Culture

Clinicians and surgeons are increasingly using medical devices based on artificial intelligence. These AI devices, which rely on data-driven algorithms to inform health care decisions, presently aid in diagnosing cancers, heart conditions and diseases of the eye, with many more applications on the way.

Given this surge in AI, two Stanford University faculty members are calling for efforts to ensure that this technology does not exacerbate existing heath care disparities.

In a new perspective paper, Stanford faculty discuss sex, gender and race bias in medicine and how these biases could be perpetuated by AI devices. The authors suggest several short- and long-term approaches to prevent AI-related bias, such as changing policies at medical funding agencies and scientific publications to ensure the data collected for studies are diverse, and incorporating more social, cultural and ethical awareness into university curricula.

"The white body and the male body have long been the norm in medicine guiding drug discovery, treatment and standards of care, so it's important that we do not let AI devices fall into that historical pattern," said Londa Schiebinger, the John L. Hinds Professor in the History of Science in the School of Humanities and Sciences and senior author of the paper published May 4 in the journal EBioMedicine.

"As we're developing AI technologies for health care, we want to make sure these technologies have broad benefits for diverse demographics and populations," said James Zou, assistant professor of biomedical data science and, by courtesy, of computer science and of electrical engineering at Stanford and co-author of the study.

The matter of bias will only become more important as personalized, precision medicine grows in the coming years, said the researchers. Personalized medicine, which is tailored to each patient based on factors such as their demographics and genetics, is vulnerable to inequity if AI medical devices cannot adequately account for individuals' differences.

"We're hoping to engage the AI biomedical community in preventing bias and creating equity in the initial design of research, rather than having to fix things after the fact," said Schiebinger.

Constructive - if constructed appropriately

In the medical field, AI encompasses a suite of technologies that can help diagnose patients' ailments, improve health care delivery and enhance basic research. The technologies involve algorithms, or instructions, run by software. These algorithms can act like an extra set of eyes perusing lab tests and radiological images; for instance, by parsing CT scans for particular shapes and color densities that could indicate disease or injury.

Problems of bias can emerge, however, at various stages of these devices' development and deployment, Zou explained. One major factor is that the data for forming models used by algorithms as baselines can come from nonrepresentative patient datasets.

By failing to properly take race, sex and socioeconomic status into account, these models can be poor predictors for certain groups. To make matters worse, clinicians might lack any awareness of AI medical devices potentially producing skewed results.

As an illustrative example of potential bias, Schiebinger and Zou discuss pulse oximeters in their study. First patented around 50 years ago, pulse oximeters can quickly and noninvasively report oxygen levels in a patient's blood. The devices have proven critically important in treating COVID-19, where patients with low oxygen levels should immediately receive supplemental oxygen to prevent organ damage and failure.

Pulse oximeters work by shining a light through a patient's skin to register light absorption by oxygenated and deoxygenated red blood cells. Melanin, the primary pigment that gives skin its color, also absorbs light, however, potentially scrambling readings in people with highly pigmented skin. It's no surprise, then, that studies have shown today's industry-standard oximeters are three times more likely to incorrectly report blood gas levels in Black patients compared to white patients. Oximeters additionally have a sex bias, tending to misstate levels in women more often than men. These oximeter biases mean that dark-skinned individuals, especially females, are at risk of not receiving emergency supplemental oxygen.

"The pulse oximeter is an instructive example of how developing a medical technology without varied demographic data collection can lead to biased measurements and thus poorer patient outcomes," said Zou.

This issue extends to the evaluation of devices after approval for clinical use. In another recent study, published in Nature Medicine and cited in the EBioMedicine paper, Zou and colleagues at Stanford reviewed the 130 medical AI devices approved at the time by the U.S. Food and Drug Administration. The researchers found that 126 out of the 130 devices were evaluated using only previously collected data, meaning that no one gauged how well the AI algorithms work on patients in combination with active human clinician input. Moreover, less than 13 percent of the publicly available summaries of approved device performances reported sex, gender or race/ethnicity.

