Publisher Health

Simulations that help determine how a large-scale pandemic will spread can take weeks or even months to run. A recent study in PLOS Computational Biology offers a new approach to epidemic modeling that could drastically speed up the process.
The study uses sparsification, a method from graph theory and computer science, to identify which links in a network are the most important for the spread of disease.
By focusing on critical links, the authors found they could reduce the computation time for simulating the spread of diseases through highly complex social networks by 90% or more.
“Epidemic simulations require substantial computational resources and time to run, which means your results might be outdated by the time you are ready to publish,” says lead author Alexander Mercier, a former Undergraduate Research Fellow at the Santa Fe Institute and now a Ph.D. student at the Harvard T.H. Chan School of Public Health. “Our research could ultimately enable us to use more complex models and larger data sets while still acting on a reasonable timescale when simulating the spread of pandemics such as COVID-19.”
For the study, Mercier, with SFI researchers Samuel Scarpino and Cristopher Moore, used data from the U.S. Census Bureau to develop a mobility network describing how people across the country commute.
Then, they applied several different sparsification methods to see if they could reduce the network’s density while retaining the overall dynamics of a disease spreading across the network.
The most successful sparsification technique they found was effective resistance. This technique comes from computer science and is based on the total resistance between two endpoints in an electrical circuit. In the new study, effective resistance works by prioritizing the edges, or links, between nodes in the mobility network that are the most likely avenues of disease transmission while ignoring links that can be easily bypassed by alternate paths.
“It’s common in the life sciences to naively ignore low-weight links in a network, assuming that they have a small probability of spreading a disease,” says Scarpino. “But as in the catchphrase ‘the strength of weak ties,’ even a low-weight link can be structurally important in an epidemic — for instance, if it connects two distant regions or distinct communities.”
Using their effective resistance sparsification approach, the researchers created a network containing 25 million fewer edges — or about 7% of the original U.S. commuting network — while preserving overall epidemic dynamics.
“Computer scientists Daniel Spielman and Nikhil Srivastava had shown that sparsification can simplify linear problems, but discovering that it works even for nonlinear, stochastic problems like an epidemic was a real surprise,” says Moore.
While still in an early stage of development, the research not only helps reduce the computational cost of simulating large-scale pandemics but also preserves important details about disease spread, such as the probability of a specific census tract getting infected and when the epidemic is likely to arrive there.
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There is new evidence that a 50-year-old blood pressure drug could find new purpose as a treatment to mitigate the often life-altering effects of increasingly prevalent PTSD, scientists say.
Clonidine is commonly used as a high blood pressure medication and for ADHD. It’s also already been studied in PTSD because clonidine works on adrenergic receptors in the brain, likely best known for their role in “fight or flight,” a heightened state of response that helps keep us safe. These receptors are thought to be activated in PTSD and to have a role in consolidating a traumatic memory. Clonidine’s sister drug guanfacine, which also activates these receptors, also has been studied in PTSD. Conflicting results from the clinical trials have clonidine, which has shown promise in PTSD, put aside along with guanfacine, which has not.
Scientists at the Medical College of Georgia at Augusta University say it’s time for another look at clonidine.
They have laboratory evidence that while the two drugs bind to the same receptors, they do different things there, says Qin Wang, MD, PhD, neuropharmacologist and founding director of the Program for Alzheimer’s Therapeutics Discovery at MCG.
Their results published in the journal Molecular Psychiatry suggest that clonidine could provide immediate treatment to the significant number of people emerging from the current pandemic with PTSD, as well as from longer-established causes like wars and other violence.
Large-scale clinical trials of clonidine in PTSD are warranted, the scientists write. Their studies also indicate that other new therapies could be identified by looking at the impact on activation of a key protein called cofilin by existing drugs.

The new studies looked in genetically modified mice as well as neurons that came from human stem cells, which have the capacity to make many cell types.
In the hippocampus, the center of learning and memory, they found that a novel axis on an adrenergic receptor called ɑ2A is essential to maintaining fear memories in which you associate a place or situation, like the site of a horrific car accident or school shooting, with fear or other distressing emotions that are hallmarks of PTSD.
In this axis, they found the protein spinophilin interacts with cofilin, which is known to control protrusions on the synapses of neurons called dendritic spines, where memories are consolidated and stored.
