“Timely identification of infants at highest risk of RSV-related morbidity is key to prevention,” said lead author Brittney M. Snyder, PhD, assistant professor, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center. “Our personalized risk prediction tool may have applications in allocating expensive and/or limited immunoprophylaxis (immunization with nirsevimab or palivizumab) to achieve the greatest benefit and in promoting RSV prevention among families with high-risk infants.”

More than half of RSV LRTIs are among healthy, term infants who are generally considered low risk. These infants are, in fact, at risk for requiring intensive care unit -level care, and some may die from their illness. Early immunization with nirsevimab is recommended for all infants by the Centers for Disease Control & Prevention, yet in October 2023 nirsevimab was in short supply and the CDC recommended giving it only to high-risk infants who weren’t eligible for immunization with palivizumab.Both products, which prevent RSV LRTI in newborns and young children, are monoclonal antibodies (nirsevimab is long-acting and only requires one dose, while palivizumab is short-acting and requires monthly injections during RSV season).

In the population-based study by Dr. Snyder and colleagues including children insured by the Tennessee Medicaid Program, the researchers assessed infants who did not receive RSV immunoprophylaxis in the first year of life. They gathered demographic and clinical data from administrative health care encounters and linked birth certificates. “To predict whether these infants developed severe RSV LRTI requiring ICU admission during the first year of life, we developed a multivariable logistic regression model. The model includes demographic and clinical variables collected at or shortly after birth-19 variables in all, such as prenatal smoking, delivery method, maternal age and assisted breathing (ventilation) during birth hospitalization,” said lead biostatistician Tebeb Gebretsadik, MPH, Department of Biostatistics, Vanderbilt University Medical Center.

Among 429,365 infants in the study, 713 had severe RSV LRTI requiring ICU admission. The tool had good predictive accuracy and internal validation that indicated a good fit.

“Our objective was to develop a personalized tool for use in all newborns using readily available birth and postnatal data to predict risk of RSV LRTI requiring ICU admission, useful for prioritizing RSV prevention products with limited availability,” said Principal Investigator Tina V. Hartert, MD, MPH, professor of medicine and pediatrics at Vanderbilt University Medical Center. Even though the recent nirsevimab shortage has, fortunately, eased up, it is not known whether shortages will occur in the future. “This tool may be particularly helpful in prioritizing which infants should be immunized during times of limited availability of RSV prevention medicines. Using the tool to identify if their infant is at high risk for RSV infection requiring ICU care may also persuade vaccine-hesitant families to accept RSV immunoprophylaxis, by showing them their newborn is at high risk,” she added.

“To ensure compatibility with nirsevimab and maternal vaccination, our tool was developed for use in all infants,” concluded co-author Niek Achten, MD, postdoctoral fellow in pediatrics, Erasmus University Medical Center, Rotterdam, Netherlands, who imagined the need for such a tool. “In addition to use in the United States during times of limited availability, our tool may prove useful in countries with budgetary constraints needing to prioritize administration to the highest risk infants.”

The authors note that next steps to ensure optimal usefulness include validation of the tool in external populations, further cost-effectiveness analyses and decision curve analyses.

For the first time, a team of researchers from the National Park Service, U.S. Geological Survey, the University of California, Davis, and other institutions have documented and sampled some of the impaired waters, pinpointing 75 locations across a Texas-sized area of northern Alaska’s Brooks Range.

These degraded rivers and streams could have significant implications for drinking water and fisheries in Arctic watersheds as the climate changes, the researchers said.

“The more we flew around, we started noticing more and more orange rivers and streams,” said lead author Jon O’Donnell, an ecologist for the NPS’ Arctic Inventory and Monitoring Network. “There are certain sites that look almost like a milky orange juice.

Those orange streams can be problematic both in terms of being toxic but might also prevent migration of fish to spawning areas.”

Visible from space

O’Donnell first noticed an issue when he visited a river in 2018 that appeared rusty despite having been clear the year prior. He began asking around and compiling locations while grabbing water samples when possible in the remote region, where helicopters are generally the only way to access the rivers and streams.

“The stained rivers are so big we can see them from space,” said Brett Poulin, an assistant professor of environmental toxicology at UC Davis who was a principal investigator in the research. “These have to be stained a lot to pick them up from space.”

Poulin, whose expertise is in water chemistry, thought the staining looked similar to what happens with acid mine drainage, except no mines are near any of the impaired rivers, including along the famed Salmon River and other federally protected waters.

