Macquarie University researchers have debunked a 75-year-old theory about how humans determine where sounds are coming from, and it could unlock the secret to creating a next generation of more adaptable and efficient hearing devices ranging from hearing aids to smartphones.
In the 1940s, an engineering model was developed to explain how humans can locate a sound source based on differences of just a few tens of millionths of a second in when the sound reaches each ear.
This model worked on the theory that we must have a set of specialised detectors whose only function was to determine where a sound was coming from, with location in space represented by a dedicated neuron.
Its assumptions have been guiding and influencing research — and the design of audio technologies — ever since.
But a new research paper published in Current Biology by Macquarie University Hearing researchers has finally revealed that the idea of a neural network dedicated to spatial hearing does not hold.
Lead author, Macquarie University Distinguished Professor of Hearing, David McAlpine, has spent the past 25 years proving that one animal after another was actually using a much sparser neural network, with neurons on both sides of the brain performing this function in addition to others.
Showing this in action in humans was more difficult.

Now through the combination of a specialised hearing test, advanced brain imaging, and comparisons with the brains of other mammals including rhesus monkeys, he and his team have shown for the first time that humans also use these simpler networks.
“We like to think that our brains must be far more advanced than other animals in every way, but that is just hubris,” Professor McAlpine says.
“We’ve been able to show that gerbils are like guinea pigs, guinea pigs are like rhesus monkeys, and rhesus monkeys are like humans in this regard.
“A sparse, energy efficient form of neural circuitry performs this function — our gerbil brain, if you like.”
The research team also proved that the same neural network separates speech from background sounds — a finding that is significant for the design of both hearing devices and the electronic assistants in our phones.
All types of machine hearing struggles with the challenge of hearing in noise, known as the ‘cocktail party problem’. It makes it difficult for people with hearing devices to pick out one voice in a crowded space, and for our smart devices to understand when we talk to them.

Professor McAlpine says his team’s latest findings suggest that rather than focusing on the large language models (LLMs) that are currently used, we should be taking a far simpler approach.
“LLMs are brilliant at predicting the next word in a sentence, but they’re trying to do too much,” he says.
“Being able to locate the source of a sound is the important thing here, and to do that, we don’t need a ‘deep mind’ language brain. Other animals can do it, and they don’t have language.
“When we are listening, our brains don’t keep tracking sound the whole time, which the large language processors are trying to do.
“Instead, we, and other animals, use our ‘shallow brain’ to pick out very small snippets of sound, including speech, and use these snippets to tag the location and maybe even the identity of the source.
“We don’t have to reconstruct a high-fidelity signal to do this, but instead understand how our brain represents that signal neurally, well before it reaches a language centre in the cortex.
“This shows us that a machine doesn’t have to be trained for language like a human brain to be able to listen effectively.
“We only need that gerbil brain.”
The next step for the team is to identify the minimum amount of information that can be conveyed in a sound but still get the maximum amount of spatial listening.

Published4 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Natasha PreskeyBBC NewsThe black leather sofa in the corner of Dr Ellen Wiebe’s office looks out of place in a doctor’s surgery. But this is no ordinary clinic. Canadian clinician Dr Wiebe is showing Liz Carr, a comedian, actress and disability rights campaigner, where people sit when they come to end their lives with the help of a doctor. “They can snuggle up with their loved ones if they want,” says Dr Wiebe. “It’s a good place for some people.”Carr became a wheelchair user when she was seven due to arthrogryposis multiplex congenita, a condition which causes limitation of joint movement. “Apart from the fact I don’t have the desire, I think probably I would be eligible [for assisted dying] under Canadian law,” Carr suggests to Dr Wiebe. Dr Wiebe doesn’t disagree – though she does tell Carr she would have to convince her she was “suffering unbearably” in order to be given a cocktail of drugs to end her life.In Canada, people with a disability can have an assisted death, provided they feel they are suffering intolerably and their condition cannot be reversed.Carr has been a vocal opponent of assisted dying for more than a decade. But in the last six months, the debate has accelerated, with Scotland set to debate an assisted dying bill this autumn, and Labour leader Sir Keir Starmer saying he would back a UK-wide change to the law.What is assisted dying and what is the law?Could assisted dying be coming to Scotland?Canada wrestles with euthanasia for the mentally ill The Silent Witness actress is concerned about how this could affect vulnerable or disabled people. These fears are central to her new documentary Better Off Dead, in which she makes the case against assisted dying in the UK. Assisted suicide is banned in England, Wales and Northern Ireland, with a maximum prison sentence of 14 years. While there is no specific offence of assisted suicide in Scotland, euthanasia is illegal and can be prosecuted as murder or culpable homicide.Just last week, broadcaster Esther Rantzen, who is terminally ill with lung cancer, begged MPs to attend a debate on a petition which argues that “terminally ill people who are mentally sound and near the end of their lives should not suffer unbearably against their will”.Carr is afraid that changing the law for terminally ill people could eventually result in those who are poor, disabled or mentally ill being allowed to have an assisted death in the UK – or even feeling compelled to do so. The actress says the possibility is “terrifying”. She points to Canada where the law was changed in 2016 to allow those whose death was “reasonably foreseeable” to have an assisted death, and then changed again in 2021 to include those with a medical condition who were “suffering unbearably”. Journalist Melanie Reid, who became tetraplegic (paralysed from the neck down) in 2010 after a horse-riding accident, doesn’t see a potential change to the law as something to fear, and tells Carr she has “a human right to decide what happens to my body”.She believes the law should also allow people who are not terminally ill, but who are suffering in other ways, to end their lives.But Dr Katherine Sleeman, a specialist in palliative care, says she is concerned for people who may feel they are a burden to their families. “Patients will say to me: ‘I don’t want to go to a care home really, but I know my family want me to do it and I know it will be easier for them so I think I’m going to say yes’,” Dr Sleeman explains. “Substitute the words ‘go to a care home’ with ‘have an assisted death’ and I think it’s a completely different picture.”The specialist believes no assisted dying law can be completely safe, and that some people who do not really want to die will always “slip through the net”. Lord Falconer, a King’s Counsel who has sponsored four bills that would allow people with less than six months to live to have medical assistance to die, says assisted dying should only be for those with a terminal illness – and that there would need to be legal safeguards to protect vulnerable people.”Being disabled is most certainly not the same as being terminally ill,” he tells Carr. “The line in the sand for me is terminal illness and it goes no further than that.”Better Off Dead?, BBC One and iPlayer, will air on Tuesday 14 May at 21:00If you have been affected by the issues in this story, help and support is available via the BBC Action Line.More on this storyWhat is the law on assisted suicide and euthanasia?Published28 MarchCould assisted dying be coming to Scotland?Published28 March

