Culture

For much of the nation's food supply, removing unsafe products off of store shelves can take up to 10 months, according to news reports -- even when people are getting sick.

The growing complexity and scope of modern supply chains result in painfully slow product recalls, even when consumer well-being is at stake. For example, in 2009, salmonella-tainted peanuts killed nine people and sickened more than 700 in 46 states, and the resulting nationwide recall cost peanut farmers, their wholesale customers and retailers more than $1 billion in lost production and sales. Tyson Foods' 2019 recall of nearly 12 million pounds of frozen chicken strips also cost the company millions.

The risk to health increases for each day that bad food remains in circulation, and little is known about food companies' underlying recall process to identify and remove tainted products from the supply chain. However, new research from the University of Notre Dame helps to close the gap between what is and isn't known about food recalls.

There are two key drivers of recall uncertainty -- upstream and downstream complexity, according to "Food for Thought: Recalls and Outcomes," forthcoming in the Journal of Business Logistics from lead author Kaitlin Wowak, associate professor of information technology, analytics and operations in Notre Dame's Mendoza College of Business.

"This research is the first to propose that managers embed recall options into their decision-making when trying to manage recall uncertainty," Wowak said. "Our study suggests that product recalls may not cleanly fall into recall categories as previously thought, but instead take the form of recall layering -- that is, nested recalls or a recall within a larger recall. Understanding that recall layering may be present can help companies segment a recall to more effectively manage it."

Recall options give decision-makers the opportunity but not the obligation to take certain actions in the future and can help managers make better-informed decisions as the recall process unfolds. Wowak says three recall options emerged from the study, all of which can provide major potential value under conditions of recall uncertainty.

"Scale options enable managers to expand recalls over time," she noted. "Deferral options allow managers to postpone executing a recall until a later point in time when they have a better understanding of the recall situation, and abandonment recall options occur when a recall was incorrectly initiated and thus is terminated when more information is revealed."

The study suggests that recall layering can inform a firm's strategy for how to effectively manage recalls as they evolve. For example, when a firm encounters the need for a recall, it can invoke different recall options depending on the nested recalls that surface within the larger recall.

"The specific nested recalls that emerge may change from recall to recall and could evolve as the larger recall unfolds, depending on the degree of uncertainty," Wowak explained. "Assume a firm initiates a recall that has a high degree of upstream complexity. A nested recall within that larger recall could be effectively managed with a deferral recall option. Once the firm has a better understanding of the situation, the next nested recall that emerges may be effectively managed with a scale recall option."

The study provides insights about which recall options may be used in various situations to help decision-makers manage the recall when facing uncertainty and makes designing, revising and improving the recall process more actionable for managers and scholars.

On the evening of May 6, 1937, the largest aircraft ever built by mankind, a towering example of technological prowess, slipped through the stormy skies of New Jersey and prepared to land. The airship Hindenburg was nearing the end of a three-day voyage across the Atlantic Ocean from Frankfurt, Germany. It was a spectacle and a news event. Onlookers and news crews gathered to watch the 800-foot-long behemoth touch down.

And then, in one horrifying half minute, it was all over. Flames erupted from the airship's skin, fed by the flammable hydrogen gas that kept it aloft, and consumed the entire structure, ending 36 lives.

The ship, already famous before its demise, was seared into the world's memory. The disaster, despite happening nearly a hundred years ago, has remained one of the iconic tragedies of the 20th century, alongside other accidents that captured the public imagination, like the sinking of the Titanic, the Challenger explosion, and the meltdown of the Chernobyl nuclear reactor.

Perhaps one reason why the Hindenburg's final, fiery moments have remained such a source of fascination is the enduring mystery surrounding them. For the past eight decades, people have speculated about how the airship could have been completely devoured by flames in less than a minute.

Now, NOVA, the popular PBS science television show, is taking a new look at the disaster. Its producers tapped Caltech's Konstantinos Giapis, professor of chemical engineering, to help them recreate the ship's last moments and unravel its secrets.

Giapis is not an expert on zeppelins or aircraft crashes, nor is he a forensic scientist. He does, however, have an extensive background studying how electrical charges move on surfaces, and how they can build up to sufficient levels to ionize air and cause sparks. That expertise would prove fortuitous in his search for what caused the disaster, and as it turned out, he would end up exploring many of the same phenomena he studies in his more typical work on transistors and other microelectronic devices.

Still, he was skeptical when approached by the NOVA producers.

"My first reaction was, 'Who cares? This happened 84 years ago. Why would anybody want to find out?'" he says.

But the more he thought about it, the more the problem intrigued him.

"My second reaction was, 'Why isn't the cause known? Why hasn't it been solved in all that time?'"

Digging up the past

Giapis began looking into historical records of the accident, and soon realized that no one had done experiments to try and find out what had actually happened. Indeed, nearly all the evidence burned up in the blaze. All that existed was a lot of speculation.

What has always been known is that the zeppelin, which was designed by the Zeppelin Company, a German firm known for its large and luxurious airships, contained 7 million cubic feet of flammable hydrogen. Imagine a cigar-shaped balloon as large as a skyscraper filled with explosive gas. Combine that hydrogen with oxygen from the air, and a source of ignition, and you have "literally a bomb," Giapis says.

The key, but long-unanswered, question: How was the fire sparked? Some experts have theorized that the Hindenburg's engines, which burned diesel fuel, were responsible. Others have suggested that the catastrophe was an act of sabotage, meant to make the government of Nazi Germany look bad.

The most credible theories, however, have focused on electrostatic discharge: the same shock you get when you rub your stocking feet on carpet and touch something metallic. Giapis thought this was most likely. The basic idea is that as the Hindenburg moved in the stormy atmosphere, its skin built up a static charge. And just like the jolt your finger gets when you reach for a doorknob, the Hindenburg might have been zapped when it came in for its landing in New Jersey. If the ship's hydrogen had been leaking, as it is believed, that zap could have set the gas afire.

There were holes in that theory though. First, the zeppelin did not catch fire the moment it dropped its mooring ropes to the ground, as would be expected if the ropes completed the circuit necessary to create a spark. Second, the chances of a single spark happening in the very same spot on the Hindenburg where the hydrogen was leaking seemed too slim to be likely.

To get to the bottom of the mystery, Giapis would have to resolve both of these issues.

'Modeling' the problem

Now fully onboard with the project, Giapis first built a model of a portion of the zeppelin's outer surface in his laboratory on the Caltech campus. This setup consisted of a cotton cloth similar to the original, stretched with natural-fiber strings over an aluminum alloy scaffold and impregnated with multiple layers of Cellon dope, which is a paint containing a polymer, chemical binders, and aluminum flakes. This turned out to be more complex than Giapis first expected because some of the details of the zeppelin's construction have been lost to time and others were trade secrets closely guarded by the Zeppelin Company.

"I found some historical records of what was in those layers, but the precise composition was kept secret," he says. "I analyzed old samples of the skin using modern techniques to get clues. In the end, I had to create multiple versions of this coating for the fabric and evaluate their electrical properties."

The skin was lashed to the aircraft's aluminum frame, but kept from touching it by wooden pegs inserted between the two. The gap between the frame and the skin would prove fatal to 35 of the 97 individuals onboard the airship plus one ground-crew member.

Witnesses at the scene claimed to have seen a glowing aura on parts of the ship. The American and German investigation committees concluded this charge meant the airship was charged to a high voltage, but disagreed on the exact mechanism of how that caused the disaster.

