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  • A Novel Toxic Gas Sensor by KRISS Improves the Limit of Detection

    A Novel Toxic Gas Sensor by KRISS Improves the Limit of Detection

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    Newswise — The Korea Research Institute of Standards and Science (KRISS, President Dr. Ho Seong Lee) developed a toxic gas sensor with the world’s highest sensitivity. This sensor can precisely monitor nitrogen dioxide (NO2), a toxic gas in the atmosphere, at room temperature with low power consumption and ultra-high sensitivity. It can be applied to diverse fields, such as detection of residual gases during semiconductor manufacturing process and research on electrolysis catalysts.

    NO2, produced by the high-temperature combustion of fossil fuels and primarily emitted through automobile exhaust or factory smoke, contributes to an increase in mortality due to air pollution. In South Korea, the annual average concentration of NO2 in the air is regulated to be 30 ppb* or lower by presidential decree. Highly sensitive sensors, therefore, are required to accurately detect gases at extremely low concentrations.
    * ppb: parts per billion

    In recent times, the use of toxic gases which are potentially fatal to humans has been on the rise due to the development of high-tech industries, including semiconductor manufacturing. While some laboratories and factories have adopted semiconductor-type sensors for safety, the challenge lies in their low response sensitivity, making them unable to detect toxic gases that may even be perceptible to the human nose. To increase the sensitivity, they consume a lot of energy in the end because they must operate at high temperatures.

    The newly developed sensor, a next-generation semiconductor-type toxic gas sensor based on advanced materials, exhibits significantly improved performance and usability compared to conventional sensors. With its outstanding sensitivity to chemical reactions, the new sensor can detect NO2 much more sensitively than previously reported semiconductor-type sensors, a sensitivity that is 60 times higher. Moreover, the novel sensor consumes minimal power operating at room temperature, and its optimal semiconductor manufacturing process enables large-area synthesis at low temperatures, thereby reducing fabrication costs.

    The key to the technology lies in the MoS2 nanobranch material developed by KRISS. Unlike the conventional 2D flat structure of MoS2, this material is synthesized in a 3D structure resembling tree branches, thereby enhancing the sensitivity. Besides its strength of uniform material synthesis on a large area, it can create a 3D structure by adjusting the carbon ratio in the raw material without additional processes.

    The KRISS Semiconductor Integrated Metrology Team has experimentally demonstrated that their gas sensor can detect NO2 in the atmosphere at concentrations as low as 5 ppb. The calculated detection limit of the sensor is 1.58 ppt**, marking the world’s highest level of sensitivity.
    ** ppt: parts per trillion

    This achievement enables precise monitoring of NO2 in the atmosphere with low power consumption. The sensor not only saves time and cost but also offers excellent resolution. It is expected to contribute to research on improving atmospheric conditions by detecting annual average concentrations of NO2 and monitoring real-time changes.

    Another characteristic of this technology is its ability to adjust the carbon content in the raw material during the material synthesis stage, thereby altering the electrochemical properties. This can be utilized to develop sensors capable of detecting gases other than NO2, such as residual gases produced during the semiconductor manufacturing processes. The excellent chemical reactivity of the material can also be exploited to enhance the performance of electrolysis catalysts for hydrogen production.

    Dr. Jihun Mun, a senior researcher of the KRISS Semiconductor Integrated Metrology Team, said, “This technology, which overcomes the limitations of conventional gas sensors, will not only meet government regulations but also facilitate precise monitoring of domestic atmospheric conditions. We will continue follow-up research so that this technology can be applied to the development of various toxic gas sensors and catalysts, extending beyond the monitoring of NO2 in the atmosphere.”

     

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    As a national metrology institute (NMI) of Korea founded in 1975, KRISS (Korea Research Institute of Standards and Science) has developed measurement standards technology and played a pivotal role in upgrading Korea’s main industries to the global level.

    The results of this study, supported by the fundamental project of KRISS and the Nanomaterial Technology Development Project of Ministry of Science and ICT, were published in the August issue of Small Structures (IF: 15.9), a prestigious academic journal in the field of materials science.

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    National Research Council of Science and Technology

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  • Developing nanocatalysts to overcome limitations of water electrolysis technology

    Developing nanocatalysts to overcome limitations of water electrolysis technology

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    Newswise — Green hydrogen can be produced through water electrolysis technology, which uses renewable energy to split water into hydrogen and oxygen without emitting carbon dioxide. However, the production cost of green hydrogen is currently around $5 per kilogram, which is two to three times higher than gray hydrogen obtained from natural gas. For the practical use of green hydroten, the innovation in water electrolysis technology is required for the realization of hydrogen economy, especially for Korea where the utilization of renewable energy is limited owing to geographical reasons.

    Dr. Kyung Joong Yoon’s research team at the Energy Materials Research Center of the Korea Institute of Science and Technology (KIST) has developed a nanocatalyst for high-temperature water electrolysis that can retain a high current density of more than 1A/cm2 for a long time at temperatures above 600 degrees. While the degradation mechanisms of nanomaterials at high temperatures have been elusive thus far, the team identified the fundamental reasons of abnormal behavior of nanomateirals and successfully resolved issues, eventually improving performance and stability in realistic water electrolysis cells.

    The electrolysis technology can be classified into low- and high-temperature electrolysis. While low-temperature electrolysis operating at temperatures below 100 degrees Celsius has long been developed and is technologically more mature, high-temperature electrolysis operating above 600 degrees Celsius offers higher efficiency and is considered as a next-generation technology with a strong potential for further cost-down. However, its commercialization has been hindered by the lack of thermal stability and insufficient lifetime owing to high-temperature degradation, such as corrosion and structural deformation. In particular, nanocatalysts, which are widely used to improve the performance of low-temperature water electrolyzers, quickly deteriorate at high operating temperatures, making it difficult to effectively use them for high-temperature water electrolysis.

    To overcome this limitation, the team developed a new nanocatalyst synthetic techniques that suppresses the formation of harmful compounds causing high temperature degradation. By systematically analyzing the nanoscale phenomena using transmission electron microscopy, the researchers identified specific substances causing severe structural alterations, such as strontium carbonate and cobalt oxide and successfully removed them to achieve highly stable nanocatalysts in terms of chemical and physical properties.

    When the team applied the nanocatalyst to a high-temperature water electrolysis cell, it more than doubled hydrogen production rate and operated for more than 400 hours at 650 degrees without degradation. This technique was also sucessfully applied to a practical large-area water electrolysis cell, confirming its strong potential for scale-up and commercial use.

    “Our newly developed nanomaterials achieved both high performance ans stability for high-temperature water electrolysis technology, and it can contribute to lower the production cost of green hydrogen, making it economically competitive with gray hydrogen in the future,” said Dr. Kyungjoong Yoon of KIST. “For commercialization, we plan to develop automated processing techniques for mass production in cooperation with industry cell manufacturers.”

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    KIST was established in 1966 as the first government-funded research institute in Korea. KIST now strives to solve national and social challenges and secure growth engines through leading and innovative research. For more information, please visit KIST’s website at https://eng.kist.re.kr/

    This research was supported by the Ministry of Science and ICT (Minister Lee Jong-ho) through the KIST Major Project and Climate Change Response Technology Development Project (2020M1A2A2080862), and the results were published in the latest issue of the Chemical Engineering Journal (IF 15.1, top 3.2% in JCR), an international journal in the field of chemical engineering.

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    National Research Council of Science and Technology

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  • Artificial intelligence lowers the barrier to ultrasound brain disease treatment

    Artificial intelligence lowers the barrier to ultrasound brain disease treatment

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    Newswise — Focused ultrasound technology is a non-invasive treatment method that focuses ultrasound energy on a few millimeters of the brain, including deep regions, to treat neurological disorders without opening the skull. It has been applied to the treatment of various intractable brain diseases such as depression and Alzheimer’s disease because it minimizes the impact on the surrounding healthy tissue and reduces side effects such as complications and infections. However, its use has been limited so far because it is difficult to reflect the distortion of ultrasound waves caused by the different shapes of the skulls of different patients in real-time.

    A research team led by Dr. Kim, Hyungmin of the Bionics Research Center at the Korea Institute of Science and Technology (KIST) has developed a real-time acoustic simulation technology based on generative AI to predict and correct the distortion of the ultrasound focus position caused by the skull in real-time during focused ultrasound therapy. Until now, the clinical applicability of AI simulation models in the field of non-invasive focused ultrasound therapy technology has not been validated.

    To predict the location of the invisible acoustic focus, navigation systems based on medical images taken before treatment are currently utilized, which provide information about the relative position of the patient and the ultrasound transducer. However, they are limited by their inability to account for the distortion of ultrasound waves caused by the skull, and while various simulation techniques have been used to compensate for this, they still require significant computational time, making them difficult to apply in actual clinical practice.

    The research team developed a real-time focused ultrasound simulation technology through an artificial intelligence model based on a generative adversarial neural network (GAN), a deep learning model widely used for image generation in the medical field. The technology reduces the update time of three-dimensional simulation information reflecting changes in ultrasound acoustic waves from 14 s to 0.1 s, while showing an average maximum acoustic pressure error of less than 7% and a focal position error of less than 6mm, both of which are within the error range of existing simulation technologies, increasing the possibility of clinical application.