A single neuron can have hundreds of these spines which change shape based on brain activity and whose changing impacts the strength of the synapse, the juncture between two neurons where they swap information.
“Normally whenever there is a stimulation, good or bad, in order to memorize it, you have to go through a process in which the spines store the information and get bigger,” Wang says, morphing from a slender profile to a more mushroom-like shape.

“The mushroom spine is very important for your memory formation,” says corresponding author Wang, Georgia Research Alliance Eminent Scholar in Neuropharmacology. For these mushroom shapes to happen, levels of cofilin must be significantly reduced in the synapse where the spines reside. That is where clonidine comes in.
The scientists found clonidine interferes with cofilin’s exit by encouraging it to interact with the receptor which consequently interferes with the dendritic spine’s ability to resume a mushroom shape and retain the memory. Guanfacine, on the other hand, had no effect on this key player cofilin.
The findings help clarify the disparate results in the clinical trials of these two similar drugs, Wang says. In fact, when mice got both drugs, the guanfacine appeared to lessen the impact of clonidine in the essential step of reconsolidating — and so sustaining — a traumatic memory, indicating their polar-opposite impact at least on this biological function, Wang says.
There was also living evidence. In their studies that mimicked how PTSD happens, mice were given a mild shock then treated with clonidine right after they were returned to the place where they received the shock and should be recalling what happened earlier. Clonidine-treated mice had a significantly reduced response, like freezing in their tracks, compared to untreated mice when brought back to the scene. In fact, their response was more like the mice who were never shocked. Guanfacine had no effect on freezing behavior.
Obviously, Wang says, they cannot know for certain how much the mice remember of what previously happened, but clearly those treated with clonidine did not have the same overt reaction as untreated mice or those receiving guanfacine.
“The interpretation is that they don’t have as strong a memory,” she says, noting that the goal is not to erase memories like those of wartime, rather diminish their disruption in a soldier’s life.
When a memory is recalled, like when you return to an intersection where you were involved in a horrific car wreck, the synapses that hold the memory of what happened there become temporarily unstable, or labile, before the memory restabilizes, or reconsolidates. This natural dynamic provides an opportunity to intervene in reconsolidation and so at least diminish the strength of a bad memory, Wang says. Clonidine appears to be one way to do that.
Adrenergic drugs like clonidine bind to receptors in the central nervous system to reduce blood levels of the stress hormones you produce like epinephrine (adrenaline) and norepinephrine, which do things like increase blood pressure and heart rate.
Studies like one that came out 15 years ago, which only looked at guanfacine, indicated it was of no benefit in PTSD. But then in 2021, a retrospective look at a cohort of 79 veterans with PTSD treated with clonidine, for example, indicated 72% experienced improvement and 49% were much improved or very much improved with minimal side effects.
Previous basic science studies also have indicated that manipulating the adrenergic receptor can impact fear memory formation and memory, but how has remained unknown.
PTSD has emerged as a major neuropsychiatric component of the COVID-19 pandemic, affecting about 30% of survivors, a similar percentage of the health care workers who care for them and an estimated 20% of the total population, Wang says, which means the impact on human health and health care systems could be “profound.”
Psychotherapy is generally considered the most effective treatment for PTSD, and some medications, like antidepressants, can also be used, but there are limited drug options, which include only two drugs which have Food and Drug Administration approval specifically for the condition, she says. The lack of approved drugs has led to off-label uses of drugs like clonidine.
Cofilin is a key element in helping muscle cells and other cell types contract as well as the flexibility of the cytoskeleton of the dendritic spine. A single neuron can have thousands of dendritic spines which change shape based on brain activity and whose changing shape impacts the strength of the synapse.
The U.S. Department of Veterans Affairs defines post-traumatic stress disorder as a mental health problem that some people develop after experiencing or witnessing a life-threatening or traumatic event. While problems like feeling on edge, trouble sleeping and/or nightmares may last a few weeks or more after the event, if symptoms like these as well as flashbacks and increasingly negative thoughts continue, it’s likely PTSD. Sometimes symptoms don’t surface until months after the initial event.
The research is funded by the National Institute of Mental Health.

