users what companies and products are associated with supporting the ongoing war, either through taxes or through specific technologies, such as communications tools.

While this news does not mean any trade restrictions for Xiaomi, local distributors are free to make their own decisions about the products they sell to local users.

Mobile operators and major retail chains operating in the Ukrainian market have not commented on this situation yet.

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Chilean Bishop: Wide turnout at referendum shows wish for unity – Vatican News

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Chilean Bishop: Wide turnout at referendum shows wish for unity - Vatican News

By Benedetta Capelli

The voting consultation in Chile saw wide popular participation at close to 62 percent of voters. Some seven million Chileans voted against the amendment while 38 percent, 4.2 million, voted in favor of the text. President Gabriel Boric reacted by saying he is ready to resume the path of dialogue in agreement with Parliament.

Bishops: Time for reflection

The country’s bishops said the national referendum calls for reflection, especially given the wide turnout. Auxiliary Bishop of Santiago, Chile, Alberto Lorenzelli, underscored this point when describing his reaction in an interview with Vatican News answering the following questions.

What is your reaction with respect to Sunday’s vote?

We are very happy about the wide participation of the people in taking part actively in this vote. But most of all we are happy with what this reflects about the soul of the Chilean people who want unity, who want fraternity, who want to overcome conflicts, who want to see a country at peace where people come together again to overcome violence, overcome divisions, and have a Constitution that responds to the sentiments of all.

What is the social situation like in Chile right now?

The social situation Chile is experiencing is concerned with the presence of violent groups that do not respect work or city life. This upsets matters and causes suffering. We hope that now with the outcome of the voting there will be a moment of reflection for everyone, even for all these groups that do not identify with the outcome of this referendum. It is important that we seek unity, respect for people, and that violence and destruction not have the upper hand in the life of the country.

Aid operations in Sudan suspended after three staff members killed in unrest

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Aid operations in Sudan suspended after three staff members killed in unrest
© UN Photo/Albert Gonzalez Farran - World Food Programme (WFP) staff members load bags of split yellow peas onto a truck in a WFP warehouse based in El Fasher, North Darfur, Sudan.

The World Food Programme (WFP) has temporarily halted aid operations in Sudan as a result of the fighting between rival military groups in Sudan, which led to the deaths of three WFP employees on Saturday. The UN Secretary-General has called for those responsible to be brought to justice.

According to a statement attributable to the Executive Director of the UN agency, Cindy McCain, the workers were carrying out life-saving duties in Kabkabiya, North Darfur.

In a separate incident on Saturday, a WFP-managed UN Humanitarian Air Service (UNHAS) aircraft was significantly damaged at Khartoum International airport during an exchange of gunfire, seriously impacting WFP’s ability to move humanitarian workers and aid within the country.

In the statement, Ms. McCain explained that aid operations in Sudan have been suspended, pending a review of the evolving security situation.

“WFP is committed to assisting the Sudanese people facing dire food insecurity,” said Ms. McCain, “but we cannot do our lifesaving work if the safety and security of our teams and partners is not guaranteed. All parties must come to an agreement that ensures the safety of humanitarian workers on the ground and enables the continued delivery of life saving humanitarian assistance to the people of Sudan. They remain our top priority.”

Any loss of life in humanitarian service is unacceptable and I demand immediate steps to guarantee the safety of those who remain.

Ms. McCain emphasized that threats to WFP teams make it impossible for them to operate safely and effectively in the country and carry out the UN agency’s critical work.

‘Justice without delay’: UN Secretary-General

Responding to the crisis on Sunday, UN Secretary-General António Guterres called for those responsible to be brought to justice without delay.

In a statement attributable to Mr. Guterres, he expressed deep concern about the continued clashes, and reminded the warring parties of the need to respect international law, including the obligation to ensure the safety and security of all United Nations and associated personnel, their premises, and their assets.

The Secretary-General reiterated his call for an immediate halt to the fighting and for a return to dialogue, and emphasized that he continues to engage with regional leaders and with Sudanese stakeholders to find a way out of this crisis.

Aid workers ‘not a target’, looting of UN premises must stop

The Special Representative of the Secretary-General for Sudan and Head of the UN Integrated Transition Assistance Mission (UNITAMS) Mr. Volker Perthes strongly condemned the attacks on Sunday, and insisted that civilians and humanitarian aid workers are “not a target.”

