Publisher Health

In a new study, scientists explored the links between three measures known to independently predict healthy aging: nutrient intake, brain structure and cognitive function. Their analysis adds to the evidence that these factors jointly contribute to brain health in older adults.
Reported in the Journal of Nutrition, the study found that blood markers of two saturated fatty acids, along with certain omega-6, -7 and -9 fatty acids, correlated with better scores on tests of memory and with larger brain structures in the frontal, temporal, parietal and insular cortices. Watch a video about the research.
While other studies have found one-to-one associations between individual nutrients or classes of nutrients and specific brain regions or functions, very little research takes a comprehensive look at brain health, cognition and broad dietary patterns overall, said Aron Barbey, a professor of psychology, bioengineering and neuroscience at the University of Illinois Urbana-Champaign who led the study with postdoctoral researcher Tanveer Talukdar and psychology research scientist Chris Zwilling. The three co-authors all are affiliated with the Beckman Institute for Advanced Science and Technology at the U. of I.
“Our findings reveal that we can use nutrient biomarkers, cognitive tests and MRI measures of brain structure to account for much of the variation in healthy aging,” Barbey said. “This allows us to better understand how nutrition contributes to health, aging and disease,”
The researchers collected data from 111 healthy older adults with MRI structural scans, blood-based biomarkers of 52 dietary nutrients and cognitive performance on tests of memory and intelligence. By combining these measures using a data-fusion approach, the team found associations between dozens of features that appear to work in tandem to promote brain and cognitive health in older adults.
Data-fusion allows researchers to look across multiple data sets to map traits or features that have common patterns of variability, said Talukdar, who tailored this method to incorporate the nutrition, cognition and brain volumetric data.

“We’re looking at relationships among all of these together,” he said. “This allows us to identify certain features that cluster together.”
This overcomes some of the limitations of analyzing individual factors, Barbey said.
“If we just look at nutrition as it relates to brain structures and we don’t study cognition, or if we look at nutrition as it relates to cognition and we don’t study the brain, then we’re actually missing really important pieces of information.”
The most obvious features that clustered together in the new analysis involved the size of gray-matter volumes in the frontal, temporal and parietal cortices; performance on tests of auditory memory and short- and long-term memory; and blood markers related to consumption of monounsaturated and polyunsaturated fatty acids. Study participants who scored higher on the memory tests tended to have larger gray-matter volumes and higher levels of markers of omega-6, -7 and -9 fatty acids in their blood. Those who did more poorly on the cognitive tests also had smaller gray-matter volumes in those brain regions and lower levels of those dietary markers, the analysis revealed.
While the study only reveals associations between these factors and does not prove that dietary habits directly promote brain health, it adds to the evidence that nutrition is a key player in healthy aging, the researchers said.
“Our work motivates a more comprehensive picture of healthy aging,” Zwilling said. This gives insight into the importance of diet and nutrition and the value of data-fusion methods for studying their contributions to adult development and the neuroscience of aging.”
This work was supported by a grant from Abbott Nutrition through the Center for Nutrition, Learning, and Memory at the U. of I.

MIT engineers have designed a new nanoparticle sensor that could enable early diagnosis of cancer with a simple urine test. The sensors, which can detect many different cancerous proteins, could also be used to distinguish the type of a tumor or how it is responding to treatment.
The nanoparticles are designed so that when they encounter a tumor, they shed short sequences of DNA that are excreted in the urine. Analyzing these DNA “barcodes” can reveal distinguishing features of a particular patient’s tumor. The researchers designed their test so that it can be performed using a strip of paper, similar to an at-home Covid test, which they hope could make it affordable and accessible to as many patients as possible.
“We are trying to innovate in a context of making technology available to low- and middle-resource settings. Putting this diagnostic on paper is part of our goal of democratizing diagnostics and creating inexpensive technologies that can give you a fast answer at the point of care,” says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science.
In tests in mice, the researchers showed that they could use the sensors to detect the activity of five different enzymes that are expressed in tumors. They also showed that their approach could be scaled up to distinguish at least 46 different DNA barcodes in a single sample, using a microfluidic device to analyze the samples.
