Culture

While many cities and eight states have banned single-use plastics, bags and other polyethylene packaging still clog landfills and pollute rivers and oceans.

One major problem with recycling polyethylene, which makes up one-third of all plastic production worldwide, is economic: Recycled bags end up in low-value products, such as decks and construction material, providing little incentive to reuse the waste.

A new chemical process developed at the University of California, Berkeley, converts polyethylene plastic into a strong and more valuable adhesive and could change that calculus.

"The vision is that you would take a plastic bag that is of no value, and instead of throwing it away, where it ends up in a landfill, you would turn it into something of high value," said John Hartwig, the Henry Rapoport Chair in Organic Chemistry at UC Berkeley and leader of the research team. "You couldn't take all of this recycled plastic -- hundreds of billions of pounds of polyethylene are produced each year -- and turn it into a material with adhesive properties, but if you take some fraction of that and turn it into something that is of high value, that can change the economics of turning the rest of it into something that is of lower value."

For most plastics, recycling means chopping it up and forming it into generic products, in the process tossing out many of the properties painstakingly engineered into the original plastic, such as pliability and ease of processing. And while new methods of recycling can break down plastics into their chemical constituents for use as fuels or lubricants, these products, too, are low-value and can be environmentally questionable -- another fossil fuel to burn -- or have a short lifetime.

To make recycling more attractive, researchers and the plastics industry have been looking for ways to "upcycle" -- that is, convert recycled plastic into something more valuable and longer-lived.

The chemical process that Hartwig and his colleagues developed keeps many of the original properties of polyethylene, but adds a chemical group to the polymer that makes it stick to metal: something polyethylene normally does poorly. His team showed that the modified polyethylene can even be painted with water-based latex. Latex easily peels off standard low-density polyethylene, referred to as LDPE.

The paper describing this process will be published online Dec. 17 in the journal Chem and will appear in January's printed edition.

"We are able to enhance adhesion, while preserving all the other traits of polyethylene that the industry finds so useful," said co-author Phillip Messersmith, the Class of 1941 Professor in UC Berkeley's departments of bioengineering and materials science and engineering. "The processability, thermal stability and mechanical properties seem to be unharmed while enhancing adhesion. That is tricky to do. That is really where we have some exciting things to show."

While the process is not yet economical for industrial use, Hartwig believes that it can be improved and could be the starting point for adding other properties besides stickiness. The success also hints that other catalysts could work with other types of plastics, such as the polypropylene found in recycled plastic bottles, to produce higher-value products that are economically attractive.

Tweaking hydrocarbon chains

Hartwig specializes in designing new catalytic processes -- in this case, adding small chemical units to large hydrocarbon chains, or polymers, in very specific places -- to create "functionalized polymers" with new and useful properties. Such reactions are difficult, because a major selling point of plastics is that they are resistant to chemical reactions.

For this project, he wanted to see if he could add a hydroxyl group -- oxygen bound to hydrogen, or OH -- at a small fraction of the carbon-hydrogen bonds along the polyethylene chain.

"Polyethylene usually has between 2,000 and 10,000 carbons in a chain, with two hydrogens on each carbon -- really, it is an ocean of CH2 groups, called methylenes," he said. "We dipped into the literature to look for the most active catalyst we could find for functionalization of a methylene position."

The catalyst would have to work at high temperatures, since the solid recycled plastic has to be melted. Also, it would have to work in a solvent that is nonpolar, and thus able to mix with polyethylene, which is nonpolar. This is one reason it does not stick to metals, which are polar, or charged.

Hartwig and postdoctoral associate Liye Chen settled on a ruthenium-based catalyst (polyfluorinated ruthenium porphyrin) that satisfied these requirements and also could add OH groups to the polymer chain without the highly reactive hydroxyl breaking the polymer chain apart.

The reaction, surprisingly, produced a polyethylene compound that sticks tightly to aluminum metal, presumably by means of the OH molecules affixed along polyethylene's hydrocarbon chain. To better understand the adhesion, Chen teamed up with Katerina Malollari, a graduate student in Messersmith's lab, which focuses on biological tissues with adhesive properties -- in particular, a glue produced by mussels.

Chen and Malollari discovered that adding a relatively small percentage of alcohol to the polymer boosted adhesion 20 times.

"The catalysis introduced chemical changes to less than 10% of the polymer, yet enhanced dramatically its ability to adhere to other surfaces," Messersmith said.

Getting polyethylene to adhere to things -- including latex paint -- opens up many opportunities, he added. Artificial hip sockets and knee implants often integrate polyethylene with metal components and could be made to adhere better to metal. Functionalized polyethylene could be used to coat electrical wire, provide the glue that sticks other polymers together -- in milk cartons, for example -- or make more durable composites of plastic and metal, such as in toys.

"The utility here is being able to introduce these functional groups, which help solve many longstanding problems in polyethylene adhesion: adhesion of polyethylene to other polyethylene or to other polymers, as well as to metal," Messersmith said.

Hartwig foresees more opportunities for functionalization of complex polymers, including the most common plastic, polypropylene.

"We are one of the only groups anywhere that has been able to selectively introduce a functional group to long-chain hydrocarbon polymers," he said. "Other people can break the chains, and others can cyclize the chains, but to actually introduce a polar functional group into the chains is something that nobody else has been able to do."

Since antiquity, cultures around the world have been extracting vegetable oil from plants to use as food and fuel. Some vegetable oils have important health benefits, including lowering cholesterol levels and decreasing the risk of cardiovascular disease.