Mr. Perthes referred to reports of projectiles hitting UN and other humanitarian premises, and of looting at these premises, in several locations in Darfur.

The UNITAMS chief said that these acts of violence disrupt the delivery of life-saving assistance, and must end. “When incidents like this occur, it is women, men, and children in desperate need of assistance who suffer the most.”

Mr. Perthes announced on Sunday that he had convinced the two warring parties to the current fighting to briefly pause hostilities, on humanitarian grounds, between four and seven PM, local time.

Security Council members call for calm

The members of the Security Council added their voices to the calls for an end to hostilities on Sunday, in a statement expressing their regret for the loss of lives and injuries.

In the statement, they urged the parties to restore calm, and return to dialogue to resolve the current crisis in Sudan.

They went on to stress the importance that humanitarian access is maintained and the safety of UN personnel is ensured, and reaffirmed their “strong commitment to the unity, sovereignty, independence and territorial integrity of the Republic of the Sudan.”

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Tiny DNA circles are key drivers of cancer

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Tiny DNA circles are key drivers of cancer

Tiny circles of DNA harbor cancer-associated oncogenes and immunomodulatory genes promoting cancer development. They arise during transformation from pre-cancer to cancer, say Stanford Medicine-led team.

Tiny circles of DNA that defy the accepted laws of genetics are key drivers of cancer formation, according to an international study led by researchers at Stanford Medicine.

Tiny circles of DNA (small rings) upend conventional genetic principles that govern inheritance of genes on chromosomes (oblongs). The large blue circles are cell nuclei. Image credit: Paul Mischel lab

The circles called extrachromosomal DNA or ecDNA, often harbor cancer-associated genes called oncogenes. Because they can exist in large numbers in a cell, they deliver a super-charged growth signal that can override a cell’s natural programming. The researchers found they also contain genes likely to dampen the immune system’s response to nascent cancer.

Previous research had suggested that the circles, which are widespread in human cancers but rarely found in healthy cells, primarily arise in advanced tumors as the abnormal cells increasingly botch the intricate steps required to copy their DNA before each cell division.

But the new study shows that the roly-poly circles can be found even in precancerous cells — and their presence jump-starts a cancerous transformation. The researchers believe that blocking their formation, or their effect on the cells that carry them, might stop cancers from developing.

DNA analysis in a medical lab – illustrative photo. Image credit: CDC

“This study has profound implications for our understanding of ecDNA in tumor development,” said professor of pathology Paul Mischel, MD. “It shows the power and diversity of ecDNA as a fundamental process in cancer. It has implications for early diagnosis of precancers that put patients at risk, and it highlights the potential for earlier intervention as treatments are developed.” 

Mischel is one of six senior authors of the research, which was published in NatureHoward Chang, MD, PhD, professor of genetics and Virginia and D.K. Ludwig Professor in Cancer Research, is also a senior author.

Other senior authors include senior staff scientist Thomas Paulson, PhD, from Seattle’s Fred Hutchison Cancer Center; assistant professor of pediatrics Sihan Wu, PhD, assistant professor at Children’s Medical Center Research Institute at the University of Texas Southwestern Medical Center; professor of computer science and engineering Vineet Bafna, PhD, from UC San Diego; and professor of cancer prevention and director of the Early Cancer Institute Rebecca Fitzgerald, MD, from the University of Cambridge.  

“People with ecDNA in their precancerous cells are 20 to 30 times more likely than others to develop cancer,” Chang said.

“This is a huge increase, and it means we really need to pay attention to this. Because we also found that some ecDNAs carry genes that affect the immune system, it suggests that they may also promote early immune escape.”

A grand challenge

Deciphering ecDNA’s role in cancer was one of four Cancer Grand Challenges awarded by the National Cancer Institute and Cancer Research UK in 2022. The grand challenges program was launched to bring together researchers from around the world to tackle complex research topics too daunting for any one group.

Mischel was awarded $25 million to lead a team of international researchers to learn more about the circles. But first they had to jettison some key genetic principles that have guided the field for nearly 200 years.

“When we think about how a tumor evolves in a patient and in response to treatment, we think of the branching trees of life proposed by Charles Darwin,” Mischel said.

“This idea is so powerful that researchers often sequence the DNA from multiple parts of a tumor and draw these trees to learn about its evolution. If a mutation is there at the trunk of the tree and in all of its branches, we assume it is a key driver event in the formation of the tumor; if it is in only some branches, we assume it happened later in tumor development and may not be a good target for drug development.”