The American committee theorized that the hydrogen was ignited by a phenomenon known as corona discharge, or St. Elmo's fire; this "soft" leakage of high voltage charge from a surface sometimes occurs on the masts of ships at sea, or on airplane surfaces in flight during stormy weather. In contrast, the German investigation committee suggested that a high-intensity spark had instead triggered the explosion.

Giapis did not believe that the American theory could explain the ignition.

"This diffuse glow occurs outside the airship and its energy is very low," he says. "It generally is not sufficient to ignite hydrogen." Thinking the German theory was more plausible, he set out to test it in his lab.

As the NOVA crew filmed, Giapis charged his model of the skin to an electrical voltage consistent with atmospheric charging in stormy conditions at the airship's elevation. Then he grounded the scaffold frame he had built.

Nothing happened.

Then he sprayed a mist of water to the skin, simulating the light rain that was falling that spring evening in New Jersey. Within moments, loud and powerful sparks jumped across the gap from the skin to the frame, just as the German committee had proposed.

An unexpected result

Next, Giapis needed to determine why there was a four-minute delay between when the Hindenburg was moored to the ground and when it caught fire. The members of the German investigation committee proposed that the delay could be explained by the light rain. Their theory was that the ropes only began conducting electricity after they got wet, and so the frame only became grounded once the ropes had become sufficiently moist.

In his lab, Giapis suspended a section of large rope very similar to the mooring ropes used on the Hindenburg and applied a high voltage to it.

To his surprise, the rope was conductive even while dry. It was previously thought that electricity would not flow through dry rope, that it was an insulator.

"The Germans said the rope became conductive after four minutes in the rain, but my experiment showed that the rope was conductive enough to ground the frame the moment it was dropped. And that meant the theory fell apart, because the spark should have occurred much sooner. By my estimates, it takes 10-15 seconds to ground the frame with a dry rope, not four minutes."

Giapis agonized over how to explain that discrepancy. Because of delays due to COVID-19 shutdowns, he was not able to run the rope conductivity test until just a few days before the shoot. "We were about to start filming and my theory had a gaping hole in it. I had to think hard and fast." And then, just two days before the shoot, the answer came to him: After the ship was grounded, it became more electrically charged.

Before the mooring ropes made connection with the ground, the Hindenburg collected a positive charge. However, this continued only to a point; indeed, as the skin became more positively charged, it also more strongly repelled any additional charge from collecting.

Then, when the mooring ropes were dropped, electrons from Earth's surface moved up to the frame, giving the ship a positively charged skin and a negatively charged frame.

Just like how the north end of a bar magnet will be attracted to the south end of another bar magnet, that negatively charged frame began pulling more positive charge out of the stormy atmosphere and onto the ship's skin. In other words, by grounding the frame with the mooring ropes, the landing crew had inadvertently made more "room" for positive charge to gather on the ship, setting the stage for the disaster.

"When you ground the frame, you form a capacitor--one of the simplest electric devices for storing electricity--and that means you can accumulate more charge from the outside," Giapis says. "I did some calculations and I found that it would take four minutes to charge a capacitor of this size!"

With the ship now acting as a giant capacitor, it could store enough electrical energy to produce the powerful sparks required for igniting the hydrogen gas--which, based on eyewitness accounts, may have been leaking from the rear of the ship near its tail.

This theory could also help explain a question that puzzled Giapis from the start: How did a spark occur in just the right spot to ignite leaking hydrogen?

"Hydrogen was leaking at one specific location in this humongous thing. If there is a spark somewhere else on the ship, there is no way you would ignite a leak hundreds of feet away. Charge could move on wet skin over short distances but doing that from the front of the airship all the way to the back is more difficult," he says. "So how did the spark find this leak?"

Any place where a part of the frame was in close proximity to the skin would have formed a capacitor, and there were hundreds of these places all over the ship, Giapis says.

"That means the giant capacitor was actually composed of multiple smaller capacitors, each capable of creating its own spark. So I believe there were multiple sparks happening all over the ship, including where the leak was," he says.

Science, but make it entertainment

Science in an academic setting tends to follow a pretty standard formula: Identify a topic to study, find funding, conduct the research, write a paper on the findings, and get published in a peer-review journal.

Doing experiments for a popular-science television show is very different from that, but in some ways, there are similarities, too, Giapis says.

"This is entertainment, but from my perspective, it's a scientific experiment, and I wanted to get the numbers right and get the story right," he says.

What he did not realize at first when he agreed to work with NOVA was that the show has its own form of peer review. For this episode, NOVA's producers asked Andy Ingersoll, professor of planetary science at Caltech and a member of the science teams of several NASA research missions, including Voyager and Cassini, to review Giapis's work.

"It's a nice little physics problem, and it was a pleasure to have Kostas explain it to me," Ingersoll says.

And Giapis said he enjoyed working on it.

"This was a very interesting story. It requires experimentation. It requires thinking. It requires some forensics, explaining the timeline of events," he says.

And now he says he understands why people are still so fascinated by the Hindenburg, nearly 100 years after its final, fateful voyage.

"What an apparition it must have been to see. People were mesmerized by it," he says. "It was one of the wonders of the world and the best of its day. It was an unbelievable mode of transportation, a flying hotel for the richest of the rich. And it was the first televised major air disaster that people watched all around the world."

Cultural diversity -- indicated by linguistic diversity -- and biodiversity are linked, and their connection may be another way to preserve both natural environments and Indigenous populations in Africa and perhaps worldwide, according to an international team of researchers.

"The punchline is, that if you are interested in conserving biological diversity, excluding the Indigenous people who likely helped create that diversity in the first place may be a really bad idea," said Larry Gorenflo, professor of landscape architecture, geography and African studies, Penn State. "Humans are part of ecosystems and I hope this study will usher in a more committed effort to engage Indigenous people in conserving localities containing key biodiversity."

Gorenflo, working with linguist Suzanne Romaine, Merton College, University of Oxford, UK, looked at 48 localities in Africa designated by the United Nations Education, Scientific and Cultural Organization (UNESCO) as Natural World Heritage Sites. These sites host "globally important natural or combined natural and cultural resources," they report. This paper was placed online as an unedited manuscript in January 2021 ahead of final online publication in April 2021 in Conservation Biology.

They analyzed geographic information system data on Indigenous languages in these areas and found that 147 languages overlapped with the UNESCO sites. Indigenous languages occurred in all but one of the Natural World Heritage Sites examined.

"The Namib Sand Sea desert in Namibia is a pretty dry area," said Gorenflo. "Kind of desolate, with wonderful sand dunes and natural features, but so harsh that there is no one living there as far as I know."

But in all the other Natural World Heritage Sites in continental Africa and on nearby islands, Indigenous people not only live, but, to some extent, manage the environment in which they live and have been doing so for a long time.

"The big message is basically that there is increasing evidence that cultural diversity and biodiversity are interrelated, and we found this at a fairly fine geographic scale," said Gorenflo. "If this is the case, then it makes a strong argument for Indigenous people to be part of ecosystem management in sites where they live.

"In terms of management approach, when there is more than one linguistic group associated with a specific site, the strategy probably should be to let the people associated with individual areas deal with those areas," he said.

In addition to finding that speakers of Indigenous languages often live in high-profile UNESCO sites, the researchers also found that the number of languages in these localities correlated with the number of species whose ranges of occurrence include these sites.