Bhatia is the senior author of the paper, which appears today in Nature Nanotechnology. Liangliang Hao, a former MIT research scientist who is now an assistant professor of biomedical engineering at Boston University, is the lead author of the study.
DNA barcodes
For several years, Bhatia’s lab has been developing “synthetic biomarkers” that could be used to diagnose cancer. This work builds on the concept of detecting cancer biomarkers, such as proteins or circulating tumor cells, in a patient’s blood sample. These naturally occurring biomarkers are so rare that it’s nearly impossible to find them, especially at an early stage, but synthetic biomarkers can be used amplify smaller-scale changes that occur within small tumors.

In previous work, Bhatia created nanoparticles that can detect the activity of enzymes called proteases, which help cancer cells to escape their original locations, or settle into new ones, by cutting through proteins of the extracellular matrix. The nanoparticles are coated with peptides that are cleaved by different proteases, and once these peptides are released into the bloodstream, they can then be concentrated and more easily detected in a urine sample.
The original peptide biomarkers were designed to be detected based on small engineered variations in their mass, using a mass spectrometer. This kind of equipment might not be available in low-resource settings, so the researchers set out to develop sensors that could be analyzed more easily and affordably, using DNA barcodes that can be read using CRISPR technology.
For this approach to work, the researchers had to use a chemical modification called phosphorothioate to protect the circulating DNA reporter barcodes from being broken down in the blood. This modification has already been used to improve the stability of modern RNA vaccines, allowing them to survive longer in the body.
Similar to the peptide reporters, each DNA barcode is attached to a nanoparticle by a linker that can be cleaved by a specific protease. If that protease is present, the DNA molecule is released and free to circulate, eventually ending up in the urine. For this study, the researchers used two different types of nanoparticles: one, a particle made from polymers that have been FDA-approved for use in humans, and the other a “nanobody” — an antibody fragment that can be designed to accumulate at a tumor site.
Once the sensors are secreted in the urine, the sample can be analyzed using a paper strip that recognizes a reporter that is activated by a CRISPR enzyme called Cas12a. When a particular DNA barcode is present in the sample, Cas12a amplifies the signal so that it can be seen as a dark strip on a paper test.

The particles can be designed to carry many different DNA barcodes, each of which detects a different type of protease activity, which allows for “multiplexed” sensing. Using a larger number of sensors provides a boost in both sensitivity and specificity, allowing the test to more easily distinguish between tumor types.
Disease signatures
In tests in mice, the researchers showed that a panel of five DNA barcodes could accurately distinguish tumors that first arose in the lungs from tumors formed by colorectal cancer cells that had metastasized to the lungs.
“Our goal here is to build up disease signatures and to see whether we can use these barcoded panels not only read out a disease but also to classify a disease or distinguish different cancer types,” Hao says.
For use in humans, the researchers expect that they may need to use more than five barcodes because there is so much variety between patients’ tumors. To help reach that goal, they worked with researchers at the Broad Institute of MIT and Harvard led by Harvard University Professor Pardis Sabeti, to create a microfluidic chip that can be used to read up to 46 different DNA barcodes from one sample.
This kind of testing could be used not only for detecting cancer, but also for measuring how well a patient’s tumor responds to treatment and whether it has recurred after treatment. The researchers are now working on further developing the particles with the goal of testing them in humans. Glympse Bio, a company co-founded by Bhatia, has performed phase 1 clinical trials of an earlier version of the urinary diagnostic particles and found them to be safe in patients.
In addition to Bhatia, Hao, and Sabeti, the study’s co-authors include Renee T. Zhao, Nicole L. Welch, Edward Kah Wei Tan, Qian Zhong, Nour Saida Harzallah, Chayanon Ngambenjawong, Henry Ko, and Heather E. Fleming.
The research was funded by the Koch Institute Support (core) Grant from the National Cancer Institute, a Core Center Grant from the National Institute of Environmental Health Sciences, the Marble Center for Cancer Nanomedicine at the Koch Institute, the Koch Institute Frontier Research Program, the Virginia and D.K. Ludwig Fund for Cancer Research, and a Pathway to Independence Award from the National Cancer Institute.

