Thursday, November 28, 2024

 

Gordon Bell Climate Prize goes to Kaust Frontier Users’ Exascale Climate Emulator



Team awarded for developing highly scalable climate emulator that offers faster, radically enhanced high-resolution simulations without the need for massive data storage



DOE/Oak Ridge National Laboratory

KAUST researchers winners of the 2024 Gordon Bell Climate Prize 

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KAUST researchers were awarded this year's Gordon Bell Prize for Climate Modeling for developing an extreme-scale climate emulator that offers radically enhanced high-resolution simulation but without the need for massive data storage. 

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Credit: Lillie Elliot, SC Photography




The 2024 Gordon Bell Prize for Climate Modelling has been awarded to a team of researchers led by the King Abdullah University of Science and Technology, or KAUST, Saudi Arabia, who used the Frontier supercomputer to develop an exascale climate emulator with radically enhanced resolution but without the computational expense and data storage requirements of state-of-the-art climate models.

Team members also include researchers from the National Center for Atmospheric Research, the University of Notre Dame, NVIDIA, Saint Louis University and Lahore University of Management Sciences.

The winners of the climate prize, awarded by the Association for Computing Machinery, were announced on Nov. 21 at the International Conference for High Performance Computing, Networking, Storage, and Analysis in Atlanta, Georgia.

“This is a tremendous honor and we are extremely proud of our achievement,” said Marc Genton, Al-Khawarizmi distinguished professor of statistics at KAUST. “We believe this emulator will significantly enhance our ability to understand climate events much better at the local level as well as on the global scale.”

“Climate models are incredibly complex and can take weeks or months to run, even on the fastest supercomputers,” he added. They generate massive amounts of data that become nearly impossible to store, and it’s becoming a bigger and bigger problem as climate scientists are constantly pushing for higher resolution.”

Earth system models, or ESMs, are supercomputer programs used to calculate changes in the atmosphere, oceans, land and ice sheets. The simulations are based on the quantifiable laws of physics and are some of the most computationally demanding calculations to perform in terms of complexity, power consumption and processing time. Nevertheless, ESMs are essential tools for predicting the impacts of climate change.

“The climate emulator solves two problems: speeding up computations and reducing storage needs,” Genton said. “It’s designed to mimic model outputs on demand without storing petabytes of data. Instead of saving every result, all we have to store are the emulator code and necessary parameters, which, in principle, allows us to generate an infinite number of emulations whenever we need them.”

Less is more

By leveraging the latest advances in graphics processing units, or GPUs, hardware and mixed-precision arithmetic, the team’s climate emulator offers a remarkable resolution of 3.5 kilometers (approximately 2.2 miles) and can replicate local conditions on a timescale from days to hours.

“Using mixed precision to improve performance is something rather innovative in the field that also helps us preserve the emulator’s accuracy,” said Sameh Abdulah, a high-performance computing research scientist at KAUST.

“Not every element in the simulation needs to be calculated in double precision,” Abdulah added. “Mixing the precision allows us to prioritize the accuracy based on the most important elements, which in turn speeds up the overall calculations.”

The emulator is highly scalable and has demonstrated exceptional performance on four of the world’s top 10 most powerful supercomputers, including the Frontier and Summit supercomputers at the Oak Ridge Leadership Computing Facility. The OLCF is a Department of Energy Office of Science user facility and is located at DOE’s Oak Ridge National Laboratory.

The emulator also performed well on the Alps supercomputer, ranked no. 6, at the Swiss National Supercomputing Centre in Lugano, Switzerland, and on the Leonardo supercomputer, ranked no. 7, at the CINECA data center in Bologna, Italy. The team also made extensive use of KAUST’s Shaheen III, ranked no. 23, the largest and most powerful supercomputer in the Middle East.

“Sustainable computing is another advantage. Getting the answer faster means less storage, which also means saving energy,” Genton said. “Supercomputing requires a lot of energy. By mixing the precision, we reduce the time we need to run, making it more sustainable for climate studies by getting more out of the machine.”