But there's a problem: Vegetable oils are traditionally extracted from fruits or seeds, and the extraction process often leads to the rest of the plant being discarded in the process. Now, Jay Thelen, a professor of biochemistry at the University of Missouri, has found a way to boost the production of triacylglycerol -- the main component of vegetable oil -- in plant leaves, a technique that could allow producers to harvest oil from large, leafy plants that also have other uses. Sorghum, for example -- a global source of grain prized for its drought-resistant qualities -- could serve a dual role as a source of vegetable oil, creating a more efficient and valuable crop.

Thelen and Yajin Ye, a postdoctoral fellow in Thelen's lab at MU, used the gene editing tool CRISPR to "knock out" a family of genes they have found to be responsible for regulating fatty acid production in the leaves of Arabidopsis, a plant regularly used by researchers to study plant biochemistry. The results were recently published in the prestigious journal Nature Communications.

"We know that plants synthesize fatty acids when provided light," said Thelen, who has dual appointments in the College of Agriculture, Food and Natural Resources and the Bond Life Sciences Center. "This study taught us that there are three proteins that restrain this process in leaves, and that we can turn off their cognate genes using CRISPR. That frees up the plant to produce higher amounts of triacylglycerol in the leaves rather than just the seed."

Thelen said this method could lead to greater and cheaper production of vegetable oils, and the possibility of dual uses for leafy crops like sorghum and soybeans could place less of a burden on making a higher-oil seed. That burden often has undesirable consequences -- including a decrease in protein, which is the principal commodity in soybean seeds. His lab is now in the process of further testing the method on crops to confirm its viability.

A hunger for research

If anyone seemed prepared to make this discovery, it was Jay Thelen. Hailing from the small town of Seward, Nebraska, Thelen has been seriously pursuing science research since high school more than three decades ago, when he found himself in the classroom of Jim Landon, a nationally renowned science teacher with an unorthodox style.

"We got out of the classroom and did ecological experiments on nature reserves," Thelen said. "We went hiking, assisted with invasive species studies and even helped out on prehistoric digs. We uncovered mastodon bones. It was really impactful stuff."

Landon took Thelen under his wing, arranging for him to participate in university-caliber research at the University of Nebraska during the summer and -- once in a while -- on weekends during the school year. Landon, now in his seventies and enjoying retirement in the state of Washington, remembers his former student clearly.

"Jay was a great kid; very inquisitive," Landon said. "I remember when he was chosen to present his research at the 40th International Science and Engineering Fair in Pittsburgh in 1989. Only a handful of students from Nebraska, Kansas and Oklahoma were selected, and I can still see him standing up there and doing his presentation. In high school, when the athletes sometimes get all the glory, it was great to see Jay take the initiative to do research and even better to see that initiative rewarded."

Teacher and student have gone on to separate career paths, but they still talk once in a while, reflecting the impact each had on the other. Thelen credits Landon for sparking his fascination with science, while Landon speaks lavishly of how students like Thelen have fueled his passion for teaching throughout his career.

"It just amazes me what the kids I've taught have gone on to accomplish," Landon said. "For Jay's research to be published in a journal as prestigious as Nature Communications, it just makes me so proud."

Despite his success, Thelen has no plans to slow down when it comes to the research that drives his love of science.

"For me, understanding how plant metabolism is regulated is an itch that needs to be scratched," Thelen said. "Plants are the original 'green' factories for food, chemical feedstock and fuel production. Discovering new metabolic constraints and leveraging these findings to help us adapt to a warming planet -- that's something that motivates me, and there's still much more to be done."

Irvine, Calif., Dec. 17, 2020 --University of California, Irvine health sciences researchers have created a machine-learning model to predict the probability that a COVID-19 patient will need a ventilator or ICU care. The tool is free and available online for any healthcare organization to use.

"The goal is to give an earlier alert to clinicians to identify patients who may be vulnerable at the onset," said Daniel S. Chow, an assistant professor in residence in radiological sciences and first author of the study, published in PLOS ONE. The tool predicts whether a patient's condition will worsen within 72 hours.

Coupled with decision-making specific to the healthcare setting in which the tool is used, the model uses a patient's medical history to determine who can be sent home and who will need critical care. The study found that at UCI Health, the tool's predictions were accurate about 95 percent of the time.

"We might think about this tool in terms of predicting the number of ICU beds that we might need," said Alpesh N. Amin, the Thomas & Mary Cesario Chair of Medicine and a study author.

The researchers started collecting COVID-19 patient data at UCI Health in January 2020, allowing them to produce a prototype of the tool by March and begin this study shortly after.

The machine-learning model used UCI Health patient data to create an algorithm that uses pre-existing conditions - such as asthma, hypertension and obesity - hospital test results and demographic data to calculate the likelihood that a patient will need a ventilator or ICU care.

Though the study was based on UCI Health patients - who share a location and were primarily Asian-American, Latino and Caucasian - the researchers also tested the tool with 40 patients at Emory University in Atlanta to see whether it worked with a different patient population. It did.

While the calculator will predict the general severity score of COVID-19 patients at any hospital, clinicians must make decisions on how to proceed based on local practices and their own number of beds, number of patients, likely spread of the disease locally, etc. At UCI Health, the tool has guided patient care based on feedback from emergency, hospital medicine, critical care and infectious disease physicians.

"You have to talk to your specialists, your doctors; you have to assess how many beds you have available and come together as a group to figure out how you want to use the tool," said Peter Chang, the assistant professor in residence in radiological sciences who designed the machine-learning model.