Zou said these problems of needing more diverse data collection and monitoring of AI technologies in medical contexts "are among the lowest hanging fruit in addressing bias."

Addressing bias at the macro level

Over the longer term, the study explores how structural changes to the broader biomedical infrastructure can help overcome the challenges posed by AI inequities.

A starting point is funding agencies, such as the National Institutes of Health. Some progress has been made in recent years, Schiebinger said, pointing to how in 2016, the NIH started requiring funding applicants to include sex as a biological variable in their research, if relevant. Schiebinger anticipates the NIH instituting a similar policy for gender, as well as race and ethnicity. Her group at Stanford, meanwhile, is developing gender as a sociocultural variable during clinical trials, as reported in a February study in Biology of Sex Differences.

"We want to start with policy up front in funding agencies to set the direction of research," said Schiebinger. "These agencies have a great role to play because they are distributing taxpayer money, which means that the funded research must benefit all people across the whole of society."

Another opportunity area centers on biomedical publications, including journals and conference reports. The Stanford study authors suggest that publications set policies to require sex and gender analyses where appropriate, along with ethical considerations and societal consequences.

For medical schools, the authors suggest enhancing curricula to increase awareness of how AI might reinforce social inequities. Stanford and other universities are already making strides toward this goal by embedding of ethical reasoning into computer science courses.

Another example of using an interdisciplinary approach to reduce bias is the ongoing collaboration between Schiebinger, who has taught at Stanford for 17 years and is a leading international authority on gender and science, and Zou, an expert in computer science and biomedical AI.

"Bringing together a humanist and a technologist is something Stanford is good at and should do more of," said Schiebinger. "We're proud to be in the forefront of the efforts to debias AI in medicine, all the more important considering the many other facets of human life that AI will eventually impact."

The American College of Cardiology's (ACC) Global Heart Attack Treatment Initiative (GHATI) had measurable positive impacts on care delivery for heart attacks in low- and middle-income countries, according to data from the program's first year. Results were presented at the ACC's 70th Annual Scientific Session.

Globally, more than 17 million people die each year from cardiovascular disease. Three-quarters of these deaths take place in low- and middle-income countries, which annually see about 3 million ST-elevation myocardial infarctions (STEMIs), the deadliest type of heart attack in which an artery in the heart is completely blocked. While a person who suffers a heart attack in the U.S. or Europe has a 95-97% chance of survival, the odds are significantly worse in low- and middle-income countries, where the chance of survival is 80-90%.

ACC launched GHATI in 2019 to improve heart attack outcomes in low and middle-income countries by encouraging adherence to guideline-directed medical therapy. By the end of its first year, the program had tracked STEMI treatment metrics and outcomes for more than 2,000 patients at 18 medical centers in 13 countries on four continents. Overall, the data reveal that around 90% of hospital admissions for a heart attack adhered to guideline-directed medical therapy; the study also documented improvements in several key metrics over the course of the year.

"It is obvious that there are chances to improve the systems and lower rates of cardiovascular death in low- and middle-income countries, and indeed in all countries," said Benny J. Levenson, MD, PhD, of CV Center Berlin-Charlottenburg, Vivantes Klinikum Am Urban/Berlin in Germany and immediate past chair of GHATI. "We were pleased that the results, at one year, were heading in the right direction. We intend to continue to grow this program to be a model for many other countries to improve systems of care for heart attack and ultimately make a big impact on reducing mortality."

The quality improvement program brings ACC experts from around the world, including members of the College's Assembly of International Governors, together with cardiology teams at participating institutions to establish systems for tracking patient encounters and collecting data on outcomes. Over the course of the year, the average time patients spent in transit to the hospital decreased by 38 minutes; cardiac arrest upon arrival decreased by 4.6%; and the time from first medical contact to the use of a device to open blocked arteries improved by 28%. All these factors are known to improve outcomes after a heart attack.

While the study is not a randomized controlled trial and cannot definitively attribute the improvements to the program, feedback from participants and a robust body of previous research on quality improvement suggests the program has helped to encourage positive change, according to the researchers.