According to Abdulah at the time of the achievement, the next step the team wanted to take was straightforward: “winning the prize,” he said. “And now we’ve finally done it.”

Read the full story, Frontier Users’ Exascale Climate Emulator Nominated for Gordon Bell Climate Prize

UT-Battelle manages ORNL for DOE’s Office of Science, the single largest supporter of basic research in the physical sciences in the United States. The Office of Science is working to address some of the most pressing challenges of our time. For more information, please visit energy.gov/science


New AI tool generates realistic satellite images of future flooding


The method could help communities visualize and prepare for approaching storms



Massachusetts Institute of Technology



Visualizing the potential impacts of a hurricane on people’s homes before it hits can help residents prepare and decide whether to evacuate. 

MIT scientists have developed a method that generates satellite imagery from the future to depict how a region would look after a potential flooding event. The method combines a generative artificial intelligence model with a physics-based flood model to create realistic, birds-eye-view images of a region, showing where flooding is likely to occur given the strength of an oncoming storm. 

As a test case, the team applied the method to Houston and generated satellite images depicting what certain locations around the city would look like after a storm comparable to Hurricane Harvey, which hit the region in 2017. The team compared these generated images with actual satellite images taken of the same regions after Harvey hit. They also compared AI-generated images that did not include a physics-based flood model. 

The team’s physics-reinforced method generated satellite images of future flooding that were more realistic and accurate. The AI-only method, in contrast, generated images of flooding in places where flooding is not physically possible. 

The team’s method is a proof-of-concept, meant to demonstrate a case in which generative AI models can generate realistic, trustworthy content when paired with a physics-based model. In order to apply the method to other regions to depict flooding from future storms, it will need to be trained on many more satellite images to learn how flooding would look in other regions.

“The idea is: One day, we could use this before a hurricane, where it provides an additional visualization layer for the public,” says Björn Lütjens, a postdoc in MIT’s Department of Earth, Atmospheric and Planetary Sciences, who led the research while he was a doctoral student in MIT’s Department of Aeronautics and Astronautics (AeroAstro). “One of the biggest challenges is encouraging people to evacuate when they are at risk. Maybe this could be another visualization to help increase that readiness.”

To illustrate the potential of the new method, which they have dubbed the “Earth Intelligence Engine,” the team has made it available as an online resource for others to try.

The researchers report their results today in the journal IEEE Transactions on Geoscience and Remote Sensing. The study’s MIT co-authors include Brandon Leschchinskiy; Aruna Sankaranarayanan; and Dava Newman, professor of AeroAstro and director of the MIT Media Lab; along with collaborators from multiple institutions.

Generative adversarial images

The new study is an extension of the team’s efforts to apply generative AI tools to visualize future climate scenarios. 

“Providing a hyper-local perspective of climate seems to be the most effective way to communicate our scientific results,” says Newman, the study’s senior author. “People relate to their own zip code, their local environment where their family and friends live. Providing local climate simulations becomes intuitive, personal, and relatable.”

For this study, the authors use a conditional generative adversarial network, or GAN, a type of machine learning method that can generate realistic images using two competing, or “adversarial,” neural networks. The first “generator” network is trained on pairs of real data, such as satellite images before and after a hurricane. The second “discriminator” network is then trained to distinguish between the real satellite imagery and the one synthesized by the first network.

Each network automatically improves its performance based on feedback from the other network. The idea, then, is that such an adversarial push and pull should ultimately produce synthetic images that are indistinguishable from the real thing. Nevertheless, GANs can still produce “hallucinations,” or factually incorrect features in an otherwise realistic image that shouldn’t be there. 

“Hallucinations can mislead viewers,” says Lütjens, who began to wonder whether such hallucinations could be avoided, such that generative AI tools can be trusted to help inform people, particularly in risk-sensitive scenarios. “We were thinking: How can we use these generative AI models in a climate-impact setting, where having trusted data sources is so important?” 

Flood hallucinations

In their new work, the researchers considered a risk-sensitive scenario in which generative AI is tasked with creating satellite images of future flooding that could be trustworthy enough to inform decisions of how to prepare and potentially evacuate people out of harm’s way.