The drug, which will be sold as Qalsody by the pharmaceutical company Biogen, targets a genetic cause of a devastating neurological illness.The Food and Drug Administration on Tuesday authorized the first drug for a rare genetic form of the neurological disorder A.L.S., despite uncertainty about the treatment’s effectiveness.The decision reflects the agency’s push toward greater flexibility in approving treatments for patients with devastating illnesses and few, if any, options.Biogen, the pharmaceutical company bringing the drug to market, said it would price the drug “within a range comparable to other recently launched A.L.S. treatments.” An A.L.S. therapy approved last year was priced at $158,000 annually.The drug, which is known scientifically as tofersen and will be sold under the brand name Qalsody, targets a mutation in a gene known as SOD1 that is present in about 2 percent of the roughly 6,000 cases of A.L.S. diagnosed in the United States each year. Fewer than 500 people in the United States at any given time are expected to be eligible.The agency authorized the treatment via a policy that allows a drug to be fast-tracked onto the market under certain circumstances before there is conclusive proof that it works. Biogen will be required to provide confirmatory evidence, from ongoing clinical research, to keep the drug on the market.The decision marks the first conditional approval granted for a medication for A.L.S., or amyotrophic lateral sclerosis, which generally causes paralysis and death within a few years. Less than half of the patients eligible for Qalsody survive more than three years after their diagnosis.The approval is based on evidence that the drug can significantly reduce levels of a protein that has been linked to damage to nerve cells. Biogen has argued that these results are reasonably likely to help patients, even though the drug, in a clinical trial, did not significantly slow the progression of the disease, as measured by patients’ ability to speak, swallow and perform other activities of daily living.Despite the uncertainty about its benefit, Qalsody’s approval is widely seen as more justifiable than that of Aduhelm, another drug from Biogen that prompted an outcry when it was approved by the F.D.A. in 2021 to treat Alzheimer’s despite a lack of evidence that it worked.At a meeting last month, a panel of independent advisers to the F.D.A. unanimously recommended that the agency grant conditional approval of Qalsody, despite a majority of advisers concluding that there was not convincing evidence that it was effective.A.L.S. patients and advocacy groups mounted an impassioned campaign for the drug. F.D.A. officials last month wrote that their approach to evaluating such medications has been shaped by the agency’s “interactions with patients and their caregivers who describe their willingness to accept less certainty about effectiveness in return for earlier access to much-needed medicines.”Patients receive Qalsody as an injection into the spinal canal every few weeks. The drug was found to be generally safe, though a small number of patients developed inflammation of the spinal cord.Before Qalsody, there were only three approved A.L.S. medications in the United States, which have not significantly altered the course of the disease.

Typically T cells of the immune system respond to a specific feature (antigen) of a microbe, thereby generating protective immunity. As reported in the journal Immunity, an international team of scientists have discovered an exception to this rule. Namely, a group of divergent bacterial pathogens, including pneumococci, all share a small highly conserved protein sequence, which is both presented and recognized by human T cells in a conserved population-wide manner.
The study set out to understand immune mechanisms that protect against pneumococcus, a bacterial pathobiont that can reside harmlessly in the upper respiratory mucosae but can also cause infectious disease, especially in infants and older adults, which can range from middle ear and sinus infections to pneumococcal pneumonia and invasive bloodstream infections.
Most currently used pneumococcal polysaccharide-based conjugate vaccines (PCVs) are effective against 10-13 serotypes, but growing serotype replacement becomes a problem.
WHO estimates that 1.6 million people die of pneumococcal disease every year, including 0.7-1 million children aged under 5, most of whom live in developing countries.
The Monash Biomedicine Discovery Institute-co-led study, in collaboration with the National Institute for Public Health and the Environment (RIVM) and Utrecht University in the Netherlands and Cardiff University in the UK, identified a crucial fragment of the pneumococcal toxin pneumolysin that was commonly presented by a particular class of human antigen presenting molecules and recognized by T cells from most people who naturally develop specific immunity to pneumococcal proteins.