"The benefit to participating institutions starts with participating," Levenson said. "Places that have never collected data are now doing so. This leads to a culture change, because people and institutions learn to look closely at their practices and discuss their results with others. Just by gathering data, we can start to see a positive effect."

The results suggest that doctors in low- and middle-income countries are generally familiar with ACC's treatment guidelines and often show high adherence to them. However, systemic factors outside of the hospital environment, such as the availability of ambulances and emergency-response systems, likely still have a substantial impact on outcomes and may be challenging to change, Levenson said.

Researchers said the program will continue to expand into more sites and countries, including top-performing medical centers and higher-income countries. "Clinicians on cardiology care teams are by nature competitive--we have an internal drive to continue to improve metrics and outcomes," Levenson said. "We know from many years of experience that even the best can improve."

The ACC GHATI Work Group is led by GHATI Chair Cesar Herrera, MD, FACC, the Americas Representative, ACC Assembly of International Governors, and director CEDIMAT Cardiovascular Center in Santo Domingo, Dominican Republic, and B. Hadley Wilson, MD, FACC, chair-elect of the ACC Governance Committee and a cardiologist at Sanger Heart and Vascular Institute.

More information about GHATI is available at ACC.org/ghati.

Levenson will present the study, "Worldwide ST-Elevation Myocardial Infarction Care: One-year Results of the American College of Cardiology Global Heart Attack Treatment Initiative," on Monday, May 17, at 12:30 p.m. ET / 16:30 UTC, virtually.

COLUMBUS, Ohio ­- Up to 38.6% of people with colon cancer who have a hereditary cancer syndrome--including 6.3% of those with Lynch syndrome--could have their conditions remain undetected with current universal tumor-screening methods, and at least 7.1% of people with colorectal cancer have an identifiable inherited genetic mutation, according to new data published by scientists at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James).

Experts say their data, which was gathered from a cohort of more than 3,300 colorectal cancer patients treated at 51 hospitals across Ohio, makes a strong scientific argument for implementing multi-gene panel testing as part of the standard of care for all colorectal cancer patients.

"Finding ways to identify high-risk individuals among colorectal cancer patients is critically needed to better manage this disease and proactively identify family members who may also be impacted," says Rachel Pearlman, MS, LGC, first author of the study and a genetic counselor/researcher at the OSUCCC - James. "Genetic screening has changed dramatically in the past 10 years, allowing us to screen individuals for numerous known genetic mutations for much lower costs. This is a powerful tool that we need to embrace more broadly for cancer prevention and surveillance."

Study Methods and Results

For this study, OSUCCC - James researchers wanted to know if using a multi-level genetic testing approach could better identify hereditary genetic risk factors (passed down through families) that dramatically increase a person's lifetime risk of cancer but often go undetected until cancer occurs.

Researchers identified 3,310 adults who had undergone surgery for invasive colorectal cancer from January 2013 to December 2016. Individuals were recruited as part of the Pelotonia-funded Ohio Colorectal Cancer Prevention Initiative (OCCPI), a statewide research initiative led by Heather Hampel, MS, LGC. Hampel is a member of the OSUCCC - James Molecular Carcinogenesis and Chemoprevention Program, as well as a professor and associate director of the Division of Human Genetics at the Ohio State College of Medicine.

The study was launched to screen newly diagnosed colorectal cancer patients and their biological relatives for Lynch syndrome, a cancer-causing condition that occurs if a person inherits a mutation in one of four genes. People with Lynch syndrome are at higher risk to develop colorectal, endometrial (uterine), ovarian and stomach cancer than are average-risk individuals.

All study participants received universal tumor screening for mismatch repair (MMR) deficiency. This characteristic is common in tumors from patients with Lynch syndrome and suggests that the tumor would respond well to immunotherapy, which is a novel cancer treatment using your body's own immune system to fight the tumor, if necessary.