    The research team also developed a medical image-based navigation system to verify the performance of the developed technology in order to rapidly deploy it to real-world clinical practice. The system can provide real-time acoustic simulations at the rate of 5 Hz depending on the position of the ultrasound transducer, and succeeded in predicting the position of the ultrasound energy and focus within the skull in real-time during focused ultrasound therapy.

    Previously, due to the long calculation time, the ultrasound transducer had to be precisely positioned in a pre-planned location to utilize the simulation results. However, with the newly developed simulation-guided navigation system, it is now possible to adjust the ultrasound focus based on the acoustic simulation results obtained in real-time. In the future, it is expected to improve the accuracy of focused ultrasound and provide safe treatment for patients by being able to quickly respond to unexpected situations that may occur during the treatment process.

    “As the accuracy and safety of focused ultrasound brain disease treatment has been improved through this research, more clinical applications will emerge,” said Dr. Kim, Hyungmin of KIST. “For practical use, we plan to verify the system by diversifying the ultrasound sonication environment, such as multi-array ultrasound transducers.”

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    KIST was established in 1966 as the first government-funded research institute in Korea. KIST now strives to solve national and social challenges and secure growth engines through leading and innovative research. For more information, please visit KIST’s website at https://eng.kist.re.kr/

    This research was supported by the Ministry of Science and ICT (Minister Lee Jong-ho) under the Creative Convergence Research Project (CAP-18014-000) of the National Research Council of Korea. The research results were published on October 14 in the top international journal NeuroImage (top 3.6% in JCR).

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    National Research Council of Science and Technology

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  • Scientists Probe the Emergent Structure of the Carbon Nucleus

    Scientists Probe the Emergent Structure of the Carbon Nucleus

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    The Science

    Newswise — The element carbon is critical to organic chemistry and life as we know it. The physics of its most common isotope, carbon-12, are extremely complex. Many experimental and theoretical investigations have been devoted to determining the energies and underlying structures of the nuclear states of carbon-12. In this work, researchers computed these states from first principles—the most basic components of physics theory. The approach used supercomputers and nuclear lattice simulations to calculate the three-dimensional shape formed by the protons and neutrons comprising the nucleus. The results show that all of the low-lying energy states of carbon-12 have a substructure where the six protons and six neutrons cluster together into alpha particles. Alpha particles are helium-4 nuclei, which contain two protons and two neutrons.

    The Impact

    One well-known nuclear state of carbon-12 is the Hoyle state. This state has an energy that sits near the energy threshold for three alpha particles or helium nuclei. This energy thereby greatly enhances the production of carbon in helium-burning stars. This helps to explain the presence of carbon in the Universe. The results obtained in this research show that the Hoyle state is composed of a “bent arm” or obtuse triangular arrangement of alpha particles. All the low-lying energy states of carbon-12 have an intrinsic shape composed of three alpha particles forming either an equilateral triangle or an obtuse triangle. The new results give information about the possible geometrical shapes of nuclear states.

    Summary

    The carbon atom provides the backbone for the complex organic chemistry composing the building blocks of life. The physics of the carbon nucleus in its predominant isotope, carbon-12, are also full of complexity. Researchers from the University of Bonn, Forschungszentrum Jülich in Germany, the Gaziantep Islamic Science and Technology University in Turkey, the Graduate School of China Academy of Engineering Physics, Tbilisi State University, and the Facility for Rare Isotope Beams at Michigan State University calculated the structure of the nuclear states of carbon-12 using the ab initio framework of nuclear lattice effective field theory.

    The research found that all the low-lying states of carbon-12 have an intrinsic shape composed of three alpha clusters forming either an equilateral triangle or an obtuse triangle. The states with the equilateral triangle shape also have a dual description in terms of particle-hole excitations in a mean-field picture. The results agree with experimental data and provide the first model-independent density map of the nuclear states of carbon-12. The results help to explain the origins of carbon from the helium and hydrogen that made up the Universe shortly after the Big Bang.

    Funding

    This research was funded by the Deutsche Forschungsgemeinschaft (the German Research Foundation), the National Natural Science Foundation of China , the Chinese Academy of Sciences President’s International Fellowship Initiative, the National Security Academic Fund of China, Volkswagen Stiftung, the European Research Council, the Department of Energy, and the Nuclear Computational Low-Energy Initiative SciDAC-4 project, as well as computational resources provided by the Gauss Centre for Supercomputing e.V. and the Oak Ridge Leadership Computing Facility.


    Journal Link: Nature Communications, May-2023

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    Department of Energy, Office of Science

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  • NUS team discovers new method of cultivating human norovirus using zebrafish embryo

    NUS team discovers new method of cultivating human norovirus using zebrafish embryo

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    Food virologists from the National University of Singapore (NUS) have successfully propagated the human norovirus using zebrafish embryos, providing a valuable platform to assess the effectiveness of virus inactivation for the water treatment and food industries.

    Human norovirus (HuNoV) is currently the predominant cause of acute gastroenteritis worldwide, contributing to an estimated 684 million diarrhoea cases, resulting in 212,000 annual fatalities. For a substantial period, the absence of an in vitro culture system has been a major hurdle in norovirus research. The most recently optimised human intestinal enteroid model, designed to support HuNoV replication, relies on human biopsy specimens obtained from surgical or endoscopic procedures, which are typically scarce. Moreover, the maintenance of these cells is both labour and resource intensive.

    A research team led by Assistant Professor Li Dan from the NUS Department of Food Science and Technology, in collaboration with Professor Gong Zhiyuan from the NUS Department of Biological Sciences, serendipitously discovered that zebrafish embryo can be used as a host for cultivating HuNoV. The zebrafish embryo model is easy to handle, robust and has a capacity to efficiently replicate HuNoVs. This study, to the best of their knowledge, represents an inaugural demonstration of the highest fold-increase over the baseline. Most notably, this model enables the continuous passaging of HuNoV within a laboratory setting. With this model, researchers can effectively propagate and sustain the presence of HuNoV over time, enabling them to study in more depth its behaviour, replication, and other properties.

    Asst Prof Li said, “The zebrafish embryo model represents an essential improvement in the HuNoV cultivation method. With its high efficiency and robustness, this tool is able to enhance both the breadth and depth of HuNoV-related research. It is expected that this tool will not only benefit the advancement of epidemiological research on HuNoV but will also be invaluable in establishing HuNoV inactivation parameters. These parameters are highly needed by the water treatment and food industries to develop more effective methods for preventing the spread of the virus.”

    This research was published in the journal Applied and Environmental Microbiology on 21 March 2023.

    In the future, the research team plans to utilise the zebrafish embryo model to investigate inactivation methods for HuNoVs in food products. To date, the successful detection of infectious HuNoV in food products remains an elusive goal. While further refinement and optimisation efforts are still required, the research team’s ongoing work holds great promise in tackling this challenging task.

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    National University of Singapore (NUS)

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  • Inside the Matrix: Nanoscale Patterns Revealed Within Model Research Organism

    Inside the Matrix: Nanoscale Patterns Revealed Within Model Research Organism

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    BYLINE: Mario Aguilera

    Newswise — Species throughout the animal kingdom feature vital interfaces between the outermost layers of their bodies and the environment. Intricate microscopic structures—featured on the outer skin layers of humans, as one example—are known to assemble in matrix patterns.

    But how these complex structures, known as apical extracellular matrices (aECMs) are assembled into elaborately woven architectures has remained an elusive question.

    Now, following years of research and the power of a technologically advanced instrument, University of California San Diego scientists have unraveled the underpinnings of such matrices in a tiny nematode. The roundworm Caenorhabditis elegans has been studied extensively for decades due to its transparent structure that allows researchers to peer inside its body and examine its skin.

    Described in the journal Nature Communications, School of Biological Sciences researchers have now deciphered the assemblage of aECM patterns in roundworms at the nanoscale. A powerful, super-resolution microscope helped reveal previously unseen patterns related to columns, known as struts, that are key to the proper development and functioning of aECMs.

    “Struts are like tiny pillars that connect the different layers of the matrix and serve as a type of scaffolding,” said Andrew Chisholm, a professor in the School of Biological Sciences and the paper’s senior author.

    Although roundworms serve as a model organism for laboratory studies due to their simple, transparent bodies, below the surface they feature intricate architectures. They also have nearly 20,000 genes, not unlike the number of human genes, and therefore provide lessons on structure and function of more advanced organisms.

    Focusing on the roundworm exoskeleton known as the cuticle, the researchers found that defects in struts result in unnatural layer swelling, or “blistering.” Within the cuticle layer, the research study focused on collagens, which are the most abundant family of proteins in our bodies and help keep bodily materials conjoined.

    “The struts hold the critical layers together,” said Chisholm. “Without them, the layers separate and cause disorders such as blistering. In blistering mutants you don’t see any struts.”

    Conventional laboratory instruments had previously imaged struts without detail, often resulting in undefined blobs. But through Biological Sciences Assistant Professor Andreas Ernst’s laboratory they accessed advanced instrumentation—known as 3D-structured illumination super resolution microscopy (3D-SIM)—which put the struts into stunning focus and allowed their functions to be more easily defined. The researchers were then able to solve the nanoscale organization of struts and previously undocumented levels of patterning in the cuticle layer.