A new screening algorithm for preeclampsia combining maternal history, ultrasound data and several tests for blood markers may better predict the majority of preeclampsia cases in the first trimester of pregnancy, when it may still be preventable, according to new research published today in Hypertension, an American Heart Association journal.
Preeclampsia is the most dangerous form of high blood pressure during pregnancy (blood pressure measures ≥140/90 mm Hg), and it is a leading cause of maternal death worldwide. Preeclampsia is potentially life-threatening when untreated. It affects 1 in 25 pregnancies in the U.S. and is more common in first-time pregnancies. Symptoms include headaches, vision changes and swelling of the mother’s hands, feet, face or eyes; or a change in the well-being of the baby. Recent research has found that preeclampsia can be linked to an increased risk of developing cardiovascular complications for women later in life.
“Preeclampsia is one of the most severe illnesses of pregnancy and may lead to preterm birth and/or maternal death,” said senior study author Emmanuel Bujold, M.D., M.Sc., professor in the department of obstetrics and gynecology at the Université Laval in Québec City, Canada.
The biological mechanisms that lead preeclampsia usually start in the first trimester of pregnancy (weeks 1 through 12), however, the initial symptoms of preeclampsia most often do not appear before week 20, Bujold noted.
The current risk factor-based guidelines from the American College of Obstetricians and Gynecologists (ACOG) recommend pregnant women take aspirin if they have a major risk factor such as chronic high blood pressure, Type 2 diabetes, chronic kidney disease, lupus or preeclampsia in a prior pregnancy. Aspirin is also recommended by ACOG for pregnant women with two moderate risk factors such as being a Black woman, having a sister or mother with history of preeclampsia, having a first pregnancy, obesity or an IVF pregnancy.
“Following those guidelines, almost all Black women should take aspirin during pregnancy, as should about one-third of all women of other races and ethnicities,” Bujold said.
Previous studies from the Fetal Medicine Foundation have found that preterm preeclampsia, defined as developing preeclampsia before 37 weeks of gestation, can be predicted in the first trimester using a combination of ultrasound and blood biomarker tests. In this study, researchers recruited over 7,000 women with first-time pregnancies across Canada who were between 11 and 14 weeks pregnant to evaluate the Fetal Medicine Foundation’s screening model. The model consisted of maternal history, ultrasound data and several tests for blood markers.