Of the nearly 4 million births each year in the United States, roughly 50,000 are marked by life-threatening complications, and up to 900 result in maternal death during delivery. One major, often life-threatening complication is placenta accreta spectrum (PAS), which poses a threat to both the mother and the baby. Currently, PAS cases are identified by ultrasounds, MRIs, and predictive confounding conditions — but these methods leave between 33% and 50% of PAS cases undetected prior to delivery. A new study by investigators from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, embarked on a study to create a targeted test for predicting PAS during pregnancy, thus better preparing patients and practitioners for the delivery day. By studying circulating microparticle (CMP) protein panels in pregnant women, the team identified five unique CMP proteins that can predict PAS as early as the second trimester of pregnancy. Their results are published in Scientific Reports.
“PAS is a significant contributor to maternal morbidity and mortality worldwide,” said corresponding author Hope Yu, MD, a Maternal-Fetal Medicine physician in the Department of Obstetrics and Gynecology at the Brigham. “Before our study, up to half of these cases weren’t able to be detected before delivery. Our study aims to improve that detection rate using a blood test and to eventually improve health outcomes worldwide.”
Placenta accreta, a condition where the placenta attaches excessively into the uterine wall, gets its “spectrum” designation because of varying degrees of placental penetration into the body that can occur. In some cases, the placenta attaches to the uterine muscle; in more severe cases, the placenta attaches through the uterine wall and to other organs, like the bladder. There are two major complications for PAS patients: abnormal placenta delivery after birth and heavy bleeding. Identification of PAS cases prior to delivery can help reduce and prepare for such complications.
To identify PAS early, the Brigham team looked to proteins associated with CMPs. CMPs are tiny, extracellular vesicles that cells use to communicate with one another and have been studied extensively in other disciplines since they provide a glimpse into cell crosstalk. The team set out to study CMPs at the maternal-fetal interface, with the goals of pinpointing a clinically useful PAS biomarker and investigating CMP mechanisms of PAS pathogenesis. The team’s primary goal was to construct a blood panel to identify PAS pregnancies.
The team conducted a nested case-control study with 35 PAS patients and 70 control patients, who all were retroactively diagnosed after delivery. CMP proteins were isolated and identified from patient plasma sampled during the second and third trimesters of pregnancy. In samples collected from patients who were 26 weeks pregnant, five CMP proteins distinguished PAS patients from control patients; at 35 weeks pregnant, four CMP proteins distinguished PAS patients from control patients. Additionally, in the second trimester iron homeostasis and erythropoietin signaling were overrepresented — a trend that, in the third trimester, revealed abnormal immune function.
The study successfully identified five second trimester CMP protein PAS indicators and four third trimester CMP protein PAS indicators, enabling safe predication of PAS well before delivery. The authors note that more research and clinical trials will be needed to further test the applicability of the protein panel. Next steps include widening the patient sample size and creating a standardized commercial test.
“It is so important to identify these cases prior to delivery,” said Yu. “If we can identify a PAS case during pregnancy, the patient can then make a potentially life-saving choice to deliver in a tertiary delivery center with specialized providers. Having an experienced, multidisciplinary team by your side during a PAS birth can make an enormous difference when it comes to mortality and morbidity outcomes.”
“This is another step toward proactive, personalized prenatal care,” added Thomas McElrath, MD, PhD, senior author and also a Maternal-Fetal Medicine physician in the Department of Obstetrics and Gynecology at the Brigham. “Right now, prenatal care too often assumes that every person has the same risks of complications during pregnancy. To be able to personalize and make each patient’s care profile particular to their needs is the ultimate goal.”
Disclosures: P Gurnani, RC Doss, and KP Rosenblatt are employees of NX Prenatal Inc. TF McElrath serves on the Scientific Advisory Board of NX Prenatal in which he holds equity. The remaining authors report no competing interests.
Funding: The study was funded by Sidman Family Foundation (TFM).
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Research led by Associate Professor Duc Dong, Ph.D., has shown for the first time that the effects of Alagille syndrome, an incurable genetic disorder that affects the liver, could be reversed with a single drug. The study, published in the Proceedings of the National Academy of Sciences, has the potential to transform treatment for this rare disease and may also have implications for more common diseases.
“Alagille syndrome is widely considered an incurable disease, but we believe we’re on the way to changing that,” says Dong, who is also the associate dean of admissions for Sanford Burnham Prebys’ graduate school. “We aim to advance this drug into clinical trials, and our results demonstrate its effectiveness for the first time.”