For their language data, the team used Ethnologue, a linguistic database originally established to translate the bible and the only global dataset for languages with detailed geographic information.

"The database is certainly not totally correct," said Gorenflo. "But it does show major patterns."

For the species data, the researchers used the International Union for Conservation of Nature's Red List of Endangered Species which includes species range data. They looked at amphibians, mammals, reptiles and a collection of freshwater species. They also used data from Birdlife International and "Handbook of the Birds of the World" for bird species.

"What we found numerically is that within UNESCO World Heritage Sites, if you plot language numbers against species range numbers, you find that there is a positive relationship," said Gorenflo. "It may be because more natural complexity generates more cultural complexity, though we do not know for sure."

Study results revealed that in the UNESCO sties in Africa, Indigenous languages overlapped with the ranges of more than 8,200 species in the groups considered.

Gorenflo suggests that there might be a reduction in biodiversity in these globally important African sites if Indigenous groups are displaced or somehow have their influence on managing these localities marginalized.

"Our ultimate goal is to try to look at a few places and figure out how we might redesign and reconsider management strategies and get Indigenous people more involved in shared governance."

Focusing on these high-profile UNESCO sites provides a basis for engaging Indigenous people in governance that hopefully will extend to less noteworthy places in Africa and beyond, according to Gorenflo.

He hopes to examine specific areas to increase their understanding of the relationship between biological and linguistic diversity, focusing first on the Eastern Arc Mountains of Tanzania where much of the linguistic and biological diversity occur in this nation. He also plans to examine Vanuatu, an archipelago in the eastern Melanesian Islands Biodiversity Hotspot with particularly dense linguistic diversity. Two other biodiversity hotspots of interest are Indo-Burma -- Cambodia, Lao, Viet Nam, Myanmar and Southern China -- and Mesoamerica, two regions where linguistic diversity is also quite high.

Indigenous people have lived in the Bears Ears region of southeastern Utah for millennia. Ancestral Pueblos built elaborate houses, check dams, agricultural terraces and other modifications of the landscape, leaving ecological legacies that persist to this day. Identifying how humans interacted with past environments is critical for informing how best to protect archaeological sites and ecological diversity in the present. This "archaeo-ecosystem" approach would facilitate co-management of public lands in ways that promote Indigenous health, cultural reclamation and sovereignty.

For the first time, a new study evaluated ecological legacies, archaeo-ecosystem restoration and Indigenous co-management practices in the Bears Ears region on the Colorado Plateau. The study published on May 17, 2021 in the journal Proceedings of the National Academy of Sciences.

"Bears Ears is not just about boundaries, it's about management," said the study's lead author Bruce Pavlik, director of conservation at Red Butte Garden. "And it's not just about artifacts. It's also about the archaeo-ecosystems that are there. That's what's sacred to Native people."

The authors surveyed 25 archaeological sites in the Bears Ears region that represented a wide range of locations, environments and archaeological complexity. By collecting plant specimens found at those sites, they compiled a list of 117 culturally significant plant species--those used for food, medicinal, ceremonial and utilitarian purposes by the Hopi Tribe, Ute Mountain Ute Tribe, Apache Tribe, Pueblo of Zuni and the Navajo (Diné) Nation who trace ancestry to or currently reside in the region. They found that dense concentrations of archaeological features, probably the result of larger populations of people, had a higher diversity of culturally significant plant species called ethnographic species richness. The implication is that people left behind those plants as a living legacy, either through intentional propagation or accidental release when they discarded unused seeds or fruits.

"The medicines on the landscape all have a story," said co-author Cynthia Wilson, director of the Traditional Foods Program for Utah Diné Bikéyah and member of the Navajo (Diné) Nation. "The original proposal to designate 1.9 million acres for Bears Ears National Monument came from listening to the elders and medicine people who mapped culturally significant plants to protect our narratives. In terms of management, traditional knowledge is crucial to protect the entire ecosystem as a cultural living landscape. Our ancestors tended to these ancient gardens that warrant special management regime. Right now, there's no real security to prevent damage."

Co-author Arnold Clifford, renowned botanist at Carrizo Mountain Environmental & Herbarium, Inc., and member of the Navajo (Diné) Nation, noted that seven plant species that occurred within these Bears Ears sites are held as sacred as lifeway medicines. Some plant species found at archaeological sites, such as sagebrush and pinyon pine, are common across the landscape. However, at least 31 plant species were extremely rare outside of the habitation structures, including the Four Corners potato (Solanum jamesii), a native tuber that is an important medicine and food source.

"In other words, the plants weren't randomly just there," said Pavlik. "People brought propagules of the species in with them. This is one of the rare times in the archaeological literature where people invested in native species and brought them to their habitations. It indicates this higher level of landscape manipulation, what we call an ecological legacy of past human occupation."

Using data on known archaeological sites from Utah's State Historic Preservation Office, co-author Brian Codding, anthropologist and director of the University of Utah Archaeological Center, worked with anthropology Ph.D. students Peter Yaworsky and Kenneth B. Vernon to develop a statistical model assessing botanical richness based on archaeological and environmental variables for an additional 240 archaeological sites across the Bears Ears region.

"We used what we recorded in the field to project our findings across the whole region," Codding said. "The model can help Tribal and federal land managers identify places that need the most protection to preserve complex archaeological sites and important plant species."

Effective stewardship of the Bears Ears region will require special management policies applied to these botanically and culturally rich archaeo-ecosystems. A blend of western science and deep Indigenous ecological knowledge can be used to mitigate the effects of increased visitation, proposed development and expanded resource extraction.

"What Tribal members have said all along is that you don't just preserve the archaeological site," said Lisbeth Louderback, curator of archaeology and director of the archaeobotany lab at the Natural History Museum of Utah and anthropologist at the University of Utah. "You have to preserve the entire resource space around the site, including the plants. Building a management plan incorporating both western science and traditional knowledge will get a full picture of the best way to take care of the resources and the monument."

"The knowledge that came from this publication is not only an important contribution to Bears Ears, but also to Grand Staircase-Escalante National Monument," Wilson said. "The ancestral Pueblo people travelled long distances to transport, trade and take care of plants like the Four Corners potato across the region and they have left these seeds for us to continue taking care of today."

MUSC Hollings Cancer Center lung cancer researcher Gerard Silvestri, M.D., found that a lack of insurance leads to worse cancer survival than for those with Medicare, in a paper published in the May issue of Health Affairs. This work, a joint effort between Silvestri and researchers at the American Cancer Society, highlights the current dire barrier in medical care: Many people cannot take advantage of the newer potentially lifesaving treatments due to the high costs.

Silvestri said the research began last year, inspired by the hotly debated topic of expanding Medicare insurance coverage to those under 65. Using the National Cancer Database, which contained data collected between 2004 through 2016 from over 1.2 million cancer patients, Silvestri began investigating lung cancer outcomes based on insurance status and age.

The findings in lung cancer were so surprising that the American Cancer Society recommended looking at 1-year, 2-year, and 5-year survival rates across the 16 most common cancers, including lung, breast, colon and prostate cancer. Due to the large study population, comorbidities and other disease factors were able to be matched across these four groups: uninsured patients 60 to 64 years old, private insurance patients 60 to 64 years old, Medicare patients 66 to 69 years old and Medicare plus private insurance 66 to 69 years old.