The study further found that the uniformly presented and broadly recognized bacterial protein fragment was not unique for the pneumococcal pneumolysin but was shared by a large family of bacterial so-called cholesterol dependent cytolysins (CDCs). These are produced by divergent bacterial pathogens mostly affecting humans and cause a range of respiratory, gastro-intestinal, or vaginal infectious diseases.
First author Dr Lisa Ciacchi said “The use of the National synchrotron was key to provide molecular insight into how the T cell receptors see these conserved antigens when presented by common Human Leukocyte Antigen (HLA) molecules.”
Shared first author Dr Martijn van de Garde said “We have not yet identified the exact function of the near-ubiquitous T cell populations to this commonly presented conserved protein fragment during ongoing colonizations or infections with CDC producing bacteria. Whether the T cells have a cross-protective mode of action or have an anti-inflammatory tolerizing function, remains to be investigated.”
Shared first author Dr Kristin Ladell said “The identification of T cells that recognize a ubiquitous bacterial motif using T cell receptors that are shared between individuals with prevalent HLAs is very exciting. Reagents generated for this study can now be used to study patient groups to examine how prevalent these shared TCRs are and how they are related to immune protection.”
Continuing investigations could instruct the development of interventions for people to more efficiently resist or clear CDC-related bacterial diseases.

Drug-resistant infections are one of the most serious threats to global health, and there is an urgent need to develop new, effective antimicrobials. One promising solution could be antimicrobial peptides (AMPs). These are compounds naturally produced by most living organisms, including animals, and have important roles in innate immunity, our first line of defence against bacterial infections.
However, some AMPs are also used widely in livestock production, both to control infections and as growth promoters. This has raised concerns that agricultural AMP use may generate cross-resistant bacteria that could then overcome the human innate immune response.
In this new study, led by the University of Oxford, researchers have demonstrated that evolution of such cross-resistant bacteria is not only possible, but also highly likely.
To test the idea, the researchers used colistin, an AMP produced by a bacterium (Bacillus polymyxa) that is chemically and functionally similar to AMPs produced in animals. Colistin has become increasingly important as a ‘last-line of defence’ for treating infections caused by multidrug-resistant bacteria. However, extensive use of colistin in livestock production since the 1980s has driven the spread of E. coli bacteria carrying mobile colistin resistance (MCR) genes.
In this study, E. coli carrying an MCR gene (MCR-1) were exposed to AMPs known to play important roles in innate immunity in chickens, pigs, and humans. The bacteria were also tested for their susceptibility to human serum, which contains a complex cocktail of antimicrobial compounds, and for their ability to infect wax moth larvae (Galleria mellonella).
Key findings: On average, the MCR-1 gene increased resistance to host AMPs by 62%, compared with bacteria lacking the gene. This increased resistance provided a strong selective advantage to the MCR-1 gene in the presence of AMPs. Similarly, E. coli carrying MCR-1 were at least twice as resistant to being killed by human serum. E. coli carrying MCR-1 had increased virulence on wax moth larvae, compared with control strains lacking the gene. Larvae injected with MCR-1 E. coli showed an approximately 50% reduced survival, compared with larvae injected with control E. coli.The results demonstrate that use of bacterial AMPs in agriculture can generate broad cross-resistance to the human innate immune response.
According to the researchers, cross-resistance to human AMPs is likely to be widespread, given that AMPs tend to have similar cellular targets and physico-chemical properties. Pigs and chickens in agriculture are already known to act as important reservoirs of colistin-resistant E. coli.
Lead researcher Professor Craig MacLean (Department of Biology, University of Oxford) said: ‘Our study clearly shows that anthropogenic use of AMPs such as colistin can drive the accidental evolution of resistance to the innate immune system of humans and animals. This has major implications for the design and use of therapeutic AMPs and suggests that resistant genes may be difficult to eradicate, even if AMP use in agriculture is withdrawn.’