The team plans to expand the tool to other institutions and use it for further research. In their next study, they aim to predict which patients are most likely to benefit from COVID-19 drug trials.

This study was a collaboration between the School of Medicine, the Sue and Bill Gross School of Nursing, the Program in Public Health and the Department of Computer Science.

Research-grade air quality sensors are costly--around $40,000. For cities trying to monitor their greenhouse gas emissions, the cost may limit the number of sensors they can install and the data they can collect.

Unless. . .

Since 2014, the University of Utah has maintained research-grade suites of air quality instruments installed on light rail trains that move throughout the Salt Lake Valley every day. These mobile sensors, researchers estimate in a new study, cover the same area as 30 stationary sensors, providing the Salt Lake Valley with a highly cost-effective way to monitor its greenhouse emissions and fill in gaps in emissions estimates. The study is published in Environmental Science & Technology.

"Pollutant levels in the atmosphere are going to be rapidly changing in the coming decade as clean energy technologies are deployed," says Logan Mitchell, research assistant professor of atmospheric sciences, and a co-author of the study. "Cost-effective atmospheric monitoring will help policymakers understand what policies lead to reductions in pollutant levels, where there needs to be more focus, and if there are environmental inequalities emerging as some areas reduce their emissions faster than other areas."

Taking the show on the road

The upwind atmospheric area sampled by four current stationary air quality monitors (left) compared with the area sampled by a train-based mobile sensor.

The story of mounting sensors on the trains of the Utah Transit Authority's TRAX system begins in 2009 with then-doctoral student Heather Holmes (now an associate professor of chemical engineering). Holmes installed a particulate matter sensor on a train but for only a short period of time.

When Mitchell arrived at the U as a postdoctoral scholar in 2013 he discussed reviving Holmes' project with faculty advisors Jim Ehleringer, distinguished professor of biology, and John Lin, professor of atmospheric sciences and a co-author of the current study. With support from UTA, Mitchell ran a preliminary study in 2014.

They first test placed air inlet tubes out the window of an unoccupied driver's cab. "I noticed that there was a small CO2 bump every time the TRAX train stopped at a train station," Mitchell says. "This confused me initially, but I realized that the inlet tubes sticking out of the driver window were actually picking up human respiration from people standing at the train platform waiting to board the train!"

The test was a success, and Mitchell partnered with professor John Horel's research group to launch a full-fledged research effort to monitor air quality and greenhouse gases--this time with the sensors on the roof of the train so they aren't affected by people waiting on the train platforms.

Now the program has expanded to additional TRAX lines and ongoing state funding supports the air quality monitoring while additional funding from the National Oceanic and Atmospheric Administration supported this study on greenhouse gas emissions.

Top-down emissions measurement

The study evaluates the TRAX air sensors as a top-down measurement of greenhouse gas emissions. "Top-down" analysis means measuring the atmospheric concentration, and then figuring out where the emissions come from. Another approach, "bottom-up" analysis, inventories all the possible emissions sources and adds them together to estimate the total.

"Top-down measurements allow us to evaluate if the bottom-up emission inventories are accurate," says Derek Mallia, lead author of the study and research assistant professor of atmospheric sciences. "If an emission inventory is off by a little bit or is missing an emissions source, the top-down approach gives us a way to figure that out."

NASA satellites can also be used to estimate top-down emission estimates for cities around the world, an effort Lin and his group are also pursuing. "These satellite measurements are useful for assessing whole cities and for cities that lack ground observations," Lin says, "but the TRAX-based sensors allow for more granularity in emissions throughout the city and can complement the space-based observations."

Top-down measurements of this type over a large area can focus in on particular elements of a city's emissions inventory to identify ways that the inventory needs to change.

"A really simple example of this would be looking at on-road emissions," Mallia says. The researchers found underestimates of on-road emissions by bottom-up inventories, which if observed by only a stationary sensor near a single main road would suggest only potential underestimations for that particular road. But if on-road emissions are being underestimated consistently over an entire city, Mallia says, "fundamentally, this tells us that we are not accounting for something about on-road emissions, in general. This could be really important to understand as more and more people start driving electric vehicles that have zero tailpipe emissions."

As cities work to reduce environmental inequalities, mobile air monitoring can also help monitor if some urban areas' air is improving faster than others, Mitchell adds.

A model for cities to follow

"The TRAX-based measurements, combined with the network of stationary sites, means that Salt Lake City is one of the best-instrumented cities in the world in terms of pollution observations," Lin says.

To the researchers' knowledge, air quality sensors have been installed on public transport platforms in only a handful of cities in Europe. But the same approach could be used in any city with similar light rail systems--Portland, Oregon and Denver, for example. In cities with rail systems that run partially or entirely underground, sensors could be mounted on electric buses.

The cost savings of such an approach is staggering. One research-grade mobile sensor costing $40,000, the authors find, can cover the same area as around 30 stationary sensors costing upwards of $1.2 million.

"This excludes the manpower needed to maintain a 30-station network, which would be immense," Mitchell says. "Long story short--based on our preliminary analysis, semi-continuous mobile measurements on public transit vehicles are a very cost-effective strategy for monitoring emissions in cities."

WASHINGTON, Dec. 17, 2020 -- Kombucha is a bubbly, fermented tea that has gained popularity in the health and wellness scene over the last decade -- but what is it exactly? This week, the Reactions team breaks down kombucha's chemistry and investigates which ordinary beverages they can turn into kombucha: https://youtu.be/YxARRckS9dA.

New UBC Okanagan research is changing the way aircraft and wind turbine operators are addressing the risks related to ice build-up.