Generally, when comparing cancer survival among patients with similar stages and types of cancer, younger patients have better outcomes than their older counterparts, Silvestri said. However, this study found that across all 16 cancer types those younger than Medicare age (60 to 64 years old) without health insurance had significantly worse survival than their older counterparts.

"Further, there was a dose response gradient across the different insurance groups. Uninsured younger patients had the lowest survival, followed by older Medicare patients without supplemental private insurance, then older Medicare patients with supplemental private insurance, with younger privately insured patients having the best survival. The survival difference was quite surprising," he said.

"Even in cancers with poor five-year survival amongst all insurance groups, the differences observed between uninsured individuals 60 to 64 years old versus individuals ages 66 to 69 years old could be seen at one and two years with Medicare patients having significantly better survival at those yearly landmarks compared to younger uninsured patients," explained Silvestri, an MUSC Health lung cancer pulmonologist at Hollings.

Silvestri said this research is important to him given his personal experiences. As one of seven children in his family, Silvestri vividly remembers his family dealing with his father's cancer as he battled through treatments for more than five years. After his father's death, the financial burden did not stop as his mother kept paying the medical bills monthly for many years thereafter, despite his family having medical insurance.

Unexpected medical expenses are one of the leading causes of personal bankruptcy. Research published in a 2018 article in the American Journal of Public Health found that over 66% of personal bankruptcy is due to medical debt.

Due to the financial hurdle, uninsured patients often present with advanced, non-curable disease because they may delay medical care or be unable to afford screenings. Additionally, some cancer drugs cost tens of thousands of dollars annually, which may be more than double a household's annual income, he said.

"The results of this study lead me to ask this simple question: 'Is it OK for a patient to die from cancer simply because he or she does not have health insurance?' If the answer is 'no' to that question, then a true policy discussion needs to happen at a high level," Silvestri said.

As a pulmonologist, Silvestri is particularly interested in the insurance and survival disparities in lung cancer. Lung cancer is unique because it occurs primarily in smokers. According to the Centers for Disease Control and Prevention (CDC), approximately 30% of uninsured adults smoke, and smoking is more prevalent among people with a low annual household income. Since many smokers fall into a segment of the population that lacks insurance, this can affect their ability to pursue care, as many uninsured individuals will not seek regular lung cancer screening, he said.

"Fortunately, the cancer center is really well-positioned to help smokers with programmatic support," said Silvestri. Hollings, which is the state's only National Cancer Institute-designated cancer center, has a robust smoking cessation program, a lung cancer screening program, as well as rigorous disparities research, which has led to the implementation of novel programs across the state, he said.

While the current study focused on insurance disparities and survival outcomes in cancer, it is highly probable that these findings could be replicated in studies of other chronic diseases, such as diabetes and heart disease. Silvestri hopes this research will be a catalyst for conversations about the financial toxicity of cancer treatment, at the state and national level.

"Although I was initially surprised to see that lack of insurance was a greater predictor of worse outcomes in lung cancer than older age, I was even more shocked to see that this phenomenon was true across all major cancer types. People who want to change the paradigm need to make it personal and share the numerous stories of patients who, after they are told they have cancer and their world is turned upside down, are forced to ask, 'How am I going to afford this?' rather than 'What can we do to cure me?'" said Silvestri.

ATS 2021, New York, NY - The COVID-19 pandemic has, and will continue to have, a tremendous impact on ICU nurses' mental health and willingness to continue in the critical care work force, according to research presented at the ATS 2021 International Conference.

Jill Guttormson, PhD, RN, associate dean for Academic Affairs and associate professor, College of Nursing, Marquette University, and colleagues sought to describe the impact of COVID-19 on ICU nurses through a survey using valid and reliable measures of burnout, moral distress, depression, anxiety, and posttraumatic stress symptoms.

The researchers recruited a national sample of nurses who have worked in the ICU during the COVID-19 pandemic between October and December 2020, through the American Association of Critical Care Nurses newsletters and social media.

Four hundred eighty-eight U.S. critical care nurses responded to the survey. Staff nurses comprised 92.5 percent of respondents, 29 percent were reassigned to a COVID unit other than their usual ICU, and 68 percent experienced a shortage of personal protective equipment (PPE).

Nurse respondents reported higher levels of moral distress and burnout than reported for ICU or trauma nurses prior to the pandemic.

They also stated that they had higher anxiety and depression than reported in the general population and higher risk for having post-traumatic stress disorder (PTSD) than recent veterans or patients after traumatic injury. Symptoms of moderate to severe depression and anxiety were reported, respectively, by 44.6 percent and 31 percent of respondents. Forty-seven percent of respondents were at risk for having PTSD.

"It is vitally important that we allow space and time for critical care nurses to share their experiences during the COVID-19 pandemic and that this support not stop when the pandemic is over," stated Dr. Guttormson. "Based on these results, the pandemic will have long-term repercussions for critical care nurses and may result in nurses leaving critical care or the nursing profession."

This study offers important insights about the mental health of nurses during a global pandemic that can guide the development of tailored interventions for ICU nurses to support them as the pandemic continues, as well as after the crisis, noted the authors. "Interventions are needed that allow and support critical care nurses to make sense of and find meaning from their experiences during the pandemic."

In a surprise find, scientists have discovered sugar-coated RNA molecules decorating the surface of cells.

These so-called "glycoRNAs" poke out from mammalian cells' outer membrane, where they can interact with other molecules. This discovery, reported May 17, 2021, in the journal Cell, upends the current understanding of how the cell handles RNAs and glycans.

"This was probably the biggest scientific shock of my life," says study author Carolyn Bertozzi, a Howard Hughes Medical Institute Investigator at Stanford University. "Based on the framework by which we understand cell biology, there's no place where glycan sugars and RNA would physically touch each other."

Normally, RNA is made in the nucleus and transported to the cytoplasm, where it serves as a template for making proteins. Until now, scientists thought glycans were kept separate. But the new work suggests that the two molecules actually meet up, and the sugar-coated RNAs take a trip to the cell surface.

Bertozzi's team's initial findings drew considerable attention when she posted them on the preprint server bioRxiv.org in 2019. Now, the scientists report a new physical position for the glycoRNAs, opening a possible role for the sugar-coated RNAs in immune disease.

A molecule that shouldn't exist

Researchers have been studying "glycobiology" for decades. Sugars serve a key role in cellular communication, among other functions. Previously, scientists had found glycans attached to proteins and fats. Glycomolecules even stud the cell walls of bacteria and fungi, helping cells communicate and infect their hosts.

Until now, glycobiology and RNA biology did not overlap. Scientists in the two fields use different chemistry and techniques to study their molecules. Study coauthor Ryan Flynn, who spent his graduate school years working on RNA, hadn't encountered glycobiology until a chance meeting with a student in Bertozzi's lab. "Glycans are critical in biology, and I somehow didn't know anything about them," he says. Flynn was intrigued.

Bertozzi brought Flynn on as a postdoc in 2017. The more he learned, the more he wondered whether glycans might link up with RNAs. The team knew, for instance, of a glycan enzyme that could bind RNAs. That made Flynn wonder if RNA itself could connect with the sugars. And although most glycans reside in a cellular compartment called the Golgi, one type of glycan does mingle in the cytoplasm, where RNA typically dwells.

