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Tag: Top Hit Stories

  • sPHENIX Assembly Update: Magnet Mapped, Detectors Prepared

    sPHENIX Assembly Update: Magnet Mapped, Detectors Prepared

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    Newswise — Physicists, engineers, and technicians at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory are rounding out the year with key developments to a house-sized particle detector that will begin capturing collision snapshots for the first time next spring.

    The state-of-the-art, three-story, 1,000-ton detector—known as sPHENIX—will precisely track particles streaming from collisions at the Relativistic Heavy Ion Collider (RHIC), a DOE Office of Science user facility for nuclear physics research. It’s an ongoing makeover of the PHENIX experiment, which took data at RHIC from 2000 until 2016. The upgraded, state-of-the-art sPHENIX will enable scientists to better understand the properties of quark-gluon plasma (QGP) —a soup of subatomic particles that are the inner building blocks of protons and neutrons. Scientists want to measure those particles to learn more about how those building blocks interact to form the visible matter that makes up our world.

    With the recent completion of essential particle-tracking components and a project to map the magnetic field of a superconducting electromagnet at the detector’s core, sPHENIX crews are gearing up for final installations.

    “There’s this whole choreography of a very intricate process of how these remaining pieces go together that’s going to play out in the next months and have us in shape to take data in the spring,” said Brookhaven Lab nuclear physicist and sPHENIX co-spokesperson David Morrison.

    CERN crew maps magnetic field

    A central component of sPHENIX is a 20-ton cylindrical superconducting solenoid magnet. It was once the centerpiece of an experiment called BaBar at SLAC National Accelerator Laboratory in California. Crews transported it across the country in 2015, tested it at low-field in 2016 and high-field in 2018, and carefully installed it at sPHENIX last year.

    The magnet generates a precise and uniform magnetic field—1.4 Tesla, or about as strong as the magnet used for magnetic resonance imaging (MRI) scans. The powerful field will bend the trajectories of charged particles that are among the “debris” produced when nuclei collide at RHIC.

    Remaining detectors soon to be layered inside the magnet’s drum will measure very accurately the position of the particles that stream out of these nuclear smashups, from which other properties can be obtained. Scientists seek to “connect the dots” of those measurements to discern very small differences among three kinds of “parent” particles called upsilons. The upsilon data is only one of numerous studies with sPHENIX at RHIC which will reveal clues about how QGP transitions from a hot soup of quarks and gluons to matter as we know it.

    But before these final tracking components can be installed, the sPHENIX crew sought to map the solenoid’s magnetic field.

    “Once you fill up the middle of the magnet, you can’t place a mapping machine inside,” said Brookhaven physicist Kin Yip.

    A team from CERN, Europe’s particle physics laboratory, came to Brookhaven in November to tackle the precision task.

    “CERN’s detector technologies group are the world experts in magnet mapping,” Yip said.

    The CERN team used the same mapping machine they’d previously used to map the magnet that forms the backbone of the ATLAS experiment at CERN’s Large Hadron Collider.

    The mapping machine, shipped from Geneva, Switzerland, fit into precision rails inside of the magnet’s drum, where some panels of the sPHENIX electromagnetic calorimeter (EMCal)—which will measure different types of charged and uncharged particles in RHIC collisions—had not yet been installed. The cryogenic group from Brookhaven’s Collider-Accelerator Department used liquid helium to cool the solenoid’s superconducting cables to 4.6 degrees Kelvin (-451.4 degrees Fahrenheit)—the temperature needed to generate the magnetic field. Two arms run by air-powered motors rotated like propellers to measure the magnetic field as crews stepped the machine along points from one end of the cylindrical magnet to the other. (Technicians installed the final EMCal segments soon after the mapping project ended.)

    “We thank Brookhaven Lab and in particular the people at sPHENIX for tasking us with the mapping of the sPHENIX solenoid,” said Nicola Pacifico of CERN’s mapping group, which included Francois Garnier, Raphael Dumps, Pritindra Bhowmick. “Every mapping campaign is an R&D exercise on its own, presenting its specific challenges. We enjoyed the support of a very competent team on site, which allowed us to complete the mapping in a timely manner. We wish sPHENIX and its team full success in its physics programme, and au revoir until the next mapping at Brookhaven Lab!”

    sPHENIX scientists had been using a calculated map of the solenoid’s magnetic field to run RHIC collision simulations. The new precision measurements will increase the accuracy of deciphering data from the complex experiment once it’s up and running.

    “In general, in experimental physics, more information is better than less information,” said John Haggerty, a Brookhaven physicist who led the acquisition of the magnet in the early days of sPHENIX. “We can only calculate what we think we built, not what we may have inadvertently built. Now, we have the best possible map.”

    Key sub-detector arrives at Brookhaven

    The massive magnet isn’t the only major detector component that made a cross-country trek to sPHENIX. Pieces of a pixel-based vertex detector known as MVTX, were built at CERN, then shipped to DOE’s Lawrence Berkeley National Laboratory (LBNL) in California for expert assembly, before arriving safely at Brookhaven in October. The detector was shipped in two halves for the 3,000-mile cross-country road trip. Crews used a truck with special suspension and took care to consider a safe route and weather conditions.

    The MVTX is one of three components that will work together to measure the position to determine the momentum of all charged particles emerging from RHIC’s collisions. (The other two are an Intermediate Silicon Strip Tracker (INTT, see below) and a Time Projection Chamber (TPC) being built at Stony Brook University.

    The MVTX, which will sit within the sPHENIX magnet’s central core, offers a very precise answer to the question: did a particle come exactly from the collision or even a fraction of a hair’s width away? It turns out that differences of such tiny distances can make a big difference.

    “Thousands of particles come out of our collisions,” Morrison explained. “Some of those particles decay, turning into other types of particles almost right away—making it maybe 50 microns, about the thickness of a strand of hair. MVTX tells us extremely precisely where particles came from, with a precision of about five microns, so we know if the particle was created in the collision itself or is a product of such as decay.”

    The part of MVTX that actually makes measurements is compact—about a foot long, 3.5 inches in diameter, and weighing in at about 3 ounces. All together, MVTX is made up of three overlapping layers of silicon sensors, which line two halves of a carbon fiber tube. At one end, the tube widens like the bell of a trumpet to fit lots of cables and fibers that power and readout the detector.

     “In this compact package there are 300 million channels, elements that can say ‘I saw something,’” said Edward O’Brien, the sPHENIX project director. “If we think of those channels as pixels, MVTX has a factor of 40 more pixels than your high-definition TV crammed into a space that’s over 20 times smaller.”

    Before installing the pixel-based detector early next year, sPHENIX engineers and technicians will practice placing a mockup of this delicate component around the experiment’s beam pipe., They’ll have only a tiny amount of clearance—about a millimeter—to slide the device into its final position after the other detector components are installed. “It’s like playing the game ‘Operation’ in reverse,” Morrison said. When it comes time to put that final piece in place, he says, the sPHENIX crew will be ready.

    Tracking super-fast, overlapping events

    Meanwhile the team is making progress on those other particle-tracking components.

    With a response time of 60 nanoseconds—60 billionths of second—the INTT will be key in capturing continuous snapshots of 15,000 particle collisions per second, more than three times faster than the former PHENIX detector.

    The INTT takes measurements in the space where MVTX and TPC do not, allowing physicists to reconstruct a complete particle track. It’s super-fast response time enables it to distinguish which tracks come from overlapping events when collisions are piling up.

    The sub-detector was completed in mid-September by an international collaboration that included technicians, engineers, postdocs, and scientists from Japan, Taiwan, and the U.S. The project is funded primarily through the RIKEN BNL Research Center (RBRC) with additional U.S and international contributions.

    The INTT consists of four layers of overlapping silicon strips that form a semiconductor particle detector based on ionizing radiation detection. The layers sit in two halves of a 10-foot-long cylinder. Bringing the two-halves of the detector together for testing, and soon installation, was a tricky task with many moving parts.

    “It’s like flying a 747 airplane,” said Rachid Nouicer, a Brookhaven Lab nuclear physicist, RBRC senior visiting scientist, Stony Brook University adjunct professor, and co-manager of the INTT detector construction.

    To ensure a “safe landing” the INTT assembly team used a machine with two “claws” that picked up each half and pressed them together while technicians tightened screws and knobs around the device. They had to be careful to prevent any cracks in the silicon strips. They also needed to ensure there are no gaps between overlapping silicon layers so the detector can receive all particle signals when its operational.

    “Physics is always moving towards precision and detector technology has to keep up with it—we want detectors to be faster, more precise,” Nouicer said. “It’s a great accomplishment to see all the INTT detector’s channels working. Now, we want to do physics with it.”

    As work progresses on the TPC, a gas tracking detector, at Stony Brook, the time for physics is fast approaching. Stay tuned for another update on that detector component.

    “We’re right at the end of detector component construction. O’Brien said. “We’re done within errors. The challenge ahead is completing installation in the next few months”

    “As you can see, the construction and assembly of these complex detector components is a major international effort,” said sPHENIX co-spokesperson Gunther Roland, a physicist at the Massachusetts Institute of Technology. “This work brings together so many great physicists from all over the world—80 universities and labs from 14 countries and close to 400 collaborators —to make the vision for this detector and the science it will enable a reality.”

    The upgrade and operations at RHIC are funded by the DOE Office of Science (NP).

     Brookhaven National Laboratory is supported by the Office of Science of the U.S. Department of Energy. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, please visit science.energy.gov.

    Follow @BrookhavenLab on Twitter or find us on Facebook.

     

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    Brookhaven National Laboratory

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  • Using Machine Learning to Better Understand How Water Behaves

    Using Machine Learning to Better Understand How Water Behaves

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    Newswise — Water has puzzled scientists for decades. For the last 30 years or so, they have theorized that when cooled down to a very low temperature like -100C, water might be able to separate into two liquid phases of different densities. Like oil and water, these phases don’t mix and may help explain some of water’s other strange behavior, like how it becomes less dense as it cools.

    It’s almost impossible to study this phenomenon in a lab, though, because water crystallizes into ice so quickly at such low temperatures. Now, new research from the Georgia Institute of Technology uses machine learning models to better understand water’s phase changes, opening more avenues for a better theoretical understanding of various substances. With this technique, the researchers found strong computational evidence in support of water’s liquid-liquid transition that can be applied to real-world systems that use water to operate.

    “We are doing this with very detailed quantum chemistry calculations that are trying to be as close as possible to the real physics and physical chemistry of water,” said Thomas Gartner, an assistant professor in the School of Chemical and Biomolecular Engineering at Georgia Tech. “This is the first time anyone has been able to study this transition with this level of accuracy.”

    The research was presented in the paper, “Liquid-Liquid Transition in Water From First Principles,” in the journal Physical Review Letters, with co-authors from Princeton University.

    Simulating Water

    To better understand how water interacts, the researchers ran molecular simulations on supercomputers, which Gartner compared to a virtual microscope.

    “If you had an infinitely powerful microscope, you could zoom in all the way down to the level of the individual molecules and watch them move and interact in real time,” he said. “This is what we’re doing by creating almost a computational movie.”

    The researchers analyzed how the molecules move and characterized the liquid structure at different water temperatures and pressures, mimicking the phase separation between the high and low-density liquids. They collected extensive data — running some simulations for up to a year — and continued to fine-tune their algorithms for more accurate results.

    Even a decade ago, running such long and detailed simulations wouldn’t have been possible, but machine learning today offered a shortcut. The researchers used a machine learning algorithm that calculated the energy of how water molecules interact with each other. This model performed the calculation significantly faster than traditional techniques, allowing the simulations to progress much more efficiently.

    Machine learning isn’t perfect, so these long simulations also improved the accuracy of the predictions. The researchers were careful to test their predictions with different types of simulation algorithms. If multiple simulations gave similar results, then it validated their accuracy.

    “One of the challenges with this work is that there’s not a lot of data that we can compare to because it’s a problem that’s almost impossible to study experimentally,” Gartner said. “We’re really pushing the boundaries here, so that’s another reason why it’s so important that we try to do this using multiple different computational techniques.”

    Beyond Water

    Some of the conditions the researchers tested were extremes that probably don’t exist on Earth directly, but potentially could be present in various water environments of the solar system, from the oceans of Europa to water in the center of comets. Yet these findings could also help researchers better explain and predict water’s strange and complex physical chemistry, informing water’s use in industrial processes, developing better climate models, and more.  

    The work is even more generalizable, according to Gartner. Water is a well-studied research area, but this methodology could be expanded to other difficult-to-simulate materials like polymers, or complex phenomena like chemical reactions.