He added: ‘AMPs have been advocated as a promising alternative to antibiotics for treating bacterial infections. Using AMPs in this way will lead to the evolution of AMP resistance in pathogenic bacteria. Our results provide strong evidence that we will need to properly assess the impacts of resistance to new therapeutic AMPs on bacterial virulence before they are used to treat patients. If not, we will run the risk of accidentally arming pathogenic bacteria against our own immune system.’
Cóilín Nunan, Scientific Adviser to the Alliance to Save Our Antibiotics (who were not involved in the study) said: ‘This new study shows that colistin resistance is probably even more dangerous than previously thought. It is astonishing that so many governments, like the UK’s, are refusing to ban colistin use in farming. It is also remarkable that the British government is still opposed to banning preventative mass medication of intensively farmed animals with antibiotics, even though the EU banned such use over a year ago.’
Dr Jessica Blair (University of Birmingham), Editor in Chief of NPJ Antimicrobials and Resistance (who was not involved in the study) said: ‘Antimicrobial peptides, including colistin, have been heralded as a potential part of the solution to the rise of multidrug-resistant infections. This study, however, suggests that resistance to these antimicrobials may have unintended consequences on the ability of pathogens to cause infection and survive within the host. This is particularly worrying because it suggests that E. coli carrying the MCR-1 gene may have a clear selective advantage even if the use of colistin is carefully controlled.’

A new study takes a closer look at the neurobiology of psychedelic experiences caused by nitrous oxide, ketamine and LSD.
Nitrous oxide, colloquially known as laughing gas, has been used clinically as an anesthetic to dull pain since the 19th century. However, in smaller amounts, it can induce mind-altered experiences, including feelings of bliss, spirituality, and the feeling of being outside of one’s body — much like those induced by the psychedelic substances LSD and ketamine.
A study led by George Mashour, M.D., Ph.D. and Richard Harris, Ph.D., of the recently founded Michigan Psychedelic Center at the University of Michigan Medical School takes a closer look at the neurobiology of psychedelic experiences.
Using fMRI, the team examined the brain activity of healthy people who were administered nitrous oxide and compared that activity to data collected from participants in different studies who were given ketamine and LSD to see whether the neurobiology of the psychedelic experience was similar.
In addition, this data was compared to a control group comprised of participants administered propofol, a commonly used anesthesia drug, to distinguish between brain changes not related to the psychedelic experience.
The team noted that participants under the influence of each psychedelic drug had decreased connectivity within a particular network but increased connectivity across various networks. Although there were notable differences, each psychedelic increased connectivity between the right temporoparietal junction and intraparietal sulcus in both hemispheres of the brain and between precuneus and left intraparietal sulcus.
These nodes, they note, are located in the so-called cortical “hot zone” of the brain, an area proposed to be critical for determining the content of conscious experience. This could help explain the altered states of consciousness described by people administered these psychedelic substances.
The fact that the patterns of activity associated with nitrous oxide, ketamine, and LSD overlapped hints at common underlying biology, they add. Further research to determine the specifics of this biology could help researchers determine how best to use psychedelics as therapeutics.

A world-first trial at UCL and UCLH has found a new genetic therapy for Alzheimer’s disease that is able to safely and successfully lower levels of the harmful tau protein known to cause the disease.
The trial, led by consultant neurologist Dr Catherine Mummery (UCL Queen Square Institute of Neurology & the National Hospital for Neurology and Neurosurgery), represents the first time that a ‘gene silencing’ approach has been taken in dementia and Alzheimer’s disease.
The approach uses a drug called BIIB080 (/IONIS-MAPTRx), which is an antisense oligonucleaotide (used to stop RNA producing a protein), to ‘silence’ the gene coding for the tau protein — known as the microtubule-associated protein tau (MAPT) gene. This prevents the gene from being translated into the protein in a doseable and reversible way. It will also lower the production of that protein and alter the course of disease.
Further trials will be needed in larger groups of patients to determine whether this leads to clinical benefit, but the phase 1 results published in Nature Medicine — with results from 46 patients — are the first indication that this method has a biological effect.