    “We could see exactly where these proteins were going in the matrix,” said Chisholm. “This is potentially a paradigm for how the matrix assembles into very complex structures and very intricate patterning.”

    The two first authors, Jennifer Adams (senior research associate) and Murugesan Pooranachithra (postdoctoral fellow), contributed equally to the paper. Other coauthors are Erin Jyo, Sherry Li Zheng, Alexandr Goncharov, Jennifer Crew, James Kramer, Professor of Neurobiology Yishi Jin, Assistant Professor of Cell and Developmental Biology Andreas Ernst and Andrew Chisholm.

    Sherry Zheng was a UC San Diego Triton Research and Experiential Learning Scholar and received the Gabriele Wienhausen Biological Sciences Scholarship. Funding for the research was provided by the Howard Hughes Medical Institute; the National Institutes of Health  (R35 GM142433, R01 GM054657 and R35 GM134970).

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    University of California San Diego

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  • Novel AI-based approach for more accurate RNA 3D structure prediction

    Novel AI-based approach for more accurate RNA 3D structure prediction

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    Newswise — A research team from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) has successfully harnessed artificial intelligence (AI) and deep-learning techniques to model atomic-level RNA 3D structures from primary RNA sequences. Called DRfold, this novel AI-based method improves the accuracy of RNA models by more than 70 percent, compared to traditional approaches.

    The team, which is led by Professor ZHANG Yang from CSI Singapore and NUS School of Computing, published their findings in the scientific journal Nature Communications on 16 September 2023.

    RNAs are large biomolecules consisting of a single chain of nucleotides, which derive their sequence order from double-stranded DNA molecules during transcription. RNAs are widely known for their role in transcription and translation processes, which facilitates the transfer of gene information embodied in DNA sequences into protein amino acid sequences. In recent years, RNAs have been found to play important roles in regulating various biological processes, hence positioning them as novel drug targets.

    It has been estimated that targeting RNAs with small molecules will expand the drug design landscape exponentially, compared to traditional protein-targeted drug discovery. Accordingly, RNA biology and its applications in developing new therapeutics represent a critical emerging field, garnering significant academic and industry investment worldwide.

    Predicting RNA structures

    Compared to well-folded protein structures, RNA structures and their folds are generally considered less stable due to the relatively shallow energy landscape. Therefore, traditional physics- and statistics-based force fields, which are often error-prone, cannot accurately describe the elegant and intricate folding interactions of RNAs. Meanwhile, the limited availability of experimental RNA structures in the Protein Data Bank (PDB) further constrains the accuracy of these traditional knowledge-based force fields, which are derived from the statistics of the PDB structures.

    To address these challenges, DRfold created two complementary deep-learning network pipelines – one focused on end-to-end learning, and the other on geometrical restraint learning. This innovative approach significantly improved the accuracy of the AI-based force field. The synergistic coupling of these two networks also further enhanced the accuracy of the single neural network-based AI potentials.

    The key innovation lies in introducing a deep learning approach for predicting RNA tertiary structure. While traditional methods relied on homologous modelling or physics-based folding simulations, which suffer from the limitation of the force field accuracy, DRfold uses self-attention transformer networks to predict 3D structures from RNA sequences, marking a revolutionary shift in addressing this crucial challenge. DRfold’s new strategy of integrating two parallel and complementary networks built on end-to-end and geometry learnings helps to enhance the accuracy of the potential function and RNA model prediction, making it light, highly flexible, scalable, and hence, the preferred prediction method.

    Dr LI Yang, a Research Scientist at CSI Singapore and first author of this study, said, “Since the biological functions of RNAs depend on the specific tertiary structures, it becomes increasingly important and necessary to determine the 3D structures of RNAs in order to facilitate RNA-based function annotation and drug discovery.”

    He added, “The golden standard in structural biology, such as using biophysical experiments — X-ray crystallography, Cryogenic Electron Microscopy (Cryo-EM), and Nuclear Magnetic Resonance (NMR) Spectroscopy — to determine RNA structures, are often cost- and labour-intensive, limiting their application to a tiny portion of known RNAs. Currently, there are more than 30 million known RNA sequences in the RNA central database, but only less than 500 (or 0.0017 per cent) have experimentally solved structures. This frustratingly leaves more than 99 per cent of RNA targets with no structural information. Hence, our study’s core aim is to develop new computational methods capable of predicting high-quality RNA structure models, filling this substantial information gap.”

    Potential applications in drug design and virtual screening

    Commenting on the significance of their research, Prof Zhang, Senior Principal Investigator at CSI Singapore and corresponding author of the study, highlighted, “Our primary goal for this study is to bridge the gap between the scarcity of experimental RNA structures and the increasing demand of the RNA biology field and drug industry. In this regard, high-confident DRfold models can be used as a starting point to guide the RNA drug design and virtual screening, or to help elucidate the biological functions of the RNA molecules in cells.”

    “Considering the potency and effectiveness of mRNA vaccines in combating pandemics, tools such as DRfold play a crucial role in predicting and optimising RNA structures and the stability of vaccines. Furthermore, these tools can be used to study the biological functions of RNAs, particularly non-coding RNAs, and design novel RNA experiments using predicted models which follow the sequence-to-structure-to-function paradigm,” Prof Zhang added.

    The group has opened the source codes of DRfold to the public community via their webpage: https://zhanggroup.org/DRfold. Its high scalability and open-source framework render it incredibly flexible and applicable for solving other related problems, such as RNA-protein interaction modelling.

    Next steps

    Moving forward, the team envisions extending their AI strategy to encompass protein-RNA interactions, an area where reliable AI approaches for high-quality protein-RNA complex structure prediction are currently absent. Such tools are highly relevant for RNA function annotation and RNA drug discovery.

    In addition, the team hopes to further improve DRfold’s accuracy in single-chain RNA structure prediction. One of the inherent barriers stems from the limited availability of experimental RNA structures, which impacts the accuracy of the deep learning models, especially for large-sized RNAs (approximately more than 200 nucleotides). Novel strategies and ideas are needed to break through the bottleneck of high-accuracy RNA structure predictions, and the researchers are currently working on it with encouraging progress.

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    National University of Singapore (NUS)

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  • Chemical exposure in households may decrease pregnancy likelihood, study finds.

    Chemical exposure in households may decrease pregnancy likelihood, study finds.

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    Newswise — Exposure to phthalates, a group of plasticizing and solvent chemicals found in many household products, was linked to a lower probability of getting pregnant, but not to pregnancy loss, according to research by a University of Massachusetts Amherst environmental and reproductive epidemiologist.

    The study, published this week in the journal Environmental Health Perspectives, also noted an association between preconception exposure to phthalates and changes in women’s reproductive hormones, as well as increased inflammation and oxidative stress.  

    “Phthalates are ubiquitous endocrine disruptors and we’re exposed to them every day,” says lead author Carrie Nobles, assistant professor of environmental health sciences in the School of Public Health and Health Sciences.

    Phthalates are found in such common products as shampoo, makeup, vinyl flooring, toys and medical devices. People are exposed primarily by ingesting food and liquid that has come in contact with products containing the chemicals, according to a Centers for Disease Control and Prevention fact sheet. 

    Nobles and team analyzed data from a “unique cohort” of women in the preconception time-to-pregnancy study known as EAGeR (Effects of Aspirin in Gestation and Reproduction), which evaluated the effect of low-dose aspirin on live-birth rates. The study includes detailed information on 1,228 participants during six menstrual cycles when they are attempting to get pregnant. The women who became pregnant were followed through pregnancy.

    “We were able to look at some environmental exposures like phthalates and how that relates to how long it takes to get pregnant. There was detailed data for each menstrual cycle, so we had a good handle on the date of ovulation and the timing of pregnancy when that happened,” Nobles says. 

    The body breaks down phthalates into metabolites that are excreted in urine and can be analyzed. The researchers measured 20 phthalate metabolites in urine samples taken when the participants enrolled in the study.

    “We found there were three parent compounds that seem to be most strongly associated with taking longer to get pregnant, although we saw a general trend toward it taking longer to get pregnant across the phthalates we looked at,” Nobles says. “As exposure got higher, we saw more and more of an effect.”

    The researchers also looked at a global marker of inflammation, C-reactive protein, and found the women who had higher levels of phthalates exposure also had higher levels of inflammation and oxidative stress, which can lead to organ and tissue damage and ultimately to disease. 

    In addition, women who showed higher levels of phthalates had lower estradiol and higher follicle-stimulating hormone across the menstrual cycle, which play an important role in ovulation and the early establishment of pregnancy. 

    “This profile – estradiol staying low and follicle-stimulating hormone staying high – is actually something that we see in women who have ovarian insufficiency, which can happen with age as well as due to some other factors,” Nobles says. “Ovulation just isn’t happening as well as it used to.”

    While women can check consumer product labels and look for phthalate-free options, the ubiquitous nature of the chemicals makes it difficult for an individual to control their exposure.

    In Europe, certain phthalates are banned or severely restricted in their use, but the U.S. has no formal prohibitions. Nobles says the research findings add to the evidence that phthalates exposures have a negative impact on women’s reproductive health and can be used to help inform policy making.