    “Water is so central to life and industry, so this particular question of whether water can undergo this phase transition has been a longstanding problem, and if we can move toward an answer, that’s important,” he said. “But now we have this really powerful new computational technique, but we don’t yet know what the boundaries are and there’s a lot of room to move the field forward.”

    CITATION: T.E. Gartner, III, P.M. Piaggi, R. Car, A.Z. Panagiotopoulos, P.G. Debenedetti, “Liquid-liquid transition in water from first principles,”* Phys. Rev. Lett., 2022.

    DOI:10.1103/PhysRevLett.129.255702

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    The Georgia Institute of Technology, or Georgia Tech, is one of the top public research universities in the U.S., developing leaders who advance technology and improve the human condition. The Institute offers business, computing, design, engineering, liberal arts, and sciences degrees. Its more than 46,000 students, representing 50 states and more than 150 countries, study at the main campus in Atlanta, at campuses in France and China, and through distance and online learning. As a leading technological university, Georgia Tech is an engine of economic development for Georgia, the Southeast, and the nation, conducting more than $1 billion in research annually for government, industry, and society. 

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    Georgia Institute of Technology

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  • Deblurring Can Reveal 3D Features of Heavy-Ion Collisions

    Deblurring Can Reveal 3D Features of Heavy-Ion Collisions

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    The Science

    When the nuclei of atoms are about to collide in an experiment, their centers never perfectly align along the direction of relative motion. This leads to collisions with complex three-dimensional geometry. Emissions from the dense hot region of nuclear matter form patterns during a collision. In relation to the geometry of the collisions, the patterns of emissions offer insights into characteristics of the compressed matter. The proposed deblurring strategy can reveal the emission patterns as if the initial nuclear centers were under a tight control in an experiment.

    The Impact

    The proposed strategy offers a new way to analyze and present data from the collisions of atomic nuclei. The strategy may make it easier for physicists to arrive at qualitative conclusions from collision data when the results from an experiment refer directly to the geometry of a collision. Until now, this sort of direct reference to collision geometry was only possible with theoretical simulations. This means simulations can focus on what researchers had believed was beyond the reach of experiment. This will help scientists to better understand compressed matter. The optical strategy may also help in nuclear experiments where the methodology makes it hard to obtain the desired information.

    Summary

    The deblurring strategy was inspired by a deblurring algorithm used in optics experiments to sharpen images. Outside of nuclear science, deblurring is used to decipher speed-camera photos. It was suggested by a research collaboration between the Facility for Rare Isotope Beams, a Department of Energy (DOE) Office of Science user facility at Michigan State University, and RIKEN Nishina Center in Japan. The strategy is an effective means of finding triple-differential distributions of products from heavy-ion collisions for a fixed direction of the reaction plane. The reaction plane is defined by the direction of relative velocity and the centers of nuclei entering a collision. At intermediate energies for the collisions, products emerge from a collision exhibiting correlations with the plane. Those correlations help to coarsely identify the orientation of that plane in an experiment. The proposed strategy can benefit the analysis of data from experiments focusing on properties of the compressed nuclear matter at facilities worldwide.

     

    Funding

    This research was supported by the Department of Energy Office of Science, Office of Nuclear Physics.


    Journal Link: Physical Review C
    Journal Link:

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    Department of Energy, Office of Science

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  • International recommendations for diagnosis and treatment of new-onset refractory status epilepticus (NORSE)

    International recommendations for diagnosis and treatment of new-onset refractory status epilepticus (NORSE)

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    Newswise — The following is the transcript from an episode of ILAE’s podcast, Sharp Waves.

    Sharp Waves episodes are meant for educational purposes only, and not as medical or clinical advice.

    Download the episode 

    You can listen to and download all Sharp Waves episodes, including this one, on Spotify, Apple Podcasts, Google Podcasts, Amazon Music, or the ILAE website.

    First-line immunotherapy and the ketogenic diet are two main recommendations for treatment of NORSE of unknown cause, according to results from an international consensus group. Dr. Maryam Nabavi Nouri interviews first author Dr. Ronny Wickstrom.

    Dr. Nabavi Nouri: So thank you for joining us on this episode of Sharp Waves – I’m joined by Dr. Ronny Wickstrom from Stockholm. He’s going to tell us about the international consensus recommendation for management of new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES), and I know there are two papers published: one is on summary and clinical tools and the other one statements and supporting evidence.

    Dr. Wickstrom: Thanks for the opportunity to present these papers. I’m Ronny Wickstrom; I’m a pediatric neurologist and epileptologist in Stockholm in Sweden. I’m also professor of child neurology at Karolinska. 

    So my field for a long time has been working with neuroinflammatory diseases, both demyelinating diseases and also encephalitis cases of different kinds, and then I work with epilepsy. And these have been my two fields, and these two fields meet in FIRES, so that’s how I came to start with this. 

    I had a case actually, six or seven years ago, a FIRES case, that did not end well, of course, like they often do not. He survived but he had severe sequelae. It sort of puzzled me, this whole FIRES thing and I wasn’t aware of FIRES until then. I’d heard of it, but this is an epilepsy phenotype where we believe that autoimmune or some sort of immunological at least components are involved. So that’s where I came into it, because those were my two worlds met anyway. 

    But when it started out, it started as a FIRES discussion. And we in the pediatric field had some FIRES communities. And what’s happened over the last couple of years, and which I’ve had the privilege of being involved in, is that this has merged with the NORSE community, which was also existing. So NORSE was perceived as an adult disease and FIRES as a pediatric disease, and one of the things we want to emphasize here is that that’s probably not true.

    One of the things we were doing in the FIRES field and also in the NORSE field is there’s a lot of research trying to be done, and there’s some data coming out, but it’s very hard, these are hard areas to study. One of course is that this is new onset, so there’s no population to study until they end up in refractory status epilepticus. And this, it’s very rare, and also it’s rare in a very hyperacute thing, so if you try to set up clinical trials, with standardized sampling and standardized testing and standardized treatment for these patients, it’s very difficult because you’re in a hyperacute situation where you have to do everything for your patient. So designing trials is extremely difficult. 

    We went through all the data before we started this and there’s a lot of case series and case presentations, and even in the larger case series and the ones we tried to compile, for instance, all the children that have been treated with IL-1 inhibition – one of the lessons we learned from that is even though we tried to standardize the data when we looked at it, it really ended up being 26 children, 26 individuals. It’s really, really difficult. That means what you’re left with as a clinician is there’s not a lot of solid data to base anything on. 

    So what we wanted to do with this Delphi approach, which, I’d been a part of another Delphi approach where we tried to summarize treatment in NMDA encephalitis. So I thought one way to do this or to try to summarize what we do know and give some sort of recommendations — we’ve been careful not to call these guidelines or anything like that because they’re not — we don’t have any evidence to say that they are guidelines. This is a recommendation, something to hold onto as a clinician and as a researcher. And we tried to compile this group of people that we thought for one or another reason were important to have as a part of it, and compile recommendations that covered everything from what is NORSE and FIRES, and also diagnostics and workup, treatment and long-term treatment, and then, and that’s the second part of why we undertook this and why I thought it was important, it also provided a possibility to try to bring everyone together because that’s the next step here. 

    This is a very rare and hyperacute and complicated thing. We at least need to try to, I mean we obviously need to study it better and we need large consortia to do this, and we need a common understanding, and common data elements, and speak the same language, and tests standardized and things like that, even if it’s only real-world studies. So the second idea of bringing this together was to create a platform like a solid ground, and this is the first step, to start a research consortium and international consortium where we can do these studies.

    Dr. Nabavi Nouri: Thank you. I understand there was a core group, and then a bigger group, an expert panel of 48 people internationally. Of course the Delphi method is quite interesting too, in that in this particular project there was a pre-set of questions and then it led to a stage 1 and a stage 2.

    Dr. Wickstrom: Yeah, so the Delphi methodology is an interesting way of doing things. It’s a standardized way of reaching a consensus, basically that’s what that is. You can be very orthodox or less orthodox and there are different ways of doing it. But the basic principle is the same. The idea is that rather than asking questions, you try to phrase statements like a recommendation or a guideline, if you have enough data for that. And for statements where you reach a consensus that’s all fine, and in statements where you do not reach a consensus for some reason, the idea is that you try to mold or adjust these statements until they are acceptable by the group as a consensus. 

    So a couple of things here. One is of course how do you select the group, how do you choose what group? How do you form the questions or the statements? And then, what is a consensus? I mean 100% is obviously a consensus but is 70% a consensus? There’s no definition, I mean no clear definition on this. We chose the methods that had most often been used in how to do this.

    So a couple of things were unusual in this case. One is that for a Delphi process, having 48 experts is a very large group. It’s almost impossible. Of course this gives you so much input, and so that’s not the problem. The problem of course is if there’s too much input, and trying to get a consensus, and also trying to get all of these people together is very difficult. The other side of that is that I think the people in this group were perfect. I think we could have probably found 48 others too that should have been on this group. Looking at representation, it’s very heavy in Europe and North America and there’s a lot of great research coming out of Asia, for instance, and we have suboptimal representation from Japan, Korea, China, and other places. 

    And then what we did, which is also unusual, is that we had this initial question of, we’re dealing with two things, there are two ways of slicing this if you want to. We’re dealing with adults and children, and should we, are the questions usable for both groups or should we divide them? 

    And also we’re dealing with NORSE and FIRES and those are more or less the same, because NORSE children are perceived to have FIRES and adults have NORSE. So we asked the group, and we were divided on this: Should we perform one Delphi, which is what we did, or should we divide it and do a pediatric and an adult one? 

    The reason we actually decided to go with the Delphi, one Delphi, is that there’s not a whole lot of evidence supporting that this is pediatric disease on one hand and NORSE is different. A lot of evidence points to this being very overlapping diseases or conditions. And if nothing else the traditional or the use of anti-inflammatory treatment in children as, for instance, IL-1 inhibition using anakinra, whereas in adults it’s IL-6 inhibition and in this case it was tocilizumab. There’s no real reason for this, it’s just in adults that’s been used more and it’s different traditions. We felt in this case the differences, we can probably learn more from the differences from the adult and pediatrics sides that it won’t cause a problem. 

    Joining or defining FIRES as a part of NORSE, we corroborated that here. But that’s in the definitions that was published in 2019 and 2018, even. So that was nothing new, but it’s important to emphasize that if you look at adults with NORSE in the Yale cohort for instance right now, their preliminary data show that more than half of the adult NORSE patients actually fulfill FIRES criteria as well. And conversely there are children who don’t fulfill FIRES criteria. But it’s quite rare. It’s obvious that the children, in children, in younger ages, the prevalence of an infection preceding the illness is much higher. It’s not 100% but it’s getting there.

    The important things in this is to try to look at all kinds of NORSE, including FIRES, as a potentially immunological problem. Especially cryptogenic NORSE. So NORSE today is a condition that can include infectious diseases, it can include autoimmune diseases, and if you find that of course you treat that. If you don’t find that and then you’re stuck with, so you have inconclusive results, cases of no etiology, we want to emphasize the importance of trying to break a vicious circle which is probably, I’m not going to say it’s inflammatory but at least it’s immunological. And that’s been more used in the pediatric field because it’s so obvious, I mean from a preceding illness, that this could be some sort of activation, whereas that’s not the case in adults. There are some data looking at refractory status epilepticus in adults showing that immunological treatments are not really on the table, or definitely not as early as they should be. 

    So to think that this is possibly immunological, there’s an immunological component in this and you have to target that, because if you don’t break that circle, none of your regular anti-seizure medications are going to work. So that’s one of the things, to start early with first-line immunotherapy, and escalate early and aggressively to second-line immunotherapy.

    The other thing that’s also in this, which is not primarily immunological, is that we advocate the use of ketogenic diet as early as possible. And that’s also used in pediatrics but not so much in adults. The reason for advocating that is that’s one of the few treatments that has actually been shown in small but still case series to be effective. So we believe that adding ketogenic diet early, which is in this case was defined in the recommendations as seven days, is of importance. 

    Dr. Nabavi Nouri: Thank you. What would be the implications of the results?

    Dr. Wickstrom: The important implication is to look at your local guidelines on how you treat status epilepticus and refractory status epilepticus in your hospitals. We can see, we haven’t shown that here but there’s data showing that a lot of hospitals don’t have clear guidelines on this and the ones that do have them rarely include immunotherapy. So looking at these guidelines, this would affect your local guidelines for refractory status epilepticus and super-refractory status epilepticus, if these are new onset, during the first week of treatment. 

    When it comes to workup and diagnostics, there’s a lot of recommendations on how to do this. And this also differs a little bit. We know that in pediatrics, for instance, we sometimes don’t take all the antibodies that we should do. We know in adult situations, it’s perceived as not so important to look at genetics or metabolic disease, of course because it’s not as prevalent, but it should be part of your workup. So during the first couple of days, during the workup, the implications of these papers is that that it can give you recommendations on where to look and try to widen your screening. 