Individuals who met at least one of the trial-inclusion criteria also received multi-gene panel testing to identify harmful mutations. Genetic testing criteria included: MMR deficiency; colorectal cancer diagnosis before age 50; multiple primary tumors (colorectal cancer/endometrial cancer); or a first-degree relative with colorectal or endometrial cancer.

Researchers report in this new analysis that about 16% (525 patients) of participants had MMR deficiency, and about 7% had an inherited mutation. The scientists note that if universal tumor screening for Lynch syndrome had been the only method used to screen for hereditary cancer syndromes, more than 38% of patients who tested positive would have been missed--including more than 6% of individuals found to have Lynch syndrome through multi-gene testing methods.

"This is a significant and important discovery. By using pan-cancer multi-gene panel testing for all colorectal cancer patients, we could identify many individuals who are at increased risk for future cancer development and identify actionable therapeutic targets for their current cancer," says Hampel, senior author of the study. "Adopting modern testing methods as part of standard clinical practice for patients with colorectal cancer could literally save thousands of lives through early detection and surveillance of other family members who are at increased risk to develop the cancer based on inherited genetic mutations."

PHILADELPHIA (May 17, 2021) - Researchers have known for some time that insulin plays a vital role in regeneration and growth in some types of neurons that relay environmental sensory information to our brains, such as sight. However, they know relatively little about the role of insulin in the sense of smell. Now, investigators at the Monell Chemical Senses Center have shown that insulin plays a critical role in the maturation, after injury, of immature olfactory sensory neurons (OSNs). The team published their findings in eNeuro earlier this month.

"Our findings suggest that applying insulin into the nasal passage could be developed as a therapy for injury caused by a host of issues," said first author Akihito Kuboki, MD, a postdoctoral fellow in the lab of Johannes Reisert, PhD."

Knowing that insulin is part of the body's repair pathway for visual neurons, Kuboki suspected that the hormone might also play a role in the maturation of OSNs after injury. He also notes there are many insulin receptors in the olfactory region of the brain. Taking these factors into account, Kuboki concluded that insulin may also be involved in the sense of smell.

"Although scientists don't yet have a clear idea of how it works, we know that insulin plays a key role in preventing cell death," said Kuboki. "If insulin levels are reduced, diabetes patients have a high susceptibility to cell death, which can cause smell loss." He is pursuing this research path to shed light on why people with diabetes often suffer from smell loss, or anosmia.

The research team induced diabetes type 1 in mice to reduce levels of circulating insulin reaching the OSNs. The reduced insulin interfered with the regeneration of OSNs, resulting in an impaired sense of smell. They analyzed how the structure of the olfactory tissue in the nasal cavity and the olfactory bulb is impaired by comparing the number of mature OSNs and how well the axons of OSNs reached the olfactory bulb. The team also recorded odorant-induced responses in the OSNs in the nasal cavity. An odor-guided behavioral task, in which the mice needed to find a cookie reward depending on their ability to smell, measured olfactory function.

In addition, the team injured OSNs, which have a unique ability to regenerate in mammals. This approach allowed the investigators to ask whether OSNs required insulin to regenerate, which they found to be true. What's more, they discovered that OSNs are highly susceptible to insulin deprivation-induced cell death eight to 13 days after an injury. This time window indicates that during a critical stage newly generated OSNs are dependent on insulin. They also found that insulin must be applied to regenerating OSNs at this critical time point in the neurons' growth to be able to restore a mouse's sense of smell.

Also of significance, the team found that insulin promotes regeneration of regenerating OSNs in both type 1 diabetic and nondiabetic mice. "Even in nondiabetic mice, we found that insulin can promote the regeneration of OSNs, which suggests that this could be a therapy for olfactory dysfunction in patients without diabetes," said Kuboki. Specifically, the team only examined the OSN regeneration process after injury in type 1-diabetic mice and did not examine the effects of type 2 diabetes, but plan to in the future.