There are currently no treatments targeting tau. The drugs aducanumab and lecanemab — recently approved for use in some situations by the FDA — target a separate disease mechanism in AD, the accumulation of amyloid plaques*.
The phase 1 trial looked at the safety of BIIB080, what it does in the body, and how well it targets the MAPT gene. It involved the UCL Dementia Research Centre, was supported by the NIHR UCLH Biomedical Research Centre, was supported by the NIHR UCLH Biomedical Research Centre, and took place at the Leonard Wolfson Experimental Neurology Centre at NHNN.

46 patients, with an average age of 66, were enrolled in the trial — which took place from 2017 to 2020. The trial looked at three doses of the drug, given by intrathecal injection (an injection into the nervous system via the spinal canal), compared with the placebo.
Results show that the drug was well tolerated, with all patients completing the treatment period and over 90% completing the post-treatment period.
Patients in both the treatment and placebo groups experienced either mild or moderate side effects — the most common being a headache after injection of the drug. However, no serious adverse events were seen in patients given the drug.
The research team also looked at two forms of the tau protein in the central nervous system (CNS) — a reliable indicator of disease — over the duration of the study.
They found a greater than 50% reduction in levels of total tau and phosphor tau concentration in the CNS after 24 weeks in the two treatment groups that received the highest dose of the drug.
Dr Mummery said: “We will need further research to understand the extent to which the drug can slow progression of physical symptoms of disease and evaluate the drug in older and larger groups of people and in more diverse populations.
“But the results are a significant step forward in demonstrating that we can successfully target tau with a gene silencing drug to slow — or possibly even reverse — Alzheimer’s disease, and other diseases caused by tau accumulation in the future.”

Viruses like influenza A and Ebola invade human cells in a number of steps. In an interdisciplinary approach, research teams from Heidelberg University and Heidelberg University Hospital investigated the final stages of viral penetration using electron tomography and computer simulations. In the case of influenza A, they were able to determine how the immune system fights off the virus using a small protein. For Ebola viruses, they discovered that a specific protein structure must be disassembled in order for an infection to take hold. So-called fusion pores, through which the viral genome is released into the host cell, play a central role in these processes. If they can be prevented from forming, the virus is also blocked. The Heidelberg scientists describe previously unknown mechanisms, which might lead to new approaches to prevent infections.
Many viruses that infect humans are covered with a lipid membrane that has glycoproteins that can dock with human cells. In viruses like influenza A, which enter through the respiratory tract, these are the spike proteins that mainly bind to epithelial cells in the nose and lungs. In contrast, the highly infectious Ebola virus spreads through direct contact with infected bodily fluids and can penetrate a broad spectrum of cell types. After invading human cells, these viruses must open a fusion pore between the virus membrane and the host membrane to release their genome into the host cell and propagate.
To fight off the virus, the human immune system attempts to block the formation of the fusion pore in a multi-stage process. Infected cells sense the presence of the foreign genome and send a signal, in the form of an interferon molecule, to as yet uninfected cells. This signal triggers the uninfected cells to produce a small cellular protein called interferon-induced transmembrane protein 3 (IFITM3). “This specialised protein can effectively prevent viruses such as influenza A, SARS-CoV-2, and Ebola from penetrating, but the underlying mechanisms were unknown,” states virologist Dr Petr Chlanda, whose working group belongs to the BioQuant Center of Heidelberg University and the Center for Integrative Infectious Disease Research of Heidelberg University Hospital. The researchers were now able to demonstrate that for influenza A viruses, IFITM3 selectively sorts the lipids in the membrane locally. This prevents the fusion pores from forming. “The viruses are literally captured in a lipid trap. Our research indicates that they are ultimately destroyed,” explains Dr Chlanda.
To analyse the structural details of viruses, Dr Chlanda and his team took advantage of equipment from the Cryo-Electron Microscopy Network at Ruperto Carola. In an interdisciplinary approach, the research groups led by Prof. Dr Ulrich Schwarz of the BioQuant-Center and the Institute for Theoretical Physics along with Prof. Dr Walter Nickel of the Heidelberg University Biochemistry Center predicted this process with the aid of computer simulations. In the context of antiviral therapy, the researchers believe it is possible to develop lipid-sorting peptides that insert themselves into the virus membrane, rendering the viruses incapable of membrane fusion. “Such peptides could be used in a nasal spray, for example,” states Petr Chlanda.