    And then the big implications is of course the treatment implication from day three, and that includes primary immunotherapy or first line immunotherapy, and then escalating that by day seven.

    Dr. Nabavi-Nouri: Well I think having those timeframes arguably could be altering outcomes, especially when we’re really dealing with, as you mentioned you had one case and it will never leave you for the rest of your career, always trying to understand what you can do better. What would be the next steps of this, next steps of this very impressive consensus group?

    Dr. Wickstrom: So the next step everyone is dreaming about, which we were thinking about, I mean it’s been a couple of years that we’ve been thinking that this should have been started, is clinical trials of treatments. It’s just it’s very, very difficult it turns out. It’s difficult to agree on if we do a treatment, how do we do it, is it head-to-head treatment and if so, what do we use? It’s going to be really, really hard to design those trials at this point. I don’t think we have enough data for anyone because you as a treating clinician, you need to treat your patient the way you think is best, and it’s hard to randomize patients. You have to have compliance from the group. And that was part of doing this, was to increase compliance and let everyone have a say in how to design these clinical trials. 

    I’m hoping we can fairly soon arrive at clinical trials, but I also think we need to think differently than that and think about how we can design real-life studies that are usable. For instance, can we look at some sort of clinical decision support that can serve both the purpose of filling up a biobank of data and possibly samples, at the same time that it offers you as a clinician help.

    But I hope the work that we’ve done is to create awareness in this group and in other groups that there is a consortium or there will be a consortium and this is open – the more people who want to join the better the stronger we can get. And we can use this to do good research, to get funding to do research and also to try to help these children and adults. And hopefully expand into refractory status epilepticus (RSE), because I mean – one debate now is, what actually differs? Why is NORSE different from other RSE? That’s a valid question.  I think in many cases it will be, for instance if you have structural, some sort of etiologies, or if you have an ongoing epilepsy, that’s probably a different sort. But immunological components may be a part even in that case. 

    But I think what NORSE as a concept offers is it offers a sort of umbrella that can help us in forwarding and advancing our knowledge. And maybe in 2 years or 5 or 10 years we’ll decide there’s no such thing as NORSE, it’s just RSE that happens to be new onset and we understand what it is. 

    Dr. Nabavi Nouri: Lastly, and second to last question would be about the CSF cytokines. I’m very intrigued that it made it to the consensus. It’s been a big point of debate for two reasons: one is for clinical availability in terms of using reliable labs that can give you a clinical turnaround time as quickly as you would like to use it as a biomarker to guide treatment, and the other one is always timing, I find, because the cytokine profile can change quite drastically. I see there were two questions in the consensus – one whether it would be used for a biomarker of disease progression and response to treatment, and the other one was a choice of medication. 

    Dr. Wickstrom: So one of the hypotheses concerning FIRES and also NORSE is that it at least involves, maybe that’s not the whole mechanism, but it involves cytokine release. And that part of the immunological activation is actually the problem. There is some evidence to support that from animal data, and also there’s evidence in humans from blocking IL-1 and IL-6 mainly, with good results. So that’s the idea why cytokines appear to be important. 

    Just as you mentioned, there are several problems with cytokines. One is that it’s hugely complex – it’s really a web of different cytokines and they affect one another. For instance, we know that IL-1, which is a regulator of the proinflammatory system, we hardly ever see it because it has a very short half-life. Just by looking at lab data we have for IL-1, for instance, you would never use an IL-1 blocker, that would be a logical result of that, and still we know that it works. Looking at IL-1 levels doesn’t really help. 

    The second problem with cytokines is that they’re hard to analyze, if you don’t have access to a lab, but they’re also hard to sample. Whereas antibodies are very stable, cytokines are not stable, so you really, if you don’t sample it the right way for instance from the start, then you go to your bacterial or microbiology lab and say do you have any CSF left, and it’s been standing on a lab bench for two hours and cytokines have degenerated.

    I would love to say you should look at cytokines and you should use that, but we don’t know that. But tentatively, if we believe that cytokines are involved in this, it should or could be possible to have it both as a marker of disease and also as disease progression. But just like you said, it’s not a question of whether this goes up and then it goes down and then it’s gone. Inflammation is a tricky thing because it’s an endogenous response you want to have. And one of the consequences of a proinflammatory response – when we say inflammation, we usually mean proinflammation – the other thing is we have anti-inflammation. The proinflammatory cytokines will increase the anti-inflammatory response and we know for instance in studies of encephalitis cases, you really need to look at the ratio between pro- and anti-inflammatory to understand it. 

    Dr. Nabavi Nouri: What do young clinician researchers listening, how can they get more involved in this type of research? Are there any organizations or consensus groups with in the ILAE or within this consortium that they could approach and explore being more involved in this type of research?

    Dr. Wickstrom: Right now this consortium that I’m referring to isn’t really a consortium, it’s something we want to evolve into. But people are there and it’s open, 100% open to everyone who wants to join, both from a learning perspective and because this is an area to which you want to contribute is fantastic. 

    One way of accessing this or being involved is via the NORSE Institute. And that’s NORSEinstitute.org. It’s a North American institute that was started by the mother of a patient who died from this, and she’s done a fantastic job in trying to promote this research and bringing all of us together. You can find the names and email addresses of many of the people who have been part of this, and we regularly update it with published literature and how to find your way to the different ongoing studies, and that’s a way in.

    Dr. Nabavi-Nouri: To conclude, I’d like to ask if there’s anything more that you’d like to add and most importantly any take home messages that we’d like to leave our listeners with.

    Dr. Wickstrom: I really, really want to emphasize the immunological treatment because I can see that’s not working perfectly, of course not, but it could be improved a lot in kids, but even more so in adults, because they’re not using immunological treatment at all, and I’m convinced it will help so many adults with NORSE. And FIRES, probably both NORSE and FIRES. That’s an important take-home message.

    ##

    The recommendations and clinical tools are available now:

    International consensus recommendations for management of new-onset refractory status epilepticus (NORSE) including febrile infection-related epilepsy syndrome (FIRES): Summary and clinical tools

    International consensus recommendations for management of new-onset refractory status epilepticus (NORSE) including febrile infection-related epilepsy syndrome (FIRES): Statements and supporting evidence

    Families affected by NORSE/FIRES can join the NORSE Family Registry and contribute information that may help shape and initiate research. NORSE Family Registry registration is available in multiple languages: English | français | Mandarin | español

     

    Founded in 1909, the International League Against Epilepsy (ILAE) is a global organization with more than 125 national chapters.

    Through promoting research, education and training to improve the diagnosis, treatment and prevention of the disease, ILAE is working toward a world where no person’s life is limited by epilepsy.

    Website | Facebook | Instagram | YouTube

    Twitter: English French Japanese Portuguese Spanish

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    International League Against Epilepsy

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  • USU, Federal Mental Health Experts Earn Prestigious Military Family Research Institute Award

    USU, Federal Mental Health Experts Earn Prestigious Military Family Research Institute Award

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    Newswise — Bethesda, Md. – In recognition of their outstanding research that has brought visibility to issues impacting the Armed Forces and their families, several behavioral health professionals from the Uniformed Services University of the Health Sciences (USU) were the recipients of the Military Family Research Institute at Purdue University (MFRI)’s 2022 Barbara Thompson Excellence in Research on Military and Veteran Families Award. The award is based on their scientific publication, “The role of posttraumatic stress symptoms and negative affect in predicting substantiated intimate partner violence incidents among military personnel,” published in the journal Military Behavioral Health in August 2021.

    Dr. Stephen Cozza, a psychiatrist in USU’s Center for the Study of Traumatic Stress (CSTS) Dr. Eddie McCarroll, a CSTS scientist and social worker, and Dr. David Riggs, chair of USU’s Department of Psychology, were among the participating scientists in a multi-institutional research project led by Dr. Valerie Stander at the Naval Research Center in San Diego, who received the award. 

    The researchers looked at symptoms of Post-traumatic Stress Disorder (PTSD) among active-duty service members, seeking to determine whether any particular symptoms might be associated with an increased risk for intimate partner violence. They studied the extent to which PTSD symptoms – particularly hyperarousal and persistent negative emotions, like fear, anger, or shame – might be unique risk factors, compared to symptoms associated with other comorbid conditions (e.g. depression, anxiety, insomnia, alcohol dependence, or binge drinking). Ultimately, they found that general symptoms of negative affect (e.g. anger/irritability and sleep disruption), which are common in PTSD, and comorbid alcohol dependence, were the strongest predictors of intimate partner violence.

    The publication was selected for the prestigious award through a rigorous and highly selective process, through which applications and nominations are not accepted. According to the institute, a large panel of accomplished scholars examines every relevant research article published during the eligible year. The final decision is made after multiple rounds of review involving standardized quantitative assessments. About 500 articles were considered.

    The MFRI established the Barbara Thompson Award in 2015, in partnership with Military REACH at Auburn University, to bring visibility to issues of military and veteran families, and to outstanding new research. The award aims to increase the impact of rigorous research on programs, policies, and practices that impact military members and their families, while strengthening connections between researchers and practitioners interested in military and veteran families.  

    “Uniformed Services University faculty members are highly sought out, not only for their expertise, but also for their willingness to contribute to mission-relevant team efforts. It is not surprising that members of different specialties and, indeed, from different departments at USU, were able to make significant contributions to this effort,” said Dr. David Benedek, chair of USU’s Department of Psychiatry and associate director of USU’s CSTS.

    The award recipients presented their research in detail and discussed the implications for future research during a virtual award ceremony on Dec. 9. 

    # # #

    About the Uniformed Services University of the Health Sciences: The Uniformed Services University of the Health Sciences, founded by an act of Congress in 1972, is the nation’s federal health sciences university and the academic heart of the Military Health System. USU students are primarily active-duty uniformed officers in the Army, Navy, Air Force and Public Health Service who receive specialized education in tropical and infectious diseases, TBI and PTSD, disaster response and humanitarian assistance, global health, and acute trauma care. USU also has graduate programs in oral biology, biomedical sciences and public health committed to excellence in research. The University’s research program covers a wide range of areas important to both the military and public health. For more information about USU and its programs, visit www.usuhs.edu.

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    Uniformed Services University of the Health Sciences (USU)

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  • Study: Without more data, a black hole’s origins can be “spun” in any direction

    Study: Without more data, a black hole’s origins can be “spun” in any direction

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    Newswise — Clues to a black hole’s origins can be found in the way it spins. This is especially true for binaries, in which two black holes circle close together before merging. The spin and tilt of the respective black holes just before they merge can reveal whether the invisible giants arose from a quiet galactic disk or a more dynamic cluster of stars.

    Astronomers are hoping to tease out which of these origin stories is more likely by analyzing the 69 confirmed binaries detected to date. But a new study finds that for now, the current catalog of binaries is not enough to reveal anything fundamental about how black holes form.

    In a study appearing in the journal Astronomy and Astrophysics Letters, MIT physicists show that when all the known binaries and their spins are worked into models of black hole formation, the conclusions can look very different, depending on the particular model used to interpret the data. 

    A black hole’s origins can therefore be “spun” in different ways, depending on a model’s assumptions of how the universe works.

    “When you change the model and make it more flexible or make different assumptions, you get a different answer about how black holes formed in the universe,” says study co-author Sylvia Biscoveanu, an MIT graduate student working in the LIGO Laboratory. “We show that people need to be careful because we are not yet at the stage with our data where we can believe what the model tells us.”

    The study’s co-authors include Colm Talbot, an MIT postdoc; and Salvatore Vitale, an associate professor of physics and a member of the Kavli Institute of Astrophysics and Space Research at MIT.

    A tale of two origins

    Black holes in binary systems are thought to arise via one of two paths. The first is through “field binary evolution,” in which two stars evolve together and eventually explode in supernovae, leaving behind two black holes that continue circling in a binary system. In this scenario, the black holes should have relatively aligned spins, as they would have had time — first as stars, then black holes — to pull and tug each other into similar orientations. If a binary’s black holes have roughly the same spin, scientists believe they must have evolved in a relatively quiet environment, such as a galactic disk.

    Black hole binaries can also form through “dynamical assembly,” where two black holes evolve separately, each with its own distinct tilt and spin. By some extreme astrophysical processes, the black holes are eventually brought together, close enough to form a binary system. Such a dynamical pairing would likely occur not in a quiet galactic disk, but in a more dense environment, such as a globular cluster, where the interaction of thousands of stars can knock two black holes together. If a binary’s black holes have randomly oriented spins, they likely formed in a globular cluster.

    But what fraction of binaries form through one channel versus the other? The answer, astronomers believe, should lie in data, and particularly, measurements of black hole spins.