But these assumptions hinge on the idea that all of a tumor’s DNA is neatly contained on chromosomes, which are evenly divided among daughter cells each time a cancer cell divides — ensuring that each new cell gets one, and only one, copy of each chromosome.

In contrast, the tiny ecDNA circles swirl in a dividing cell like bubbles circling a bathtub drain and are portioned willy-nilly between the new daughter cells. One may get nearly all the circles; the other, almost none. As the generations accumulate, the evolutionary tree favored by Darwin begins to look decidedly odd, with the appearance of ecDNA-bearing cells sprinkled among the branches like haphazardly hung Christmas lights.

“Some researchers have looked at the evolutionary trees and decided that, because you see it here, but not there, it must be that ecDNA formation is a late event and probably isn’t important when considering treatments,” Mischel said. “Our team thought that interpretation was wrong.”

Pinpointing a reason

To get to the bottom of the tiny circles, Mischel, Chang and their collaborators turned to a specific example of cancer development — people with a condition known as Barrett’s esophagus, which occurs when the cells lining the lower part of the esophagus are damaged by acid reflux and become more like cells lining the intestine than healthy esophageal tissue.

About 1% of these people develop esophageal cancer, which is difficult to treat and has a high mortality rate. Because the outcome is so poor, people with Barrett’s esophagus are routinely monitored with endoscopies and biopsies of the abnormal tissue. Because of these frequent biopsies, the researchers had access to tissue samples collected both before and after cancers developed.

The researchers assessed the prevalence of ecDNA, and identified the genes they carried, in biopsies from nearly 300 people with Barrett’s esophagus or esophageal cancer treated at the University of Cambridge or at Seattle’s Fred Hutchison Cancer Center, where individual patients were studied as the cancer developed.

They found that the prevalence of ecDNA increased from 24% to 43% in early- versus late-stage esophageal cancer, indicating the continual formation of the DNA circles during cancer progression. More tellingly, they found that 33% of people with Barrett’s esophagus who developed esophageal cancer had ecDNA in their precancerous cells.

In contrast, only one out of 40 people who didn’t develop cancer had cells with ecDNA, and that individual passed away due to another cause.

“The conclusions were remarkable,” Mischel said. “We see that ecDNA can arise in these precancerous cells, and that if it is there, the patient is going to get cancer. We also saw the continuous formation of ecDNA as the cancer progresses, indicating that it is advantageous to cancer growth. Finally, we saw that the ecDNA can contain immune-modulatory genes in addition to oncogenes.”

“If a gene is carried on ecDNA, it is very likely to be important for cancer,” Chang said. “These circles are not only giving us new targets for cancer diagnosis and drug development; they are also teaching us what is important for tumor growth.”

What to look at next

The researchers are planning to explore more about how ecDNAs arise in cancer cells and how they work together to make proteins that drive cancer cell growth.

They saw that cancers with ecDNA were likely to also have mutations in a protein called p53. Sometimes called “the guardian of the genome,” p53 temporarily halts the cell cycle to allow cells to repair damage or mutations to their DNA before beginning to divide.

“We want to learn more about the landscape of ecDNA in precancers and the risks it confers,” Mischel said.

“We also want to know if we can stop its formation or activity; how to improve our ability to detect their presence; how they affect the immune system; and whether there are opportunities for new, novel therapies. There is much more to learn, and our team is excited to tackle all these issues. But what we do know for certain is that these tiny DNA circles are a very big deal in cancer.” 

Source: Stanford University


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The promise – and pitfalls – of medical AI headed our way

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The promise – and pitfalls – of medical AI headed our way

Stanford researchers lay out a framework for engineers as they expand and build new medical artificial intelligence models.

Robot-assisted surgery. Image credit: فاطمه درستی via Wikimedia, CC-BY-SA-4.0

A patient lies on the operating table as the surgical team reaches an impasse. They can’t find the intestinal rupture. A surgeon asks aloud: “Check whether we missed a view of any intestinal section in the visual feed of the last 15 minutes.”

An artificial intelligence medical assistant gets to work reviewing the patient’s past scans and highlighting video streams of the procedure in real time. It alerts the team when they’ve skipped a step in the procedure and reads out relevant medical literature when surgeons encounter a rare anatomical phenomenon.