Typically, policymakers can get an idea of where flooding might occur based on visualizations in the form of color-coded maps. These maps are the final product of a pipeline of physical models that usually begins with a hurricane track model, which then feeds into a wind model that simulates the pattern and strength of winds over a local region. This is combined with a flood or storm surge model that forecasts how wind might push any nearby body of water onto land. A hydraulic model then maps out where flooding will occur based on the local flood infrastructure and generates a visual, color-coded map of flood elevations over a particular region. 

“The question is: Can visualizations of satellite imagery add another level to this, that is a bit more tangible and emotionally engaging than a color-coded map of reds, yellows, and blues, while still being trustworthy?” Lütjens says. 

The team first tested how generative AI alone would produce satellite images of future flooding. They trained a GAN on actual satellite images taken by satellites as they passed over Houston before and after Hurricane Harvey. When they tasked the generator to produce new flood images of the same regions, they found that the images resembled typical satellite imagery, but a closer look revealed hallucinations in some images, in the form of floods where flooding should not be possible (for instance, in locations at higher elevation). 

To reduce hallucinations and increase the trustworthiness of the AI-generated images, the team paired the GAN with a physics-based flood model that incorporates real, physical parameters and phenomena, such as an approaching hurricane’s trajectory, storm surge, and flood patterns. With this physics-reinforced method, the team generated satellite images around Houston that depict the same flood extent, pixel by pixel, as forecasted by the flood model.

“We show a tangible way to combine machine learning with physics for a use case that’s risk-sensitive, which requires us to analyze the complexity of Earth’s systems and project future actions and possible scenarios to keep people out of harm’s way,” Newman says. “We can’t wait to get our generative AI tools into the hands of decision-makers at the local community level, which could make a significant difference and perhaps save lives.” 

The research was supported, in part, by the MIT Portugal Program, the DAF-MIT Artificial Intelligence Accelerator, NASA, and Google Cloud.

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Written by Jennifer Chu, MIT News


 

New imaging study finds evidence that emotion regulation is not always the most effective strategy to mitigate suicidal ideation



Research in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging promises to help anticipate suicide risk and perhaps more effectively intervene with potentially life-threatening responses to stress in at-risk populations



Elsevier

New Imaging Study Finds Evidence that Emotion Regulation Is Not Always the Most Effective Strategy to Mitigate Suicidal Ideation 

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A: The neural decoder for cognitive reappraisal reflects the degree to which each participant engaged this emotion regulation strategy while exposed to cues of their negative memories. The image above depicts the “mask,” or cluster of voxels, that the decoder was comprised of. B: The graph depicts each participant's fluctuating suicidal thoughts epoch-by-epoch across the ecological momentary assessment (EMA) time period. The size of the data point reflects the severity of participants' suicidal thoughts, while the color indicates whether a stressor occurred (pink) or no stressors occurred (blue) during that epoch.

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Credit: Sarah Herzog and Noam Schneck




Philadelphia, November 25, 2024  Depressed individuals who reflexively attempt to dampen their initial emotional responses to reminders of their negative memories have a low tolerance for distressing emotional stimuli in general and may respond to stress in their daily lives with greater upticks in suicidal thoughts. A new study in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier, examined the relationship of the engagement of emotion regulation to real-world responses to stress in order to better understand stress-related increases in suicide risk in depression.

Senior investigator J. John Mann, MD, Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute; and Department of Psychiatry and Department of Radiology, Columbia University Vagelos College of Physicians and Surgeons, says, "Suicide rates in the United States have increased about 37% since the year 2000. To reverse this trend, we need to understand how suicide risk emerges in daily life, and specifically the biopsychosocial factors that may influence the ebb and flow of suicide risk."

Retrospective reports show that the most immediate trigger of suicidal acts is a stressful life event, but researchers say it is very difficult to prospectively study how stress impacts the emergence of acute suicidality.