    To date, astronomers have derived the spins of black holes in 69 binaries, which have been discovered by a network of gravitational-wave detectors including LIGO in the U.S., and its Italian counterpart Virgo. Each detector listens for signs of gravitational waves — very subtle reverberations through space-time that are left over from extreme, astrophysical events such as the merging of massive black holes.

    With each binary detection, astronomers have estimated the respective black hole’s properties, including their mass and spin. They have worked the spin measurements into a generally accepted model of black hole formation, and found signs that binaries could have both a preferred, aligned spin, as well as random spins. That is, the universe could produce binaries in both galactic disks and globular clusters.

    “But we wanted to know, do we have enough data to make this distinction?” Biscoveanu says. “And it turns out, things are messy and uncertain, and it’s harder than it looks.”

    Spinning the data

    In their new study, the MIT team tested whether the same data would yield the same conclusions when worked into slightly different theoretical models of how black holes form.

    The team first reproduced LIGO’s spin measurements in a widely used model of black hole formation. This model assumes that a fraction of binaries in the universe prefer to produce black holes with aligned spins, where the rest of the binaries have random spins. They found that the data appeared to agree with this model’s assumptions and showed a peak where the model predicted there should be more black holes with similar spins.

    They then tweaked the model slightly, altering its assumptions such that it predicted a slightly different orientation of preferred black hole spins. When they worked the same data into this tweaked model, they found the data shifted to line up with the new predictions. The data also made similar shifts in 10 other models, each with a different assumption of how black holes prefer to spin.

    “Our paper shows that your result depends entirely on how you model your astrophysics, rather than the data itself,” Biscoveanu says.

    “We need more data than we thought, if we want to make a claim that is independent of the astrophysical assumptions we make,” Vitale adds.

    Just how much more data will astronomers need? Vitale estimates that once the LIGO network starts back up in early 2023, the instruments will detect one new black hole binary every few days. Over the next year, that could add up to hundreds more measurements to add to the data.

    “The measurements of the spins we have now are very uncertain,” Vitale says. “But as we build up a lot of them, we can gain better information. Then we can say, no matter the detail of my model, the data always tells me the same story — a story that we could then believe.”

    This research was supported in part by the National Science Foundation.

    ###

     

    Additional background

    Paper: “Spin it as you like: the (lack of a) measurement of the spin tilt
    distribution with LIGO-Virgo-KAGRA binary black holes”

    https://www.aanda.org/articles/aa/full_html/2022/12/aa45084-22/aa45084-22.html

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    Massachusetts Institute of Technology (MIT)

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  • Tobacco use, incidence of adverse oral health outcomes

    Tobacco use, incidence of adverse oral health outcomes

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    Newswise — About The Study: This nationally representative cohort study found associations of current combustible tobacco use with the incidence of adverse oral health outcomes and also found an association between current electronic nicotine delivery systems use and the incidence of bleeding after brushing or flossing. These findings highlight the importance of longitudinal studies and emphasize the continued importance of tobacco cessation counseling and resources in clinical practice. 

    Authors: Marushka L. Silveira, B.D.S., M.P.H., Ph.D., of the National Institutes of Health in Bethesda, Maryland, is the corresponding author. 

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

    #  #  #

    Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time http://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2022.45909?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=120922

    About JAMA Network Open: JAMA Network Open is an online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.

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    JAMA – Journal of the American Medical Association

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  • Expanding the arsenal of drugs against COVID-19

    Expanding the arsenal of drugs against COVID-19

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    Newswise — Tokyo, Japan – The ongoing COVID-19 pandemic, caused by the SARS-CoV-2 virus, has been devastating the entire world. While the vaccination program is advancing, drug treatments for COVID-19 are still highly important for those who become infected. Now, a team at Tokyo Medical and Dental University (TMDU), National Center for Global Health and Medicine (NCGM), Tohoku University, NCI/NIH, and Kumamoto University has designed and synthesized compounds that have the potential to be novel drugs targeting SARS-CoV-2.

    The SARS-CoV-2 virus contains an enzyme called the “main protease”, or Mpro, that cleaves other proteins encoded in the SARS-CoV-2 genome as part of viral activity and replication. Mpro is an important and appealing target for drugs treating COVID-19 because it is both essential for viral replication and very different from any human molecules, so drugs targeting Mpro are likely to have few side effects and be very effective.

    When testing a panel of compounds known to have inhibitory activity against SARS-CoV, the virus responsible for the 2002 SARS outbreak, the team identified a compound named 5h/YH-53 that showed some activity inhibiting SARS-CoV-2 Mpro, but was inefficient and unstable. Therefore, they used 5h as a starting point to develop other compounds with increased efficiency and stability. “Our strategy involved introducing fluorine atoms into the part of the molecule responsible for inhibiting Mpro to increase its binding affinity, as well as replacing a bond within 5h that is easily broken down by the liver with a different structure to increase biostability,” explains lead author Kohei Tsuji.

    “Of the compounds we developed, compound 3 showed high potency and was able to block SARS-CoV-2 infection in vitro without any viral breakthrough,” explains senior author Hirokazu Tamamura. “Compound 4, a derivative of compound 3 in which an easily broken-down amide bond had been replaced with a stable thioamide bond, also showed remarkable anti-SARS-CoV-2 activity.” Although compound 4 had lower Mpro inhibitory activity than compound 3, the increased stability meant that the overall activity of compound 4 was comparable to that of compound 3.

    When they tested these novel compounds on a variety of strains of SARS-CoV-2, compound 3 was as effective on mutant strains of the virus as on the ancestral Wuhan strain. Additionally, neither compound 3 or 4 showed any toxicity to cultured cells. These data suggest that these compounds show high potential as drug treatments for COVID-19.

    A repertory of drug choice is important for treating disease, and so the development of efficient drugs to target the novel SARS-CoV-2 virus is highly important. This work identifies two compounds as potential drugs, and further development of these compounds continues. It also proves the principle that easily broken-down amide bonds can be replaced with thioamide bonds in drug development to increase the stability of the resulting compounds. Taken together, this is an important advance in both the wider drug development field as well as for drugs to treat COVID-19.

    ###

    The article, “Potent and Biostable Inhibitors of the Main Protease of SARS-CoV-2”, was published in iScience at DOI: 10.1016/j.isci.2022.105365

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    Tokyo Medical and Dental University

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  • Fred Hutch at ASH: Global insights on AML outcomes, COVID-19 and cancer, CD19 CAR T-cell therapy updates, latest on precision oncology — and more

    Fred Hutch at ASH: Global insights on AML outcomes, COVID-19 and cancer, CD19 CAR T-cell therapy updates, latest on precision oncology — and more

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    Newswise — SEATTLE — Dec. 1, 2022 — The 64th Annual Meeting and Exposition of the American Society of Hematology (ASH) will take place virtually and in person Dec. 10-13 in New Orleans, Louisiana.

    Below are highlights of Fred Hutchinson Cancer Center research to be presented, and you can follow Fred Hutch updates on Twitter #ASH22. You can also check out Fred Hutch’s booth 2622 in the exhibit hall.

    This year’s ASH press program highlights work below by Fred Hutch:

    Poster presentation: An analysis of the worldwide utilization of hematopoietic stem cell transplantation for acute myeloid leukemia Abstract: 3638 Presenter: Molly Tokaz Other Fred Hutch authors: Andrew Cowan and Mary-Beth Percival Sunday, Dec. 11, 6 p.m.

    A global study of use of transplantation for acute myeloid leukemia led by Fred Hutch fellow Dr. Molly Tokaz will be featured in a Dec. 7 virtual-only ASH briefing, “Building Solutions to Challenges in Health Equity.”

    Late-breaking session: Zanubrutinib demonstrates superior progression-free survival (PFS) compared with ibrutinib for treatment of relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma (R/R CLL/SLL): Results from final analysis of ALPINE randomized phase 3 study Abstract: LBA-6 Senior author: Mazyar Shadman (On Twitter: @mshadman) Tuesday, Dec. 13, 8:30 a.m.

    A Dec. 12 media briefing on late-breaking abstracts will include an abstract co-authored by Fred Hutch’s Dr. Mazyar Shadman, a chronic lymphocytic leukemia and lymphoma physician-investigator. The abstract gives an update on a clinical trial assessing a next-generation Bruton tyrosine kinase inhibitor.

    Also on the press program, Dr. Stephanie Lee, former president of ASH, will moderate the Dec. 10 briefing “New Drugs, New Targets.” Dr. Lee is a transplant physician-scientist and expert in chronic graft-vs.-host-disease and holds the David and Patricia Giuliani/Oliver Press Endowed Chair in Cancer Research at Fred Hutch.

    Learn more in the ASH Annual Meeting press program.

    Poster presentation: Timing of PD-L1 Blockade with Durvalumab May Affect Outcomes of CD19 CAR-T Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma Abstract: 3316 Presenter: Alexandre Hirayama (On Twitter: @xanira) Sunday, Dec. 11, 6 p.m.

    Adding checkpoint blockades may make CAR T-cell therapy more effective against blood cancers, but combination trial results so far have been disappointing. This clinical trial evaluates the importance of timing of the therapies.

    Poster presentation: CAR T-cell therapy for relapsed or refractory large B-cell lymphoma using a fully human CD10-targeted single chain variable fragment: Results of a first-in-human phase I/II study Abstract: 4654 Presenter: Nicolas Gazeau (On Twitter: @NGazeau14) Monday, Dec. 12, 6 p.m.

    CAR T-cell therapies targeting the marker CD19 on cancer cells achieve high response rates in patients with relapsed or refractory large B-cell lymphoma, but durable responses are only achieved in 30-40% of patients. Based on clinical evidence showing lack of a durable response linked to a mouse-based component of the engineered cell, a phase I/II clinical trial is evaluating the effectiveness of the CAR T rebuilt with a human-based component instead. 

    Poster presentation: 3-Year follow-up analysis of ZUMA-5: a Phase 2 study of axicabtagene ciloleucel (Axi-Cel) in patients with relapsed/refractory (R/R) indolent non-hodgkin lymphoma (iNHL)

    Abstract: 4660 Co-author: David Maloney Monday Dec. 12, 6 p.m.

    This is a 3-year follow-up of the ZUMA-5 study, which shows that the CAR T-cell therapy called axi-cel demonstrated continued durable responses in patients with relapsed/refractory indolent non-hodgkin’s lymphoma (R/R iNHL) with improved survival observed in patients with marginal zone lymphoma. Late progression or death due to lymphoma or study treatment were uncommon and no new safety signals arose since the 2-year analysis. The research team also looked at biomarkers related to outcomes and found that preinfusion immunosuppressive Treg-related biomarkers were associated with relapse in patients with follicular lymphoma.

    Poster presentation: Circulating tumor DNA in untreated classical hodgkin lymphoma patients treated with pembrolizumab and chemotherapy: Dynamic response assessment and correlation with baseline metabolic tumor volume

    Abstract: 2913 Presenter: Ryan Lynch Sunday, Dec. 11, 6 p.m.

    This abstract presents updated results of a Fred Hutch single-center investigator-initiated clinical trial of the checkpoint inhibitor called pembrolizumab plus a chemotherapy for untreated classical Hodgkin lymphoma. The researchers continued to demonstrate a favorable safety profile with excellent efficacy (median follow up of 2.1 years, 2-year progression free survival of 97%). They also present new correlative data with circulating tumor DNA (ctDNA) for detection of minimal residual disease. It is possible that immunotherapy combinations may be associated with increased rates of uptake of residual F-fluorodeoxyglucose, which is a nonspecific imaging agent, and the team found that many of these patients have not had their cancer come back even several years later. In contrast, ctDNA was able to identify the lack of ctDNA clearance in the only patient who has relapsed today despite favorable initial PET scans. These findings indicate that ctDNA may represent a more sensitive and specific response assessment tool to be studied in larger datasets.

    Oral presentation: Self-reported experiences of adult hematopoietic cell transplantation survivors with COVID-19 vaccination and infection Abstract: 378 Presenter: Emily Liang (On Twitter: @emilyliangmd) Saturday, Dec. 10, 5:15 p.m.

    In a report of about 1700 stem cell transplant survivors, Fred Hutch clinicians found that vaccinated patients and their household contacts had a lower rate of COVID-19 infection compared with unvaccinated individuals (patients: 6% vs 68%, or 10-fold lower rate of infection; household contacts: 10% vs 46%, or 4-fold lower rate of infection) and were more likely to take additional safety precautions including masking and social distancing. The Fred Hutch team hopes the findings encourage others to receive the COVID-19 vaccination given the protective effect of vaccination and low rates of vaccine-related side effects.