In a follow-up study from one released previously this year, Assistant Professor Mohammad Zarifi and his team at UBCO's Okanagan MicroElectronics and Gigahertz Applications (OMEGA) Lab, have broadened the scope and functionality of their ice sensors.

"We received a great deal of interest from the aviation and renewable energy industries stemming from our initial findings which pushed us to expand the boundaries of the sensor's responsiveness and accuracy," explains Zarifi.

Ice build-up on aircraft and wind turbines can impact the safety and efficiency of their systems, he notes.

In this latest research, the researchers focused on improving the real-time response of the sensors to determining frost and ice build-up. The sensors can identify in real-time these accumulations while calculating the rate of melting. This is crucial data for aviation, for keeping flights on time, and renewable energy applications, says Zarifi.

"Power generation output of wind turbines diminishes as a result of ice accumulations," he adds. "So, the industry sees great promise in sensing and de-icing solutions that can mitigate those reductions in efficiency."

Zarifi says the patented sensor, which includes a protective layer, is now being tested by the aviation industry through a rigorous approval process. This needs to be done before it can become a permanent fixture on aircraft. He notes that recently announced funding from the Department of National Defense will enable his team to continue to improve the sensor's capabilities.

Zarifi is also collaborating with a number of wind turbine companies to adapt the sensors into wind farms. The wind farm application is a slightly more straightforward proposition, he says, because the sensors can be mounted at the same altitude of the blades without having to be mounted to the blades--this removes certain calculation variables that are related to motion.

In the midst of these breakthroughs, the researchers have uncovered another first when it comes to ice sensing technology. Their latest innovation can sense salty ice, which freezes at colder temperatures. Interest in understanding and monitoring saltwater ice formation is increasing due to issues caused by saltwater ice on oil rigs and marine infrastructure. Zarifi and his team at OMEGA Lab are working towards the introduction of microwave/radar-based technology to address this challenge.

By incorporating an antenna into the sensor, the results can be shared in real-time with the operator in order to address the build-up.

Zarifi says his team is as excited as the industry partners to see how their microwave and antenna, which have proven to be durable and robust, can be modified for various applications including ice and moisture sensing.

More and more evidence is coming out that people with COVID-19 are suffering from cognitive effects, such as brain fog and fatigue.

And researchers are discovering why. The SARS-CoV-2 virus, like many viruses before it, is bad news for the brain. In a study published Dec.16 in Nature Neuroscience, researchers found that the spike protein, often depicted as the red arms of the virus, can cross the blood-brain barrier in mice.

This strongly suggests that SARS-CoV-2, the cause of COVID-19, can enter the brain.

The spike protein, often called the S1 protein, dictates which cells the virus can enter. Usually, the virus does the same thing as its binding protein, said lead author William A. Banks, a professor of medicine at the University of Washington School of Medicine and a Puget Sound Veterans Affairs Healthcare System physician and researcher. Banks said binding proteins like S1 usually by themselves cause damage as they detach from the virus and cause inflammation.

"The S1 protein likely causes the brain to release cytokines and inflammatory products," he said.

In science circles, the intense inflammation caused by the COVID-19 infection is called a cytokine storm. The immune system, upon seeing the virus and its proteins, overreacts in its attempt to kill the invading virus. The infected person is left with brain fog, fatigue and other cognitive issues.

Banks and his team saw this reaction with the HIV virus and wanted to see if the same was happening with SARS CoV-2.

Banks said the S1 protein in SARS-CoV2 and the gp 120 protein in HIV-1 function similarly. They are glycoproteins - proteins that have a lot of sugars on them, hallmarks of proteins that bind to other receptors. Both these proteins function as the arms and hand for their viruses by grabbing onto other receptors. Both cross the blood-brain barrier and S1, like gp120, is likely toxic to brain tissues.

"It was like déjà vu," said Banks, who has done extensive work on HIV-1, gp120, and the blood-brain barrier.

The Banks' lab studies the blood-brain barrier in Alzheimer's, obesity, diabetes, and HIV. But they put their work on hold and all 15 people in the lab started their experiments on the S1 protein in April. They enlisted long-time collaborator Jacob Raber, a professor in the departments of Behavioral Neuroscience, Neurology, and Radiation Medicine, and his teams at Oregon Health & Science University.

The study could explain many of the complications from COVID-19.

"We know that when you have the COVID infection you have trouble breathing and that's because there's infection in your lung, but an additional explanation is that the virus enters the respiratory centers of the brain and causes problems there as well," said Banks.

Raber said in their experiments transport of S1 was faster in the olfactory bulb and kidney of males than females. This observation might relate to the increased susceptibility of men to more severe COVID-19 outcomes.

As for people taking the virus lightly, Banks has a message:

"You do not want to mess with this virus," he said. "Many of the effects that the COVID virus has could be accentuated or perpetuated or even caused by virus getting in the brain and those effects could last for a very long time."

Atherosclerosis is marked by the buildup of inflammatory cells which narrow arteries to the point of chest pain and muscle weakness. Severe cases result in lesions and internal ruptures of arteries or even thrombosis in coronary arteries. One way that investigators are working to understand how atherosclerosis occurs and progresses is by looking at long non-coding RNAs (lncRNAs), strands of RNA that are not translated into proteins and which may play integral but understudied roles in cell regulation and disease progression. Through utilization of genetically modified high-risk atherosclerotic mice, a research team from Brigham and Women's Hospital identified and characterized Macrophage-Associated Atherosclerosis lncRNA Sequence (MAARS), which is expressed specifically in macrophages in atherosclerotic plaques and contributes to the progression of the disease. Results are published in Nature Communications.