"Our findings suggest that insulin plays important roles when OSNs need to regenerate after severe injury that induces cell death in many OSNs," said Kuboki. "From this, we hope that an insulin spray can be potentially applied to treat smell loss for various reasons, including head trauma and viral infection."

Mothers who are Hispanic or who come from rural or low socioeconomic status neighborhoods are less likely to have their child's critical heart condition diagnosed before birth, according to a new study in the journal Circulation.

This is the largest and most geographically diverse study of these challenges to date. The study compared patient data of more than 1,800 children from the United State and Canada diagnosed with two of the most common, and the most serious, critical congenital heart defects: hypoplastic left heart syndrome (HLHS), when the left side of the heart is not developed completely, and transposition of the great arteries (TGA), when the two main arteries that carry blood away from the heart are reversed.

"The earlier we diagnose a heart defect, especially a serious one such as HLHS or TGA, the sooner we can make a plan for how to safely deliver the infant and reduce the impacts of that heart defect on the rest of the body," says Anita Krishnan, M.D., first author and cardiologist at Children's National Hospital. "Early detection and diagnosis of these conditions is crucial to ensuring the best possible outcome for the child, especially in protecting the brain."

Even when infants' heart defects were detected before birth, babies from neighborhoods with lower socioeconomic status were detected later in gestation than others.

"The COVID-19 pandemic has brought the idea of significant disparities in health care to the forefront of our national attention," says Dr. Krishnan. "Even though many health care providers have seen these inequities firsthand in their own clinical experience, it was still surprising to see the strength of the association between socioeconomic position and the care available to mothers."

In both the United States and Canada, expectant mothers are first screened as part of routine prenatal care in the first trimester for early signs of congenital heart defects and other genetic disorders via blood screen and ultrasound. In the second trimester, a comprehensive ultrasound evaluation for structural anomalies is routine. If any issues are detected, the mother is referred for a fetal echocardiogram and counseling.

The authors suggest that decreased linkages between neighborhoods and people identified in the study and subspecialists could contribute to the disparities found in the study.

"Prenatal detection rates may improve if we are able to leverage outreach and telehealth to strengthen the relationships between these specialties and the groups we identified in the study," Dr. Krishnan says.

The study included a total of 1,862 patients, including 1,171 patients with HLHS (91.8% prenatally diagnosed) and 691 with TGA (58% prenatally diagnosed). The study group included prenatally diagnosed fetuses with HLHS or TGA and postnatally diagnosed infants less than two months old with HLHS or TGA. Data was collected from institutions participating in the Fetal Heart Society, a non-profit 501(c) multicenter research collaborative with a mission to advance the field of fetal cardiovascular care and science.

Some 16 million Americans are believed to have alcohol use disorder, and an estimated 93,000 people in the U.S. die from alcohol-related causes each year. Both of those numbers are expected to grow as a result of heavier drinking during the COVID-19 pandemic.

Yet, in a new study involving data from more than 200,000 people with and without alcohol problems, researchers at Washington University School of Medicine in St. Louis found that although the vast majority of those with alcohol use disorder see their doctors regularly for a range of issues, fewer than one in 10 ever get treatment for drinking.

The findings are published in the June issue of the journal Alcoholism: Clinical & Experimental Research.

Analyzing data gathered from 2015 through 2019 via the National Survey on Drug Use and Health, the researchers found that about 8% of those surveyed met the current criteria for alcohol use disorder, the medical diagnosis for those with an addiction to alcohol. Of these people who met the criteria, 81% had received medical care in a doctor's office or spent time in a hospital or clinic during the previous year. But only 12% reported they had been advised to cut down on their drinking, 5% were offered information about treatment, and 6% received treatment, some of whom were not referred by their doctors but sought out treatment on their own.

"It's not that these people aren't in the health-care system," said first author Carrie M. Mintz, MD, an assistant professor of psychiatry. "But although they see doctors regularly, the vast majority aren't getting the help they need."