So Flynn went hunting for glycoRNAs. He chemically tagged glycans within the cell and then looked for RNAs among the tagged molecules. A hit would mean he found a molecule that contained both RNA and a sugar. He ran experiments for months. In all that time, "I didn't find anything," he says. But that wasn't quite true.

Flynn had also been looking for glycoRNAs in the Golgi. Because RNA was not expected to be there, the test served as a negative control - a way to confirm that his experiment was not detecting RNAs everywhere he looked.

But the negative control kept coming back positive. Somehow, RNAs were hooking up with sugars in the Golgi. The team thought the experiment must have been contaminated, Bertozzi says. "We were trying to come up with a million answers as to how this sugar would be physically associated with RNA."

Flynn did every experiment he could think of to rule out the possibility that the signal was coming from something besides RNA. The answer never changed. He found the glycoRNAs in every type of cell he could grow in the lab. He even found them in tissues from mice, and, more recently, discovered glycoRNAs on the cell surface.

"They applied every possible way one can imagine to confirm the presence of glycan-modified RNA," says chemical biologist Chuan He, an HHMI Investigator at the University of Chicago who was not involved with the new work.

Bertozzi and Flynn credit the discovery to their unusual intersection of skills. Combining tools and expertise from both RNA biology and glycobiology let them discover a phenomenon that was seemingly in plain view - if you knew how to look for it.

An unexpected connection

Meanwhile, researchers in Bertozzi's lab had also been studying a type of cell surface protein called "Siglecs." These molecules bind to glycans and play a role in the immune system. Flynn wondered if Siglecs could also bind to the newly discovered glycoRNAs.

"This was one of those, 'let's just give it a try, who knows' experiments," Bertozzi says. Flynn tested 12 different Siglec molecules and found that two of them stuck to glycoRNAs.

A literature search revealed that one of the Siglec molecules had been previously linked to the autoimmune disease lupus. Finding connections between these different kinds of molecules starts to fill in a new and emerging picture of biology, Bertozzi says. That picture may look something like this: RNA hangs out on the cell surface, decorated with sugars. These sugars stick to Siglec proteins that help the immune system distinguish friend from foe.

Scientists have much more to learn before understanding how ¬- or if - glycoRNAs are involved in immune signaling, Flynn says. He is now running his own lab at Boston Children's Hospital and Harvard University's stem cell and regenerative biology department and plans to investigate these questions.

Bertozzi says the freedom to pursue an unlikely observation made the glycoRNA discovery possible. "That's what HHMI provided," she says. "If I were a junior scientist who stumbled into this and put out an NIH grant, we'd get laughed out of the study section."

DALLAS, May 17, 2021 -- Detecting a critical heart defect before birth (congenital heart defects) is less likely when a mother lives in a rural area, lives in a neighborhood with low socioeconomic status or is Hispanic, according to new research published today in the American Heart Association's flagship journal Circulation.

Diagnosing a heart defect before birth reduces infant death rates, increases access to prompt medical treatment, improves neurodevelopmental outcomes and decreases the risk of brain injury for the infant after birth.

"The benefits of prenatal diagnosis for heart defects have been recognized for years, yet prenatal detection occurs in less than 60% of congenital heart disease cases in many U.S. regions," said the study's first author Anita Krishnan, M.D., an associate professor of pediatrics and associate director of echocardiography at Children's National Hospital in Washington, D.C.

"This is one of the largest studies to define specific populations at risk for missed prenatal screening and diagnosis of congenital heart disease," she said. "With these conditions, minutes can make a difference, and prenatal planning allows for improved care before, during and after birth."

Researchers evaluated data on more than 1,800 infants from 21 cardiology centers in the United States and Canada to determine whether a relationship exists between prenatal detection of transposition of the great arteries and hypoplastic left heart syndrome and socioeconomic, racial/ethnic and geographic factors.

Congenital heart defects are heart conditions present at birth. According to the American Heart Association's Heart Disease and Stroke Statistics -- 2021 Update, an estimated minimum of 40,000 infants are expected to be affected each year by congenital heart defects in the United States. At least 18 distinct types of congenital heart defects are recognized, with many additional anatomic variations.

Transposition of the great arteries occurs when the two main arteries leaving the heart are reversed and accounts for 2.6% of congenital heart defects. Hypoplastic left heart syndrome involves an underdeveloped left side of the heart and accounts for about 0.3% of the defects.

The study focused on clinical data from fetuses and infants with a first-time evaluation between 2012 and 2016 at a participating institution in the Fetal Heart Society, a non-profit multicenter research collaborative whose mission is to advance the field of fetal cardiovascular care and science. Researchers defined prenatal detection as having a fetal echocardiogram - a test that uses high frequency sound waves, or ultrasound, to view structures and functioning of the fetus' heart. Patients are referred for fetal echocardiograms for a variety of maternal or fetal conditions per the guidelines from the American Institute of Ultrasound in Medicine, or if an anomaly is suspected on a second trimester ultrasound examination. Most cases are referred due to suspected cardiac disease and not for one of the routine indications for fetal echocardiography, Krishnan explained.

Hypoplastic left heart syndrome is identifiable through echocardiogram imaging of the heart's four chambers; however, detecting transposition of the great arteries requires additional views on prenatal ultrasound screening and may be more difficult to detect prenatally than hypoplastic left heart syndrome, the authors noted.

Socioeconomic and residential information came from federal census data for the mothers, and distance from a cardiology center was derived from the mothers' address at the time of her first visit for prenatal detection. For U.S. patients, socioeconomic neighborhood status was measured in quartiles that considered median household income; median household value; neighborhood percentage of high school graduates; neighborhood percentage of college graduates; percentage of neighborhood residents in executive, managerial or professional specialty occupations; and the percentage of households receiving rental income.

Among Canadian patients - all from Alberta and Ontario - socioeconomic status was calculated from 22 variables related to cultural identities, environmental pollutants, environmental injustice studies and a deprivation index, which is a marker of social inequalities in health. These factors were then converted to be comparable with the U.S. quartiles.

The study revealed that about 92% of hypoplastic left heart syndrome cases and 58% of transposition of the great arteries cases were diagnosed before birth. However, significant socioeconomic and racial and ethnic differences emerged among the women diagnosed with fetal transposition of the great arteries.

"Mothers who lived in neighborhoods with the lowest socioeconomic position were up to 22% less likely to receive a prenatal diagnosis of transposition of the great arteries than the mothers who lived in the wealthiest neighborhoods," Krishnan said. "While the findings are not completely surprising and resonate with clinical experience, the strength of the associations was surprising."

Other findings include:

Hispanic ethnicity in the United States was associated with a 15% lower likelihood of prenatal detection of transposition of the great arteries compared to non-Hispanic mothers, and living in rural areas was associated with a 22% lower likelihood of prenatal detection of transposition of the great arteries compared to mothers who lived in more urban areas.

Among the patients in Canada, only longer distance to a cardiology center was associated with lower prenatal detection rates of hypoplastic left heart syndrome - those driving more than 135 miles for care were 24% less likely to have transposition of the great arteries detected.

Lower socioeconomic status was associated with about a four-week delay in diagnosing prenatal congenital heart disease for pregnant women in both the U.S. and Canada.

The standards of care for congenital heart disease are similar in both countries, yet some of the associations were different in the United States compared to Canada, where health care is publicly funded and available to all Canadian citizens or permanent residents without financial limitations. "This suggests that factors related to the different health care delivery systems may also play a role in the rates of screening and diagnosis," Krishnan said.