In a second study, the Heidelberg researchers investigated the penetration and fusion of the Ebola virus. The filamentous morphology of the virus is determined by a flexible protein envelope known as the VP40 matrix protein layer. “It has always puzzled us how this long virus could penetrate the cell, fuse with the membrane, and release its genome,” states Dr Chlanda. Using their structural analysis of infected but inactive cells provided by collaborators from the Friedrich Loeffler Institute in Greifswald, the researchers discovered that this virus protein envelope disassembles at a low pH, i.e. in an acidic environment. This step is not least decisive for the formation of fusion pores, as further computer simulations by Prof. Schwarz and Prof. Nickel showed. During this process, the electrostatic interactions of the VP40 matrix with the membrane are weakened, thereby reducing the energy barrier of pore formation. The results of the Heidelberg basic research suggest that a blockade of the disassembly of this layer would be one way to maintain Ebola viruses in a state that does not permit fusion pore formation. Similar to the influenza A virus, the Ebola virus would then be lured into a trap from which it could not escape.
The studies were part of the Collaborative Research Centre “Integrative Analysis of Pathogen Replication and Spread” (CRC 1129) funded by the German Research Foundation. The research results were published in both “Cell Host & Microbe” as well as the EMBO Journal.

Supply chain networks can be incredibly complex, with multiple manufacturing and distribution points — and the location of each node in those networks has a significant effect on everything from profitability to product cost to environmental impact. New research from North Carolina State University shows that efficient mathematical tools serve almost as well as more computationally demanding optimization models for determining the best places to locate elements in a supply chain, and can provide businesses with the relevant information far more quickly.
“Our work focuses on supply chains that improve economic and environmental performance by embracing sustainability,” says Amir Sadeghi, first author of the study and a Ph.D. student in NC State’s Edward P. Fitts Department of Industrial and Systems Engineering. “We looked at supply chains where elements of their products can be reused — such as printing technologies that reuse printer cartridges. These supply chains involve multiple manufacturing facilities, as well as many more distribution sites where consumers can both buy the products and return them for recycling or reuse. These multi-level supply chains are extremely complex, and the location of every point in the supply chain has significant ramifications in terms of cost, transportation time, and so on.
“While there are models that allow us to identify the exact optimal solution for where each point in the supply chain should be located, those models are computationally demanding. So we wanted to see how well more computationally efficient tools might perform, and whether they could be a suitable replacement for use in making supply chain management decisions.”
Specifically, the researchers wanted to test the performance of two well-established heuristics, which are algorithm “shortcuts” capable of providing a good — but not necessarily optimal — answer to a complex problem quickly. They compared these two heuristics, which are called the Grey Wolf Optimizer (GWO) and the Whale Optimization Algorithm (WOA), against a computational model capable of finding the exact optimal solution. The researchers tested the heuristics against the exact optimization model for 15 different problems, reflecting a range of multilevel supply chain challenges.
The heuristics and the exact optimization model were all designed to find the best sites for every point in a supply chain, and then determine the cost of putting that supply chain in place. All three tools account for many variables that influence cost, such as transportation distance and real estate and construction costs.
The researchers were surprised at how well the heuristics worked. There was some variability in the performance of the heuristics, depending on the specific supply chain challenge used in each test. However, at their best, the GWO was able to establish supply chain sites with costs that were within 0.01% of the exact optimization model while the WOA’s costs were within 0.07% of the exact optimization model. And, on average, the heuristics were able to provide their solutions in about half the time of the exact optimization model.
“If you have an established supply chain, and one of your nodes drops out unexpectedly — a store closes, a manufacturing site is shut down by flooding, etc. — you need to act quickly to reestablish the supply chain,” says Sadeghi. “If it’s a complex supply chain — and you don’t have access to a supercomputer — there may be a significant advantage in using a heuristic that can give you a very good answer about where to replace a missing link within hours, rather than waiting days to run an exact optimization model.”