    Poster presentation: A risk model for CML patients with COVID-19: Importance of molecular response in the context of age, comorbidities and country income Abstract: 4327 Presenter: Jerry Radich Monday, Dec. 12, 6 p.m.

    Researchers on the iCMLf CANDID study, a collaboration of 157 centers from 58 countries and with nearly 700 chronic myeloid leukemia patients participating, are looking for risk factors to predict which people with chronic myeloid leukemia are more likely to suffer worse outcomes from COVID-19. Dr. Jerry Radich, who holds the Kurt Enslein Endowed Chair at Fred Hutch, will report on the group’s findings, which show that age, molecular aspects of an individual’s CML, comorbidities and wealth of countries impact COVID-19 outcomes in CML patients.

    Oral presentation: Anti-leukemic activity of STRO-002 a novel folate receptor-α (FR-α)-targeting ADC in relapsed/refractory CBF2AT3-GLIS2 AML Abstract: 66 Presenter: Soheil Meshinchi Saturday, Dec. 10, 10:45 a..m.

    Acute myeloid leukemia remains one of the most difficult to treat pediatric cancers. Physician-scientist Dr. Soheil Meshinchi has led efforts to characterize the biology of this cancer in young patients and to identify targeted treatments that best suit their specific disease. At ASH, he will give an update on one such treatment, which was tested as part of Project Stella at Fred Hutch. His hope is that with detailed molecular testing of each patient followed by a targeted therapy, that children with the disease will go on to live long and healthy lives.

    Poster presentation: Umbrella trial in myeloid malignancies: The myeloMATCH national clinical trials network precision medicine initiative Abstract: 4080 Co-author: Jerry Radich Monday, Dec. 12, 6 p.m.

    Fred Hutch is part of an initiative led by the National Cancer Institute to help people newly diagnosed with acute myeloid leukemia and myelodysplastic syndromes to have a rapid (less than 3 days) testing of the clinical and molecular makeup of their disease and then be matched with treatment trials with promising therapeutic combinations. Fred Hutch, under the leadership of Dr. Jerry Radich, has been chosen to coordinate and perform the diagnostic and monitoring aspects of this nationwide initiative.

    Oral session: Allogeneic transplantation: Acute and chronic GVHD, immune reconstitution: Clinical studies exploring the immunobiology of HCT Abstract: 722 Moderator: Kate Markey (On Twitter: @katemarkey) Saturday, Dec. 10, 9:30 a.m.

    New insights – bolstered by emerging technological breakthroughs – on how the immune system recovers following transplantation are increasing our understanding of post-transplant complications like graft-versus-host disease. Fred Hutch’s Dr. Kate Markey, a physician-scientist and expert on how the microbiome affects recovery from transplantation, will moderate this session that includes clinical data from groups exploring T cell recovery after transplantation and clinical reports.

    Poster presentation: HSCs engraft in a stochastic pattern and form clonal pools following transplantation Abstract: 2527 Presenter: Stefan Radtke Sunday, Dec. 11, 6 p.m.

    Previous Fred Hutch studies discovered a subtype of hematopoietic stem cells that give rise to all other cells in the blood and immune systems, which could be a powerful therapeutic target. But because the cells are so rare, they’ve been difficult to study. Findings in this poster used a new type of bar coding to track individual cells and reveal some of the cellular dynamics that underlie their regenerative abilities.

    Poster presentation: Clinical and functional implications of MYC variants as a new class of pathogenic variants in AML Abstract: 1472 Presenter: Danielle Kirkey Saturday, Dec. 10, 5:30 p.m.

    Understanding the underlying genetics of pediatric acute myeloid leukemia can help determine how best to treat this difficult to treat disease. One of the genetic players is MYC, an oncogene involved in a majority of human cancers. In this work, Fred Hutch researchers defined the presence of different MYC variants and found that some occur in about 3.5% of pediatric patients with AML. The team did additional analyses to link MYC variants with other previously known high-risk features of AML and found those associations to be linked to clinical outcomes, which will allow for more nuanced stratification of a patient’s risk and will help determine optimal treatment regimens.

    Oral presentation: Treatment patterns and outcomes of patients with primary or secondary acute myeloid leukemia by type of site (academic or community government): A CONNECT® Myeloid Registry Study

    Abstract: 4023 Presenter: Bart Scott Monday, Dec 12, 6 p.m.

    This research was conducted to better understand management of secondary acute myeloid leukemias (SAML), which is a type of blood cancer that starts in white blood cells that grow in the bone marrow, often affecting people who have one of these blood cell diseases: myelodysplastic syndrome (MDS), myeloproliferative disorder (MPD) and aplastic anemia. The Fred Hutch team evaluated treatment patterns and outcomes in patients enrolled in the CONNECT® Myeloid Disease Registry. The findings indicate that outcomes for patients with AML in the registry are consistent with previously reported outcomes. This analysis suggests that contrary to commonly held perceptions, site of care does not affect overall patient outcomes. The clinically meaningful increase in overall survival in patients receiving an allogeneic hematopoietic stem cell transplant, regardless of primary or secondary AML further emphasizes the importance of providing patients with the opportunity for transplant.

    Poster presentation: Clinical outcome and treatment-related mortality in patients with acute myeloid leukemia treated at the Uganda Cancer Institute

    Abstract: 4031 Presenter: Clement Dove Okello Co-author: Soheil Meshinchi Monday, Dec 12, 6 p.m.

    A retrospective review of acute myeloid leukemia outcomes at the Uganda Cancer Institute examined factors associated with treatment-related mortality. Treatment of AML is similar across countries, but treatment-related mortality is significantly greater in low-income countries compared with high-income countries. This study by UCI and Fred Hutch researchers examined factors that could be contributing to greater mortality, in hopes of improving outcomes. Through the UCI-Fred Hutch Collaboration, Dr. Soheil Meshinchi, a Fred Hutch expert in AML, advised on the project.

    Poster presentation: Revised prognostic index for patients with acute myeloid leukemia and other high-grade myeloid neoplasms in first relapse

    Abstract: 1385 Presenter: Noam E. Kopmar Saturday, Dec 10, 5:30 p.m.

    Though many patients with acute myeloid leukemia will achieve a first complete remission, most patients will relapse. Fred Hutch researchers looked at predictors of relapse and examined methods to create an improved risk stratification model that will better predict likelihood of a second complete remission and overall survival after relapse. Through a better understanding of prognosis, providers may improve their ability to determine the optimal treatment approach and also better inform the counseling provided to patients regarding prognosis.

    Poster presentation: Prognostic significance of chromosomal genomic array testing in adults with newly diagnosed acute lymphoblastic leukemia

    Abstract: 4145 Presenter: Noam E. Kopmar Saturday, Dec 12, 6 p.m.

    This project led by members of the acute leukemia and myeloid malignancies research group at Fred Hutch is aimed at improving prognostic capabilities at the time of either a new diagnosis or at the time of first relapse, correlating chromosomal genomic array testing results with key demographic and outcomes data. Having a better understanding of prognosis may improve the ability of providers to determine the optimal treatment approach and also better inform the counseling that is provided to patients regarding prognosis.

    The disease-killing T cells of the immune system develop their capabilities in a small, butterfly-shaped gland in the chest called the thymus. The thymus can regenerate to keep its immune function strong, but it wears out from stress, infection and aging. At ASH, Fred Hutch researchers will report their latest findings on how to repair the thymus:

    Oral presentation: Interleukin-18 suppresses regeneration of the thymus

    Abstract: 483 Presenter: David Granadier Co-author Jarrod Dudakov (On Twitter: @Dudakov_Lab) Monday, Dec 12, 4:30 p.m.

    Research by graduate student David Granadier in Dr. Jarrod Dudakov’s lab implicates the cytokine IL-18 in regulating the ability of the thymus to repair itself. This presentation will these latest insights. More on the signaling pathways involved in thymic regeneration and their implications for therapeutics in a Fred Hutch news story.

    Poster presentation: The zinc-sensing receptor GPR39 is a master regulator of immune reconstitution after bone marrow transplant in the thymus and in the bone marrow

    Abstract: 4581 Presenter: Lorenzo Iovino Co-author Jarrod Dudakov (On Twitter: @Dudakov_Lab) Monday, Dec 12, 6 p.m.

    Zinc is well-known for its immune-boosting properties, and recently Dr. Lorenzo Iovino in Dudakov’s lab at Fred Hutch revealed how zinc supports immune function through the thymus. Iovino will give an update on the work and how it could be used to improve treatments for cancer patients.

    Note: Fred Hutch and the scientists who contributed to these discoveries may stand to benefit from their future commercialization.

    The clinical trials referenced above involve investigational products and/or therapies that have not been approved for commercial marketing by the U.S. Food and Drug Administration or any other regulatory authority. Results may vary and encouraging results from early stage clinical trials may not be supported in later stage clinical trials.  No conclusions should be drawn from the information in this report about the safety, efficacy, or likelihood of regulatory approval of these investigational products and/or therapies.

    # # #

    Fred Hutchinson Cancer Center unites comprehensive care and advanced research to provide the latest cancer treatment options and accelerate discoveries that prevent, treat and defeat cancer and infectious diseases worldwide.

    Based in Seattle, Fred Hutch is an independent, nonprofit organization and the only National Cancer Institute-designated cancer center in Washington. We have earned a global reputation for our track record of discoveries in cancer, infectious disease and basic research, including important advances in bone marrow transplantation, HIV/AIDS prevention, immunotherapy and COVID-19 vaccines. Fred Hutch operates eight clinical care sites that provide medical oncology, infusion, radiation, proton therapy and related services and has network affiliations with hospitals in four states. Fred Hutch also serves as UW Medicine’s cancer program.

    Please note that our organization was renamed Fred Hutchinson Cancer Center in April 2022, following the merger of long-time partners, Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance. 

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  • Palm e-tattoo can tell when you’re stressed out

    Palm e-tattoo can tell when you’re stressed out

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    Newswise — Our palms tell us a lot about our emotional state, tending to get wet when people are excited or nervous. This reaction is used to measure emotional stress and help people with mental health issues, but the devices to do it now are bulky, unreliable and can perpetuate social stigma by sticking very visible sensors on prominent parts of the body.

    Researchers at The University of Texas at Austin and Texas A&M University have applied emerging electronic tattoo (e-tattoo) technology to this type of monitoring, known as electrodermal activity or EDA sensing. In a new paper published recently in Nature Communications, the researchers created a graphene-based e-tattoo that attaches to the palm, is nearly invisible and connects to a smart watch.

    “It’s so unobstructive that people sometimes forget they had them on, and it also reduces the social stigma of wearing these devices in such prominent places on the body,” said Nanshu Lu, professor in the Department of Aerospace Engineering and Engineering Mechanics and leader of the project.

    Lu and her collaborators have been advancing wearable e-tattoo technology for many years. Graphene has been a favorite material because of how thin it is and how well it measures electrical potential from human body, leading to very accurate readings.

    But, such ultra-thin materials can’t handle much, if any strain. So that makes applying them to parts of the body that include a lot of movement, such as the palm/wrist, challenging.

    The secret sauce of this discovery is how the e-tattoo on the palm is able to successfully transfer data to a rigid circuit – in this case a commercially available smart watch, in out-of-lab, ambulatory settings. They used a serpentine ribbon that has two layers of graphene and gold partially overlapped. By snaking the ribbon back and forth, it can handle the strain that comes with movements of the hand for everyday activities like holding the steering wheel while driving, opening doors, running etc.

    Current palm monitoring tech uses bulky electrodes that fall off and are very visible, or EDA sensors applied to other parts of the body, which gives a less accurate reading.

    Other researchers have tried similar methods using nanometer-thick straight-line ribbons to connect the tattoo to a reader, but they couldn’t handle the strain of constant movement.

    Lu said the researchers were inspired by virtual reality (VR), gaming and the incoming metaverse for this research. VR is used in some cases to treat mental illness; however, the human-aware capability in VR remains lacking in many ways.

    “You want to know whether people are responding to this treatment,” Lu said. “Is it helping them? Right now, that’s hard to tell.”

    Other members of the team include Hongwoo Jang and Eunbin Kim from the Texas Materials Institute; Sangjun Kim and Kyoung-Ho Ha from the Walker Department of Mechanical Engineering; Xiangxing Yang from the Chandra Family Department of Electrical and Computer Engineering; and Kaan Sel and Roozbeh Jafari from Texas A&M’s Department of Electrical and Computer Engineering.

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    University of Texas at Austin (UT Austin)

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  • Human evolution wasn’t just the sheet music, but how it was played

    Human evolution wasn’t just the sheet music, but how it was played

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    Newswise — DURHAM, N.C. — A team of Duke researchers has identified a group of human DNA sequences driving changes in brain development, digestion and immunity that seem to have evolved rapidly after our family line split from that of the chimpanzees, but before we split with the Neanderthals.