    “Maybe we want to think differently about our regulatory system and how we identify important exposures that are having adverse effects on whether people can get pregnant and have a healthy pregnancy,” Nobles says.  

     

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    University of Massachusetts Amherst

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  • Immune cells shape lungs prenatally, offering novel respiratory disease treatments.

    Immune cells shape lungs prenatally, offering novel respiratory disease treatments.

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    Newswise — Immune cells play an active and intimate role in directing the growth of human lung tissue during development, researchers find, revolutionising our understanding of early lung development and the role of immune cells outside of immunity.

    The research offers new insights for understanding and treating respiratory conditions, such as chronic obstructive pulmonary disease (COPD). Respiratory conditions account for almost 20 per cent of all deaths in children under five years worldwide1.

    The work reveals a surprising coordination between the immune and respiratory systems, much earlier in development than previously thought. This discovery raises questions about the potential role of immune cells in other developing organs across the body.

    Researchers from the Wellcome Sanger Institute, University College London (UCL) and their collaborators at EMBL’s European Bioinformatics Institute used advanced single-cell technologies to map the development of early human lung immune cells over time.

    This study has created a first-of-its-kind immune cell atlas of the developing lung2. It is part of the international Human Cell Atlas3 initiative, which is mapping every cell type in the human body, to transform our understanding of health, infection and disease.

    The findings, published today (15 December) in Science Immunology, will help shed light on the mechanisms behind childhood lung diseases.

    Immune cells make up a substantial portion of the airways and mature lungs, which have critical gas exchange and barrier functions, providing protection against infection of the respiratory tract. However, the roles of immune cells in the developing organ have remained unexplored compared to structural or lining cell types. Recent discoveries confirm the presence of immune cells in human lungs as early as five weeks into development4.

    To explore whether the immune system might influence how lungs grow, the team studied immune cells in early human lungs from 5 to 22 weeks of development. They used various techniques, including single-cell sequencing and experiments with lung cell cultures, to see if immune cells could affect lung cell development.

    They identified key regulators of lung development, including signalling molecule IL-1β and IL-13 that facilitate the coordination of lung stem cells differentiating into specialised mature cell types5.

    The researchers detected an infiltration of innate, followed by adaptive immune cells. Innate cells included innate lymphoid cells (ILCs), natural killer (NK) cells, myeloid cells and progenitor cells. With respect to adaptive immune cells, as well as T cells, both developing and mature B lineage cells were detected, indicating that the lung environment supports B cell development.

    The findings fundamentally change the understanding of the immune and epithelial interactions that are crucial for foetal lung maturation. They also suggest that early immune disturbances could manifest as paediatric lung disease.

    These new insights into mechanisms in early lung formation will also contribute to the development of new therapeutic approaches for regenerating damaged lung tissue and restoring lung function.

    Dr Peng He and Dr Jo Barnes, co-first authors of the study at the Wellcome Sanger Institute and EMBL’s European Bioinformatics Institute, and UCL Division of Medicine respectively, said: “By adopting a focused strategy in mapping the immune system, we reveal a symbiotic relationship between immune cells and developing lungs. These detailed insights open the door to potential regenerative therapies in not only the lung, but in other vital human organs.”

    Dr Marko Nikolić, senior author of the study at UCL Division of Medicine and honorary consultant in respiratory medicine, said: “We now know immune-epithelial crosstalk is a feature of early lung development. This vital baseline of healthy lung development will help us understand what happens when lung developmental processes get disrupted, for example in preterm births, which can lead to respiratory deficiencies.”

    Dr Kerstin Meyer, senior author of the study at the Wellcome Sanger Institute, said: “The active participation of immune cells expands the possibilities for understanding and addressing impaired lung formation. What is super exciting about this mechanism is that it may well apply in other organ systems too.”

    Dr Sarah Teichmann, senior author of the study at the Wellcome Sanger Institute and Co-founder of the Human Cell Atlas, said: “If we are to fully understand the root causes of disease, we require a complete view of cells at all stages in the human body. This important contribution towards a comprehensive Human Cell Atlas will be a valuable reference for studying lung diseases.”

    ENDS

    Notes to Editors:

    1. https://www.who.int/data/gho/indicator-metadata-registry/imr-details/3147
    2. The researchers analysed human embryonic and foetal lung tissue between 5 and 22 weeks post-conception. Human embryonic tissue was provided by the Joint MRC/Wellcome Trust Human Developmental Biology Resource (www.hdbr.org)
    3. The Human Cell Atlas (HCA) is an international collaborative consortium which is creating comprehensive reference maps of all human cells—the fundamental units of life—as a basis for understanding human health and for diagnosing, monitoring, and treating disease. The HCA is likely to impact every aspect of biology and medicine, propelling translational discoveries and applications and ultimately leading to a new era of precision medicine.
      The HCA was co-founded in 2016 by Dr Sarah Teichmann at the Wellcome Sanger Institute (UK) and Dr Aviv Regev, then at the Broad Institute of MIT and Harvard (USA). A truly global initiative, there are now more than 3,100 HCA members, from 98 countries around the world. https://www.humancellatlas.org
    4. https://www.cell.com/cell/fulltext/S0092-8674(22)01415-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867422014155%3Fshowall%3Dtrue
    5. Experimentation showed that IL-1β, a cytokine produced by immune cells, directly induced airway epithelial progenitor cells to differentiate into mature lung lining cells. They do this by decreasing SOX9 expression and proliferation, driving lung epithelial progenitor cells to stop self-renewal.

    Publication:
    J.L. Barnes et al. (2023) ‘Early human lung immune cell development and its role in epithelial cell fate.’ Science Immunology. DOI: 10.1126/sciimmunol.adf9988

    Funding:
    This research was supported by Wellcome. For full funding acknowledgements, please refer to the publication.

    Selected websites:

    About UCL (University College London)
    UCL was founded in 1826. We were the first English university established after Oxford and Cambridge, the first to open up university education to those previously excluded from it, and the first to provide systematic teaching of law, architecture and medicine. We are among the world’s top universities, as reflected by performance in a range of international rankings and tables. UCL currently has over 39,000 students from 150 countries and over 12,500 staff. Our annual income is more than £1 billion. www.ucl.ac.uk | Follow us on Twitter @uclnews | Watch our YouTube channel YouTube.com/UCLTV

    The Wellcome Sanger Institute
    The Wellcome Sanger Institute is a world leader in genomics research. We apply and explore genomic technologies at scale to advance understanding of biology and improve health. Making discoveries not easily made elsewhere, our research delivers insights across health, disease, evolution and pathogen biology. We are open and collaborative; our data, results, tools, technologies and training are freely shared across the globe to advance science.

    Funded by Wellcome, we have the freedom to think long-term and push the boundaries of genomics. We take on the challenges of applying our research to the real world, where we aim to bring benefit to people and society.

    Find out more at www.sanger.ac.uk or follow us on Twitter, Instagram, Facebook, LinkedIn and on our Blog.

    About Wellcome
    Wellcome supports science to solve the urgent health challenges facing everyone. We support discovery research into life, health and wellbeing, and we’re taking on three worldwide health challenges: mental health, infectious disease and climate and health. https://wellcome.org/

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    Wellcome Trust Sanger Institute

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  • Triggering positive points crucial for climate crisis resolution.

    Triggering positive points crucial for climate crisis resolution.

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    Newswise — Positive tipping points must be triggered if we are to avoid the severe consequences of damaging Earth system tipping points, researchers say.

    With global warming on course to breach 1.5oC, at least five Earth system tipping points are likely to be triggered – and more could follow.

    Once triggered, Earth system tipping points would have profound local and global impacts, including sea-level rise from major ice sheet melting, mass species extinction from dieback of the Amazon rainforest and disruption to weather patterns from a collapse of large-scale ocean circulation currents.

    The new commentary – published in One Earth by researchers from the Global Systems Institute at the University of Exeter – says positive tipping points must be triggered to help reach the levels of decarbonisation required. 

    “One reason for hope is that many of the tipping thresholds that are likely to be crossed first are so-called slow tipping systems, which can be briefly exceeded without a commitment to tipping,” said lead author Dr Paul Ritchie.

    “However, rapid decarbonisation that minimises the distance of any overshoot and – even more importantly – limits the time spent beyond a threshold is critical for avoiding triggering climate tipping points.”

    Dr Jesse Abrams said: “One mechanism for achieving the rapid decarbonisation levels required is ironically through positive tipping points, moments when beneficial changes rapidly gain momentum.”

    The research team point to the sales seen in electric vehicles, particularly across Scandinavia, as evidence for the capability of human systems exhibiting positive tipping points.

    Professor Tim Lenton added: “Under the correct enabling conditions, such as affordability, attractiveness and accessibility, Norway have managed to transition the market share of electric vehicles from under 10% to near 90% within a decade.”

    The article is entitled: “Tipping points: Both problem and solution.”

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    University of Exeter

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  • Mathematical framework for evolutionary developmental dynamics (evo-devo).

    Mathematical framework for evolutionary developmental dynamics (evo-devo).