The study found: Using the Fetal Medicine Foundation’s screening model for participants between 11 and 13 weeks of pregnancy, the preeclampsia detection rate was 63.1% for preterm preeclampsia (before 37 weeks of gestation) and 77.3% for early preeclampsia (before 34 weeks of gestation). The false positive rate was 15.8%. Using the risk factor-based guidelines from the American College of Obstetricians and Gynecologists, the detection rate for preterm preeclampsia would be 61.5% and 59.1% for early preeclampsia, with a false-positive rate of 34.3%. This would be more than twice the false-positive rate of the Fetal Medicine Foundation’s screening model.The only way to resolve preeclampsia once it has developed is to deliver the baby. A previous meta-analysis by the study authors found that taking one low-dose aspirin daily may reduce the risk of developing preeclampsia by up to 53%.
“Using this new screening model, treatment decisions were based on each individual’s personal risk,” Bujold said. “With their personal risk calculated, it’s much easier for a woman to make the right decision, for example, if she chooses to take daily low-dose aspirin, she is much more likely to follow through because it’s based on personalized screening test.”
Study background and details: The study was conducted between 2014 and 2020 at five health centers across Canada. Of note: Canada has a national health care service, and coverage is universal for all Canadian citizens and permanent residents. 7,554 women who were pregnant for the first time were recruited between 11 and 14 weeks of pregnancy. 7,325 delivered after 20 weeks and remained eligible for the final analysis; 229 had pregnancies with fetal anomalies and were excluded from the analyses for the study. At time of enrollment in the study, participants underwent screening for preeclampsia. The data collected included age, weight, ethnicity, smoking status and chronic health conditions (chronic hypertension, Type 1 diabetes or Type 2 diabetes and antiphospholipid syndrome, an autoimmune disease that may be associated with pregnancy complications). The study participants had an average age of 29 years. 92% of participants self-identified as white; 4% as Black; 2.6% as South Asian; 0.9% as East Asian; 0.3% as First Nations; and 0.2% as mixed race or undetermined. The study excluded women who were taking antihypertensive medication for chronic hypertension, low-dose aspirin or low-molecular-weight-heparin (a blood thinner) on a daily basis were excluded from the study. Participants were followed until delivery. The primary outcome was preterm preeclampsia. The secondary outcome was early preeclampsia. Of the 7,325 women included in the analysis, 65 (0.9%) developed preterm preeclampsia, and 22 (0.3%) developed early preeclampsia.Among the study’s limitations, several women with risk factors for preeclampsia, such as high blood pressure and Type 2 diabetes before pregnancy, were not included in the study if they were already taking aspirin for preeclampsia prevention. This would make it difficult to determine whether this population would rely solely on the Fetal Medicine Foundation’s screening model to decide whether or not to take daily, low-dose aspirin, Bujold noted. Additionally, only one lab was used to analyze blood samples, and blood samples collected at other centers across Canada were frozen and shipped for analysis, meaning that biomarkers were measured several weeks after the blood was drawn, which may have affected the results.
“It’s reasonable to believe that the inclusion of the entire population and immediate analysis of blood samples may both have improved the screening process. If we implemented a screening program in big cities across North America, the screening would be expected to be even better and more accurate,” Bujold said. “The good news is that we now have a more precise screening approach using existing tests that can predict preeclampsia early in pregnancy. The next step is to make this screening available to all pregnant women so that more women could receive a diagnosis early in pregnancy and begin preventative aspirin treatment, potentially preventing complications of severe preeclampsia.”
According to Sadiya S. Khan, M.D., M.Sc., FAHA, chair of the writing group for the Association’s 2023 scientific statement on Optimizing Prepregnancy Cardiovascular Health to Improve Outcomes in Pregnant and Postpartum Individuals and Offspring, predicting risk for term and preterm preeclampsia remains an important goal and priority to improve maternal health and mitigate disparities. Khan is the Magerstadt Professor of Cardiovascular Epidemiology and an associate professor of medicine and preventive medicine at the Northwestern University Feinberg School of Medicine in Chicago and a preventive cardiologist at Northwestern Medicine.
“Since the risks for preeclampsia may be largely influenced by health before pregnancy, the ability of a screening model to be applied in early pregnancy is very helpful and can initiate conversations between the clinician and patient about strategies to optimize heart health,” Khan said. “However, challenges remain with implementation of models such as this one that integrate biomarkers that are not routinely assessed and may not be widely available, especially among people in vulnerable populations who are most likely to have the highest risk for preterm preeclampsia.”

Using powerful technologies, scientists found staggering amounts of lead and other toxic substances in the composer’s hair that may have come from wine, or other sources.At 7 p.m. on May 7, 1824, Ludwig van Beethoven, then 53, strode onto the stage of the magnificent Theater am Kärntnertor in Vienna to help conduct the world premiere of his Ninth Symphony, the last he would ever complete.That performance, whose 200th anniversary is on Tuesday, was unforgettable in many ways. But it was marked by an incident at the start of the second movement that revealed to the audience of about 1,800 people how deaf the revered composer had become.Ted Albrecht, a professor emeritus of musicology at Kent State University in Ohio and author of a recent book on the Ninth Symphony, described the scene.The movement began with loud kettledrums, and the crowd cheered wildly.But Beethoven was oblivious to the applause and his music. He stood with his back to the audience, beating time. At that moment, a soloist grasped his sleeve and turned him around to see the raucous adulation he could not hear.It was one more humiliation for a composer who had been mortified by his deafness since he had begun to lose his hearing in his twenties.But why had he gone deaf? And why was he plagued by unrelenting abdominal cramps, flatulence and diarrhea?We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

After being diagnosed with advanced breast cancer when she was 23, she became determined to educate other young people about early detection.When Kris Hallenga was diagnosed with Stage 4 breast cancer — the most advanced form — at 23, questions swirled through her head: “Why didn’t anyone tell me to check my boobs? Why didn’t I know I could get breast cancer at 23?”If she hadn’t known that she could have breast cancer so young, there was a very good chance others were equally uninformed, she said in a 2021 interview with The Guardian. She spent the next 15 years educating young people about early detection through her nonprofit organization, CoppaFeel, and in a 2021 memoir, “Glittering a Turd.”On Monday, CoppaFeel announced that Ms. Hallenga had died at 38. A spokesman for the organization said she had died at home in Cornwall, England, and that the cause was breast cancer.“Survival was never enough,” she said during a publicity tour in 2021. “I don’t just want to survive, I want to be able to really look at my life and go, ‘I’m glad to still be here, and I’m getting the most of what I want from life.’”Kristen Hallenga was born on Nov. 11, 1985, in Norden, a small town in northern Germany, to a German father and an English mother, both of whom were teachers, according to The Times of London. When she was 9, she moved to Daventry in central England with her mother, Jane Hallenga; her twin sister, Maren Hallenga; and their older sister Maike Hallenga, all three of whom survive her. Her father, Reiner Hallenga, died of a heart attack when she was 20.Ms. Hallenga first felt a lump in 2009 when she was in Beijing working for a travel company and teaching on the side. During a visit back home in the Midlands in central England, Ms. Hallenga went to her internist. She told The Guardian that her doctor had blamed the lump on hormonal changes associated with her birth control pill.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