More than 4,000 babies each year are born with Alagille syndrome, which is caused by a mutation that prevents the formation and regeneration of bile ducts in the liver. Children with Alagille syndrome frequently require a liver transplant, but donor livers are limited, and not all children with Alagille syndrome qualify. Without a transplant, the disease has a 75% mortality rate by late adolescence.
“Duc and his team continue to do thrilling research on Alagille syndrome, and these breakthroughs certainly offer hope for families living with this very complicated and complex disorder,” says Roberta Smith, CNMT, president of the Alagille Syndrome Alliance. “We have been longtime supporters of Duc’s work and have come to know him as a driven, dedicated scientist who is passionate about moving the needle one step closer toward a cure.”
Their new drug, called NoRA1, activates the Notch pathway, a cell-to-cell signaling system present in nearly all animals. Notch signaling helps orchestrate fundamental biological processes and plays a role in many diseases in addition to Alagille syndrome. In children with Alagille syndrome, a genetic mutation causes a reduction in Notch signaling, which results in poor liver duct growth and regeneration.
The researchers found that in animals with mutations in the same gene affected in Alagille syndrome, NoRA1 increases Notch signaling and triggers duct cells to regenerate and repopulate in the liver, reversing liver damage and increasing survival.
“The liver is well known for its great capacity to regenerate, but this doesn’t happen in most children with Alagille syndrome because of compromised Notch signaling,” says first author Chengjian Zhao, a postdoctoral researcher in Dong’s lab. “Our research suggests that nudging the Notch pathway up with a drug could be enough to restore the liver’s normal regenerative potential.”
The researchers are currently testing the drug on miniature livers cultured in the lab with stem cells derived from the cells of Alagille patients.
“Instead of forcing the cells to do something unusual, we are just encouraging a natural regenerative process to occur, so I’m optimistic that this will be an effective therapeutic for Alagille syndrome,” adds Dong.
Dong is also taking steps to form a start-up company to drive this drug toward clinical trials. The new company will initially focus on Alagille syndrome, but also plans to develop this drug for other, more prevalent diseases, including certain cancers.
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Published1 hour agoShareclose panelShare pageCopy linkAbout sharingImage source, State TVBy Fan WangBBC News The growing number of Chinese public figures whose deaths are being made public is prompting people to question the official Covid death toll.The death of Chu Lanlan, a 40-year-old opera singer, last month came as a shock to many, given how young she was.Her family said they were saddened by her “abrupt departure”, but did not give details of the cause of her death. China scrapped its strict zero-Covid policy in December and has seen a rapid surge of infections and deaths. There are reports of hospitals and crematoria becoming overwhelmed.But the country has stopped publishing daily cases data, and has announced only 22 Covid deaths since December, using its own strict criteria.Now only those who die from respiratory illnesses such as pneumonia are counted.On Wednesday the World Health Organization (WHO) warned that China was under-representing the true impact of Covid in the country – in particular deaths.How is China trying to beat its latest Covid surge?China under-representing Covid deaths, WHO warnsBut the deaths of Chu Lanlan and others is sparking speculation about greater losses than those reported on official accounts.According to the specialist news website Operawire, Chu Lanlan was a soprano who specialised in Peking Opera – a theatrical art in which performers use speech, song, dance and combat movements to tell stories – and was also involved in charitable causes. This video can not be playedTo play this video you need to enable JavaScript in your browser.On New Year’s Day news of the death of actor Gong Jintang devastated many Chinese internet users. Gong, 83, was known to many households for his performance in the country’s longest-running TV series, In-Laws, Out-laws. His portrait of Father Kang had captivated fans for more than two decades since the show first aired in 2000.The cause of his death is unclear, but many social media users linked it to the recent deaths of other older people.”Please god, please treat the elderly better,” his co-star Hu Yanfen wrote on Chinese social media platform Weibo.”R.I.P Father Kang. This wave have really claimed many elders’ lives, let’s make sure we protect the elderly in our families,” one user wrote on Weibo.Acclaimed scriptwriter Ni Zhen was also among recent deaths. The 84-year-old was famous for his work on the 1991 film Raise the Red Lantern, which is widely considered to be one of the best Chinese films by critics.Meanwhile Hu Fuming, a former journalist and retired professor of Nanjing University, died on 2 January at the age of 87. He was the main author of a famous commentary published in 1978 that marked the start of the China’s “Boluan Fanzheng” period – a time of eliminating chaos and returning to normal after the upheaval of the Cultural Revolution under the