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    Newswise — Natural selection acts on phenotypes constructed over development, which raises the question of how development affects evolution. Classic evolutionary theory indicates that development affects evolution by modulating the genetic covariation upon which selection acts, thus affecting genetic constraints. However, whether genetic constraints are relative, thus diverting adaptation from the direction of steepest fitness ascent, or absolute, thus blocking adaptation in certain directions, remains uncertain. This limits understanding of long-term evolution of developmentally constructed phenotypes. Here we formulate a general, tractable mathematical framework that integrates age progression, explicit development (i.e., the construction of the phenotype across life subject to developmental constraints), and evolutionary dynamics, thus describing the evolutionary and developmental (evo-devo) dynamics. .The framework yields simple equations that can be arranged in a layered structure that we call the evo-devo process, whereby five core elementary components generate all equations including those mechanistically describing genetic covariation and the evo-devo dynamics. The framework recovers evolutionary dynamic equations in gradient form and describes the evolution of genetic covariation from the evolution of genotype, phenotype, environment, and mutational covariation. This shows that genotypic and phenotypic evolution must be followed simultaneously to yield a dynamically sufficient description of long-term phenotypic evolution in gradient form, such that evolution described as the climbing of a fitness landscape occurs in “geno-phenotype” space. Genetic constraints in geno-phenotype space are necessarily absolute because the phenotype is related to the genotype by development. Thus, the long-term evolutionary dynamics of developed phenotypes is strongly non-standard: (1) evolutionary equilibria are either absent or infinite in number and depend on genetic covariation and hence on development; (2) developmental constraints determine the admissible evolutionary path and hence which evolutionary equilibria are admissible; and (3) evolutionary outcomes occur at admissible evolutionary equilibria, which do not generally occur at fitness landscape peaks in geno-phenotype space, but at peaks in the admissible evolutionary path where “total genotypic selection” vanishes if exogenous plastic response vanishes and mutational variation exists in all directions of genotype space. Hence, selection and development jointly define the evolutionary outcomes if absolute mutational constraints and exogenous plastic response are absent, rather than the outcomes being defined only by selection. Moreover, our framework provides formulas for the sensitivities of a recurrence and an alternative method to dynamic optimization (i.e., dynamic programming or optimal control) to identify evolutionary outcomes in models with developmentally dynamic traits. These results show that development has major evolutionary effects.

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    University of St. Andrews

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  • Rembrandt innovated by infusing canvas with lead for The Night Watch.

    Rembrandt innovated by infusing canvas with lead for The Night Watch.

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    Newswise — New research has revealed that Rembrandt impregnated the canvas for his famous 1642 militia painting ‘The Night Watch’ with a lead-containing substance even before applying the first ground layer. Such lead-based impregnation has never before been observed with Rembrandt or his contemporaries. The discovery, published today in Science Advances, underlines Rembrandt’s inventive way of working,  in which he did not shy away from using new techniques.

    The surprising observation is yet another result from Operation Night Watch, the largest and most wide-ranging research and conservation project in the history of Rembrandt’s masterpiece. It resulted from advanced analysis of an actual paint sample taken from the historical painting. First author of the paper is Fréderique Broers, a researcher at the Rijksmuseum and PhD student with professors Katrien Keune (University of Amsterdam), Koen Janssens (University of Antwerp) and Florian Meirer (Utrecht University). Her research forms part of the research project 3D Understanding of Degradation Products in Paintings of the Netherlands Institute for Conservation+Art+Science+ (NICAS), funded by the Dutch Research Council NWO. Broers and coworkers employed a combination of x-ray fluorescence and ptychography to identify and visualize sub-microscale chemical compounds in the lower layers of the canvas. By sampling the small Night Watch paint fragment at DESY (Deutsches Elektronen-Synchrotron, Hamburg), they discovered the lead-rich layer below the quartz-clay ground layer of the canvas. 

    Protection against moisture

    It was already known from earlier studies that Rembrandt had used a quartz-clay ground on the Night Watch. In earlier paintings he had used double grounds, consisting of a first ground containing red earth pigments followed by a second lead white containing ground. The large size of The Night Watch may have motivated Rembrandt to look for a cheaper, less heavy and more flexible alternative for the ground layer. Another issue he had to overcome was that the large canvas was intended for a damp outer wall of the great hall of the Kloveniersdoelen (musketeers’ shooting range) in Amsterdam. It had been reported that under humid conditions the common method of preparing the canvas using animal glue could fail. A contemporary source on painting techniques written by Théodore de Mayerne suggested impregnation with lead-rich oil as an alternative. This may have inspired Rembrandt for his unusual impregnation procedure to improve the durability of his masterpiece.

    Computational imaging

    The presence of this lead-containing ‘layer’ was discovered by the first-ever use of correlated x-ray fluorescence and ptychographic nano-tomography on a historical paint sample. This was performed at the PETRA III synchrotron radiation source at DESY. X-ray fluorescence is used to investigate the distribution of relatively heavy elements (calcium and heavier). Ptychography, a computational imaging technique based on experimentally obtained datasets, is capable of visualizing even the lightest elements and organic fractions. 

    Analysis of the micro sample taken from The Night Watch revealed that on the side of the sample closest to the canvas support a homogenous layer of dispersed lead was present in the ground layer. Since lead components were not to be expected in the quartz-clay ground layer, this was a rather puzzling observation. The results were then combined with the lead distribution map of the full Night Watch, obtained by X-ray fluorescence scanning of the painting in the Rijksmuseum’s Gallery of Honour. This map reveals the presence of lead throughout the painting and suggests application using large semi-circular brushstrokes, supporting the assumption that it results from an impregnation procedure. Even an imprint of the original strainer onto which the canvas was stretched when the preparatory layers were applied, is visible in the lead distribution map. This brings us yet another step closer to understanding Rembrandt’s creative process in painting The Night Watch, as well as its current condition. 

    Publication details

    Fréderique T.H. Broers, Ige Verslype, Koen W. Bossers, Frederik Vanmeert, Victor Gonzalez, Jan Garrevoet, Annelies van Loon, Esther van Duijn, Anna Krekeler, Nouchka De Keyser, Ilse Steeman, Petria Noble, Koen Janssens, Florian Meirer, Katrien Keune: Correlated x-ray fluorescence and ptychographic nanotomography on Rembrandt’s The Night Watch reveals unknown lead “layer”. Science Advances, 15 December 2023. DOI: 10.1126/sciadv.adj9394

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    Universiteit van Amsterdam

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  • Menstrual products contain endocrine disruptors: tampons, pads, liners.

    Menstrual products contain endocrine disruptors: tampons, pads, liners.

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    Newswise — The average menstruator will use over 11,000 tampons or sanitary pads in their lifetime. Vaginal and vulvar tissue that touch pads and tampons is highly permeable. Through this permeable tissue chemicals are absorbed without being metabolized, which makes endocrine-disrupting chemicals potentially dangerous when found in menstrual products. Endocrine-disrupting chemicals can interfere with human hormones and cause medical issues, including gynecological conditions such as endometriosis and uterine fibroids. 

    Joanna Marroquin, a Mason PhD in Public Health student, and Associate Professor Anna Pollack, reviewed studies conducted since 2103 that measured chemicals in menstrual products and that measured human biomarkers of chemical exposure and determined that endocrine-disrupting chemicals were found in menstrual products including tampons, pads, and liners. 

    “Identifying chemicals in menstrual products that menstruators regularly use is important because exposure through these products can impact menstruators’ reproductive health,” said Marroquin, the paper’s first author.  

    The study found that menstrual products contain a variety of endocrine-disrupting chemicals including phthalates, volatile organic compounds, parabens, environmental phenols, fragrance chemicals, dioxins and dioxin-like compounds. 

    This issue is even more relevant thanks to the Robin Danielson Menstrual Product and Intimate Care Product Safety Act of 2023, which was introduced in the U.S. House of Representatives in October 2023. The Act would establish a program of research regarding the risks posed by the presence of dioxins, phthalates, pesticides, chemical fragrances, and other components in menstrual products and intimate care products. 

    This literature reviewed 15 papers published between 2013 and 2023 that tested menstrual products in the U.S., Japan, and South Korea. The researchers note that there are few publications available that measure chemicals in menstrual products.  

    Additionally, though forever chemicals (PFAS) have been found in menstrual underwear, there is a lack of peer-reviewed research on menstrual underwear and other newly-popular-in-the-U.S. products such as menstrual cups and discs. 

    Chemicals in menstrual products: A systematic review was published in BJOG, an international journal of obstetrics and gynecology in September 2023. Additional authors include Marianthi-Anna Kiomourtzoglou from Mailman School of Public Health, Columbia University and Alexandra Scranton from Women’s Voices for the Earth.  

    The research was supported by Pollack’s National Institute of Environmental Health Sciences R01ES31079 award.  

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    George Mason University

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  • From Lecture to Dialogue: How Brief Training Improves Med Students’ Communication

    From Lecture to Dialogue: How Brief Training Improves Med Students’ Communication

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    Newswise — (Boston)—Teaching is an integral communication skill central to the practice of medicine. The art of teaching extends beyond disseminating information. The skill directly translates to health provider-patient communication, the success of which is positively correlated with improved patient outcomes.