In the 1940s and 1950s, the ocean off the coast of Los Angeles was a dumping ground for the nation’s largest manufacturer of the pesticide DDT — a chemical now known to harm humans and wildlife. Due to the stubborn chemistry of DDT and its toxic breakdown products, this pollution continues to plague L.A.’s coastal waters more than half a century later. While legal at the time, details of this industrial-scale pollution of the marine environment at a dump site some 15 miles offshore near Catalina Island have deeply concerned scientists and the public since they gained wider recognition in 2020.
Now, new research from scientists at UC San Diego’s Scripps Institution of Oceanography and San Diego State University (SDSU) finds deep-sea fish and sediments collected from near the Catalina Island offshore dump site are contaminated with numerous DDT-related chemicals.
The study, published May 6 in the journal Environmental Science and Technology Letters and funded by the National Oceanic and Atmospheric Administration, suggests that the DDT-related chemicals dumped into the ocean decades ago may still be making their way into marine food webs.
Since the rediscovery of the offshore dump site near Catalina Island, scientists have been working to discern the extent and severity of the problem today. Of particular urgency are the questions of whether the decades-old chemicals, now settled on the seafloor thousands of feet underwater, are staying put or whether they are circulating in marine ecosystems where the compounds could be harming wildlife or even posing health risks to humans.
“These are deep-sea organisms that don’t spend much time at the surface and they are contaminated with these DDT-related chemicals,” said Lihini Aluwihare, a professor of ocean chemistry at Scripps and co-author of the study. “Establishing the current distribution of DDT contamination in deep-sea food webs lays the groundwork for thinking about whether those contaminants are also moving up through deep-ocean food webs into species that might be consumed by people.”
From 1948 until at least 1961, barges contracted by DDT-producer Montrose Chemical Corporation would motor from the Port of Los Angeles out toward Catalina and pump manufacturing waste laden with sulfuric acid and up to 2% pure DDT directly into the Pacific Ocean. Legal until 1972, this offshore dumping largely escaped public scrutiny because it was overshadowed by Montrose’s other waste disposal practice: Pumping a more dilute acidic slurry that also contained DDT through L.A. County sewers and into the ocean off Palos Verdes. An estimated 100 tons of DDT ended up in the sediments of the Palos Verdes Shelf, and the Environmental Protection Agency declared it an underwater Superfund Site in 1996. In 2000, a judge ordered the company to pay $140 million to remedy the environmental damages. Research has since linked the DDT pollution on the Palos Verdes Shelf to contamination and health problems in local wildlife including sea lions, dolphins, bottom-feeding fish, and even coastal California condors (likely from consuming dead marine mammals).
In 2011, UC Santa Barbara researcher David Valentine used an undersea robot to rediscover Montrose’s offshore dumping near Catalina at a place now known as Dumpsite 2. The findings leapt into the public consciousness in 2020 when the Los Angeles Times published the first in a series of expose?s unspooling the region’s toxic legacy of offshore dumping.

Valentine and Scripps researchers have helped map the extent of the dumping. To date, they’ve found DDT-related chemicals across an area of the seafloor larger than the city of San Francisco. What’s still unknown is if that pollution is staying put or if it is moving through the undersea environment in ways that pose dangers to marine life or humans.
Beginning in 2021, Aluwihare, study co-author Eunha Hoh of SDSU, and other collaborators began a series of research efforts to work on two key questions: Are the DDT-related chemicals lurking on the seafloor near Dumpsite 2 being stirred up and ingested by marine life in the deep? And could they identify a kind of chemical fingerprint unique to the contamination from Dumpsite 2 and other offshore dump sites that could be used to distinguish them from pollutants emanating from the Palos Verdes Shelf?
The team opportunistically collected sediment samples and deep-sea animals from the water column in the San Pedro Basin near Dumpsite 2 to test for a wide range DDT-related compounds. The research cruises to collect these samples were funded by the National Science Foundation and the Schmidt Ocean Institute.
Typically, testing for DDT looks for four to eight chemicals, but a 2016 paper co-authored by Hoh and Aluwihare identified 45 DDT-related chemicals in the blubber of dolphins from off the coast of Southern California. The results demonstrated that wildlife was being exposed to a much larger suite of DDT compounds in the real world. In the present study, the team tested for this larger suite of DDT-related chemicals, known as DDT+, in hopes that it could help develop a chemical fingerprint for Dumpsite 2 and the other offshore dump sites used by Montrose. Also, testing for DDT+ will provide a more holistic picture of the degree of contamination in sediment and animals that might otherwise go undetected.
When the researchers analyzed the sediments for the presence of DDT+ they found no fewer than 15 chemicals, 14 of which had been previously detected in birds and marine mammals in Southern California.
The researchers collected 215 fish spanning three common species near Dumpsite 2. Chemical analysis revealed that the fish contained 10 DDT-related compounds, all of which were also present in the sediment samples.