Doctors across all disciplines, with assistance from artificial intelligence, may soon have the ability to quickly consult a patient’s entire medical file against the backdrop of all medical healthcare data and every published piece of medical literature online. This potential versatility in the doctor’s office is only now possible due to the latest generation of AI models.

“We see a paradigm shift coming in the field of medical AI,” said Jure Leskovec, professor of computer science at Stanford Engineering. “Previously, medical AI models could only address very small, narrow pieces of the health care puzzle. Now we are entering a new era, where it’s much more about larger pieces of the puzzle in this high stakes field.”

Stanford researchers and their collaborators describe generalist medical artificial intelligence, or GMAI, as a new class of medical AI models that are knowledgeable, flexible, and reusable across many medical applications and data types. Their perspective on this advance is published in the issue of Nature.

Leskovec and his collaborators chronicle how GMAI will interpret varying combinations of data from imaging, electronic health records, lab results, genomics, and medical text well beyond the abilities of concurrent models like ChatGPT. These GMAI models will provide spoken explanations, offer recommendations, draw sketches, and annotate images.

“A lot of inefficiencies and errors that happen in medicine today occur because of the hyper-specialization of human doctors and the slow and spotty flow of information,” said co-first author Michael Moor, an MD and now postdoctoral scholar at Stanford Engineering. “The potential impact of generalist medical AI models could be profound because they wouldn’t be just an expert in their own narrow area, but would have more abilities across specialties.”

Medicine without borders

Of the more than 500 AI models for clinical medicine approved by the FDA, most only perform one or two narrow tasks, such as scanning a chest X-ray for signs of pneumonia. But recent advances in foundation model research promise to solve more diverse and challenging tasks.

“The exciting and the groundbreaking part is that generalist medical AI models will be able to ingest different types of medical information – for example, imaging studies, lab results, and genomics data – to then perform tasks that we instruct them to do on the fly,” said Leskovec.

“We expect to see a significant change in the way medical AI will operate,” continued Moor. “Next, we will have devices that, rather than doing just a single task, can do maybe a thousand tasks, some of which were not even anticipated during model development.”

The authors, which also include Oishi Banerjee and Pranav Rajpurkar from Harvard University, Harlan Krumholz from Yale, Zahra Shakeri Hossein Abad from University of Toronto, and Eric Topol at the Scripps Research Translational Institute, outline how GMAI could tackle a variety of applications from chatbots with patients, to note-taking, all the way to bedside decision support for doctors.

In the radiology department, the authors propose, models could draft radiology reports that visually point out abnormalities, while taking the patient’s history into account. Radiologists could improve their understanding of cases by chatting with GMAI models: “Can you highlight any new multiple sclerosis lesions that were not present in the previous image?”

In their paper, the scientists describe additional requirements and capabilities that are needed to develop GMAI into a trustworthy technology. They point out that the model needs to consume all of the personal medical data, as well as historical medical knowledge, and refer to it only when interacting with authorized users. It then needs to be able to hold a conversation with a patient, much like a triage nurse, or doctor to collect new evidence and data or suggest various treatment plans.

Concerns for future development

In their research paper, the co-authors address the implications of a model capable of 1,000 medical assignments with the potential to learn even more. “We think the biggest problem for generalist models in medicine is verification. How do we know that the model is correct – and not just making things up?” Leskovec said.

They point to the flaws already being caught in the ChatGPT language model. Likewise, an AI-generated image of the pope wearing a designer puffy coat is funny. “But if there’s a high-stake scenario and the AI system decides about life and death, verification becomes really important,” said Moor.

The authors continue that safeguarding privacy is also a necessity. “This is a huge problem because with models like ChatGPT and GPT-4, the online community has already identified ways to jailbreak the current safeguards in place,” Moor said.

“Deciphering between the data and social biases also poses a grand challenge for GMAI,” Leskovec added. GMAI models need the ability to focus on signals that are causal for a given disease and ignore spurious signals that only tend to correlate with the outcome.

Assuming that model size is only going to get bigger, Moor points to early research that shows larger models tend to exhibit more social biases than smaller models. “It is the responsibility of the owners and developers of such models and vendors, especially if they’re deploying them in hospitals, to really make sure that those biases are identified and addressed early on,” said Moor.

“The current technology is very promising, but there’s still a lot missing,” Leskovec agreed. “The question is: can we identify current missing pieces, like verification of facts, understanding of biases, and explainability/justification of answers so that we give an agenda for the community on how to make progress to fully realize the profound potential of GMAI?”

Source: Stanford University


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