     

    “Teaching is a large part of medicine – patient education is critical to providing high quality patient centered care. Education helps patients understand the ‘why’ and ‘what’ of their treatments and allows them to be better participants in their own care, and in shared decision making,” said author Susan White, MD, assistant professor of obstetrics & gynecology at Boston University Chobanian & Avedisian School of Medicine.

     

    In an effort to foster near-peer inter-professional teaching and teamwork, the school has developed a curriculum using medical students as teaching assistants, called Educational Fellows, to work with students studying to become physician assistants (PA).

     

    “Our Educational Fellows curriculum allows medical students to learn the art of teaching (pedagogy) and learning theory and to practice what they had learned in working with PA students in the classroom,” explains White, who also is director of the Physician Assistant  program at the school. “We expect that the Educational Fellow experience will make those medical students better prepared for patient education.”

     

    White and her colleagues present their experiences and lessons learned from establishing this program that 1) introduces select medical students to PA students in the context of a near-peer teaching framework during pre-clinical training; 2) trains the medical students in best practices of teaching and learning; and 3) provides an additional source of instructors for basic science courses.

     

    White believes the program could be modified for other training programs that use peer-peer or near-peer teaching for tutoring or as teaching assistants. For example, PA students might work with students in nursing or physical therapy to provide tutoring or assistance in lab setting, or PhD graduate students might be teaching assistants for undergraduate courses. He hopes that all graduate level programs in medicine will adopt the curriculum to better prepare their graduates to teach and educate their patients, whether it be bedside nurses teaching patients home care skills or surgeons explaining a complex procedure.

     

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    Boston University School of Medicine

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  • ‘Long flu’ has emerged as a consequence similar to long COVID

    ‘Long flu’ has emerged as a consequence similar to long COVID

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    BYLINE: Kristina Sauerwein

    Newswise — Since the COVID-19 pandemic began, extensive research has emerged detailing the virus’s ability to attack multiple organ systems, potentially resulting in a set of enduring and often disabling health problems known as long COVID. Now, new research from Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care System indicates that people hospitalized with seasonal influenza also can suffer long-term, negative health effects, especially involving their lungs and airways.

    The new study comparing the viruses that cause COVID-19 and the flu also revealed that in the 18 months after infection, patients hospitalized for either COVID-19 or seasonal influenza faced an increased risk of death, hospital readmission, and health problems in many organ systems. Further, the time of highest risk was 30 days or later after initial infection.

    “The study illustrates the high toll of death and loss of health following hospitalization with either COVID-19 or seasonal influenza,” said senior author Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University. “It’s critical to note that the health risks were higher after the first 30 days of infection. Many people think they’re over COVID-19 or the flu after being discharged from the hospital. That may be true for some people. But our research shows that both viruses can cause long-haul illness.”

    The findings are published Dec. 14 in The Lancet Infectious Diseases.

    The statistical analysis spanned up to 18 months post-infection and included a comparative evaluation of risks of death, hospital admissions and 94 adverse health outcomes involving the body’s major organ systems.

    “A review of past studies on COVID-19 versus the flu focused on a short-term and narrow set of health outcomes,” said Al-Aly, who treats patients within the VA St. Louis Health Care System and is an assistant professor of medicine at Washington University. “Our novel approach compared the long-term health effects of a vast array of conditions. Five years ago, it wouldn’t have occurred to me to examine the possibility of a ‘long flu.’ A major lesson we learned from SARS-CoV-2 is that an infection that initially was thought to only cause brief illness also can lead to chronic disease. This revelation motivated us to look at long-term outcomes of COVID-19 versus flu.

    “We wanted to know whether and to what degree people with flu also experience long-term health effects,” Al-Aly said. “The big answer is that both COVID-19 and the flu led to long-term health problems, and the big aha moment was the realization that the magnitude of long-term health loss eclipsed the problems that these patients endured in the early phase of the infection. Long COVID is much more of a health problem than COVID, and long flu is much more of a health problem than the flu.”

    However, the overall risk and occurrence of death, hospital admissions, and loss of health in many organ systems are substantially higher among COVID-19 patients than among those who have had seasonal influenza, Al-Aly said. “The one notable exception is that the flu poses higher risks to the pulmonary system than COVID-19,” he said. “This tells us the flu is truly more of a respiratory virus, like we’ve all thought for the past 100 years. By comparison, COVID-19 is more aggressive and indiscriminate in that it can attack the pulmonary system, but it can also strike any organ system and is more likely to cause fatal or severe conditions involving the heart, brain, kidneys and other organs.”

    The researchers analyzed de-identified medical records in a database maintained by the U.S. Department of Veterans Affairs, the nation’s largest integrated health-care delivery system. They evaluated information involving 81,280 patients hospitalized for COVID-19 at some point from March 1, 2020, through June 30, 2022, as well as 10,985 patients hospitalized for seasonal influenza at some point from Oct. 1, 2015, through Feb. 28, 2019.

    Patients represented multiple ages, races and sexes.

    Regarding both viruses, patient vaccination status did not affect results. Those in the COVID-19 cohort were hospitalized during the pre-delta, delta and omicron eras.

    During the overall 18-month study period, patients who had COVID-19 faced a 50% higher risk of death than those with seasonal influenza. This corresponded to about eight more deaths per 100 persons in the COVID-19 group than among those with the flu.

    Although COVID-19 showed a greater risk of health loss than seasonal influenza, infection with either virus carried significant risk of disability and disease. The researchers found COVID-19 exhibited increased risk of 68% of health conditions examined across all organ systems (64 of the 94 adverse health outcomes studied), while the flu was associated with elevated risk of 6% of health conditions (six of the 94) – mostly in the respiratory system.

    Also, over 18 months, COVID-19 patients experienced an increased risk of hospital readmission as well as admission to an intensive care unit (ICU). For every 100 persons in each group, there were 20 more hospital admissions and nine more ICU admissions in COVID-19 than flu.

    “Our findings highlight the continued need to reduce the risk of hospitalization for these two viruses as a way to alleviate the overall burden of health loss in populations,” Al-Aly said. “For both COVID-19 and seasonal influenza, vaccinations can help prevent severe disease and reduce the risk of hospitalizations and death. Optimizing vaccination uptake must remain a priority for governments and health systems everywhere. This is especially important for vulnerable populations such as the elderly and people who are immunocompromised.”

    In both COVID-19 and the flu, more than half of death and disability occurred in the months after infection as opposed to the first 30 days, the latter of which is known as the acute phase.

    “The idea that COVID-19 or flu are just acute illnesses overlooks their larger long-term effects on human health,” Al-Aly said. “Before the pandemic, we tended to belittle most viral infections by regarding them as somewhat inconsequential: ‘You’ll get sick and get over it in a few days.’ But we’re discovering that is not everyone’s experience. Some people are ending up with serious long-term health issues. We need to wake up to this reality and stop trivializing viral infections and understand that they are major drivers of chronic diseases.”

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    Washington University in St. Louis

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  • Consumers face perplexity with food-date labels, causing confusion in decision-making.

    Consumers face perplexity with food-date labels, causing confusion in decision-making.

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    Consumers grapple with confusion over food-date labels

    Newswise — The use of food-date labels such as “use-by” and “best if used by” causes consumer confusion that results in many Americans discarding food that is safe to eat or donate, according to the November 2023 Consumer Food Insights Report.

    The survey-based report out of Purdue University’s Center for Food Demand Analysis and Sustainability assesses food spending, consumer satisfaction and values, support of agricultural and food policies and trust in information sources. Purdue experts conducted and evaluated the survey, which included 1,200 consumers across the U.S. 

    The Congressional Research Service recently reported that 7% of all U.S. food waste is because of date labeling confusion. “The goal of this month’s CFI survey was to gather consumer perceptions about what these food date labels mean,” said the report’s lead author, Joseph Balagtas, professor of agricultural economics at Purdue and director of CFDAS.

    The USDA Food Safety and Inspection Service defines “use-by” and “best if used by” as references to peak food quality rather than the date after which the food is no longer safe to eat. However, there is no official standard for food date labeling in the U.S., which leads to an unsurprising mix of responses as to what they mean.

    “Over half of consumers connect “best if used by” and “use-by” dates with food safety, while over 30% believe these labels are related to food quality,” Balagtas said. “This information problem is a kind of market failure and leads to waste.

    “One potential fix to misinformation is for the government to set standards for food date labels to help inform consumers what is and is not safe to eat to help reduce food waste in the U.S. The recently proposed Food Date Labeling Act is an attempt to achieve that goal.”

    The November survey also looked at consumer perceptions of foodborne illness risks. Food-risk attitudes are divided into three groups: risk-averse, risk-neutral and risk-loving. The groupings were based on respondents’ self-assessed risk tolerance for food at home (FAH) and food away from home (FAFH) on a scale from 0 (risk-averse) to 10 (fully prepared to take risks or risk-loving). The summaries broken down this way focus on CFI data from January to November 2023.

    “We found that consumers believe the risk of contracting a foodborne illness is higher when eating food at a restaurant compared to eating food they prepare at home themselves, which is consistent with data on the incidence of foodborne illness,” Balagtas said. “So it is not surprising that we also see that consumers who are more risk-averse when it comes to their food, eat home-cooked meals more frequently than consumers willing to take more risks with their food consumption.”