Two of the fish species were collected between 546 meters (1,791 feet) and 784 meters (2,572 feet) — Cyclothone acclinidens and Melanostigma pammelas — and the third, Leuroglossus stilbius, was collected between 546 meters (1,791 feet) and the surface. The species collected at shallower depths contained a lower concentration of contaminants and were missing a pair of DDT-related compounds that were present in the deepest fishes.
“None of these fish species are known to feed in the sediment of the seafloor,” said Anela Choy, biological oceanographer at Scripps and co-author of the study. “There must be another mechanism that is exposing them to these contaminants. One possibility is that there are physical or biological processes resuspending sediments around Dumpsite 2 and allowing these contaminants to enter deeper water food webs.”
The findings can’t yet rule out the Palos Verdes Superfund Site as a potential source of the contamination in the fish, said Aluwihare. But several lines of evidence uncovered in the study — the lower overall concentrations and two missing DDT-related compounds in the shallower water fish species, as well as the overlap between contaminants found in the sediment and those found in marine mammals and birds — point to the alarming possibility that pollution is moving from the seafloor and into the marine food web.
“Regardless of the source, this is evidence that DDT compounds are making their way into the deep ocean food web,” said Margaret Stack, an environmental chemist at SDSU and the study’s lead author. “That is cause for concern because it’s not a big leap for it to end up in marine mammals or even humans.”
Hoh said understanding the pathways by which the DDT-related chemicals are entering the food web is vital and “will help us figure out what to do as far as mitigation and what not to do in terms of offshore development that could make this problem worse by stirring up these contaminants.”
Aluwihare said more work needs to be done to pinpoint the source of the DDT contaminants they found in the deep-sea fish and establish whether the same contamination exists in larger, open-ocean fish species that are consumed by people.
Numerous additional studies are ongoing to answer these urgent questions. Researchers at Scripps and SDSU are currently analyzing samples from fish species targeted by recreational anglers and commercial fisheries, including basses and sanddab, for DDT+. Comparing the chemicals and their concentrations found in these fish with sediment samples collected from the Palos Verdes Shelf and Dumpsite 2 may allow the team to determine the source of the toxins in these fish.
“We are still seeing this DDT contamination in deep-sea organisms and ocean sediments more than 50 years after they were dumped there,” said Hoh. “I’m not sure if that company expected the consequences of their pollution to last this long, but they have.”
In addition to Aluwihare, Stack, Choy, and Hoh, Raymmah Garcia, Tran Nguyen,, Paul Jensen, and Johanna Gutleben of Scripps as well as, William Richardot, and Nathan Dodder of SDSU co-authored the study.

Investigators at Dana-Farber Cancer Institute have examined the historical evolution of Community Outreach and Engagement initiatives at both the National Cancer Institute (NCI) and National Cancer Institute-Designated Cancer Centers (NCI-DCCs). The team’s assessment of these activities and recommendations for future efforts were recently published in CA: A Cancer Journal for Clinicians.
The toll cancer takes on lives in the U.S. has declined during the last 28 years, but not equitably. Disparities persist in many historically marginalized communities — including communities disadvantaged by race, socioeconomic status, sexual orientation or gender identity, and geographic location — despite NCI community outreach and engagement programs designed to address them.
Formed in 1971, the NCI recognizes 72 NCI-Designated Cancer Centers, including Dana-Farber. Improving community outreach and engagement has long been an important initiative for NCI, but it was not until 2012 that NCI-DCCs were required to rigorously define their catchment areas, the geographic areas that each center “serves or intends to serve in the research it conducts, the communities it engages, and the outreach it performs.” Beginning in 2016, NCI-DCCs were required to provide specific descriptions of community outreach and engagement interventions.
“The purpose of this review is to help us learn what has been working and also what has been missing in terms of community outreach and engagement efforts,” says Christopher Lathan, MD, MS, MPH, Chief Clinical Access and Equity Officer and Associate Chief Medical Officer at Dana-Farber. “It is imperative that we ensure everyone has access to the latest scientific advances, and that takes a sustained and dedicated focus on community outreach and engagement, clinical access, and health equity.”
NCI-DCCs have initiated several interventions intended to decrease health disparities and increase access to innovative medicines, clinical trials, and preventive services and reported many positive results. For instance, a program initiated by Dana-Farber in 2012 to provide diagnostic and patient navigation services to a local federally qualified health center that serves a predominantly Black community helped reduce time to cancer diagnosis from 32 to 12 days.
Due to an intense focus on scientific research, NCI-DCCs have yielded incredible advances in cancer prevention and treatment. But, the investigators conclude, efforts to reduce disparities must be as focused, integrated, and sustained as those made to advance science. According to the authors, “Until recently, our NCI-DCCs have not matched their scientific focus with an intense focus on the inclusion of historically marginalized patients in research trials, access to treatment advances, and development of innovative care delivery interventions to improve access in marginalized communities.” The newer emphasis on community outreach and engagement must be expanded to give everyone the same opportunities to benefit from the groundbreaking advancement in diagnosis and treatment.
The investigators note that most NCI-DCC community outreach and engagement work has been focused on education and disparities research rather than on the deliberate expansion of care and interventions. Programs that successfully reduced disparities have yet to be widely shared or replicated in ways that broaden their impact. Further, according to the authors, “Many patients, especially those from historically marginalized communities, or those who do not have traditional political or financial capital, feel that it is difficult to share their experiences, thoughts, and ideas for change directly with institutions themselves.” In producing the review itself, the authors were committed to representing the views of those who are impacted most; one of the authors, Barry Nelson, is a patient advocate who was integral to the writing process from start to finish.
The authors recommend the following: NCI-DCCs should engage the communities most impacted and marginalized in a proactive, bidirectional manner and integrate this engagement into the research and diagnostic efforts across the entire cancer center. NCI-DCCs should broaden clinical access for patients across the spectrum of cancer services. This includes investing in the collection of demographic data (area measures of poverty, granular race, ethnicity, sexual orientation and gender identity data) across the enterprise and using evidence-based interventions via a highly developed implementation core that connects clinical operations, health care delivery research, and the basic/translation research enterprise. Interventions should be integrated with the healthcare delivery system, not exist outside of it. NCI-DCCs should commit to evolving their current structure of community outreach and engagement by committing to utilizing their economic power to improve local communities via job training, educational collaborations, and health promotion. They should provide healthcare education to their workforce and catchment area communities. NCI-DCCs should establish and implement governance policies and standards, clearly demonstrating their commitment to elevating and empowering those patient voices so as to facilitate equitable decision-making for inclusion, transparency, and professional integrity.”We can and must make a marked impact on the health outcomes of historically marginalized communities,” says Lathan. “What is the use of developing new therapies if the communities that could benefit the most are the very ones that cannot access them?”