    Our brains are bigger, and are guts are shorter than our ape peers.

    “A lot of the traits that we think of as uniquely human, and human-specific, probably appear during that time period,” in the 7.5 million years since the split with the common ancestor we share with the chimpanzee, said Craig Lowe, Ph.D., an assistant professor of molecular genetics and microbiology in the Duke School of Medicine.

    Specifically, the DNA sequences in question, which the researchers have dubbed Human Ancestor Quickly Evolved Regions (HAQERS), pronounced like hackers, regulate genes. They are the switches that tell nearby genes when to turn on and off. The findings appear Nov.23 in the journal CELL.

    The rapid evolution of these regions of the genome seems to have served as a fine-tuning of regulatory control, Lowe said. More switches were added to the human operating system as sequences developed into regulatory regions, and they were more finely tuned to adapt to environmental or developmental cues. By and large, those changes were advantageous to our species.

    “They seem especially specific in causing genes to turn on, we think just in certain cell types at certain times of development, or even genes that turn on when the environment changes in some way,” Lowe said.

    A lot of this genomic innovation was found in brain development and the GI tract. “We see lots of regulatory elements that are turning on in these tissues,” Lowe said. “These are the tissues where humans are refining which genes are expressed and at what level.”

    Today, our brains are larger than other apes, and our guts are shorter. “People have hypothesized that those two are even linked, because they are two really expensive metabolic tissues to have around,” Lowe said. “I think what we’re seeing is that there wasn’t really one mutation that gave you a large brain and one mutation that really struck the gut, it was probably many of these small changes over time.”

    To produce the new findings, Lowe’s lab collaborated with Duke colleagues Tim Reddy, an associate professor of biostatistics and bioinformatics, and Debra Silver, an associate professor of molecular genetics and microbiology to tap their expertise. Reddy’s lab is capable of looking at millions of genetic switches at once and Silver is watching switches in action in developing mouse brains.

    “Our contribution was, if we could bring both of those technologies together, then we could look at hundreds of switches in this sort of complex developing tissue, which you can’t really get from a cell line,” Lowe said.

    “We wanted to identify switches that were totally new in humans,” Lowe said. Computationally, they were able to infer what the human-chimp ancestor’s DNA would have been like, as well as the extinct Neanderthal and Denisovan lineages. The researchers were able to compare the genome sequences of these other post-chimpanzee relatives thanks to databases created from the pioneering work of 2022 Nobel laureate Svante Pääbo.

    “So, we know the Neanderthal sequence, but let’s test that Neanderthal sequence and see if it can really turn on genes or not,” which they did dozens of times.

    “And we showed that, whoa, this really is a switch that turns on and off genes,” Lowe said. “It was really fun to see that new gene regulation came from totally new switches, rather than just sort of rewiring switches that already existed.” 

    Along with the positive traits that HAQERs gave humans, they can also be implicated in some diseases.

    Most of us have remarkably similar HAQER sequences, but there are some variances, “and we were able to show that those variants tend to correlate with certain diseases,” Lowe said, namely hypertension, neuroblastoma, unipolar depression, bipolar depression and schizophrenia. The mechanisms of action aren’t known yet, and more research will have to be done in these areas, Lowe said.

    “Maybe human-specific diseases or human-specific susceptibilities to these diseases are going to be preferentially mapped back to these new genetic switches that only exist in humans,” Lowe said.

    Support for the research came from National Human Genome Research Institute – NIH (R35-HG011332), North Carolina Biotechnology Center (2016-IDG-1013, 2020-IIG-2109), Sigma Xi, The Triangle Center for Evolutionary Medicine and the Duke Whitehead Scholarship.

    CITATION: “Adaptive Sequence Divergence Forged New Neurodevelopmental Enhancers in Humans,” Riley J. Mangan, Fernando C. Alsina, Federica Mosti, Jesus Emiliano Sotelo-Fonseca, Daniel A. Snellings, Eric H. Au, Juliana Carvalho, Laya Sathyan, Graham D. Johnson, Timothy E. Reddy, Debra L. Silver, Craig B. Lowe. CELL, Nov. 23, 2022. DOI: 10.1016/j.cell.2022.10.016

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  • Pocket feature shared by deadly coronaviruses could lead to pan-coronavirus antiviral treatment

    Pocket feature shared by deadly coronaviruses could lead to pan-coronavirus antiviral treatment

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    Newswise — Scientists have discovered why some coronaviruses are more likely to cause severe disease, which has remained a mystery, until now. Researchers of the University of Bristol-led study, published in Science Advances today [23 November], say their findings could lead to the development of a pan-coronavirus treatment to defeat all coronaviruses—from the 2002 SARS-CoV outbreak to Omicron, the current variant of SARS-CoV-2, as well as dangerous variants that may emerge in future.

    In this new study, an international team, led by Bristol’s Professor Christiane Schaffitzel, scrutinised the spike glycoproteins decorating all coronaviruses. They reveal that a tailor-made pocket feature in the SARS-CoV-2 spike protein, first discovered in 2020, is present in all deadly coronaviruses, including MERS and Omicron. In striking contrast, the pocket feature is not present in coronaviruses which cause mild infection with cold-like symptoms.

    The team say their findings suggest that the pocket, which binds a small molecule, linoleic acid—an essential fatty acid indispensable for many cellular functions including inflammation and maintaining cell membranes in the lungs so that we can breathe properly—could now be exploited to treat all deadly coronaviruses, at the same time rendering them vulnerable to a linoleic acid-based treatment targeting this pocket.   

    COVID-19, caused by SARS-CoV-2, is the third deadliest coronavirus outbreak following SARS-CoV in 2002 and MERS-CoV in 2012. The much more infectious SARS-CoV-2 continues to infect people and damage communities and economies worldwide, with new variants of concern emerging successively, and Omicron evading vaccination and immune response.

    Professor Schaffitzel from Bristol’s School of Biochemistry, explained: “In our earlier work we identified the presence of a small molecule, linoleic acid, buried in a tailor-made pocket within the SARS-Cov-2 glycoprotein, known as the ‘Spike protein’, which binds to the human cell surface, allowing the virus to penetrate the cells and start replicating, causing widespread damage.

    “We showed that binding linoleic acid in the pocket could stop virus infectivity, suggesting an anti-viral treatment. This was in the original Wuhan strain that started the pandemic. Since then, a whole range of dangerous SARS-CoV-2 variants have emerged, including Omicron, the currently dominating variant of concern. We scrutinised every new variant of concern and asked whether the pocket function is still present.”

    Omicron has undergone many mutations, enabling it to escape immune protection offered by vaccination or antibody treatments that lag behind this rapidly evolving virus.  Intriguingly, while everything else may have changed, the researchers found that the pocket remained virtually unaltered, also in Omicron.

    Christine Toelzer, Research Associate in the School of Biochemistry and lead author of the study, added: “When we realised that the pocket we had discovered remained unchanged, we looked back and asked whether SARS-CoV and MERS-CoV, two other deadly coronaviruses causing previous outbreaks years ago, also contained this linoleic acid binding pocket feature.”  

    The team applied high-resolution electron cryo-microscopy, cutting-edge computational approaches and cloud computing. Their results showed that SARS-CoV and MERS-CoV also had the pocket, and could bind the ligand, linoleic acid, by a virtually identical mechanism.  

    Professor Schaffitzel concluded: “In our current study, we provide evidence that the pocket remained the same in all deadly coronaviruses, from the first SARS-CoV outbreak 20 years ago to Omicron today. We have shown previously that linoleic acid binding to this pocket induces a locked spike, abrogating viral infectivity. We also show now that linoleic acid supplementation suppresses virus replication inside cells. We anticipate that future variants will also contain the pocket, which we can exploit to defeat the virus.”

    Halo Therapeutics, a recent University of Bristol spin-out Professor Schaffitzel co-founded, is using these findings to develop pocket-binding pan-coronavirus antivirals.

    The team included experts from the Bristol UNCOVER Group, Max Planck Bristol Centre for Minimal Biology, Bristol University spin-out Halo Therapeutics Ltd, and collaborators in Sweden and France. The studies have been supported by funds from Max Planck Gesellschaft, Wellcome Trust and European Research Council, with additional support from Oracle for Research for high-performance cloud computing resources.

    Paper

    “The free fatty acid-binding pocket is a conserved hallmark in pathogenic b-coronavirus spike proteins from SARS-CoV to Omicron” by C Toelzer et al. in Science Advances

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  • A Radical New Approach in Synthetic Chemistry

    A Radical New Approach in Synthetic Chemistry

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    Newswise — UPTON, NY—Scientists at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory helped measure how unpaired electrons in atoms at one end of a molecule can drive chemical reactivity on the molecule’s opposite side. As described in a paper recently published in the Journal of the American Chemical Society, this work, done in collaboration with Princeton University, shows how molecules containing these so-called free radicals could be used in a whole new class of reactions.

    “Most reactions involving free radicals take place at the site of the unpaired electron,” explained Brookhaven Lab chemist Matthew Bird, one of the co-corresponding authors on the paper. The Princeton team had become experts in using free radicals for a range of synthetic applications, such as polymer upcycling. But they’ve wondered whether free radicals might influence reactivity on other parts of the molecule as well, by pulling electrons away from those more distant locations.

    “Our measurements show that these radicals can exert powerful ‘electron-withdrawing’ effects that make other parts of the molecule more reactive,” Bird said.

    The Princeton team demonstrated how that long-distance pull can overcome energy barriers and bring together otherwise unreactive molecules, potentially leading to a new approach to organic molecule synthesis.

    Combining capabilities

    The research relied on the combined resources of a Princeton-led DOE Energy Frontier Research Center (EFRC) focused on Bio-Inspired Light Escalated Chemistry (BioLEC). The collaboration brings together leading synthetic chemists with groups having advanced spectroscopic techniques for studying reactions. Its funding was recently renewed for another four years.

    Robert Knowles, who led Princeton’s role in this research, said, “This project is an example of how BioLEC’s combined expertise enabled the team to quantify an important physical property of these radical species, that in turn allowed us to design the resulting synthetic methodology.”

    The Brookhaven team’s major contribution is a technique called pulse radiolysis—available only at Brookhaven and one other location in the U.S.

    “We use the Laser Electron Accelerator Facility (LEAF)—part of the Accelerator Center for Energy Research (ACER) in Brookhaven’s Chemistry Division—to generate intense high-energy electron pulses,” Bird explained. “These pulses allow us to add or subtract electrons from molecules to make reactive species that might be difficult to make using other techniques, including short-lived reaction intermediates. With this technique, we can step into one part of a reaction and monitor what happens.”

    For the current study, the team used pulse radiolysis to generate molecules with oxygen-centered radicals, and then measured the “electron-withdrawing” effects on the other side of the molecule. They measured the electron pull by tracking how much the oxygen at the opposite side attracts protons, positively charged ions sloshing around in solution. The stronger the pull from the radical, the more acidic the solution has to be for protons to bind to the molecule, Bird explained.

    The Brookhaven scientists found the acidity had to be high to enable proton capture, meaning the oxygen radical was a very strong electron withdrawing group. That was good news for the Princeton team. They then demonstrated that it’s possible to exploit the “electron-withdrawing” effect of oxygen radicals by making parts of molecules that are generally inert more chemically reactive.

    “The oxygen radical induces a transient ‘polarity reversal’ within the molecule—causing electrons that normally want to remain on that distant side to move toward the radical to make the ‘far’ side more reactive,” Bird explained.

    These findings enabled a novel substitution reaction on phenol based starting materials to make more complex phenol products.

    “This is a great example of how our technique of pulse radiolysis can be applied to cutting-edge science problems,” said Bird. “We were delighted to host an excellent graduate student, Nick Shin, from the Knowles group for this collaboration. We look forward to more collaborative projects in this second phase of BioLEC and seeing what new problems we can explore using pulse radiolysis.”

    Brookhaven Lab’s role in this work and the EFRC at Princeton were funded by the DOE Office of Science (BES). Princeton received additional funding for the synthesis work from the National Institutes of Health.

    Brookhaven National Laboratory is supported by the Office of Science of the U.S. Department of Energy. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit science.energy.gov.

    Follow @BrookhavenLab on Twitter or find us on Facebook.

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  • Remdesivir reduces COVID-19 mortality in a real-world setting

    Remdesivir reduces COVID-19 mortality in a real-world setting

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    Newswise — Tokyo, Japan – The COVID-19 pandemic has led to an explosion of clinical research resulting in the development of a variety of vaccines and treatments, although the efficacy of some remains controversial. Now, researchers from Japan report that remdesivir, a drug whose effectiveness has been debated, appears to make a big difference in Japanese patients with COVID-19 who received corticosteroids in the ICU.