Co-first author Sarah Herzog, PhD, Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute; and Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, explains, "Ecological momentary assessment allows us to observe how individuals suffering from depression react to stressful events in their daily lives, for example, with intensified suicidal thoughts and worsened mood. Our study took this a step further by linking a laboratory-based biological marker of risk in a depressed sample to naturalistic responses to real-world daily stressors. This multimodal method prmoises to improve prediction of suicide risk in those vulnerable to suicide and perhaps aiding effective intervention of potentially life-threatening reactions to stress."

A group of 82 participants with major depressive disorder was assessed using two innovative methods. First, a functional MRI (fMRI)-based neural signature for cognitive reappraisal, an emotion regulation strategy, quantified the degree to which individuals engaged emotion regulation while recalling personal negative memories. Next, researchers used ecological momentary assessment (EMA), which involves prospective, repeated measurement of participants’ thoughts and emotions in naturalistic settings. EMA provides a window into how individuals react to daily life stressors with changes in mood symptoms and suicidal thoughts. The researchers then used the fMRI-based neural signature of emotion regulation expressed during the autobiographical memory task to predict participants’ responses to daily life stressors during the EMA period.

The study found that depressed individuals who spontaneously engaged a neural signature of emotion regulation when presented with personal negative memories also experienced greater increases in suicidal thoughts during day-to-day stressful events over the course of a week. When participants were directed to use reappraisal, they showed more adaptive responses to stress.

Editor-in-Chief of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging Cameron S. Carter, MD, University of California Irvine, comments, "Flexibility in emotion regulation is generally understood to be a marker of psychological health. However, in the current study researchers found that reflexively engaging emotion regulation in the face of unexpected stressors may not be helpful or effective in all circumstances. These findings, which leverage functional imaging combined with real-world in the moment assessments, are important to further our understanding of how to effectively deal with stress in daily life."

Co-first author Noam Schneck, PhD, Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute; and Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, points out, “The use of neural decoding allows us to identify mental processes that were previously elusive to capture, such as spontaneous emotion regulation. In future work, the decoder approach can be employed to better understand how emotion regulation is engaged spontaneously to modulate hour-to-hour, day-to-day experience, thereby influencing suicide risk in a fluctuating manner.”

Senior author of the current study Barbara H. Stanley, MD, Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute; and Department of Psychiatry and Department of Radiology, Columbia University Vagelos College of Physicians and Surgeons, who passed away in 2023, was instrumental in designing this study. Recognizing her valuable contributions to this work, Dr. Mann remarks, “It was Dr. Stanley’s idea that we employ ecological momentary assessment in the same depressed patients who completed the fMRI negative autobiographical memories task. It was that combination of research procedures that led to these remarkable findings.”

 

US Online health care reviews turned negative following COVID pandemic

Disparities by Race and Urbanicity in Online Health Care Facility Reviews


University of Pennsylvania School of Medicine

Percentage of Non-Positive Yelp Reviews 

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A chart that shows the proportion of 4- and 5-star reviews health care facilities received on Yelp, demonstrating a change after the COVID-19 pandemic struck.

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Credit: Chart by Neil Sehgal, et al. Appears in JAMA Network Open.




After the COVID-19 pandemic struck, online reviews of health care facilities dropped signficiantly, and they have not yet fully recovered, according to a new analysis led by researchers at the Perelman School of Medicine at the University of Pennsylvania. More than half of reviews on the online platform, Yelp,now are negative, flipping the pre-COVID picture. The findings are published today in JAMA Network Open

"Online reviews can tell us information about the patient experience that traditional reporting metrics, like hospital-administered patient experience surveys, might miss," said the study’s lead author, Neil Sehgal, ME, an associate fellow in the Penn Leonard Davis Institute of Health Economics. "These reviews can help hospitals understand what matters most to patients and their support networks in near real time.” 

By analyzing all reviews of health care facilities in the United States on the online platform Yelp dated from 2014 through 2023, Sehgal, co-author Anish Agarwal, MD, an assistant professor of Emergency Medicine, and their team saw that the percentage of positive—four- and five-star—reviews dropped from 54.3 percent before March 2020 (marked as the beginning of the COVID pandemic in the United States) to 47.9 percent after. 