In research that may be a step forward toward finding personalized treatments for Tourette disorder, scientists at Rutgers University-New Brunswick have bred mice that exhibit some of the same behaviors and brain abnormalities seen in humans with the disorder.
As reported in the Proceedings of the National Academy of Sciences, the researchers, using a technique known as CRISPR/Cas9 DNA editing that selectively modifies the DNA of living organisms, inserted the same genetic mutations found in humans with Tourette disorder into the corresponding genes in mouse embryos. After the mice were born, the scientists observed their behavior compared with littermates without the gene mutation insertion. The mutations that were inserted were discovered by some members of the same research team who have spent more than a decade focused on investigating genetic factors in Tourette disorder.
The researchers said the findings indicate that these mice are a highly useful “model” to study the neurobiology of Tourette disorder and to test new medications.
“There are no medicines specifically developed for Tourette disorder and repurposing other drugs has worked poorly, with too many side effects,” said co-senior author Jay Tischfield, the Duncan and Nancy MacMillan Distinguished Professor of Genetics in the Department of Genetics in the Rutgers School of Arts and Sciences and a pioneer in the study of Tourette disorder. “Until now, the problem has been a lack of an animal model by which to test new or existing medications.”
Tourette disorder is a disorder of the nervous system that affects children, adolescents and adults. The condition is characterized by sudden, involuntary movements or sounds called tics. Tics can be mild, moderate or severe, and are disabling in some cases.
Tourette disorder doesn’t affect lifespan, but it often adversely impacts the experience of people with the disorder and the people with whom they interact. The Centers for Disease Control and Prevention has estimated that one of every 162 children have the disorder, though the number may be higher.
Using cameras that recorded the mice’s actions and employing a form of artificial intelligence known as machine learning, the researchers found the genetically engineered mice exhibited two key characteristics seen in humans with Tourette disorder: They engaged in repetitive motor behaviors or tics, and they exhibited what neuroscientists call “sensorimotor gating deficits,” a neural process whereby the brain filters out redundant or irrelevant stimuli.

Cara Nasello, a research associate in the Departments of Genetics and Cell Biology and Neuroscience and the first author of the study, said gating deficits in people with Tourette syndrome can be viewed as a difficulty in processing sensory information. A person without the disorder who listens to a series of sounds such as a beeping car horn wouldn’t be startled after the first honk because that person’s brain can link the second and subsequent sounds to the first one. A person with Tourette disorder might be startled by each separate sound, especially if it increases in volume.
The genetically engineered mice reacted the same way humans with the disorder would react to individual sounds that were part of a pattern — they showed a startle response to each tone, Nasello said.
In collaboration with Miriam Bocarsly from the Department of Pharmacology, Physiology and Neuroscience at Rutgers New Jersey Medical School, the team found evidence that the gene mutations altered the levels of a brain chemical known as dopamine. As with humans with Tourette disorder who are treated with a drug that alters the levels of dopamine, the processing deficits and repetitive behaviors seen in the mice decreased in intensity when they were administered the same drug.
“An easy way to think about this is that we have inserted a gene mutation and it’s changed the neural circuitry of the mice’s brains,” said Max Tischfield, an assistant professor in the Department of Cell Biology and Neuroscience in the Rutgers School of Arts and Sciences, and the senior corresponding author of the study. “And those changes are altering how a brain chemical like dopamine, which in humans is important for cognition and motor behavior, allows the mice brain cells to communicate.”
The researchers credited much of the success of their work to the contributions of families with Tourette disorder who over the past 15 years donated genetic samples to the research group.
“These families did this out of the goodness of their hearts with the idea of moving the field forward,” said Gary Heiman, a co-senior author of the study and a professor in the Department of Genetics who recruited families of members with Tourette disorder throughout the world and organized blood collection and genetic repositories. “They want to have a better understanding of this mysterious disorder and for us to come up with better treatments, not only for the people who are currently suffering with the disorder but also for future generations.”
The scientists said the techniques they employed in their research are applicable to researchers studying other complex disorders caused by multiple genes, including autism and schizophrenia.
They also hope this advance will attract more researchers to study Tourette disorder.
“So why would a researcher jump into something if there’s little known and they’re left wondering, ‘How do I even start? What do I have at my disposal that would allow me to even scratch the surface of this very complex disorder?'” Max Tischfield said. “And with these mice, not only can we scratch the surface, but we can dig underneath.”