    In a study published in September in the Journal of Medical Virology, researchers from Tokyo Medical and Dental University (TMDU) have revealed that remdesivir can reduce mortality in Asian patients if administered shortly after they begin showing COVID-19 symptoms.

    Several studies have already shown that remdesivir can shorten recovery time in patients with COVID-19, although there are conflicting reports on whether the drug prevents patients from dying. In addition, previous trials did not focus on patients who required breathing support while in the ICU.

    “Given the inconsistent evidence regarding the survival benefit it confers, we sought to investigate the effectiveness of remdesivir in patients with COVID-19, who were admitted to an ICU in Japan,” says Mariko Hanafusa, first author of the study. “All of these patients were being treated with corticosteroids for pneumonia, and some were receiving mechanical assistance for breathing.” 

    The researchers analyzed the medical records of 168 patients with COVID-19 admitted to the ICU at TMDU Hospital between April 2020 and November 2021. The patients were divided into groups based on whether or not they were also treated with remdesivir.

    “The results showed a clear difference in patient survival based on when they received treatment with remdesivir,” states Takeo Fujiwara, senior author of the study. “In-hospital mortality rates were significantly lower in ICU patients who received remdesivir and corticosteroids within 9 days of symptom onset than in patients whose treatment with remdesivir started 10 or more days after they first developed symptoms.”

    A small number of patients experienced adverse events such as a rash, requiring them to stop taking remdesivir, while a greater proportion experienced acute kidney injury or liver injury but were able to continue treatment.

    “Our findings suggest that, at least in a largely Japanese patient population with severe to critical COVID-19, early treatment with remdesivir and corticosteroids is associated with decreased mortality,” says Hanafusa.

    Given the survival benefit demonstrated in this study, the time that has elapsed since symptom onset should be considered when using remdesivir to treat patients who are critically ill with COVID-19. The varying effectiveness of remdesivir at different time points may reflect increasing viral load and lung damage over time, and could help explain why the effectiveness of this drug remains controversial.

    ###

    The article, “Effectiveness of remdesivir with corticosteroids for COVID-19 patients in intensive care unit: A hospital-based observational study,” was published in the Journal of Medical Virology at DOI: 10.1002/jmv.28168.

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    Tokyo Medical and Dental University

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  • Artificial Neural Networks Learn Better When They Spend Time Not Learning at All

    Artificial Neural Networks Learn Better When They Spend Time Not Learning at All

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    Newswise — Depending on age, humans need 7 to 13 hours of sleep per 24 hours. During this time, a lot happens: Heart rate, breathing and metabolism ebb and flow; hormone levels adjust; the body relaxes. Not so much in the brain.

    “The brain is very busy when we sleep, repeating what we have learned during the day,” said Maxim Bazhenov, PhD, professor of medicine and a sleep researcher at University of California San Diego School of Medicine. “Sleep helps reorganize memories and presents them in the most efficient way.”

    In previous published work, Bazhenov and colleagues have reported how sleep builds rational memory, the ability to remember arbitrary or indirect associations between objects, people or events, and protects against forgetting old memories.

    Artificial neural networks leverage the architecture of the human brain to improve numerous technologies and systems, from basic science and medicine to finance and social media. In some ways, they have achieved superhuman performance, such as computational speed, but they fail in one key aspect: When artificial neural networks learn sequentially, new information overwrites previous information, a phenomenon called catastrophic forgetting.

    “In contrast, the human brain learns continuously and incorporates new data into existing knowledge,” said Bazhenov, “and it typically learns best when new training is interleaved with periods of sleep for memory consolidation.”

    Writing in the November 18, 2022 issue of PLOS Computational Biology, senior author Bazhenov and colleagues discuss how biological models may help mitigate the threat of catastrophic forgetting in artificial neural networks, boosting their utility across a spectrum of research interests.

    The scientists used spiking neural networks that artificially mimic natural neural systems: Instead of information being communicated continuously, it is transmitted as discrete events (spikes) at certain time points.

    They found that when the spiking networks were trained on a new task, but with occasional off-line periods that mimicked sleep, catastrophic forgetting was mitigated. Like the human brain, said the study authors, “sleep” for the networks allowed them to replay old memories without explicitly using old training data.

    Memories are represented in the human brain by patterns of synaptic weight — the strength or amplitude of a connection between two neurons.

    “When we learn new information,” said Bazhenov, “neurons fire in specific order and this increases synapses between them. During sleep, the spiking patterns learned during our awake state are repeated spontaneously. It’s called reactivation or replay.

    “Synaptic plasticity, the capacity to be altered or molded, is still in place during sleep and it can further enhance synaptic weight patterns that represent the memory, helping to prevent forgetting or to enable transfer of knowledge from old to new tasks.”

    When Bazhenov and colleagues applied this approach to artificial neural networks, they found that it helped the networks avoid catastrophic forgetting.

    “It meant that these networks could learn continuously, like humans or animals. Understanding how human brain processes information during sleep can help to augment memory in human subjects. Augmenting sleep rhythms can lead to better memory.

    “In other projects, we use computer models to develop optimal strategies to apply stimulation during sleep, such as auditory tones, that enhance sleep rhythms and improve learning. This may be particularly important when memory is non-optimal, such as when memory declines in aging or in some conditions like Alzheimer’s disease.”

    Co-authors include: Ryan Golden and Jean Erik Delanois, both at UC San Diego; and Pavel Sanda, Institute of Computer Science of the Czech Academy of Sciences.

    Funding for this research came, in part, the Office of naval Research (grant N00014-16-1-2829), DARPA Lifelong Learning Machines program (HR0011-18-2-0021), National Science Foundation (IIS-1724405) and National Institutes of Health (1RF1MH117155, 1R01MH125557, 1R01NS109553).

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    University of California San Diego

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  • Potatoes can be part of a healthy diet

    Potatoes can be part of a healthy diet

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    Newswise — When we think of healthy vegetables, we don’t think of potatoes, but we should. Potatoes have developed a reputation for causing weight gain and an increased risk for type 2 diabetes, and often find themselves on a list of foods to avoid, especially for individuals with insulin resistance. However, a new study from Pennington Biomedical Research Center, published in the Journal of Medicinal Food, says that potatoes actually did not increase that risk, are filled with key nutrients, and packed with health benefits.

    Candida Rebello, PhD, an assistant professor at Pennington Biomedical, served as co-investigator of the study which examined how a diet including potatoes affects key health measures. Rebello, who is also a registered dietitian, said, “We demonstrated that contrary to common belief, potatoes do not negatively impact blood glucose levels. In fact, the individuals who participated in our study lost weight.”

    “People tend to eat the same weight of food regardless of calorie content in order to feel full,” Rebello explained. “By eating foods with a heavier weight that are low in calories, you can easily reduce the number of calories you consume. The key aspect of our study is that we did not reduce the portion size of meals but lowered their caloric content by including potatoes. Each participant’s meal was tailored to their personalized caloric needs, yet by replacing some meat content with potato, participants found themselves fuller, quicker, and often did not even finish their meal. In effect, you can lose weight with little effort.”

    The study involved 36 participants between the ages of 18 and 60 who were overweight, had obesity, or insulin resistance. Insulin resistance refers to a health condition in which the body’s cells do not respond well to insulin and glucose does not enter into the cells to make energy. Insulin resistance is linked to obesity, high blood pressure, high cholesterol, and type 2 diabetes

    Participants were fed precisely-controlled diets of widely available common foods including either beans, peas, and meat or fish, or white potatoes with meat or fish. Both diets were high in fruit and vegetable content and substituted an estimated 40% of typical meat consumption with either beans and peas or potatoes. Previous studies have shown that eating beans and peas improves blood glucose levels in individuals with newly diagnosed type 2 diabetes. To increase the dietary fiber component of the potatoes, they were boiled with the skin intact and then refrigerated between 12 and 24 hours. Potatoes were incorporated into the main lunch and dinner entrées, such as shepherd’s pie and creamy shrimp and potatoes, and served together with sides such as mashed potatoes, oven-roasted potato wedges, potato salad, and scalloped potatoes with lunch and dinner entrees.

    “We prepared the potatoes in a way that would maximize their fiber content. When we compared a diet with potatoes to a diet with beans and peas, we found them to be equal in terms of health benefits,” Rebello said. “People typically do not stick with a diet they don’t like or isn’t varied enough. The meal plans provided a variety of dishes, and we showed that a healthy eating plan can have varied options for individuals striving to eat healthy. In addition, potatoes are a fairly inexpensive vegetable to incorporate into a diet.”

    Pennington Biomedical Research Center’s Executive Director John Kirwan, PhD, and Principal Investigator on the study said, “Obesity is an incredibly complex disease that Pennington Biomedical is tackling on three different fronts: research that looks at how and why our bodies react the way they do, research that looks at individual responses to diet and physical activity, and policy-level discussions and community programs that bring our research into strategies our local and global communities can use to live healthier lives. These new data on the impact of potatoes on our metabolism is an exciting addition to the arsenal of evidence we have to do just that.”

    This work was supported in part by an investigator-initiated grant from the Alliance for Potato Research and Education and in part by a grant from the National Institute on Aging and from the National Institute of General Medical Sciences of the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. The funders (Alliance for Potato Research and Education and the National Institutes of Health) had no role in the design, analysis, or writing of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the sponsors.

     

    About LSU’s Pennington Biomedical Research Center

    The Pennington Biomedical Research Center is at the forefront of medical discovery as it relates to understanding the triggers of obesity, diabetes, cardiovascular disease, cancer and dementia. The Center architected the “Obecity, USA” awareness and advocacy campaign to help solve the obesity epidemic by 2040. The Center conducts basic, clinical, and population research, and is affiliated with Louisiana State University. The research enterprise at Pennington Biomedical includes over 480 employees within a network of 40 clinics and research laboratories, and 13 highly specialized core service facilities. Its scientists and physician/scientists are supported by research trainees, lab technicians, nurses, dietitians, and other support personnel. Pennington Biomedical is located in state-of-the-art research facilities on a 222-acre campus in Baton Rouge, Louisiana. For more information, see https://www.pbrc.edu.

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    Louisiana State University

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  • Study assesses environmental sustainability practices in dialysis facilities

    Study assesses environmental sustainability practices in dialysis facilities

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    Newswise — Highlights

    • Survey results from dialysis facilities in Australia and New Zealand indicate that environmental sustainability is not currently prioritized in facilities’ clinical practice, building design, or infrastructure and management systems.
    • Results highlighted major deficiencies, and thereby opportunities for improvement.

    Washington, DC (November 11, 2022) — Healthcare is a significant contributor to greenhouse gas emissions that impact climate change. In fact, if the global healthcare sector were a country, it would be the fifth-largest emitter on the planet. And within healthcare, dialysis programs contribute disproportionately, with high resource consumption and waste generation. A recent study published in CJASN examined the environmental sustainability practices of dialysis facilities, providing insights into where improvements could be made.

    For the study, Benjamin Talbot, MBBS (The George Institute for Global Health) and his colleagues sent an online survey to the heads of all dialysis facilities in Australia and New Zealand between November 2019 and December 2020. Responses were received from 132 dialysis facilities, representing 33% (122/365) of dialysis services within Australia and New Zealand. Most responses were from public satellite facilities (40%), in-center dialysis facilities (25%) and co-located dialysis and home therapies facilities (21%).

    Opportunities for improvement in environmental sustainability practices were identified in 3 domains:

    • Culture—A minority of facilities reported having an environmental sustainability strategy in place (33%) or undertaking sustainability audits (20%). Only 7% reported the inclusion of environmental training in staff induction programs.
    • Building design, infrastructure, energy use—Few facilities reported using renewable energy (14%), reclaiming reverse osmosis reject water (13%), or motion-sensor light-switches (44%).
    • Operations—A minority of facilities reported having waste management education (36%), auditing waste generation (17%), or considering environmental sustainability in procurement decisions (25%).

    “We have established a baseline of environmental sustainability practices in dialysis facilities in Australia and New Zealand, however, only 33% of dialysis facilities responded to the survey, which suggests that environmental sustainability is not a priority for most dialysis facilities. The responses to the survey regarding dialysis practices confirmed this further and demonstrate numerous areas where improvements can be made,” said Dr. Talbot. “As healthcare professionals, we have a duty to advocate for our patients and protect our planet. Dialysis is a life-saving treatment but it has a huge environmental cost, and we must all work together to find ways to reduce its impact.” 

    Additional study authors include Katherine Barraclough, MBBS, PhD, Matthew Sypek, MBBS, PhD, FRACP, Pedro Gois, MD, PhD, FRACP, FASN, Leila Arnold, MbChB, FRACP, Stephen McDonald, MBBS(Hons), PhD, FRACP, and John Knight, MBBS, MA, MBA, FRACP, FASN, GAICD.