Mintz and her colleagues evaluated data from 214,505 people. The researchers first wanted to learn whether people with alcohol use disorder had access to health care and if they did, whether they had been screened about their alcohol use; they were considered to have been screened if their doctors simply had asked how much they drink. The researchers also evaluated whether people with drinking problems had been advised to cut down on drinking, had received additional information about treatment, or had received treatment or counseling.

The researchers found that although most people with alcohol use disorder had access to health care and although 70% reported they had been asked about alcohol use, that's where the care stopped.

"Some primary care doctors may not feel comfortable telling patients they should cut down on drinking, prescribing medication to help them cut back or referring them to treatment because they don't specialize in treating alcohol misuse; but the result is that many people who need treatment aren't getting it," said senior author Laura Jean Bierut, MD, the Alumni Endowed Professor of Psychiatry. "We used to see the same thing with smoking, but when physicians became educated about smoking and learned that many of their patients wanted to quit or cut back, doctors began offering more treatment, and more people were able to quit. We think the same thing may be possible with alcohol."

Among treatments that could be prescribed are the FDA-approved medications naltrexone, acamprosate and disulfiram, as well as psychotherapy and mutual-aid approaches, such as the 12-step program used by Alcoholics Anonymous.

"Alcohol use disorder is a chronic disease, but compared to other chronic diseases, it's wildly untreated," Bierut said. "For example, two-thirds of patients with HIV and 94% of patients with diabetes receive treatment, compared with only 6% of people with alcohol use disorder."

The researchers noted that during the pandemic, alcohol sales in the U.S. increased by 34%. Consequently, they expect that as the country emerges from COVID-19 and returns to normal, the number of people with alcohol use disorder will have climbed.

"We know alcohol use and misuse have increased during the pandemic," Mintz said. "It seems there has been a shift toward heavier drinking. Plus, many doctor's offices, AA groups and other support groups were shut down for a period of time, so we would hypothesize that even the relatively small percentage of people in treatment may have declined during the past year."

When doctors or scientists want to peer into living tissue, there's always a trade-off between how deep they can probe and how clear a picture they can get.

With light microscopes, researchers can see submicron-resolution structures inside cells or tissue, but only as deep as the millimeter or so that light can penetrate without scattering. Magnetic resonance imaging (MRI) uses radio frequencies that can reach everywhere in the body, but the technique provides low resolution -- about a millimeter, or 1,000 times worse than light.

A University of California, Berkeley, researcher has now shown that microscopic diamond tracers can provide information via MRI and optical fluorescence simultaneously, potentially allowing scientists to get high-quality images up to a centimeter below the surface of tissue, 10 times deeper than light alone.

By using two modes of observation, the technique also could allow faster imaging.

The technique would be useful primarily for studying cells and tissue outside the body, probing blood or other fluids for chemical markers of disease, or for physiological studies in animals.

"This is perhaps the first demonstration that the same object can be imaged in optics and hyperpolarized MRI simultaneously," said Ashok Ajoy, UC Berkeley assistant professor of chemistry. "There is a lot of information you can get in combination, because the two modes are better than the sum of their parts. This opens up many possibilities, where you can accelerate the imaging of these diamond tracers in a medium by several orders of magnitude."

The technique, which Ajoy and his colleagues report this week in the journal Proceedings of the National Academy of Sciences, utilizes a relatively new type of biological tracer: microdiamonds that have had some of their carbon atoms kicked out and replaced by nitrogen, leaving behind empty spots in the crystal -- nitrogen vacancies -- that fluoresce when hit by laser light.

Ajoy exploits an isotope of carbon -- carbon-13 (C-13) - that occurs naturally in the diamond particles at about 1% concentration, but also could be enriched further by replacing many of the dominant carbon atoms, carbon-12. Carbon-13 nuclei are more readily aligned, or polarized, by nearby spin-polarized vacancy centers, which become polarized at the same time they fluoresce after being illuminated with a laser. The polarized C-13 nuclei yield a stronger signal for nuclear magnetic resonance (NMR) -- the technique at the heart of MRI.