Scientists at UC San Diego have developed a machine learning algorithm to simulate the time-consuming chemistry involved in the earliest phases of drug discovery, which could significantly streamline the process and open doors for never-before-seen treatments. Identifying candidate drugs for further optimization typically involves thousands of individual experiments, but the new artificial intelligence (AI) platform could potentially give the same results in a fraction of the time. The researchers used the new tool, described in Nature Communications, to synthesize 32 new drug candidates for cancer.
The technology is part of a new but growing trend in pharmaceutical science of using AI to improve drug discovery and development.
“A few years ago, AI was a dirty word in the pharmaceutical industry, but now the trend is definitely the opposite, with biotech startups finding it difficult to raise funds without addressing AI in their business plan,” said senior author Trey Ideker, professor in the Department of Medicine at UC San Diego School of Medicine and adjunct professor of bioengineering and computer science at the UC San Diego Jacobs School of Engineering. “AI-guided drug discovery has become a very active area in industry, but unlike the methods being developed in companies, we’re making our technology open source and accessible to anybody who wants to use it.”
The new platform, called POLYGON, is unique among AI tools for drug discovery in that it can identify molecules with multiple targets, while existing drug discovery protocols currently prioritize single target therapies. Multi-target drugs are of major interest to doctors and scientists because of their potential to deliver the same benefits as combination therapy, in which several different drugs are used together to treat cancer, but with fewer side effects.
“It takes many years and millions of dollars to find and develop a new drug, especially if we’re talking about one with multiple targets.” said Ideker. “The rare few multi-target drugs we do have were discovered largely by chance, but this new technology could help take chance out of the equation and kickstart a new generation of precision medicine.”
The researchers trained POLYGON on a database of over a million known bioactive molecules containing detailed information about their chemical properties and known interactions with protein targets. By learning from patterns found in the database, POLYGON is able to generate original chemical formulas for new candidate drugs that are likely to have certain properties, such as the ability to inhibit specific proteins.
“Just like AI is now very good at generating original drawings and pictures, such as creating pictures of human faces based off desired properties like age or sex, POLYGON is able to generate original molecular compounds based off of desired chemical properties,” said Ideker. “In this case, instead of telling the AI how old we want our face to look, we’re telling it how we want our future drug to interact with disease proteins.”
To put POLYGON to the test, the researchers used it to generate hundreds of candidate drugs that target various pairs of cancer-related proteins. Of these, the researchers synthesized 32 molecules that had the strongest predicted interactions with the MEK1 and mTOR proteins, a pair of cellular signaling proteins that are a promising target for cancer combination therapy. These two proteins are what scientists call synthetically lethal, which means that inhibiting both together is enough to kill cancer cells even if inhibiting one alone is not.

The researchers found that the drugs they synthesized had significant activity against MEK1 and mTOR, but had few off-target reactions with other proteins. This suggests that one or more of the drugs identified by POLYGON could be able to target both proteins as a cancer treatment, providing a list of choices for fine-tuning by human chemists.
“Once you have the candidate drugs, you still need to do all the other chemistry it takes to refine those options into a single, effective treatment,” said Ideker. “We can’t and shouldn’t try to eliminate human expertise from the drug discovery pipeline, but what we can do is shorten a few steps of the process.”
Despite this caution, the researchers are optimistic that the possibilities of AI for drug discovery are only just being explored.
“Seeing how this concept plays out over the next decade, both in academia and in the private sector, is going to be very exciting.” said Ideker. “The possibilities are virtually endless.”
This study was funded, in part, by the National Institutes of Health (Grants CA274502, GM103504, ES014811, CA243885, CA212456).

Each one of us has around 600 lymph nodes (LNs) — small, bean-shaped organs that house various types of blood cells and filter lymph fluid — scattered throughout our bodies. Many of us have also experienced some of our LNs to temporarily swelling during infections with viruses or other pathogens. This LN expansion and subsequent contraction can also result from vaccines injected nearby, and in fact is thought to reflect the ongoing vaccine immune response. While researchers have studied the early expansion of LNs following vaccination, they have not investigated whether prolonged LN expansion could affect vaccine outcomes.
Now, for the first time, researchers from the Wyss Institute for Biologically Inspired Engineering at Harvard University, Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), and Genentech, a member of the Roche Group found a way to enhance and extend LN expansion, and study how this phenomenon affects both the immune system and efficacy of vaccinations against tumors. Key to their approach was a biomaterial vaccine formulation that enabled greater and more persistent LN expansion than standard control vaccines. While the oversized LNs maintained a normal tissue organization, they displayed altered mechanical features and hosted higher numbers of various immune cell types that commonly are involved in immune responses against pathogens and cancers. Importantly, “jump-starting” lymph node expansion prior to administering a traditional vaccine against a melanoma-specific model antigen led to more effective and sustained anti-tumor responses in mice. The findings are published in Nature Biomedical Engineering.
“By enhancing the initial and sustained expansion of LNs with biomaterial scaffolds, non-invasively monitoring them individually over long time periods, and probing deeply into their tissue architecture and immune cell populations, we tightly correlate a persistent LN expansion with more robust immune and vaccination responses,” said Wyss Institute Founding Core Faculty member David Mooney, Ph.D., who led the study. “This opens a new front of investigation for immunologists, and could have far-reaching implications for future vaccine developments.” Mooney also is the Robert P. Pinkas Family Professor of Bioengineering at SEAS, and a co-principal investigator of the NIH-funded and Wyss-coordinated Immuno-Engineering to Improve Immunotherapy (i3) Center.
Mooney’s team at the Wyss Institute and SEAS had previously developed different biomaterial scaffolds as a matrix for cancer and infection vaccines. The researchers have demonstrated the potential of biomaterial vaccine formulations to successfully fight the growth of tumors in an extensive body of work performed in preclinical animal models and a first clinical trial with cancer patients. But they hadn’t yet investigated how their vaccines and those developed by others could influence the response of LNs draining leaked tissue fluid at vaccine injection sites, and have an impact on the LNs tissue organization, different cell types, and their gene expression, which could in turn affect vaccine efficacy. In their new study, they tested a previously developed vaccine formulation that is based on microscale mesoporous silica (MPS) rods that can be injected close to tumors and form a cell-permeable 3D scaffold structure under the skin. Engineered to release an immune cell-attracting cytokine (GM-CSF), and immune cell-activating adjuvant (CpG), and tumor-antigen molecules, MPS-vaccines are able to reprogram recruited so-called antigen-presenting cells that, upon migrating into nearby LNs, orchestrate complex tumor cell-killing immune responses. Their new study showed that there are more facets to that concept.
“As it turns out, the immune-boosting functions of basic MPS-vaccines actively change the state of LNs by persistently enlarging their whole organ structure, as well as changing their tissue mechanics and immune cell populations and functions,” said first-author Alexander Najibi, Ph.D., who performed his Ph.D. thesis with Mooney.
Probing LNs with ultra-sound and nano-devices
To understand the response of LNs to MPS-vaccines over time, the team applied an ultra-sound imaging technique known as high-frequency ultrasound (HFUS). Similar to monitoring a tiny fetus developing in a mother’s womb by clinical ultra-sound, HFUS, on a much smaller scale, enables non-invasively and non-destructively monitoring of anatomical details of tissues and organs in small animals such as mice. Using HFUS, the team traced individual LNs in MPS-vaccinated mice over 100 days. They identified an initial peak expansion period that lasted until day 20, in which LN volumes increased about 7-fold, significantly greater than in animals that received traditional vaccine formulations. Importantly, the LNs of MPS-vaccinated mice, while decreasing in volumes after this peak expansion, remained significantly more expanded than LNs from traditionally vaccinated mice throughout the 100-day time course.