"We hypothesized, given the unknown role of lncRNAs, that some may be highly expressed in the blood vessel wall during the process of atherosclerosis," said Mark Feinberg, MD, senior author and member of the Brigham's Division of Cardiovascular Medicine. "We want to identify who these actors are, what they are doing, and how we can understand their function in a way that provides a foundation for future therapeutic opportunities."

Feinberg and colleagues used genetically modified mice prone to atherosclerosis and placed them on a high cholesterol diet, which boosted their cholesterol to 500-1,000 units, up from a normal level of around 200 units. The mice were observed on their high cholesterol diet for 12 weeks, then placed on a normal diet and observed while their cholesterol levels returned to normal. Researchers isolated the innermost lining of the blood vessel walls of these mice and sent the samples for RNA sequencing to identify the presence of lncRNAs.

Among the list of present lncRNAs was MAARS, which piqued the interest of researchers with its specificity to macrophages and expression pattern. As atherosclerosis developed in the mice over the initial 12 weeks, the presence of MAARS increased 270-fold; once fed normal diets, the presence of MAARS decreased from its heightened expression by 60 percent. Targeted interruption of MAARS's function reduced atherosclerotic lesion formation by 52 percent by decreasing macrophage cell death and increasing efferocytosis -- the clearance of dead cellular debris -- from these lesions. These effects were largely independent of effects on circulating cholesterol.

Researchers found an important relationship between MAARS and an RNA-binding protein known as HuR. In the vessel wall, MAARS interacts with HuR, which plays a critical role in cell death. If MAARS is deliberately inhibited, HuR is released from the nucleus into the cytoplasm and the macrophages continue their cleaning. This chain of events leads to more active macrophages able to clean up more plaque and debris produced by atherosclerosis.

"lncRNAs play a really important role in cardiovascular disease," said Feinberg. "We had no idea what we were going to find, and we ended up identifying a lncRNA that has a crucial role in macrophages and pathways that could have therapeutic potential. We are shedding light on new players in old signaling pathways. It is so exciting to add more nuance to this area of research, since that means future studies will have that much more to work with."

Systemic sclerosis is an autoimmune disease associated with inflammation and fibrosis, or scarring, that affects organs including the skin, heart, kidney and lungs.

This form of scleroderma, this tightening and thickening of the skin, is a progressive, orphan illness that affects approximately 80,000 Americans and has no clear pathogenesis or FDA approved treatment option, leaving a proportion of patients affected to develop scarring so severe that they need organ transplants.

Lung fibrosis is the major cause of mortality in systemic sclerosis patients, with its prevalence on the rise and no way to stabilize or reverse the damage, according to Dinesh Khanna, M.B.B.S, M.S.c, director of Michigan Medicine’s Scleroderma Program.

“This is why I set out to identify biomarkers that help identify patients at higher risk of this progressive disease. A discovery is vital for successful clinical development of a novel treatment,” he says.

Khanna forged a collaboration with Thiru Ramalingam, M.B.B.S, Ph.D., a scientist at Genentech with expertise in biomarkers related to fibrosis. Together, using Khanna’s clinical expertise and rich database at the University of Michigan and Ramalingam’s lab, the pair investigated the potential link between autoantibodies, myeloid cell activation and lung fibrosis progression in patients with systemic sclerosis and associated lung disease (Ssc-ILD), discovering these individual factors do cooperate together to promote and progress lung fibrosis.

The research, published in Cell Reports Medicine, found a protein, osteopontin, may be responsible for triggering lung scarring. The finding was made by assessing three cohorts of systemic sclerosis patients and their immune systems.

“Scleroderma is an autoimmune disease, which means the immune system is chronically triggered by the body,” Khanna explains. “The immune system thinks there’s a microbe coming from outside of the body, and attacks proteins called autoantigens, which is common in those with autoimmune diseases. This interaction creates an immune complex.”

These immune complexes are activators of macrophages, cells of the immune system tasked with fighting off the “intruder”.

“When the macrophage is activated by immune complexes, we discovered that it secretes an abundance of a protein called osteopontin—previously implicated in fibrosis,” Ramalingam says. “High levels of this protein were confirmed by creating an in vitro culture, meaning outside the body, to emulate the immune complex immobilized in a SSc-ILD patient’s lung tissue.”

Osteopontin levels at a given time were prognostic for future deterioration of lung function, according to the study.

Khanna and Ramalingam’s research also highlighted how the amount of osteopontin circulating in the SSc-ILD patients was amplified by certain cells, including autocrine monocyte colony stimulating factor and interleukin-6, a protein that helps regulate the immune system.

Targeting interleukin-6 to decrease osteopontin levels

This research compliments another one of Khanna’s recent studies published in The Lancet Respiratory Medicine, which features the potential of tocilizumab, an anti-interleukin-6 receptor and immunosuppressive drug often used to treat rheumatoid arthritis, as a target to decrease osteopontin levels in patients with systemic sclerosis.

Spanning 20 countries and 75 sites, the randomized, double-blind, placebo-controlled Phase 3 trial found that tocilizumab led to a decrease in osteopontin, confirming the connection between this pro-inflammatory protein and interleukin-6, according to the study.

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The 162 mg of tocilizumab or placebo was delivered via injection weekly for 48 weeks.