"While prenatal detection rates of congenital heart disease are lower than they should be across the board, there are striking sociodemographic and geographic disparities," she said. "Strengthening relationships among cardiology and surgery centers and the populations identified in this study, through outreach and potentially telemedicine, may improve prenatal detection rates within these communities.

"Telehealth linkages to the tertiary care center may improve timeliness of detection as well as overall detection rates, but is likely not the only solution," Krishnan continued. "In-person collaboration or consultation is also needed. There is ongoing study of whether socioeconomic barriers exist to participation with telemedicine and internet, and our center is currently doing pilot work in rural Maryland. To successfully implement telemedicine requires investing in the hardware, educating sonographers and establishing the security infrastructure to make telemedicine easier to perform."

The study created a new registry of data variables that had not been possible using hospital databases that typically do not include prenatal care information linking maternal and pediatric records. A significant limitation is that the study only included patients who received care at one of the 21 participating fetal cardiology centers.

What The Study Did: Researchers assessed the feasibility of using positive behavior supports to promote the use of face coverings in school-aged children with autism spectrum disorders and/or attention-deficit/hyperactivity disorder (ADHD) attending a summer program during the COVID-19 pandemic.

Authors: Benjamin Aaronson, Ph.D., of the University of Washington in Seattle, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.10281)

Editor's Note: The article includes conflicts of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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Early diagnosis and improvement of breast cancer treatments have reduced breast cancer mortality in recent years, with survival rates reaching 85% today. In spite of these data, breast cancer was still the most frequently diagnosed tumour in the world in 2020, mainly due to increased population screening and social factors such as ageing. RANK protein plays a key role in the development of these tumours. Located in the membrane of cells, when it binds to its partner RANKL, it sends signals that stimulate the development of the mammary gland. When these proteins do not work properly, breast cells begin to divide and multiply uncontrollably, resulting in breast cancer.

Researchers from the Spanish National Cancer Research Centre (CNIO) and the Bellvitge Biomedical Research Institute (IDIBELL), led by Eva González-Suárez at the CNIO, have found that the hyperactivation of the RANK pathway plays a double function in breast cells: in the early stages of cancer, it activates senescence, which has a protective effect and delays the appearance of tumours; in more advanced stages, RANK-induced senescence favours the accumulation of stem cells in the breast tissue, which promotes tumour growth and increased aggressiveness. The results of the work are published this week in the journal Developmental Cell.

The authors describe throughout the paper how this double activation of senescence and tumour stem cells occurs in response to high RANK levels, using mice that produced large amounts of this protein in the epithelial cells of breast tissue. "We observe that high levels of RANK protein induce senescence and at the same time an accumulation of stem cells, which in principle seems contradictory, but is not," explains González-Suárez.

RANK protein, from bone formation to cancer

RANK proteins have been linked to bone tissue remodelling, and blocking these proteins by means of inhibitors such as denosumab antibodies has been shown to be effective in the treatment of bone-related pathologies such as osteoporosis and bone metastases.

These proteins also participate in the development of the mammary gland, which occurs mainly in women during puberty, pregnancy and the menstrual cycle in response to sex hormones. When these proteins do not work properly, breast cells begin to divide and multiply uncontrollably. "In this paper, we have detected abnormally high levels of RANK in pre-neoplastic lesions in patients with breast cancer," the researchers report. How does RANK act on epithelial cells in the mammary glands to promote cancer?

In 2010, González-Suárez first described the key role of this protein in the development of breast cancer and proposed that drug inhibition by means of RANKL inhibitors could prevent breast cancer. Over the course of a few years, "we demonstrated its therapeutic potential for the treatment of breast tumours by reducing recurrence and metastases, both because of its role in tumour cells and because of a reactivation of the anti-tumour immune response," the researcher said.

A protective mechanism that becomes harmful

Senescence is a process historically associated with the protection of cells and tissues. Cells begin their senescence programme in response to stimuli such as the activation of oncogenes - cancer-promoting genes -, the absence or failure of anticancer genes, or the shortening of telomeres - the protein structures that protect the ends of chromosomes. All of these stimuli are harmful, and senescence causes cells to enter a state of lethargy to facilitate cell integrity. But today it is known that, in addition to the protective role of senescence against the development of diseases such as cancer, it can be a double-edged sword and favour pathological processes; for example, in obesity and diabetes, it promotes the disease, increasing insulin resistance and inflammation.

In the paper published in Developmental Cell, the researchers have found that, in the early stages of breast cancer, high levels of RANK protein in the breast epithelium in mice induce senescence and a delay in tumour development. In contrast, in more advanced stages of tumours, they observed that senescence favoured the accumulation of stem cells in the breast tissue, leading to increased tumour growth and aggressiveness.

"The mammary gland contains stem cells, which are like primitive cells that have the ability to differentiate into different cell types and promote tumour formation and increase their metastatic capacity," says González-Suárez. The researcher had already seen in previous studies that RANK promotes stem cell properties in the mouse mammary epithelia. Now, the authors of the study have for the first time in breast cancer linked senescence to an increase in the stem cell properties of RANK regulated tissue, and how this leads to an increase in tumour progression and aggressiveness.

Non-tumour cells that send signals to favour cancer

In this sequence of events in which RANK is activated, the team has observed that in the earliest stages of the disease, senescence was activated primarily in the luminal cells of the breast epithelium, those that are most exposed to the lumen of the breast ducts.

In the work they suggest that these senescent, non-tumour cells release a series of substances that act in a paracrine way - at a distance from neighbouring cells- on luminal and basal cells, the latter of which are far from the lumen of the ducts. In response to this stimulus, luminal and basal cells acquire stem cell characteristics, and despite the misleading initial delay, the resulting tumours are more aggressive, growing rapidly, causing lung metastases.

Previous studies by González-Suárez and other research groups suggest that RANK inhibitors could prevent breast cancer and improve the prognosis of patients. "Preventive clinical trials on this type of compounds are currently underway in a subgroup of BRCA1 gene mutation-bearing women, who are at high risk of developing breast tumours. The inhibition of RANKL offers a much less aggressive alternative to mastectomy. Other trials are testing the potential of RANKL inhibitors to improve survival in breast cancer, among other tumours," explains González-Suárez

Doctors often recommend Omega-3s to help patients lower their cholesterol and improve heart health. Those Omega-3s can come from fatty fish like salmon and mackerel, or supplements that often contain a combination of the acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

Now, new research from the Intermountain Healthcare Heart Institute in Salt Lake City finds that higher EPA blood levels alone lowered the risk of major cardiac events and death in patients, while DHA blunted the cardiovascular benefits of EPA. Higher DHA levels at any level of EPA, worsened health outcomes.

Results of the Intermountain study, which examined nearly 1,000 patients over a 10-year-period, will be presented virtually at the 2021 American College of Cardiology's Scientific Session on Monday, May 17.

"The advice to take Omega-3s for the good of your heart is pervasive, but previous studies have shown that science doesn't really back this up for every single omega-3," said Viet T. Le, MPAS, PA, researcher and cardiovascular physician assistant at the Intermountain Heart Institute and principal investigator of the study. "Our findings show that not all Omega-3s are alike, and that EPA and DHA combined together, as they often are in supplements, may void the benefits that patients and their doctors hope to achieve."

In this study, Intermountain researchers used the INSPIRE registry, an Intermountain Healthcare database started in 1993 that has more than 35,000 blood samples from nearly 25,000 patients.