When Najibi and the team investigated the mechanical responses of the LNs using a nanoindentation device, they found that LNs in MPS-vaccinated animals, although maintaining an overall normal structure, were less stiff and more viscous in certain locations. This was accompanied by a re-organization of a protein that assembles and controls cells’ mechanically active cytoskeleton. Interestingly, Mooney’s group had shown in an earlier biomaterial study that changing mechanical features of immune cells’ environments, especially their viscoelasticity, affects immune cell development and functions. “It is very well-possible that in order to accommodate the significant growth induced by MPS-vaccines, LNs need to become softer and more viscous, and that this then further impacts immune cell recruitment, proliferation, and differentiation in a feed-forward process,” said Najibi.
From immune cell engagement to vaccine responses
Interestingly, upon MPS-vaccination, the numbers of “innate immune cells,” including monocytes, neutrophils, macrophages, and other cell types that build up the first wave of immune defenses against pathogens and unwanted cells, peaked first in expanding LNs. Peaking with a delay were dendritic cells (DCs), which normally transfer information in the form of antigens from invading pathogens and cancer cells to “adaptive immune cells” that then launch subsequent waves of highly specific immune responses against the antigen-producing invaders. In fact, along with DCs, also T and B cell types of the adaptive immune system started to reach their highest numbers. “It was fascinating to see how the distinct changes in immune cell populations that we detected in expanding LNs in response to the MPS-vaccine over time re-enacted a typical immune response to infectious pathogens,” commented Najibi.
Innate immune cells and DCs are also known as “myeloid cells,” which are known to interact with LN tissue during early expansion. To further define the impact of myeloid cells on LN expansion, Mooney’s team collaborated with the group of Shannon Turley, Ph.D., the VP of Immunology and Regenerative Medicine at Genentech, and an expert in lymph node biology and tumor immunology. “The MPS-vaccine led to extraordinary structural and cellular changes within the lymph node that supported potent antigen-specific immunity,” said Turley.
By isolating myeloid cells from LNs and analyzing the gene expression profiles of individual cells (single cell RNA-seq), the groups were able to reconstruct distinct changes in myeloid cell populations during LN expansion, and identified distinct DC populations in durably expanded LNs whose changed gene expression was associated with LN expansion. In addition, the collaborators found that the number of monocytes was increased 80-fold upon MPS-vaccination — the highest increase among all myeloid cell types — and pinpointed subpopulations of “inflammatory and antigen-presenting monocytes” as promising candidates for facilitating LN expansion. In fact, when they depleted specific subpopulations of these types of monocytes from circulating blood of mice after vaccination, the maintenance of LN expansion, and timing of the T cell response to vaccination, was altered.
Finally, the team explored whether LN expansion could enhance the effectiveness of vaccination. “Jump-starting” the immune system in LNs with an antigen-free MPS-vaccine and subsequently administering the antigen in a traditional vaccine format significantly improved anti-tumor immunity and prolonged the survival of melanoma-bearing mice, compared to the traditional vaccine alone. “The priming of lymph nodes for subsequent vaccinations using various formulations could be a low-hanging fruit for future vaccine developments,” said Mooney.
“This newfound ability to physically expand lymph nodes and enhance their various immune activities over longer treatment courses, using cleverly designed and easy-to-administer biomaterials, could provide a tremendous push to immunotherapies in patients. It is also yet another great example of how mechanics plays a key role in regulation of living systems, even immune responses where few would consider physical cues to be important,” said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and the Hansjörg Wyss Professor of Bioinspired Engineering at SEAS.
Other authors on the study are Ryan Lane, Miguel Sobral, Giovanni Bovone, Shawn Kang, Benjamin Freedman, Joel Gutierrez Estupinan, Alberto Elosegui-Artola, Christina Tringides, Maxence Dellacherie, Katherine Williams, Hamza Ijaz, and Sören Müller. The study was funded by the National Institutes of Health/National Cancer Institute (award# U54 CA244726 and R01 CA223255).