country’s first Communist leader Mao Zedong.According to a tally by Chinese media, 16 scientists from the country’s top science and engineering academies died between 21 and 26 December.None of these deaths were linked to Covid in their obituaries, but that hasn’t prevented speculation online.”Did he also die of ‘bad flu’?” one of the top-rated comments under news of Mr Ni’s death said.”Even if you trawl through the whole internet you can’t find any reference to his cause of death,” said another internet user.But there was also criticism of demonstrators who took to the streets in November in rare political protests calling for the end of leader Xi Jinping’s zero-Covid policy.”Are those people happy now, seeing old people… now paving the way for their freedom?” asked one social media user.The new generation powering China’s protestsMr Xi appeared to refer obliquely to the protests in his New Year’s address, saying it was natural in such a big country for people to have different opinions.But he urged people to come together and show unity as China entered a “new phase” in its approach to Covid.The Chinese authorities are aware of the widespread scepticism although they continue to play down the severity of this wave of Covid sweeping the country. In an interview with state TV, the director of Beijing’s Institute of Respiratory Diseases admitted the number of deaths of elderly people so far this winter was “definitely more” than in past years, while also stressing that critical cases remained a minority of the overall number of Covid cases.This week the People’s Daily, the Communist Party’s official newspaper, urged citizens to work towards a “final victory” over Covid and dismissed criticism of the previous zero-Covid policy.More on this storyEU ‘strongly’ urges Covid testing for China travel13 hours agoChina under-representing Covid deaths, WHO warns15 hours ago

Following a modified Atkins diet high in fat and low in carbohydrates plus taking medication may reduce seizures in people with tough-to-treat epilepsy, according to a study published in the January 4, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“For people with drug-resistant epilepsy, or those who have been unable to find effective treatment to reduce seizures, it’s encouraging to see that there are lifestyle changes that can be combined with standard drug therapy to reduce the number of seizures,” said study author Manjari Tripathi, MD, DM, of All India Institute of Medical Sciences in New Delhi. “Our study found that this combination may reduce the chance of seizures by more than half.”
The modified Atkins diet is a combination of the Atkins diet and a ketogenic diet that includes food items such as soy products, heavy cream, butter and oils, leafy green vegetables, and animal protein including eggs, chicken, fish, and bacon. While the ketogenic diet has been shown to be effective in reducing seizures, its stringent requirements and restrictions can make it difficult to follow.
The study involved 160 adults and adolescents who had epilepsy for more than 10 years on average and had at least 27 seizures per month despite trying an average of four antiseizure medications at the maximum tolerated dose. They were randomly assigned to receive either standard drug therapy alone or drugs plus the modified Atkins diet over six months.
Participants logged their seizures and meals. They were given food lists, sample menus and recipes. Carbohydrate intake was restricted to 20 grams per day. Federal dietary guidelines recommend between 225 and 325 grams of carbs per day.
After six months, researchers found that 26% of people who had both drug therapy and followed the modified Atkins diet had more than a 50% reduction in seizures compared to only 3% of the people who had drug therapy alone. Four people in the diet group were free of seizures by the end of the study, while no one in the medication-only group was seizure free.
The study also looked at quality of life, behavior and side effects at six months. The group that had drug therapy and followed the modified Atkins diet showed an improvement in all areas compared to the group that had drug therapy alone.
Tripathi noted that 33% of the participants did not complete the study due to poor tolerance of the diet, lack of benefit or the inability to follow-up in part due to COVID-19. However, Tripathi said tolerance of the modified Atkins diet was better than what is seen with the ketogenic diet.
“While the modified Atkins diet may be an effective treatment in controlling seizures, further research is needed to identify genetic biomarkers and other factors associated with the response to this diet,” Tripathi added. “This may improve patient care by encouraging targeted precision based earlier use of this diet.”
A limitation of the study is that seizures were self-reported or reported by caregivers, so some seizures may not have been reported.
The study was supported by the Department of Biotechnology, India.
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The transition of a low-grade, slow growing brain tumor to a lethal one can be delayed if neurosurgeons remove as much as possible soon after diagnosis, according to the results of a study led by UC San Francisco.
The findings run counter to other research indicating that extensive resection, or maximal surgical removal, may not be necessary depending on tumor characteristics.