Through INSPIRE, researchers identified 987 patients who underwent their first documented coronary angiographic study at Intermountain Healthcare between 1994 and 2012. From those blood samples, the circulating levels of EPA and DHA in their blood was measured. Researchers then tracked those patients for 10 years, looking for major cardiac adverse events, which included heart attack, stroke, heart failure requiring hospitalization or death.

They found that patients with the highest levels of EPA had reduced risk of major heart events. When evaluating how EPA and DHA affect one another, they found that higher DHA blunts the benefit of EPA. In particular, they also found that those patients with higher levels of DHA than EPA, were more at risk for heart problems.

Le said that these results raise further concerns about the use of combined EPA/DHA, particularly through supplements.

"Based on these and other findings, we can still tell our patients to eat Omega-3 rich foods, but we should not be recommending them in pill form as supplements or even as combined (EPA + DHA) prescription products," he said. "Our data adds further strength to the findings of the recent REDUCE-IT (2018) study that EPA-only prescription products reduce heart disease events."

Mitochondria - the 'batteries' that power our cells - play an unexpected role in common diseases such as type 2 diabetes and multiple sclerosis, concludes a study of over 350,000 people conducted by the University of Cambridge.

The study, published today in Nature Genetics, found that genetic variants in the DNA of mitochondria could increase the risk of developing these conditions, as well influencing characteristics such as height and lifespan.

There was also evidence that some changes in mitochondrial DNA were more common in people with Scottish, Welsh or Northumbrian genetic ancestry, implying that mitochondrial DNA and nuclear DNA (which accounts for 99.9% of our genetic make-up) interact with each other.

Almost all of the DNA that makes up the human genome - the body's 'blueprint' - is contained within the nuclei of our cells. Among other functions, nuclear DNA codes for the characteristics that make us individual as well as for the proteins that do most of the work in our bodies.

Our cells also contain mitochondria, often referred to as 'batteries', which provide the energy for our cells to function. They do this by converting the food that we eat into ATP, a molecule capable of releasing energy very quickly. Each of these mitochondria is coded for by a tiny amount of 'mitochondrial DNA'. Mitochondrial DNA makes up only 0.1% of the overall human genome and is passed down exclusively from mother to child.

While errors in mitochondrial DNA can lead to so-called mitochondrial diseases, which can be severely disabling, until now there had been little evidence that these variants can influence more common diseases. Several small-scale studies have hinted at this possibility, but scientists have been unable to replicate their findings.

Now, a team at the University of Cambridge has developed a new technique to study mitochondrial DNA and its relation to human diseases and characteristics in samples taken from 358,000 volunteers as part of UK Biobank, a large-scale biomedical database and research resource.

Dr Joanna Howson, who carried out the work while at the Department of Public Health and Primary Care at the University of Cambridge, said: "Using this new method, we've been able to look for associations between the numerous features that have been recorded for participants of UK Biobank and see whether any correlate with mitochondrial DNA.

"Aside from mitochondrial diseases, we don't generally associate mitochondrial DNA variants with common diseases. But what we've shown is that mitochondrial DNA - which we inherit from our mother - influences the risk of some diseases such as type 2 diabetes and MS as well as a number of common characteristics."

Among those factors found to be influenced by mitochondrial DNA are: type 2 diabetes, multiple sclerosis, liver and kidney function, blood count parameters, life span and height. While some of the effects are seen more extremely in patients with rare inherited mitochondrial diseases - for example, patients with severe disease are often shorter than average - the effect in healthy individuals tends to be much subtler, likely accounting for just a few millimetres' height difference, for example.

There are several possible explanations for how mitochondrial DNA exerts its influence. One is that changes to mitochondrial DNA lead to subtle differences in our ability to produce energy. However, it is likely to be more complicated, affecting complex biological pathways inside our bodies - the signals that allow our cells to operate in a coordinated fashion.

Professor Patrick Chinnery from the MRC Mitochondrial Biology Unit at Cambridge said: "If you want a complete picture of common diseases, then clearly you're going to need to factor in the influence of mitochondrial DNA. The ultimate aim of studies of our DNA is to understand the mechanisms that underlie these diseases and find new ways to treat them. Our work could help identify potential new drug targets."

Unlike nuclear DNA, which is passed down from both the mother and the father, mitochondria DNA is inherited exclusively from the mother. This suggests that the two systems are inherited independently and hence there should be no association between an individual's nuclear and mitochondrial DNA - however, this was not what the team found.

The researchers showed that certain nuclear genetic backgrounds are associated preferentially with certain mitochondrial genetic backgrounds, particularly in Scotland, Wales and Northumbria. This suggests that our nuclear and mitochondrial genomes have evolved - and continue to evolve - side-by-side and interact with each other.

One reason that may explain this is the need for compatibility. ATP is produced by a group of proteins inside the mitochondria, called the respiratory chain. There are over 100 components of the respiratory chain, 13 of which are coded for by mitochondrial DNA; the remainder are coded for by nuclear DNA. Even though proteins in the respiratory chain are being produced by two different genomes, the proteins need to physically interlock like pieces of a jigsaw.

If the mitochondrial DNA inherited by a child was not compatible with the nuclear DNA inherited from the father, the jigsaw would not fit together properly, thereby affecting the respiratory chain and, consequently, energy production. This might subtly influence an individual's health or physiology, which over time could be disadvantageous from an evolutionary perspective. Conversely, matches would be encouraged by evolution and therefore become more common.

This could have implications for the success of mitochondrial transfer therapy - a new technique that enables scientists to replace a mother's defective mitochondria with those from a donor, thereby preventing her child from having a potentially life-threatening mitochondrial disease.

"It looks like our mitochondrial DNA is matched to our nuclear DNA to some extent - in other words, you can't just swap the mitochondria with any donor, just as you can't take a blood transfusion from anyone," explained Professor Chinnery. "Fortunately, this possibility has already been factored into the approach taken by the team at Newcastle who have pioneered this therapy."

In the largest genetic study of bipolar disorder to date, researchers have identified 64 regions of the genome containing DNA variations that increase risk of bipolar disorder - more than double the number previously identified.

The research team also found overlap in the genetic bases of bipolar disorder and other psychiatric disorders. Furthermore, the study supports a role of sleep habits, alcohol, and substance usage in the development of bipolar disorder, although further research is needed to confirm these findings. The study results are published May 17 in Nature Genetics.

Bipolar disorder, a complex psychiatric disorder characterized by recurrent episodes of severely high and low mood, affects an estimated 40 to 50 million people worldwide. It typically begins in young adulthood, often takes a chronic course, and carries an increased risk of suicide, making it a major public health concern and cause of global disability.

To help elucidate the underlying biology of bipolar disorder, an international team of scientists from within the Psychiatric Genomics Consortium conducted a genome-wide association study. This means they scanned the DNA of lots of people, looking for genetic markers that were more common in those who had bipolar disorder. This involved scanning more than 7.5 million common variations in the DNA sequence of nearly 415,000 people, more than 40,000 of whom had bipolar disorder. The study identified 64 regions of the genome that contain DNA variations that increase risk of bipolar disorder.

"It is well-established that bipolar disorder has a substantial genetic basis and identifying DNA variations that increase risk can yield insights into the condition's underlying biology," says Niamh Mullins, PhD, Assistant Professor of Psychiatric Genomics at the Icahn School of Medicine at Mount Sinai and lead author of the paper. "Our study found DNA variations involved in brain cell communication and calcium signaling that increase risk of bipolar disorder.