As a result, these hyperpolarized diamonds can be detected both optically -- because of the fluorescent nitrogen vacancy centers -- and at radio frequencies, because of the spin-polarized carbon-13. This allows simultaneous imaging by two of the best techniques available, with particular benefit when looking deep inside tissues that scatter visible light.

"Optical imaging suffers greatly when you go in deep tissue. Even beyond 1 millimeter, you get a lot of optical scattering. This is a major problem," Ajoy said. "The advantage here is that the imaging can be done in radio frequencies and optical light using the same diamond tracer. The same version of MRI that you use for imaging inside people can be used for imaging these diamond particles, even when the optical fluorescence signature is completely scattered out."

Detecting nuclear spin

Ajoy focuses on improving NMR -- a very precise way of identifying molecules -- and its medical imaging counterpart, MRI, in hopes of lowering the cost and reducing the size of the machines. One limitation of NMR and MRI is that large, powerful and costly magnets are needed to align or polarize the nuclear spins of molecules inside samples or the body so that they can be detected by pulses of radio waves. But humans can't withstand the very high magnetic fields needed to get lots of spins polarized at once, which would provide better images.

One way to overcome this is to tweak the nuclear spins of the atoms you want to detect so that more of them are aligned in the same direction, instead of randomly. With more spins aligned, called hyperpolarization, the signal detected by radio is stronger, and less powerful magnets can be used.

In his latest experiments, Ajoy employed a magnetic field equivalent to that of a cheap refrigerator magnet and an inexpensive green laser to hyperpolarize the carbon-13 atoms in the crystal lattice of the microdiamonds.

"It turns out that if you shine light on these particles, you can align their spins to a very, very high degree -- about three to four orders of magnitude higher than the alignment of spins in an MRI machine," Ajoy said. "Compared to conventional hospital MRIs, which use a magnetic field of 1.5 teslas, the carbons are polarized effectively like they were in a 1,000-tesla magnetic field."

When the diamonds are targeted to specific sites in cells or tissue -- by antibodies, for example, which are often used with fluorescent tracers -- they can be detected both by NMR imaging of the hyperpolarized C-13 and the fluorescence of the nitrogen vacancy centers in the diamond. The nitrogen vacancy-center diamonds are already becoming more widely used as tracers for their fluorescence alone.

"We show one important cool feature of these diamond particles, the fact that they spin polarize -- therefore they can glow very bright in an MRI machine -- but they also fluoresce optically," he said. "The same thing that endows them with the spin polarization also allows them to fluoresce optically."

The diamond tracers also are inexpensive and relatively easy to work with, Ajoy said. Together, these new developments could, in the future, allow for an inexpensive NMR imaging machine on every chemist's benchtop. Today, only large hospitals can afford the million-dollar price tag for MRIs. He currently is working on other techniques to improve NMR and MRI, including using hyperpolarized diamond particles to hyperpolarize other molecules.

An international study has found that four out of five women in prison in Scotland have a history of head injury, mostly sustained through domestic violence. Published recently in The Lancet, researchers, including SFU psychology graduate student Hira Aslam, say the study has important implications for the female prison population more broadly and could help to inform mental health and criminal justice policy development.

"The findings are incredibly sobering," says Aslam. "While we anticipated that the incidence of head injuries among women who are involved in the criminal justice system would be high, these estimates exceeded our expectations."

Researchers also found that violent criminal behaviour was three times more likely among women who had a history of significant head injury, while women who sustained such injuries generally had prison sentences that were three times longer. Two-thirds were found to have suffered repeated head injuries, and nearly all reported a history of abuse.

Aslam, the study's second author who led the interviews and assessments with offenders, says expanding the study to Canadian and other prison populations would be a critical next step. She can talk about the impact of trauma, head injury and the overall vulnerability of female offenders in the study sample.

"The relationship between head trauma and both violent crime and length of incarceration suggests that this may be an important consideration in the assessment and management of violent offending, as well as in reducing the risk for reoffending," says Aslam. "There is a need to consider these vulnerability factors in Canada and elsewhere in developing appropriate policy and interventions for this population."

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."