    Disclosures: B Talbot and J Knight are employees of Ellen Medical Devices developing the Affordable Dialysis program. K Barraclough has received research funding from Fresenius Medical Care. P Gois has received consultancy and honoraria fees from Alexion Pharmaceuticals. S McDonald has received research funding from Baxter Healthcare and Astellas Pharmaceuticals and has had advisory or leadership roles with Fresenius Kidney Care Australia. L Arnold reports employment and ownership interest in M and M Renal Limited.

    The article, titled “A Survey of Environmental Sustainability Practices in Dialysis Facilities in Australia and New Zealand,” will appear online at http://cjasn.asnjournals.org/ on November 11, 2022, doi: 10.2215/CJN.08090722.

    The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies.

    About ASN Since 1966, ASN has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients. ASN has more than 20,000 members representing 132 countries. For more information, visit www.asn-online.org and follow us on Facebook, Twitter, LinkedIn, and Instagram.

      

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  • Linking mass extinctions to the expansion and radiation of land plants

    Linking mass extinctions to the expansion and radiation of land plants

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    Newswise — Boulder, Colo., USA: The Devonian Period, 419 to 358 million years ago, was one of the most turbulent times in Earth’s past and was marked by at least six significant marine extinctions, including one of the five largest mass extinctions ever to have occurred. Additionally, it was during the Devonian that trees and complex land plants similar to those we know today first evolved and spread across the landscape. This evolutionary advancement included the development of significant and complex root systems capable of affecting soil biogeochemistry on a scale the ancient Earth had yet to experience.

    It has been theorized that these two seemingly separate events, marine extinctions and plant evolution and expansion, were intricately linked in the Devonian. Specifically, it has been proposed that plant evolution and root development occurred so rapidly and on such a massive scale that nutrient export from the land to the ancient oceans would have drastically increased. This scenario is seen in modern systems where anthropogenically sourced nutrient export has vastly increased the nutrient load into areas such as the Gulf of Mexico and the Great Lakes, leading to large-scale algal blooms that ultimately deplete the oxygen in the water column. This effect, known as eutrophication, magnified on a global scale, would have been catastrophic to ancient oceans, fueling algal blooms that would have depleted most of the ocean’s oxygen.

    The key to linking mass extinctions and the expansion and radiation of land plants lies in identifying a nutrient flux elevated above background levels, linking that nutrient flux to either indirect or direct evidence of the presence of deeply rooting land plants and finally showing that this phenomenon occurred in multiple locations and times.

    This study, the first of its kind, was able to do precisely that by utilizing geochemical records from ancient lake deposits in Greenland, northern Scotland, and Orkney. Utilizing lake records, elevated values of the nutrient phosphorus were detected in five distinct locations during the height of plant evolution and expansion in the Devonian. In each case, elevated values of nutrient input were coincident with evidence of the presence of early trees in the form of fossilized spores and, in some cases, fossilized stems of the earliest deeply rooting tree, Archaeopteris. In two cases, that evidence coincided with a Devonian marine extinction event, including the most significant Devonian mass extinction, the Frasnian–Famennian extinction (also known as the Late Devonian mass extinction).

    Additionally, this study, published yesterday in the Geological Society of America Bulletin, linked the periodic wet/dry climate cycles known to exist in the region during the Devonian with specific episodes of plant colonization. While elevated nutrient export was noted during both wet and dry climate cycles, the most significant export events occurred during wet cycles, suggesting that plant expansion was episodic and tied to climate cyclicity.

    The episodic nature of plant expansion could help explain why there are at least six significant marine extinctions in the Devonian. While the scope of this study was limited to a single geographic region, it is likely that these events occurred throughout the Devonian Earth. The colonization of different types of land plants in different regions and at different times would have resulted in episodic nutrient pulses significant enough to sustain eutrophication and cause (or at least contribute) to the numerous marine extinction events throughout the mid- to Late Devonian.

    FEATURED ARTICLE
    Enhanced terrestrial nutrient release during the Devonian emergence and expansion of forests: Evidence from lacustrine phosphorus and geochemical records
    Matthew Smart; Gabriel Filippelli; William Gilhooly; John Marshall; Jessica Whiteside
    Contact: Matthew Smart, [email protected], Indiana University–Purdue University Indianapolis, Earth Sciences, Indianapolis, Indiana
    URL: https://pubs.geoscienceworld.org/gsa/gsabulletin/article-abstract/doi/10.1130/B36384.1/618814/Enhanced-terrestrial-nutrient-release-during-the

    GSA BULLETIN articles published ahead of print are online at https://bulletin.geoscienceworld.org/content/early/recent . Representatives of the media may obtain complimentary copies of articles by contacting Kea Giles. Please discuss articles of interest with the authors before publishing stories on their work, and please make reference to The Geological Society of America Bulletin in articles published. Non-media requests for articles may be directed to GSA Sales and Service, [email protected]

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  • Bobby Brooke Herrera Joins Rutgers Global Health Institute as Principal Faculty Member

    Bobby Brooke Herrera Joins Rutgers Global Health Institute as Principal Faculty Member

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    Newswise — Research scientist Bobby Brooke Herrera, renowned for developing tools to accelerate diagnosis and treatment of infectious diseases such as COVID-19, has joined Rutgers Global Health Institute.

    Herrera, a Rutgers Presidential Faculty Scholar and an assistant professor of global health at the institute, conducts multidisciplinary research on epidemic viruses and infectious diseases and holds joint appointments in the Division of Allergy, Immunology and Infectious Diseases in the Department of Medicine and at the Child Health Institute of New Jersey. Both are part of Rutgers Robert Wood Johnson Medical School. Herrera is known for his bench-to-bedside translational research. His laboratory at Rutgers focuses on understanding adaptive immunity against globally relevant pathogens that cause lethal human diseases and for which there are limited options for treatment or vaccination.

    He has developed diagnostic testing related to the SARS-CoV-2 virus and COVID-19 disease, the Zika virus, and the rare but often deadly Ebola virus disease. Collaborating internationally with research scientists in Brazil, Nigeria and Senegal, his academic and industry work has received more than $9 million in grant funding, including support from the National Institutes of Health and the Bill & Melinda Gates Foundation as well as venture capital financing.

    Disease outbreak preparedness and response motivate and drive Herrera’s research, which incorporates approaches in epidemiology, immunology, molecular biology and virology. He seeks to uncover new knowledge about human immune responses that will spur fundamental advancements in disease diagnostic capabilities and vaccine design. Herrera is studying asymptomatic viral infections, which occur when an individual infected with a virus develops little to no symptoms of disease, to better understand the human antibody and T cell responses in such instances.

    “I hope that my research group at Rutgers will contribute to a foreseeable expansion of vaccines or therapeutics for infectious diseases in the decades to come, with particular focus on deciphering at the molecular level what may make some antibodies or T cells more effective than others,” Herrera said. “There are many hypotheses as to why that happens and why some people develop disease symptoms and some remain asymptomatic. It could be genetics, immune status, environmental factors or reasons related to the virus itself. These are questions I’m interested in pursuing in my academic lab. The knowledge we produce can lead to better, more personalized diagnostics as well as more potent therapeutics for these viruses.”

    Herrera has investigated various dynamics of asymptomatic human infections by mosquito-borne viruses, including the flaviviruses Zika and dengue as well as the alphavirus chikungunya. His findings indicated that human transmission of Zika and dengue viruses in Nigeria and Senegal occurred in absence of robust disease outbreaks. In Brazil, he tested a diagnostic tool he developed to distinguish between infections by distinct virus strains. Also in Nigeria, Herrera’s research demonstrated that individuals who experienced asymptomatic infections by Ebola virus could produce T cell responses that were greater in magnitude when compared with survivors of severe Ebola virus disease.

    Herrera, originally from New Mexico, received a doctoral degree in biological sciences in public health at Harvard University and performed postdoctoral training at Harvard Medical School. Since 2019, he served as a visiting scientist at the Harvard T.H. Chan School of Public Health. He cofounded two biotechnology startup companies and was named to the “Forbes 30 under 30” list for health care in 2020.

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  • Study Shows Temporary Isolation Wards Provided Effective Protection Against Healthcare-Associated COVID-19 Transmission

    Study Shows Temporary Isolation Wards Provided Effective Protection Against Healthcare-Associated COVID-19 Transmission

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    Newswise — Arlington, Va., October 28, 2022 – Temporary isolation wards utilized to house COVID-19 patients at a large Singapore hospital during the global pandemic allowed for safe management of COVID-19 cases over an 18-month period, without healthcare-associated SARS-CoV-2 transmission. The study finding, published today in the American Journal of Infection Control (AJIC), suggests that these wards can provide a safe option for managing patients during future pandemics caused by a novel respiratory pathogen.

    “This study provides important information that supports the safety of temporary isolation units – which became a critical option for many healthcare facilities worldwide during the COVID-19 pandemic – and can inform practice during subsequent pandemics,” said Wee Liang En Ian, Associate Consultant in the Department of Infectious Diseases at Singapore General Hospital (SGH), one of the paper’s lead authors. “Despite environmental SARS-CoV-2 contamination observed in the temporary isolation wards at our institution, we found no evidence of transmission to healthcare workers over a prolonged period.”

    During the COVID-19 pandemic, demand for airborne infection isolation rooms to safely manage patients with the disease often outstripped availability. Many healthcare facilities created temporary isolation wards at the peak of the pandemic to provide surge-capacity. However, there has been very little research evaluating the effectiveness of these wards in managing COVID-19 cases.

    During the 18-month period from July 2020 to December 2021, Dr. Wee and colleagues conducted environmental sampling for SARS-CoV-2 RNA in temporary isolation wards constructed from prefabricated containers (N=20) or converted from normal-pressure general wards (N=47) at SGH. The researchers completed sampling at the point of patient discharge/transfer out and prior to terminal cleaning. During this period, the hospital also conducted contact-tracing, active surveillance, and whole genome sequencing (WGS) for all COVID-19 cases among hospital healthcare workers (HCWs).

    Researchers collected and evaluated a total of 355 environmental swabs and determined that 22.4% (15/67) of patients had at least one positive sample. As compared to patients in the converted isolation wards, patients housed in isolation rooms constructed from prefabricated containers had greater odds of detectable environmental contamination (adjusted-odds-ratio, aOR=10.46, 95%CI=3.89-58.91, p=0.008), with the majority of positive environmental samples obtained from the toilet area (60.0%, 12/20) and another substantial portion from patient equipment, including electronic devices used for patient communication (8/20, 40.0%). Among patients in the converted temporary isolation wards, environmental contamination was also detected most frequently in the toilet area (17.0%, 8/47), while only 4.3% (2/47) of these patients had positive samples from patient equipment (call-bell).

    During the study period, SGH reported 441 cases of COVID-19 infection among HCWs, 5.7% (25/441) of which were among HCWs working in any of the hospital’s COVID-19 isolation areas. While seven of these cases occurred among HCWs working in the temporary isolation wards, WGS and epidemiological investigations provided no evidence of patient-to-HCW or HCW-HCW transmission.

    “This study suggests that with the right combination of infection prevention practices, including well-designed isolation units, appropriate cleaning processes, compliance with prevention protocols and appropriate use of personal-protective-equipment, temporary isolation units are a viable option to help safely manage patients during respiratory disease outbreaks,” said Linda Dickey, RN, MPH, CIC, FAPIC, 2022 APIC president.

    About APIC

    Founded in 1972, the Association for Professionals in Infection Control and Epidemiology (APIC) is the leading association for infection preventionists and epidemiologists. With more than 15,000 members, APIC advances the science and practice of infection prevention and control. APIC carries out its mission through research, advocacy, and patient safety; education, credentialing, and certification; and fostering development of the infection prevention and control workforce of the future. Together with our members and partners, we are working toward a safer world through the prevention of infection. Join us and learn more at apic.org.

    About AJIC

    As the official peer-reviewed journal of APIC, The American Journal of Infection Control (AJIC) is the foremost resource on infection control, epidemiology, infectious diseases, quality management, occupational health, and disease prevention. Published by Elsevier, AJIC also publishes infection control guidelines from APIC and the CDC. AJIC is included in Index Medicus and CINAHL. Visit AJIC at ajicjournal.org.

    NOTE FOR EDITORS

    “Environmental contamination and evaluation of healthcare-associated SARS-CoV-2 transmission risk in temporary isolation wards during the COVID-19 pandemic,” by Wee Liang En Ian, Shalvi Arora and collaborators, was published online in AJIC on October 27, 2022. The article may be found at: https://doi.org/10.1016/j.ajic.2022.09.004

     

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