    A variety of store-bought goods have the potential to contain foodborne bacteria that cause illness. Even so, consumers were more likely to select raw meat items as foods that pose a high risk of foodborne illnesses.

    “We see a gap of more than 20 percentage points in the rate at which raw meats were selected compared to leafy greens, milk, flour and raw fruits and vegetables, despite the fact that some of these items that are perceived as ‘safer’ have caused foodborne illness outbreaks in the past,” Balagtas noted.

    The Interagency Food Safety Analytics Collaboration, a group tasked with monitoring the causes of foodborne illnesses in the U.S., recently reported that the contribution of fresh produce to foodborne outbreaks is comparable to that of raw meats, and in some cases, greater.

    The November survey also showed that food insecurity has dropped slightly for the fifth straight month, to 12.6%. “We do observe higher rates of food insecurity among risk-loving consumers, though this difference is likely the result of the correlation between age and food risk attitudes,” said Elijah Bryant, a survey research analyst at the center and co-author of the report.

    Generally, older consumers with more resources, on average, tend to be more food secure and less willing to take food risks, while younger people more willing to take risks tend to have fewer resources, resulting in higher rates of food insecurity.”

    Consumers also were asked to recall their food behaviors over the last month. “Those who are classified as risk-loving reported eating fruits and vegetables without washing them, eating rare or undercooked meat and eating raw dough or batter more frequently than those who are risk-averse,” Bryant said.

    Consumers less willing to take risks with their food were also less likely to agree with claims about the health benefits of non-conventional food items. These claims include organic being more nutritious than non-organic, plant-based milk is healthier than dairy milk and gluten-free food is healthier than products containing gluten.

    This may be indicative of risk-averse consumers being more resistant to alternative foods in the food system that stray from what they perceive as the norm, Bryant said.

    The Center for Food Demand Analysis and Sustainability is part of Purdue’s Next Moves in agriculture and food systems and uses innovative data analysis shared through user-friendly platforms to improve the food system. In addition to the Consumer Food Insights Report, the center offers a portfolio of online dashboards.

    Writer: Steve Koppes

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    Purdue University

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  • “Energy Droughts” in Wind and Solar Can Last Nearly a Week, Research Shows

    “Energy Droughts” in Wind and Solar Can Last Nearly a Week, Research Shows

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    Newswise — Solar and wind power may be free, renewable fuels, but they also depend on natural processes that humans cannot control. It’s one thing to acknowledge the risks that come with renewable energy: the sun doesn’t always shine and the wind doesn’t always blow, but what happens when the grid loses both of these energy sources at the same time?

    This phenomenon is known as a compound energy drought. In a new paper, researchers at Pacific Northwest National Laboratory (PNNL) found that in some parts of the country, these energy droughts can last nearly a week.

    “When we have a completely decarbonized grid and depend heavily on solar and wind, energy droughts could have huge amounts of impact on the grid,” said Cameron Bracken, an Earth scientist at PNNL and lead author on the paper. Grid operators need to know when energy droughts will occur so they can prepare to pull energy from different sources. On top of that, understanding where, when, and for how long energy droughts occur will help experts manage grid-level battery systems that can store enough electricity to deploy during times when energy is needed most.

    The team published the findings October 31 in the journal Renewable Energy and will be presenting at this week’s annual meeting of the American Geophysical Union.

    Hunting for cloudy, windless days

    In the past, researchers studied compound energy droughts on a state or regional scale. But not much has been studied on a nationwide scale. To find out more about the risk of energy droughts over the entire continental U.S., the researchers dug into weather data and then used historical energy demand data to understand how often an energy drought occurs when that energy is needed the most.

    The team examined 4 decades of hourly weather data for the continental U.S. and homed in on geographical areas where actual solar and wind energy plants operate today. Weather data included wind speeds at the height of wind turbines as well as the intensity of solar energy falling on solar panels. Times when the weather data showed stagnant air and cloudy skies translated into lower energy generation from the wind and solar plants—a compound energy drought.

    “We essentially took a snapshot of the infrastructure as of 2020 and ran it through the 40 years of weather data, starting in 1980,” Bracken said. “We are basically saying ‘here is how the current infrastructure would have performed under historical weather conditions.’”

    The researchers found that energy droughts can occur in any season across the continental U.S., though they vary widely in frequency and duration. In California, for instance, cloudy and windless conditions might last several days, whereas the same conditions might last for only a few hours in Texas. Utah, Colorado, and Kansas experience frequent energy droughts both over several-hour timescales as well as several-day timescales. The Pacific Northwest and Northeast, meanwhile, seem to experience energy droughts that last several hours more frequently than several days. The different timescales (hourly versus daily) will help inform the energy drought’s impact on the grid—will it last just a few hours, or several days?

    Overall, researchers found that the longest potential compound energy drought on an hourly timescale was 37 hours (in Texas), while the longest energy drought on a daily timescale was six days (in California).

    Energy drought at peak demand

    Simply knowing the where and how of energy droughts is just one piece of the puzzle, Bracken said. He also stressed that a drought of solar and wind power won’t necessarily cause an energy shortage. Grid operators can turn to other sources of energy like hydropower, fossil fuels, or energy transmitted from other regions in the U.S.

    But as the nation aims to move away from fossil fuels and rely more on solar and wind power, grid operators must understand whether energy droughts will occur during times when the demand for electricity might exceed supply. Climate change brings hotter summers and more intense winter storms, and these are times when not only people use more energy to stay safe (for cooling or heating), but access to electricity might mean life or death.

    To understand the possible connection between energy droughts and energy demand, the team mapped their historical, hypothetical generation data onto 40 years of historical energy demand data that also covered real power plants across the continent.

    The data showed that “wind and solar droughts happen during peak demand events more than you would expect due to chance,” Bracken said, meaning that more often than not, windless and cloudless periods occurred during times when demand for power was high. For now, Bracken isn’t certain that the correlation means causation.

    “This could be due to well-understood meteorological phenomenon such as inversions suppressing wind and increasing temperatures, but further study is needed,” Bracken said.

    Energy storage for energy droughts

    Studying patterns in the frequency and duration of energy droughts will also help inform the deployment of long-duration energy storage projects, said Nathalie Voisin, an Earth scientist at PNNL and coauthor on the paper. The paper is the first to provide a uniform standard of what a compound energy drought is and how long it can last in different parts of the country.

    “We’re providing insight on how to adequately design and manage multi-day storage. So when you know an energy drought is going to last for five hours or five days, you can incentivize storage to be managed accordingly,” Voisin said.

    Next, Bracken and the team will extrapolate weather and demand data into the future to see how climate change will affect the frequency and duration of energy droughts. The team plans to model energy droughts all the way to the end of the century combined with evolving infrastructure.

    This research was funded by PNNL through its internal GODEEEP initiative.

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    Pacific Northwest National Laboratory

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  • Analysis Group Researchers Evaluated Long-Term Patient Experience with Dupilumab Using Groundbreaking Method for Generating Real-World Data

    Analysis Group Researchers Evaluated Long-Term Patient Experience with Dupilumab Using Groundbreaking Method for Generating Real-World Data

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    Newswise — BOSTON, Dec. 12, 2023 /PRNewswire/ — Researchers from Analysis Group, a global leader in health economics and outcomes research (HEOR), have coauthored a follow-up analysis of patient-reported outcomes (PROs) that evaluated outcomes three years after initiation of dupilumab among adults with atopic dermatitis (AD). The study, published in the journal Dermatology and Therapy, extends the one-year results of the previously published RELIEVE-AD study in JAMA Dermatology, which was based on a groundbreaking method for generating real-world data (RWD).

    The study methodology, Longitudinal Surveys of Patients with Recruitment Through Patient Support Programs (LEAP), represents an advance over other RWD approaches, as it engages patients in patient support programs from the time of treatment initiation and tracks individual patient responses to follow-up surveys administered at pre-defined time intervals. This approach provides a true baseline against which to compare longitudinal data over time. This latest edition of the study provides RWD generated through an online survey given at 30–36 months after initiation of treatment, adding to the existing body of data collected at one, two, three, six, nine, and 12 months.

    “Generating real-world data is particularly challenging for conditions like atopic dermatitis that require long-term therapy extending beyond the initial study period. For such chronic conditions, it is important to determine whether long-term treatment creates sustained benefits from the patient’s perspective,” said the study’s senior author, Dr. Alexa B. Kimball, President and CEO at Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center and Professor of Dermatology at Harvard Medical School. “With the LEAP methodology, we were able to effectively identify and evaluate flare-ups, fluctuations in symptoms, and a host of other invaluable RWD points tied to a true baseline with impressive patient participation and, over time, retention.”

    “While clinical trials remain the gold standard for product approval, they are widely recognized as  lacking the type of RWD that regulators, payers, clinicians, and patients want, or require, after a drug’s approval,” said study investigator Min Yang, Vice President at Analysis Group. “LEAP was created to address this problem by generating patient-centric data early after a launch, grounded by a baseline tied to the clinical trial with the ability for longitudinal follow-up and strong retention rates. It’s exciting to be at the forefront of efforts to fill such an important gap, along with Sanofi and Regeneron HEOR researchers, and the clinical experts who were so integral to the success of the LEAP approach.”