“Collectively, these data suggest a plausible link between autoantibodies and lung fibrosis progression. Osteopontin has potential to be a promising biomarker and potential target for future therapies for those with SSc-ILD,” Khanna says. “If you asked our team what one disease we wish we had a treatment for, we’d say scleroderma. This answer has stayed consistent over the last 15 years, too. You watch patients die a slow death, and it’s devastating. We’ve accepted the challenge of trying to help patients the best we can, by continuing a search for a treatment or cure.”

A new study looking at the patterns of movement from 400,000 people offers fresh insights into how a neighborhood's economic conditions mixed with the mobility patterns of its residents and visitors relates to the well-being of the neighborhood and can serve as a predictor of violence.

The analysis, published in the American Sociological Review, develops the concept of neighborhoods that have a "triple disadvantage." These are neighborhoods that score high on common traits measuring "disadvantage" -- such as concentrated poverty, unemployment, and how many residents receive public assistance -- but also have deep connections with similarly disadvantaged neighborhoods through its resident's own mobility and through mobility into the neighborhood from around the city. The authors suggest these networks are formed through everyday movements, such as going to work, leisure activities, or visiting friends or family. Overall, the theory argues that a neighborhood's well-being depends not only on its own socioeconomic conditions but on the conditions of the neighborhoods its residents visit and are visited by.

The findings underscore that neighborhoods, even ones distant from each other, are not islands in isolation but are inherently connected. In fact, the implications of triple disadvantaged neighborhoods are broad and potentially affect a wide range of issues, including community capacity, gentrification, transmission in a pandemic, and racial inequality.

"We're trying to get researchers but also policymakers to think beyond just the characteristics of one neighborhood in isolation, which has driven a lot of research, including my own," said Robert J. Sampson, the Henry Ford II Professor of the Social Sciences and author on the paper. "What we're arguing is that triple disadvantage essentially exacerbates racial segregation [and other related factors]. ... [It's] the compounding of inequality by not just living in poor neighborhoods, but having disproportionate contact with other poor neighborhoods."

The authors draw on a long tradition of research showing that violence is highly concentrated in certain neighborhoods and that a neighborhood's poverty rate is strongly related to homicide. The researchers go beyond this traditional focus on residential areas and combine it with mobility data to study cross neighborhood ties and networks in entire cities.

Analyzing nearly 32,000 neighborhoods and 9,700 homicides in 37 of the largest U.S. cities, the authors show that triple disadvantage metrics can independently predict homicides after adjusting for known links of violence, such as density, race, age, and residential stability.

The authors look at neighborhoods in cities like New York City, Houston, Chicago, and many others, including smaller cities like Kansas City, Miami, Oakland, and Tulsa. Maps are available for all cities.

The researchers found that mobility-based disadvantage - meaning people flowing in and out of disadvantaged neighborhoods -- accounts for roughly one-fifth of the relationship between residential disadvantage and homicide. Digging further, they saw that using measures of triple disadvantage rather than residential disadvantage increased the authors' ability to predict neighborhood homicide counts by almost a third.

"The key there is that taking into account triple disadvantage, or taking into account these everyday mobility patterns, gives us added value in the prediction of homicide patterns," Sampson said. "In other words, that it goes beyond just residential poverty--we show that there's this additional explanatory value with respect to triple disadvantage."

In the study, the authors also show what makes a neighborhood triply disadvantaged can swing the opposite way, too. When those from already advantaged neighborhoods visit and are visited by those from other advantaged neighborhoods, they become triply advantaged. This isolates and segregates affluent neighborhoods.

Working on the paper with Sampson was Brian L. Levy, an assistant professor at George Mason University, and Nolan E. Phillips, a data scientist at Accenture. Both were former postdoctoral fellows at Harvard.

The researchers say their work represents only the tip of the spear and builds on earlier work on segregation. They hope to expand their theory and have others use their methodologies, data, and new geographic data sources to run their own assessments.

"There's a sense in which we hope that these ideas can be used by other researchers to create measures for studies around the world," Sampson said. "Furthermore, we can imagine that researchers and even policymakers could create metrics for other kinds of indicators beyond what we started. ... [The theory] has very expansive possibilities in our view."

In a new paper published in Stem Cell Reports, Bhanu Telugu and co-inventor Chi-Hun Park of the University of Maryland (UMD) Department of Animal and Avian Sciences show for the first time that newly established stem cells from pigs, when injected into embryos, contributed to the development of only the organ of interest (the embryonic gut and liver), laying the groundwork for stem cell therapeutics and organ transplantation. Telugu's start-up company, Renovate Biosciences Inc. (RBI), was founded with the goal of leveraging the potential of stem cells to treat terminal diseases that would otherwise require organ transplants, either by avoiding the need for transplants altogether or creating a new pipeline for growing transplantable human organs. With the number of people who suffer from organ failures and the 20 deaths per day in the U.S. alone purely from a lack of available organs for transplant, finding a new way to provide organs and therapeutic options to transplant patients is a critical need. In this paper, Telugu and his team are sharing their first steps towards growing fully transplantable human organs in a pig host.

"This paper is really about using the stem cells from pigs for the first time and showing that they actually can be injected into embryos and only go to the endodermal target organs like the liver, which is very important for delivering safe therapeutic solutions going forward," says Telugu. "This is an important milestone. It's a pipe dream in a way because a lot of things need to work out between here and full organ transplantation, but this paper sets the stage for all our future research. We can't really just go and start working with humans in work like this, so we started with pig-to-pig transfer in this paper, working with the stem cells and putting them back into other pigs to track the process to make sure it is safe for liver production as proof-of-concept."