In their study, publishing in the Journal of Clinical Oncology on Jan. 4, 2023, researchers tracked 392 patients at UCSF with diffuse low-grade glioma for up to 20 years. The results were validated in two external cohorts of 365 patients.
The tumor type strikes 20,000 people a year in the United States, most commonly in young adulthood or midlife. Because of its diffuse nature, undetectable pockets of tumor cells grow slowly after resection, leading to recurrence and eventually culminating in malignant transformation and death, often in less than two years.
Diffuse low-grade glioma has two subtypes: astrocytoma IDH-mutant and oligodendroglioma IDH-mutant 1p19q-codeleted, which were reclassified to match their microscopic appearance and molecular characteristics.
Shorter Studies May Have Undermined Importance of Surgery
“Studies that did not follow patients for as long as we did have raised questions about the need for maximal surgery, especially in oligodendroglioma. But we found that resecting as much as possible soon after diagnosis offered a distinct survival advantage when we looked at the disease trajectory 10 years later,” said co-senior author Annette Molinaro, PhD, a professor in the UCSF Department of Neurosurgical Surgery and a member of the Weill Institute for Neurosciences.

The researchers found that those with larger post-operative and/or pre-operative astrocytoma lived a median of nine years post diagnosis, compared to more than 20 years with smaller residual tumors. Patients with larger post-operative and/or pre-operative oligodendroglioma lived a median of 19.9 years, compared to more than 20 years with smaller pre- and post-operative tumors.
Additionally, patients who had undergone a potentially riskier procedure, gross total resection (GTR), in which all of the tumor visible on an MRI is removed, lived longer than those with residual tumors. Astrocytoma patients with residual tumors lived a median of 11.4 years, versus 16.2 years with GTR. Oligodendroglioma patients with remaining tumors lived a median of 22.2 years, compared to longer for GTR.
A surgical procedure called GTR-plus, in which a margin of apparently healthy tissue is resected together with the tumor, led to extended survival for astrocytoma patients, but did not demonstrate a significant difference for oligodendroglioma patients.
Better Surgical Outcomes in Smaller Tumors
Smaller tumors are more likely to result in a GTR or GTR-plus, noted co-senior author Mitchel Berger, MD, a professor in the UCSF Department of Neurological Surgery and a member of the Weill Institute for Neurosciences. “When we see incidental small tumors, we don’t wait because we can get a better resection, which translates to improved survival. However, GTR and GTR-plus are never done at the expense of deficits,” he said.

In addition to data from UCSF, the researchers drew from cohorts at Brigham and Women’s Hospital in Boston and St. Olavs University Hospital in Norway, totaling 757 patients, to understand the interactive effects of molecular, clinical and treatment variables on tumor progression. They looked at two pivotal periods in the disease’s trajectory: progression-free survival, which precedes recurrence, and malignant transformation-free survival, which marks the escalation of the tumor from a more manageable grade 2 to grades 3 and 4.
Similar to their earlier findings, the researchers noted that larger astrocytoma was associated with shorter progression-free and malignant transformation-free survival periods. Patients with smaller astrocytoma and all patients with oligodendroglioma survived longer with tumors that were either not progressing or had not yet undergone malignant transformation.
Drawing from data of the three patient cohorts, the researchers predicted that at least 75% of a tumor needs to be resected to improve long-term outcomes.
“Our findings put an end to the controversy that maximal resection may not be required for some low-grade gliomas,” said first author Shawn Hervey-Jumper, MD, associate professor in the UCSF Department of Neurological Surgery and a member of the Weill Institute for Neurosciences. “Even for oligodendrogliomas, there is no question that maximal resection is critical for enhancing survival.”

Young children sometimes believe that the moon is following them, or that they can reach out and touch it. It appears to be much closer than is proportional to its true distance. As we move about our daily lives, we tend to think that we navigate space in a linear way. But Salk scientists have discovered that time spent exploring an environment causes neural representations to grow in surprising ways.
The findings, published in Nature Neuroscience on December 29, 2022, show that neurons in the hippocampus essential for spatial navigation, memory, and planning represent space in a manner that conforms to a nonlinear hyperbolic geometry — a three-dimensional expanse that grows outward exponentially. (In other words, it’s shaped like the interior of an expanding hourglass.) The researchers also found that the size of that space grows with time spent in a place. And the size is increasing in a logarithmic fashion that matches the maximal possible increase in information being processed by the brain.