The findings suggest that drugs, such as calcium channel blockers that are already used for the treatment of high blood pressure and other conditions of the circulatory system, could be investigated as potential treatments for bipolar disorder, yet it's important to note that future research to directly assess whether these medications are effective is essential."

The study also found overlap in the genetic basis of bipolar disorder and that of other psychiatric disorders and confirmed the existence of partially genetically distinct subtypes of the disorder. Specifically, they found that bipolar I disorder shows a strong genetic similarity with schizophrenia and bipolar II disorder is more genetically similar to major depression.

"This research would not have been possible without the collaborative efforts of scientists worldwide that enabled the study of hundreds of thousands of DNA sequences," said Ole Andreassen, MD, PhD, Professor of Psychiatry, Institute of Clinical Medicine and Oslo University Hospital and senior author of the paper. "Through this work, we prioritized some specific genes and DNA variations which can now be followed up in laboratory experiments to better understand the biological mechanisms through which they act to increase risk of bipolar disorder."

The biological insights gained from this research could ultimately lead to the development of new and improved treatments or precision medicine approaches to stratify patients at high genetic risk who may benefit from targeted treatment or intervention strategies. Understanding causal risk could aid clinical decision-making in the prevention or management of the illness. Future genetic studies in larger and more diverse populations are now needed to pinpoint the genes relevant to risk of bipolar disorder in other areas of the genome.

The Psychiatric Genomics Consortium (PGC) is an international consortium of scientists dedicated to studying the genetic basis of psychiatric disorders and includes over 800 researchers, from more than 150 institutions from over 40 countries.

A study published in the scientific journal Addiction provides the most comprehensive evidence to date of the association between recreational cannabis laws (RCLs) in US states and responses in the illegal markets for cannabis, heroin, and other drugs in those states.

As of 2021, 17 US states and the District of Columbia have implemented RCLs that allow people aged 21 and older to possess, use and supply limited amounts of cannabis for recreational purposes. This study found that the implementation of RCLs was associated with the following responses in the illegal drug market in those states:

9.2% decrease in street/illegal cannabis prices.

19.5% decrease in low-quality street/illegal cannabis prices.

64% increase in heroin prices.

54% increase in heroin potency.

7.3% increase in street/illegal oxycodone prices.

5.1% increase in street/illegal hydrocodone prices.

93% decrease in law enforcement seizures of street/illegal cannabis

>50% decrease in law enforcement seizures of heroin, oxycodone, and hydrocodone

Lead author Dr. Angélica Meinhofer (Assistant Professor of Population Health Sciences at Weill Cornell Medicine) says "Our exploratory findings suggest that markets for illegal drugs may not be independent of legal cannabis market regulation. As more states move towards legalization and additional post-RCL implementation data become available, we'll need to do more research to determine whether recreational cannabis laws cause those changes in the illegal market and what happens in the long-term."

This study used a difference-in-differences analysis of the staggered implementation of RCLs in 11 states to compare changes in outcomes between RCL and non-RCL states. This study used crowdsourced data from Price of Weed and StreetRx on the price and quality of illegal drugs, which may be subject to error and sampling bias.

Gears and mechanical transmissions are at home in the Emilia-Romagna region, the Motor Valley of northern Italy. A team of researchers from the University of Bologna and the Institute for Organic Synthesis and Photoreactivity of the National Research Council (Cnr-Isof) in Bologna, led by Massimo Baroncini and Alberto Credi, has planned, constructed and operated NanoGear, a device consisting of interlocked molecular components and designed to function as a gear. Since molecules are nanometric objects (1 nanometer = 1 millionth of a millimetre), it is an exceedingly small device: certainly, the tiniest gear ever produced in the Italian land of motors.

"The transmission and transformation of nanometric movements in biological molecules are the basis of the main functions of living organisms. Nevertheless, these phenomena are poorly understood in artificial molecules because they are extremely difficult to identify and observe. The construction of molecular devices such as NanoGear is a first step forward towards the development of ultra-miniaturized mechanical devices based on molecular motors, with potential breakthrough applications in various fields of technology and medicine ", says Alberto Credi.

THE DEVICE

The NanoGear molecule belongs to the class of rotaxanes and consists of three components: a ring that can slide along an axle that bears a rotor installed in its centre.

"The ring is free to shuttle along the axle for its entire length, but it cannot escape because two bulky groups (stoppers) positioned at the ends of the axle prevent it from slipping off. The rotor is free to rotate around its own axis and has two different 'blades' to facilitate observation of the movement", explains Massimo Baroncini. "The main design element of NanoGear lies in the fact that the rotor is directly linked to the axis with a regular chemical (covalent) bond, whereas the ring is mechanically locked around the axis by the presence of the stoppers. Both the translation of the ring and the rotation of the rotor are random oscillations determined by the thermal energy of the molecule; in other words, the gear is not coupled to any motor and functions 'in neutral'. Sophisticated nuclear magnetic resonance techniques were used to observe the movements and measure their rates".

At 65 °C, the ring shuttles from one end of the axle to the other about 7 times per minute, passing over the rotor; in the same amount of time, the latter completes about 260 rotations. Therefore the two motions are not synchronized; however, they mutually influence each other, as demonstrated by experiments carried out on molecules similar to NanoGear but devoid of the rotor or the ring.

Another significant and unexpected result is the effect of the medium in which the molecule is dispersed: by changing the solvent, one of the two movements is slowed down, while the other is accelerated. Such a 'specific lubrication' finds no correspondence in the macroscopic world, and constitutes one of the unconventional properties of nanodevices that could lead to radical technological innovations.

THE PROJECT

Artificial molecular machines, awarded with the Nobel Prize in Chemistry in 2016, convert energy from a source into controlled nanoscale movements and are one of the most striking results of nanotechnology. In order to exploit these movements, however, passive elements capable of processing them and transmitting them to other components, as it happens in macroscopic devices, are necessary. In this research, chemists operate in the same way as engineers and architects, but manipulating objects a billion times smaller, since their building blocks are atoms and molecules.

NanoGear is the result of a project born about five years ago and is part of a research activity in which the Center for Light Activated Nanostructures (Clan), a joint laboratory of the University of Bologna and the Italian National Research Council, is an international reference point.

NanoGear was created with the support of an Advanced Grant from the European Research Council (ERC), the most prestigious and competitive grant for scientific research in Europe. In the past, the same laboratory had already attracted public attention by developing molecular-based pumps (Nature Nanotechnology, 2015) and sponges (Nature Chemistry, 2015) powered by light. The central role of the research performed in Bologna on the subject of molecular machines was recognized during the "MolecularMachinesDays" event, held in Bologna in November 2018 with the participation of the three 2016 Nobel laureates in Chemistry.

THE RESULTS

The realization of artificial devices consisting of molecules is of great interest for the development of nanotechnology. "As shown by the results obtained in recent years in laboratories worldwide, nanotechnology can provide us with lighter and stronger materials, smaller and more powerful computers and robots, better systems for transforming and storing energy, new methods for medical diagnostics and therapies", says Alberto Credi. "NanoGear is a small but significant step in this direction. While it is currently difficult to identify a specific use of NanoGear, the basic research that led to its development has a revolutionary potential for science and technology that goes far beyond short-term practical applications".