Telugu and his team pitched this work at UMD Bioscience Day on behalf of his company, RBI, and received the Inventor Pitch Award and the UMD Invention of the Year Award in 2018. In order to protect the intellectual property, Telugu worked with the UMD Office of Technology Commercialization (OTC) to secure patents and open the work up for additional fundraising to carry this technology through the preclinical and clinical stages. The Maryland Stem Cell Foundation provided some funding to advance this work, and Telugu is thankful that Maryland funds technologies in the human stem cell space.

"There are many terminal cases where people need some sort of an organ replacement, like organ failure and degenerative diseases that cannot be cured by drugs," explains Telugu. "The traditional paradigm is to find a donor organ, but as of today there are still thousands of patients waiting for transplants, and there is no keeping up with the demand. Researchers have thought for a long time that stem cells could help solve this problem, and these stem cells have the ability to go into a specific organ as opposed to those that go into any lineage. In this case, you can differentiate the cells and place them where they are needed to help rescue a diseased organ, eliminating the need for transplant or at least buying the patient some time. Just making the human liver and collecting them early from a neonatal piglet, the hepatocyte [liver] cells alone are a $3 billion opportunity per year. And in the future, we can move into organ transplantation, first with the liver, and then looking at other organs of interest like the pancreas and lungs."

According to Telugu, this has distinct advantages over other methods that researchers are currently using to create donor organs in pigs, since the organs Telugu and his team are working with are actually of human origin and are therefore more likely to be accepted when transplanted. "Transplant rejections are pretty common even between humans and humans," says Telugu, "and if it is such a problem normally, you can imagine how an organ from a pig could be difficult to accept and may not essentially perform the same functions. Pig proteins may not function the same, so that remains a huge barrier for other methods that are not actually growing fully human organs like ours."

This work has the potential to solve a major problem in the treatment of organ failure and other degenerative diseases, which is what Telugu and his work is all about. "Being a veterinarian by training, we always look at the problem and try to find solutions to them," says Telugu. "Most animal scientists operate by looking for solutions, so integrating research and entrepreneurship to get this to the market where it is needed is essential. We are one of the few groups on the planet that are working in this space, and we have a great team of embryologists here at Maryland to do this work. We are uniquely positioned to accomplish this with both genome editing and stem cell biology expertise, and being able to prove the concept with this paper is a great first step towards our goals."

The Christmas season is associated with preventable harms from cards, tree decorations, and presents, as well as overeating and overdrinking, so do the benefits of Christmas outweigh the harms?

In the Christmas issue of The BMJ, Robin Ferner and Jeffrey Aronson dig out some cautionary tales from the archives.

They find that Christmas cards can be a potential source of harm. In 1876 a young man developed arsenic poisoning after painting festive cards with the highly toxic Scheele's Green paint. More recently, a woman amputated her finger tip while posting Christmas cards through the spring-loaded flap of a letter box.

Injuries from falls while decking the house with Christmas lights are common - and a reminder not to get on ladders - they may tip when you're tipsy.

Items swallowed unintentionally can also pose problems, they write. Bulbs from Christmas lights, sharp pointed confetti stars, and Christmas tree shaped decorations, have all found their way down toddlers' throats and have had to be removed.

Christmas trees, too, can bring pain as well as pleasure. Pine needles can penetrate the lungs, causing breathing difficulties, and branches can poke you in the eye, causing corneal abrasion. Burns from candles are also common (at least in Bern, Switzerland, where it is customary to light candles on Christmas trees).

Christmas presents pose unforeseen dangers too, they add - for example, a pet hamster spread lymphocytic choriomeningitis virus, while Haitian bongo drums carried anthrax bacilli in their goatskin hides.

Excessive eating and drinking too much alcohol can not only increase waistlines, but also trigger outbreaks of gastroenteritis and salmonella infection and cause heart complaints ("holiday heart syndrome").

Finally, some people take advantage of the Christmas holidays to enjoy outdoor pursuits, at least in warmer climes. In Australia, Christmas brings an increase in catastrophic injuries from jet skiing.

So is it worth it, ask the authors?

In 2002, researchers analysed the cost effectiveness of Christmas and concluded that "Christmas is not cost effective."

But cost effectiveness is not everything, they say. "Most of our sources are anecdotal, and we did not find strong evidence of widespread adverse effects. So we will leave you to decide whether the benefits of Christmas outweigh its harms."

In conclusion, they say "Stay safe, keep calm, carry on, and enjoy a very Merry Christmas!"

Hospital clowns might help improve physical symptoms and psychological wellbeing in children and adolescents having treatment for acute or chronic conditions, finds a study in the Christmas issue of The BMJ.

The findings suggest that incorporating appropriate laughter and play into clinical practice can be beneficial for young patients who need to stay in hospital.

Previous studies have suggested that hospital clowns can help to reduce stress and anxiety in children before and after surgery, but results have been inconsistent.

To address this knowledge gap, researchers based in Brazil and Canada examined evidence on the effectiveness of hospital clowns for a range of symptoms in children and adolescents admitted to hospital with acute (short-term) and chronic (long-term) conditions.

They trawled research databases looking for suitable clinical trials, published up to February 2020, and found 24 relevant trials (13 randomised controlled trials and 11 non-randomised controlled trials) involving 1612 children and adolescents.

The trials were designed differently, and were of varying quality, but the researchers were able to allow for that in their analysis.

Anxiety was the most frequently analysed symptom, followed by pain, psychological and emotional responses and perceived wellbeing, stress, cancer related fatigue, and crying.

Results suggested that children and adolescents who were in the presence of hospital clowns, either with or without a parent present, reported significantly less anxiety during a range of medical procedures, as well as improved psychological wellbeing, compared with standard care.