One hypothesis is that the permafrost, which is essentially frozen ground, stores minerals and as the climate warmed, the metal ores that were once locked up were exposed to water and oxygen, resulting in the release of acid and metals.

“Chemistry tells us minerals are weathering,” Poulin said. “Understanding what’s in the water is a fingerprint as to what occurred.”

The impacted rivers are on federal lands managed by Bureau of Land Management, Fish and Wildlife Service and NPS, including Gates of the Arctic and Kobuk Valley national parks.

Poulin and Ph.D. candidate Taylor Evinger analyzed initial samples, then collected their own on a trip last August, while others took samples in June and July. This year, they will take three trips during the summer to collect additional samples.

Acidic water releasing metals

Some samples from the impaired waters have a pH of 2.3 compared to the average pH of 8 for these rivers. This means the sulfide minerals are weathering, resulting in highly acidic and corrosive conditions that release additional metals. Elevated or high levels of iron, zinc, nickel, copper and cadmium have been measured.

“We see a lot of different types of metals in these waters,” Evinger said. “One of the most dominant metals is iron. That’s what is causing the color change.”

While O’Donnell first noticed a change in 2018, satellite images have turned up stained waters dating back to 2008.

“The issue is slowly propagating from small headwaters into bigger rivers over time,” he said. “When emergent issues or threats come about, we need to be able to understand them.”

Understanding risk

The researchers are in the second year of a three-year grant aimed at understanding what is happening in the water, modeling what other areas may be at risk and assessing implications for drinking water and fishing stocks.

The problem is growing and affecting habitat, water quality and other ecological systems, turning healthy areas into degraded habitats with fewer fish and invertebrates. If rural communities rely on these rivers for drinking water, they could require treatment eventually, and the fishing stocks that feed local residents could be affected.

“There’s a lot of implications,” O’Donnell said. “As the climate continues to warm, we would expect permafrost to continue to thaw and so wherever there are these types of minerals, there’s potential for streams to be turning orange and becoming degraded in terms of water quality.”

More work is needed to better understand the problem and whether rivers and streams can rebound, perhaps after cold weather promotes permafrost recovery.

“I think there will be a lot more detailed work to follow up to address some of the uncertainties that we currently have,” O’Donnell said.

Scientists from Alaska Pacific University, Colorado State University, University of Alaska Anchorage and UC Riverside also contributed to the research.

The research was funded by U.S. Geological Survey-NPS Water Quality Partnership program, the U.S. Geological Survey Changing Arctic Ecosystem Initiative and the NPS Arctic Inventory and Monitoring Program.

The research, published today in Clinical Cancer Research by a team from King’s College London and funded by Breast Cancer Now, marks a new method in cancer treatment.

The discovery is particular to triple negative breast cancer, which makes up 15% of all diagnosed breast cancer. This type of breast cancer is typically aggressive, resistant to chemotherapy, has a lower survival rate and is more common in women under 40.

Usual treatment involves surgery, chemotherapy and radiotherapy, however this type of cancer can evade the drugs and return to spread again.

The scientists conducted data analysis using over 6000 breast cancer samples to investigate the properties of breast cancer cells that are associated with aggressive and chemotherapy-resistant cancers.

They studied the cancer’s biology, what is expressed in the tumour and the cell surface, and the cell’s insides to understand how the cancer cells escape from cancer drugs. They established the presence of the cancer cell surface marker EGFR along with oncogenic molecules cyclin-dependent kinases (CDK), which are responsible for cell division and proliferation.

They used this knowledge against the cancer cells to link cetuximab, a tumour-selective antibody that targets the EGFR protein expressed in this type of cancer, with a CDK-blocking drug to create a tailored drug for breast cancer. Because the antibody drug conjugate specifically targets the cancer cell, it may be possible to administer a lower inhibitor dose than usual which means it’s less toxic for the patient.

Lead author Professor Sophia Karagiannis, from King’s College London, said: “We were on the hunt for cancer’s vulnerabilities and now we’ve found out how we can guide our therapies to one of these. We combined these two drugs to create a tailored antibody drug conjugate for patients with this aggressive cancer. The antibody guides the toxic drug directly to the cancer cell which offers the possibility for a lower dose and less adverse side effects to be experienced.

“More work needs to be done before this therapy can reach the clinic, but we expect that this can offer new treatment options for cancers with unfavourable prognosis. Beyond this antibody drug conjugate, we hope that our concept will lead the way for new antibody drug conjugates of this type to be tailored to patient groups likely to benefit.”