The researchers also found an unexpected advantage to the heuristics — they were more robust than the exact optimization model. In practical terms, that means that the answers provided by the heuristics were more likely to hold up when some of the variables changed. For example, if there was a slight shift in the location of a node in a supply chain network created by a heuristic, there would be a slight shift in the related cost. However, similar changes in supply chain networks developed by the exact optimization model were more likely to cause significant shifts in cost.
“Altogether, our findings here suggest there may be significant advantages for supply chain managers in adopting the use of heuristics,” says Rob Handfield, who co-authored the study.
“We don’t expect anyone to abandon the use of exact optimization models for long-term planning, but at the very least heuristics may be a useful way of testing the robustness of ‘optimal’ networks,” says Handfield, who is the Bank of America University Distinguished Professor of Operations and Supply Chain Management in NC State’s Poole College of Management. “And heuristics may be particularly valuable for supply chain managers who are forced to respond rapidly to unexpected disruptions in their networks.”

Johns Hopkins University researchers have found that traumatic brain injuries (TBIs) were the second most common injury among adults treated in U.S. emergency rooms for injuries related to walking a leashed dog from 2001 to 2020. The researchers also found that women, and all adults age 65 and older, were more likely to sustain serious injuries, such as fractures and TBIs, than people in other demographic groups. The study was published in Medicine & Science in Sports & Exercise.
“According to a 2021-2022 national pet ownership survey, nearly 53%of U.S. households own at least one dog,” says Ridge Maxson, the study’s first author and a third-year medical student at The Johns Hopkins University. “Dog ownership also increased significantly in recent years during the COVID-19 pandemic. Although dog walking is a common daily activity for many adults, few studies have characterized its injury burden. We saw a need for more comprehensive information about these kinds of incidents.”
The researchers were from the Johns Hopkins University School of Medicine and the Johns Hopkins Bloomberg School of Public Health. Using the National Electronic Injury Surveillance System database, which is operated by the U.S. Consumer Product Safety Commission, the researchers found that an estimated 422,659 adults sought treatment in U.S. emergency rooms for injuries resulting from leash-dependent dog walking from 2001 to 2020. Nearly half of all patients were adults age 40 to 64, and 75% of patients were women. Most injuries occurred due to falling after being pulled by, tangled in or tripped by the leash connected to a dog they were walking.
The three most common injuries among all adults were, in order, finger fracture, TBI, and shoulder sprain or strain. TBI and hip fracture were the two most common injuries among adults age 65 and older. TBIs identified in this study consisted of both concussions and nonconcussive internal head injuries, which can include brain contusion (a bruise of the brain tissue), epidural hematoma (bleeding in above the brain’s outer membrane) or subdural hematoma (bleeding beneath the brain’s outer membrane).
Notably, women with injuries related to dog walking were 50% more likely than men to sustain a fracture. Older dog walkers were more than three times as likely to experience a fall, more than twice as likely to have a fracture and 60% more likely to sustain a TBI than younger dog walkers.
Across the 20-year study period, the estimated annual incidence of injuries due to leash-dependent dog walking more than quadrupled. The researchers posit that this trend may be due to concurrent rising dog ownership rates and promotion of dog walking to improve fitness.
The team hopes its findings will promote awareness among dog owners and encourage clinicians to discuss the injury potential of leash-dependent dog walking with their patients.
“Clinicians should be aware of these risks and convey them to patients, especially women and older adults,” says Edward McFarland, M.D., the study’s senior author and director of the Division of Shoulder and Elbow Surgery at Johns Hopkins Medicine. “We encourage clinicians to screen for pet ownership, assess fracture and fall risk, and discuss safe dog walking practices at regular health maintenance visits for these vulnerable groups. Despite our findings, we also strongly encourage people to leash their dogs wherever it is legally required.”
The team also analyzed cases of leash-dependent dog walking injuries among children under age 18. Those findings will be released in the near future.