    While the methodology, first published in 2021 by JAMA Dermatology following rigorous peer review, was used to better understand patient outcomes with dupilumab – a monoclonal antibody used to treat diseases such as uncontrolled moderate-to-severe AD, certain types of uncontrolled moderate-to-severe asthma, and inadequately controlled chronic rhinosinusitis with nasal polyposis – LEAP is widely applicable across many diseases and condition types.

    “Collecting and synthesizing RWD to generate high-quality evidence is a complex and challenging process, especially when regulators, payers, and clinicians are interested in patient-reported outcomes about diseases and associated therapies,” commented coauthor Eric Q. Wu, Managing Principal at Analysis Group. “Leveraging manufacturers’ programs, such as patient support programs, has proven to be a breakthrough solution for generating early and long-term high-quality RWD.”

    The study, “Long-Term Effectiveness of Dupilumab in Patients with Atopic Dermatitis: Results up to 3 Years from the RELIEVE-AD Study,” was published in August by Dermatology and Therapy. In addition to Dr. Kimball, Dr. Yang, and Dr. Wu, investigators included Dr. Bruce Strober of the Yale School of Medicine; Manager Bruno Martins of Analysis Group; Gaëlle Bégo-Le-Bagousse, Chien-Chia Chuang, and Debra Sierka of Sanofi; and Zhixiao Wang, Brad Shumel, Jingdong Chao, and Dimittri Delevry of Regeneron Pharmaceuticals. Funding was provided by Sanofi and Regeneron.

    To learn more about Analysis Group’s HEOR capabilities, visit www.analysisgroup.com/healthoutcomes. 

    About Analysis Group’s HEOR, Epidemiology & Market Access Practice
    Founded in 1981, Analysis Group is one of the largest international economics consulting firms, with more than 1,200 professionals across 14 offices. Analysis Group’s health care experts apply analytical expertise to health economics and outcomes research (HEOR), clinical research, market access and commercial strategy, and health care policy engagements, as well as drug safety-related engagements in epidemiology. Analysis Group’s internal experts, together with our network of affiliated experts from academia, industry, and government, provide our clients with exceptional breadth and depth of expertise and end-to-end consulting services globally.

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    Analysis Group

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  • Blending the school curriculum to create eco warriors

    Blending the school curriculum to create eco warriors

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    Newswise — They’re among our youngest citizens, but when children learn about sustainability in their own backyard, they’re more likely to protect the environment, say University of South Australia researchers.

    In a citizen science project, UniSA researchers found that when students investigate local sustainability issues, they engage deeply with learning and develop meaningful connections to the environment.

    It’s a vital skill for the next generation, particularly as the world deals with the negative impacts of climate change, waste, and scarcity of resources.

    Now, a new research project, ‘Being Heard: Remixing Critical Literacy for Active Citizenship’, is introducing Year 5 and 6 students to a variety of climate issues through the Climate Ready Schools initiative.

    Conducted at Burton Primary School, the transdisciplinary nature of the project enabled teachers to embed core competencies from the school curriculum, ensuring students achieved required academic outcomes while concurrently developing skills as an environmentally and socially responsible citizen.

    UniSA researchers and Burton Primary School teachers, Bernadette Haggerty and Michelle Miller, say connecting students with local issues is key to building students’ motivation and learning.

    “By working on projects that are close to the students – both physically and emotionally – they’re better able to grasp what the issues are and develop solutions,” Haggerty says.

    “The breadth of projects was amazing – we had students working on beeswax lunch wraps to replace single use plastic, no waste cooking classes to stop food landfill, climate change mitigation by expanding local tree canopy, and even a machine to help plants and animals survive in the desert.

    “Learning about climate change is important for everyone. When we explore sustainability issues in a school setting, we engage the young brain to investigate and find solutions to bigger problems.

    “Students are scaffolded to understand the origins of some of our major disasters like ocean pollution, food waste, plastic pollution. The realisation that pollution starts in their own community, inspires them to take action at the grass roots – at home and the school community.”

    The Burton Primary School project is part of a literacy initiative from UniSA’s Associate Professor Joel Windle, Dr Melanie Baak and Dr David Caldwell, with the Primary Education Teaching Association Australia.

    “Our project encourages student voice and active citizenship. But by tapping into literacy skills from the English curriculum, students concurrently learn multiple skills,” Miller says.

    “It’s all part of creating a transdisciplinary unit of work that enables students to develop knowledge from multiple perspectives. For example, using maths to construct maps, biology to understand the relationship between plants and animals, technology to design solutions, art for sketching, and English for reporting.

    “In this project, students communicated their ideas using literacy skills such as slam poetry, podcasts and YouTube clips. By experimenting with news media, poetry, and film, they learnt different language techniques, skills, and communication approaches.

    “At the same time, they learn how to communicate powerful messages to reduce their ecological footprint, and how to present positive messages to the community.

    “Students have learnt to notice nature, investigate the science, and engineer solutions. They know they can make changes to the world through positive action.”

     

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    University of South Australia

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  • Cell Therapy Appears Safe and Effective for Lymphoma in Remission

    Cell Therapy Appears Safe and Effective for Lymphoma in Remission

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    DOWNLOADABLE VIDEO HERE

    Newswise — MIAMI, FLORIDA (EMBARGOED UNTIL SUNDAY, DEC. 10, 2023 AT 8:00 P.M. ET) – A study led by researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine suggests that CAR-T immunotherapy remains a viable option for patients who have lymphoma that goes into remission before the cell therapy begins.

    While the study doesn’t answer the question of whether cell therapy in remission is the right choice, it does say that it’s not the wrong choice.

    “I don’t think it answers the question of: Should we give these patients cell therapy? But I think it answers the question that we can – that it’s safe and that it’s a reasonable strategy when you’re in that spot,” said Trent Wang, D.O., a Sylvester hematologist and cellular therapy specialist who will present study findings in an oral presentation at the 65th ASH Annual Meeting and Exposition, the American Society of Hematology’s conference taking place in San Diego, California, Dec. 9-12.

    Most patients receiving cell therapy, a form of immunotherapy that uses immune cells engineered to recognize and attack the patient’s cancer, desperately need it. For some, it comes after many other treatments have failed. But Wang noticed an odd phenomenon in the past few years when treating lymphoma patients with this form of therapy: Some of his patients went into complete remission before the cells ever touched their bodies.

    This uncommon scenario occurs during the process of getting to cell therapy, which in the case of Wang’s study uses a kind of engineered immune cell known as CAR-T cells. When a patient starts the process, there’s a waiting period of three to five weeks before they get the treatment. Insurance approval is needed, and the cells themselves need to be manufactured from the patient’s own cells. But many of these patients are very sick with their cancer, so physicians will often treat them with a short course of chemotherapy or other drugs to tamp down the symptoms.

    A small handful of these patients end up in remission during this waiting period treatment, the clinicians have found.

    “That prompted this dilemma: Now what are we supposed to do?” Wang said. “Should we change the plan or give the therapy anyway? We just didn’t have a lot of information on this scenario.”

    Wang said more often than not his team would proceed with the cell therapy in these cases, mainly to prevent yet another stretch of time where the patients’ cancer might come back again. But it didn’t feel like a very informed decision.

    Wang and his colleagues noticed that their patients who received the cells while in remission tended to fare well after their infusion. But they didn’t know if those results would hold up in an analysis of a larger group. They proposed a research study to the Center for International Blood & Marrow Transplant Research, a nationwide registry that tracks patients who have received transplants and/or cell therapies.

    The study included data from 134 patients in the registry who had gone into complete remission in the waiting period before receiving their cell therapy. To find that group, the scientists screened the records for more than 5,000 cell therapy patients.

    They found that this group of patients had a 43% probability of progression-free survival over the two years following their treatment, about the same percentage as patients in the registry who were not in remission when they received CAR-T. However, the patients in remission had very low levels of toxicities related to their cell therapies, namely an immune overreaction known as cytokine release syndrome and neurotoxicity, two side effects that can sometimes accompany CAR-T cell therapy.

    The study used data from patients treated with CAR-T cell therapy between 2015 to 2021, and current frequencies of specific cell therapy use are slightly different from those that were used in practice just a few years ago, Wang said. Next, the researchers want to explore the data paralleling more recent treatment trends.

    Authors: Wang, first author, and Antonio M. Jimenez Jimenez, M.D., last author, are Sylvester researchers. Co-authors include Kwang Wooahn, Ph.D., Manmeet Kaur, and Mehdi Hamadani, M.D., Medical College of Wisconsin; Mazyar Shadman, M.D., Fred Hutchinson Cancer Center, Seattle; Alex F. Herrera, M.D., City of Hope, Duarte, California; and Craig S. Sauter, M.D., Taussig Cancer Institute, Cleveland.

    Conflicts and disclosures: A full list of disclosures is included with the abstract.

    # # #

    Presentation Title: 615 Chimeric Antigen Receptor (CAR) T Cell Infusion for Large B Cell Lymphoma in Complete Remission: A Center for International Blood & Marrow Transplant Research (CIBMTR) Analysis 

    DOWNLOADABLE VIDEO HERE 

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    Sylvester Comprehensive Cancer Center

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