This discovery provides valuable methods for analyzing data on neurocognitive disorders involving learning and memory, such as Alzheimer’s disease.
“Our study demonstrates that the brain does not always act in a linear manner. Instead, neural networks function along an expanding curve, which can be analyzed and understood using hyperbolic geometry and information theory,” says Salk Professor Tatyana Sharpee, holder of the Edwin K. Hunter Chair, who led the study. “It is exciting to see that neural responses in this area of the brain formed a map that expanded with experience based on the amount of time devoted in a given place. The effect even held for miniscule deviations in time when animal ran more slowly or faster through the environment.”
Sharpee’s lab uses advanced computational approaches to better understand how the brain works. They recently pioneered the use of hyperbolic geometry to better understand biological signals like smell molecules, as well as the perception of smell.
In the current study, the scientists found that hyperbolic geometry guides neural responses as well. Hyperbolic maps of sensory molecules and events are perceived with hyperbolic neural maps. The space representations dynamically expanded in correlation with the amount of time the rat spent exploring each environment. And, when a rat moved more slowly through an environment, it gained more information about the space, which caused the neural representations to grow even more.
“The findings provide a novel perspective on how neural representations can be altered with experience,” says Huanqiu Zhang, a graduate student in Sharpee’s lab. “The geometric principles identified in our study can also guide future endeavors in understanding neural activity in various brain systems.”
“You would think that hyperbolic geometry only applies on a cosmic scale, but that is not true,” says Sharpee. “Our brains work much slower than the speed of light, which could be a reason that hyperbolic effects are observed on graspable spaces instead of astronomical ones. Next, we would like to learn more about how these dynamic hyperbolic representations in the brain grow, interact, and communicate with one another.”
Other authors include P. Dylan Rich of Princeton University and Albert K. Lee of the Janelia Research Campus at the Howard Hughes Medical Institute.
The research was supported by an AHA-Allen Initiative in Brain Health and Cognitive Impairment award made jointly through the American Heart Association and the Paul G. Allen Frontiers Group (19PABH134610000), the Dorsett Brown Foundation, the Mary K. Chapman Foundation, an Aginsky Fellowship, the National Science Foundation (IIS-1724421), the National Science Foundation Next Generation Networks for Neuroscience Program (Award 2014217), the National Institutes of Health (U19NS112959 and P30AG068635), and the Howard Hughes Medical Institute.
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Antibiotic residues in wastewater and wastewater treatment plants in the regions around China and India risk contributing to antibiotic resistance, and the drinking water may pose a threat to human health, according to a comprehensive analysis from Karolinska Institutet published in The Lancet Planetary Health. The researchers also determined the relative contribution of various sources ofantibiotic contamination in waterways, such as hospitals,municipals, livestock, and pharmaceutical manufacturing.
“Our results can help decision-makers to target risk reduction measures against environmental residues of priority antibiotics and in high-risk sites, to protect human health and the environment,” says Nada Hanna, researcher at the Department of Global Public Health at Karolinska Institutet in Sweden, and the study’s first author. “Allocating these resources efficiently is especially vital for resource-poor countries that produce large amounts of antibiotics.”
Bacteria that become resistant to antibiotics are a global threat that can lead to untreatable bacterial infections in animals and humans.
Antibiotics can enter the environment during their production, consumption and disposal. Antibiotic residues in the environment, such as in wastewater and drinking water, can contribute to the emergence and spread of resistance.
Among the largest producers of antibiotics
The researchers have examined the levels of antibiotic residues that are likely to contribute to antibiotic resistance from different aquatic sources in the Western Pacific Region (WPR) and the South-East Asia Region (SEAR), regions as defined by the World Health Organization. These regions include China and India, which are among the world’s largest producers and consumers of antibiotics.

This was done by a systematic review of the literature published between 2006 and 2019, including 218 relevant reports from the WPR and 22 from the SEAR. The researchers also used a method called Probabilistic Environmental Hazard Assessment to determine where the concentration of antibiotics is high enough to likely contribute to antibiotic resistance.
Ninety-two antibiotics were detected in the WPR, and forty five in the SEAR. Antibiotic concentrations exceeding the level considered safe for resistance development (Predicted No Effect Concentrations, PNECs) were observed in wastewater, influents and effluents of wastewater treatment plants and in receiving aquatic environments. The highest risk was observed in wastewater and influent of wastewater treatment plants. The relative impact of various contributors, such as hospital, municipal, livestock, and pharmaceutical manufacturing was also determined.