Three trials that evaluated chronic conditions (such as cancer) showed significant reductions in stress, fatigue, pain, and distress in children who interacted with hospital clowns, compared with standard care.

Only one trial found no difference in level of distress among children who interacted with hospital clowns compared with a control group.

This was a large study that analysed a vast amount of trial data, but the researchers highlight some limitations, such as risk of bias, differences in data collection, follow-up time points, and severity and onset of the conditions, all of which may have affected the reliability of the results.

However they say, overall, their findings suggest that hospital clowns "might have a positive effect in improving psychological wellbeing and emotional responses in children and adolescents in hospital with acute as well as chronic disorders."

"Our findings also support the continued investigation of complementary treatments for better psychological adjustment during the hospital admission process in paediatrics," they conclude.

As Father Christmas gears up for the busiest 24 hours of his year, what skills does he use to get a seemingly impossible job done effectively and safely - and can they be applied to medicine?

In the Christmas issue of The BMJ, two doctors reflect on the many lessons that the medical profession can learn from Father Christmas.

Father Christmas is unique in having 364 days to prepare for an important job, note surgeon Peter Brennan and radiologist Rachel Oeppen. Even so, they warn that staying awake for more than 18 hours "leads to cognitive function deterioration similar to being twice over the UK legal alcohol limit for driving."

It's well known that regular breaks as well as adequate hydration and nutrition while working are vital to maintain performance and safety, they write.

As an effective team leader, Father Christmas ensures that his reindeers have rest and food while he delivers presents, but quite how he manages to function safely at all remains a mystery given the customary glass of wine, sherry, or spirits left out for him by many households.

They suggest leaving a glass of water to counter the physical and mental effects of fluid loss, particularly if Father Christmas is wearing full personal protective equipment (PPE) this year.

And rather than indulging in sugar-rich mince pies, they suggest Father Christmas "might be better off snacking on the carrot sticks left out for his reindeer."

Father Christmas should be commended for his exemplary engagement with checklists, but the authors note that his limited verbal communication skills ("ho ho ho") could be improved.

With such a busy workload, high expectations, and the fear of widespread disappointment in the event of an error, the pressure on Father Christmas to deliver a superlative service must be immense, say the authors.

However, they are in no doubt that he appreciates the importance of maintaining good situational awareness, effective team working, and forward planning, enabling him to think about the many 'what if?' scenarios that could occur on Christmas Eve.

In this way, he avoids the likelihood of a Christmas "never event" (a serious but preventable incident) such as wrong site stocking delivery.

And when something doesn't seem quite right, Father Christmas will instinctively know to stop the sleigh if safe to do so, step back, and reassess the situation with the whole team.

Although there is no evidence that he engages in a formal team brief, the authors say it would be naïve to think that Father Christmas does not take this vital aspect of work seriously, especially since his team works together infrequently.

Examples of good practice include agreeing roles during a possible crisis, actively lowering hierarchy, and valuing all members irrespective of seniority, sleigh pairings, or characteristic features (such as a shiny nose).

It is also important to empower team members to be able to raise concerns without fear, they add, pointing out that terms such as "Santa's little helpers" could be regarded as derogatory and subordinate.

When their job has finally ended, it is likely that they will have a team debrief to confirm what went well, and what, if anything could be improved for next Christmas. The power of thanking all on "team Christmas" cannot be emphasised enough, they conclude.

One in five doctors in Sweden has a parent who is also trained in medicine, more than triple the proportion for doctors born three decades earlier, finds a study in the Christmas issue of The BMJ.

The findings suggest that among doctors in Sweden, medicine might increasingly run in families.

Parents' occupations might influence the career choice of their children, through information, opportunities, and economic means. If a large or growing proportion of doctors are from families of medical professionals, the diversity of the healthcare workforce might be limited, and growing evidence suggests that this might affect patient outcomes.

However, the extent to which medicine runs in families is unknown.

To address this knowledge gap, a team of US researchers explored data from Swedish educational records spanning up to three generations to see whether doctors had relatives that also trained as medical professionals.

They analysed how the proportion of doctors with at least one parent also trained in medicine changed over time. The study included 47,400 people with a medical degree, born in 1950-1990, and living in Sweden at some point during 2001-2016.

They also analysed lawyers and their families to see if the pattern would also hold true for another high paying occupation.

Among 27,788 doctors, where the educational background for both parents was known, 14% had a parent who was also a doctor and 2% had two doctor parents.

The proportion of doctors with at least one doctor parent rose significantly over time, from 6% for doctors born in 1950-59 to 20% for those born in 1980-90.

A similar pattern was not seen in lawyers.

Of 29,066 doctors with at least one sibling whose educational background was known, 14% had a sibling who was also a doctor. And among 18,360 doctors with at least one aunt or uncle whose educational background was available, 9% had an aunt or uncle who was a doctor.

For 18,061 doctors with at least one grandparent whose educational background was known, 2% had at least one grandparent with a medical degree.

Except for siblings, the proportions of doctors with these more distant relatives who were also trained in medicine increased over time.

This is an observational study, and so can't establish cause. The authors also point to some limitations, including that they only studied a single country and data were missing on parental education for some doctors born outside of Sweden.

But they say that their findings are consistent with older, smaller studies that have reported similar proportions of medical students with a doctor parent.

"Our analysis showed an increasing number of physicians from families with other physicians, rather than an increasing proportion of physicians from families with more diverse economic and educational backgrounds," they write.

"Uncovering the exact mechanism that underlies our findings is important for future research", they conclude.