Lead research scientist Dr Anthony Cheung from King’s College London said: ”Triple negative breast cancer represents a molecularly and clinically diverse disease. By exploiting EGFR overexpression and dysregulated cell cycle molecules in selected patient groups, the antibody drug conjugate, but not the antibody alone, could stop the cancer cell from dividing and engender cytotoxic functions specifically against the cancer cells.”

Dr Simon Vincent, director of services, support and influencing at Breast Cancer Now, which funded this research, said: “Each year, around 8,000 women in the UK are diagnosed with triple negative breast cancer, which is typically more aggressive than other breast cancers and more likely to return or spread following treatment.

“This exciting research has not only improved our understanding of the properties of aggressive breast cancer cells that are resistant to chemotherapy but has also brought us closer to developing a targeted therapy that destroys these cancer cells while minimising side effects for patients.

“While further research is needed before this treatment can be used in people, this is an exciting step forward in developing targeted therapies for triple negative breast cancer, and we look forward to seeing how these findings could lead to new and effective ways of tackling this devastating disease.”

In a study published today in Proceedings of the National Academy of Sciences, the UC Irvine-led team said that widespread contact between ocean water and the glacier — a process that is replicated throughout Antarctica and in Greenland — causes “vigorous melting” and may require a reassessment of global sea level rise projections.

The glaciologists relied on data gathered from March to June of 2023 by Finland’s ICEYE commercial satellite mission. The ICEYE satellites form a “constellation” in polar orbit around the planet, using InSAR — interferometer synthetic aperture radar — to persistently monitor changes on the Earth’s surface. Many passes by a spacecraft over a small, defined area render smooth data results. In the case of this study, it showed the rise, fall and bending of Thwaites Glacier.

“These ICEYE data provided a long-time series of daily observations closely conforming to tidal cycles,” said lead author Eric Rignot, UC Irvine professor of Earth system science. “In the past, we had some sporadically available data, and with just those few observations it was hard to figure out what was happening. When we have a continuous time series and compare that with the tidal cycle, we see the seawater coming in at high tide and receding and sometimes going farther up underneath the glacier and getting trapped. Thanks to ICEYE, we’re beginning to witness this tidal dynamic for the first time.”

ICEYE Director of Analytics Michael Wollersheim, co-author, said, “Until now, some of the most dynamic processes in nature have been impossible to observe with sufficient detail or frequency to allow us to understand and model them. Observing these processes from space and using radar satellite images, which provide centimeter-level precision InSAR measurements at daily frequency, marks a significant leap forward.”

Rignot said the project helped him and his colleagues develop a better understanding of the behavior of seawater on undersides of Thwaites Glacier. He said that seawater coming in at the base of the ice sheet, combined with freshwater generated by geothermal flux and friction, builds up and “has to flow somewhere.” Water is distributed through natural conduits or collects in cavities, creating enough pressure to elevate the ice sheet.

“There are places where the water is almost at the pressure of the overlying ice, so just a little more pressure is needed to push up the ice,” Rignot said. “The water is then squeezed enough to jack up a column of more than half a mile of ice.”

And it’s not just any seawater. For decades, Rignot and his colleagues have been gathering evidence of the impact of climate change on ocean currents, which push warmer seawater to the shores of Antarctica and other polar ice regions. Circumpolar deep water is salty and has a lower freezing point. While freshwater freezes at zero degrees Celsius, saltwater freezes at minus two degrees, and that small difference is enough to contribute to the “vigorous melting” of basal ice as found in the study.

Co-author Christine Dow, professor in the Faculty of Environment at the University of Waterloo in Ontario, Canada, said, “Thwaites is the most unstable place in the Antarctic and contains the equivalent of 60 centimeters of sea level rise. The worry is that we are underestimating the speed that the glacier is changing, which would be devastating for coastal communities around the world.”

Rignot said that he hopes and expects the results of this project to spur further research on the conditions beneath Antarctic glaciers, exhibitions involving autonomous robots and more satellite observations.

“There is a lot of enthusiasm from the scientific community to go to these remote, polar regions to gather data and build our understanding of what’s happening, but the funding is lagging,” he said. “We operate at the same budget in 2024 in real dollars that we were in the 1990s. We need to grow the community of glaciologists and physical oceanographers to address these observation issues sooner rather than later, but right now we’re still climbing Mount Everest in tennis shoes.”

In the near term, Rignot, who is also a senior project scientist at NASA’s Jet Propulsion Laboratory, said this study will provide a lasting benefit to the ice sheet modeling community.