Potential threat to human health
In receiving aquatic environments, the highest likelihood of levels exceeding the threshold considered safe for resistance development was observed for the antibiotic ciprofloxacin in drinking water in China and the WPR.
“Antibiotic residues in wastewater and wastewater treatment plants may serve as hot spots for the development of antibiotic resistance in these regions and pose a potential threat to human health through exposure to different sources of water, including drinking water,” says Nada Hanna.
Limitations to be considered when interpreting the results are the lack of data on the environmental occurrence of antibiotics from many of the countries in the regions and the fact that only studies written in English were included.
The research has been funded by the Swedish Research Council. The researchers declare no competing interests.
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Moderate levels of two outdoor air pollutants, ozone and fine particulate matter, are associated with non-viral asthma attacks in children and adolescents who live in low-income urban areas, a study funded by the National Institutes of Health has found. The study also identifies associations between exposure to the two pollutants and molecular changes in the children’s airways during non-viral asthma attacks, suggesting potential mechanisms for those attacks. The observational study is one of the first to link elevated levels of specific outdoor air pollutants in particular urban locations to distinct changes in the airways during asthma attacks not triggered by respiratory viruses, according to the investigators. The findings were published today in the journal The Lancet Planetary Health.
“The strong association this study demonstrates between specific air pollutants among children in impoverished urban communities and non-viral asthma attacks further augments the evidence that reducing air pollution would improve human health,” said Hugh Auchincloss, M.D., acting director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH.
The study was conducted by the NIAID-funded Inner City Asthma Consortium under the leadership of Matthew C. Altman, M.D., M.Phil., and Daniel J. Jackson, M.D. Dr. Altman is an associate professor in the department of medicine at the University of Washington School of Medicine and an associate scientist at the Benaroya Research Institute at Virginia Mason in Seattle. Dr. Jackson is a professor of pediatrics and medicine in the School of Medicine and Public Health at the University of Wisconsin-Madison.
Asthma is caused by chronic inflammation of the airways. During an asthma attack, the airway lining swells, muscles around the airways contract, and the airways produce extra mucus, substantially narrowing the space for air to move in and out of the lungs. Children who live in low-income urban environments in the United States are at particularly high risk for attack-prone asthma. Asthma attacks provoked by respiratory virus infections — a common trigger — have been studied extensively, but those that occur independently of such infections have not.
In the current study, investigators examined the relationship between air pollutant levels and asthma attacks occurring in the absence of a respiratory virus among 208 children ages 6 to 17 years who had attack-prone asthma and lived in low-income neighborhoods in one of nine U.S. cities. Then the researchers validated the associations they found between air pollutant levels and non-viral asthma attacks in an independent cohort of 189 children ages 6 to 20 years with persistent asthma who also lived in low-income neighborhoods in four U.S. cities.
The investigators followed the children prospectively for up to two respiratory illnesses or approximately six months, whichever came first. Each illness was classified as viral or non-viral and as involving an asthma attack or not. The researchers matched each illness with air quality index values and levels of individual air pollutants recorded by the Environmental Protection Agency in the relevant city on the dates surrounding the illness. The investigators subsequently adjusted their data for city and season to decrease the impact of these variables on the findings.
The scientists found that asthma attacks had a non-viral cause in nearly 30% of children, two to three times the proportion seen in non-urban children, according to previously published reports. These attacks were associated with locally elevated levels of fine particulate matter and ozone in outdoor air. The investigators linked changes in the expression of specific sets of genes that play a role in airway inflammation to elevated levels of these two pollutants by analyzing nasal cell samples obtained from the children during respiratory illnesses. Some of the identified gene-expression patterns suggest that unique biological pathways may be involved in non-viral asthma attacks.
Given the study findings, it will be important to develop and test different strategies to see if they prevent or reduce pollution-associated asthma attacks in urban children. These strategies may include treatments designed to counteract the harmful effects of elevated levels of outdoor air pollutants on airway inflammatory responses linked to non-viral asthma attacks, and devices for personalized monitoring of local outdoor air pollutant levels to inform asthma management.
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Materials provided by NIH/National Institute of Allergy and Infectious Diseases. Note: Content may be edited for style and length.