“If we put this type of ocean-ice interaction into ice sheet models, I expect we will be able to do a much better job of reproducing what has happened in the past quarter century, which will lead to a higher level of confidence in our projections,” he said. “If we could add this process we outlined in the paper, which is not included in most current models, the model reconstructions should match observations much better. It would be a big win if we could achieve that.”

Dow added, “At the moment we don’t have enough information to say one way or the other how much time there is before the oceanwater intrusion is irreversible. By improving the models and focusing our research on these critical glaciers, we will try to get these numbers at least pinned down for decades versus centuries. This work will help people adapt to changing ocean levels, along with focusing on reducing carbon emissions to prevent the worst-case scenario.”

Rignot, Dow and Wollershiem were joined in this project by Enrico Ciraci, UC Irvine assistant specialist in Earth system science and NASA postdoctoral fellow; Bernd Scheuchl, UC Irvine researcher in Earth system science; and ICEYE’s Valentyn Tolpekin. ICEYE is headquartered in Finland and operates from five international locations, including the United States. The research received financial support from NASA and the National Science Foundation.

Memristors, electrical components that store information in their electrical resistance, could reduce AI’s energy needs by about a factor of 90 compared to today’s graphical processing units. Already, AI is projected to account for about half a percent of the world’s total electricity consumption in 2027, and that has the potential to balloon as more companies sell and use AI tools.

“Right now, there’s a lot of interest in AI, but to process bigger and more interesting data, the approach is to increase the network size. That’s not very efficient,” said Wei Lu, the James R. Mellor Professor of Engineering at U-M and co-corresponding author of the study with John Heron, U-M associate professor of materials science and engineering.

The problem is that GPUs operate very differently from the artificial neural networks that run the AI algorithms — the whole network and all its interactions must be sequentially loaded from the external memory, which consumes both time and energy. In contrast, memristors offer energy savings because they mimic key aspects of the way that both artificial and biological neural networks function without external memory. To an extent, the memristor network can embody the artificial neural network.

“We anticipate that our brand-new material system could improve the energy efficiency of AI chips six times over the state-of-the-art material without varying time constants,” said Sieun Chae, a recent U-M Ph.D. graduate in materials science and engineering and co-first-author of the study with Sangmin Yoo, a recent U-M PhD graduate in electrical and computer engineering.

In a biological neural network, timekeeping is achieved through relaxation. Each neuron receives electrical signals and sends them on, but it isn’t a guarantee that a signal will move forward. Some threshold of incoming signals must be reached before the neuron will send its own, and it has to be met in a certain amount of time. If too much time passes, the neuron is said to relax as the electrical energy seeps out of it. Having neurons with different relaxation times in our neural networks helps us understand sequences of events.

Memristors operate a little differently. Rather than the total presence or absence of a signal, what changes is how much of the electrical signal gets through. Exposure to a signal reduces the resistance of the memristor, allowing more of the next signal to pass. In memristors, relaxation means that the resistance rises again over time.

While Lu’s group had explored building relaxation time into memristors in the past, it was not something that could be systematically controlled. But now, Lu and Heron’s team have shown that variations on a base material can provide different relaxation times, enabling memristor networks to mimic this timekeeping mechanism.

The team built the materials on the superconductor YBCO, made of yttrium, barium, carbon and oxygen. It has no electrical resistance at temperatures below -292 Fahrenheit, but they wanted it for its crystal structure. It guided the organization of the magnesium, cobalt, nickel, copper and zinc oxides in the memristor material.

Heron calls this type of oxide, an entropy-stabilized oxide, the “kitchen sink of the atomic world” — the more elements they add, the more stable it becomes. By changing the ratios of these oxides, the team achieved time constants ranging from 159 to 278 nanoseconds, or trillionths of a second. The simple memristor network they built learned to recognize the sounds of the numbers zero to nine. Once trained, it could identify each number before the audio input was complete.

These memristors were made through an energy-intensive process because the team needed perfect crystals to precisely measure their properties, but they anticipate that a simpler process would work for mass manufacturing.

“So far, it’s a vision, but I think there are pathways to making these materials scalable and affordable,” Heron said. “These materials are earth-abundant, nontoxic, cheap and you can almost spray them on.”

The research was funded by the National Science Foundation. It was done in partnership with researchers at the University of Oklahoma, Cornell University and Pennsylvania State University.

The device was built in the Lurie Nanofabrication Facility and studied at the Michigan Center for Materials Characterization.

Lu is also a professor of electrical and computer engineering and materials science and engineering. Chae is now an assistant professor of electrical engineering and computer science at Oregon State University.