In fact, from the latter half of 2021 on, the researchers found that positive reviews were never more than 50 percent. 

“We analyzed Yelp reviews of health facilities nationwide—which includes hospitals, urgent care centers, doctors’ offices, and more,” said Sehgal. “Our analysis shows how public perception of health care changed after COVID-19. And with this information, hopefully, health care professionals can work to improve upon what’s been driving these opinions.”  

Feedback ups and downs  

In analyzing the reviews, the researchers used a language processing technique to tease out the most common topics from the reviews, organized them into themes, and measured how they changed over time.  

The themes that saw the greatest change in mentions between the pre- and post-COVID periods were “insurance and billing issues” and “customer service and staff behavior.”  

One theme mentioned less in negative reviews after the arrival of COVID—and a renewed, supercharged focus on hygiene: Facility cleanliness. 

Trends emerge along ethnic and geographic lines 

While positive reviews of health care facilities on Yelp, as a whole, declined over time, health care facilities in rural areas already had lower ratings at the start of the time period examined, and the differences became more significant after COVID struck. Post-COVID, rural facilities were 23 percent less likely to have positive reviews, compared to health facilities in urban areas, which were 7 percent less likely to have positive reviews. 

Looking at data on race, researchers found that health facilities in the sample of neighborhoods that they analyzed that had higher proportions of Black or white residents were more likely to have significant declines in positive reviews.  

But when it came to areas with higher-than-average Hispanic populations, facilities still saw a decline in positive ratings, though the dips were not as pronounced.  

“At the moment, we cannot understand what is driving these changes among different populations,” Agarwal said. “But this could help us think critically on what questions to ask next and how to better deliver care around the nation in the future.”  

Researchers also identified ethnic correlations around the most mentioned complaints. Reviews for facilities in areas with higher Black and/or Hispanic populations criticized “insurance and billing issues” more often, while the facilities in areas with higher white populations found fault with “wait times” more often.  

“Many of the themes have clear overlap but are distinct across geographic areas, which is interesting and begins to highlight a growing need for health systems and facilities to be more intentional and tailored to their local communities’ needs—and opinions,” said Agarwal.  

Moving forward, the researchers hope to look deeper into the content of the reviews to better understand how attitudes and opinions break down along socio-ethnographic lines, giving health care professionals better tools for discussing issues that are important to individuals and assuaging concerns. 

This study was partially funded by National Institutes of Health grants (NIH NHLBI R01HL1-141844, NIH/DHHS R01 MH127686, NIH-NIMHD:R01MD018340, and NIH K24 HL157621). 

 

Simple secret to living a longer life



Griffith University
Life expectancy in the USA for 4-year-olds, by physical activity level 

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• Americans over the age of 40 could live an extra 5.3 years if all were as active as the top 25% of the population

• For the least active 25% of Americans aged 40+, an extra hour’s walk could add 6.3 hours of additional life-expectancy, on average.

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Credit: Lennert Veerman, Griffith University




If everyone in the United States population was as active as the top 25 per cent, individuals over the age of 40 could add five years to their life, according to a new study led by Griffith University researchers.  

Physical activity has long been known to be good for health, however estimates have varied regarding how much benefit could be gained from a defined amount of activity, both for individuals and for populations. 

This latest study used accelerometry to gain an accurate view of the population’s physical activity levels instead of relying on survey responses as per other studies, and found the benefits were around twice as strong as previous estimates.  

It found the most active quarter of people in the community had a 73 per cent lower risk of death than their least active counterparts. 

For that least active quartile, a single one-hour walk could potentially return a benefit of around six additional hours of life.  

Lead researcher Professor Lennert Veerman said this least-active cohort had the greatest potential for health gains.  

“If you’re already very active or in that top quartile, an extra hour’s walk may not make much difference as you’ve, in a sense, already ‘maxxed out’ your benefit,” he said.   

“If the least active quartile of the population over age 40 were to increase their activity level to that of the most active quartile however, they might live, on average, about 11 years longer.  

“This is not an unreasonable prospect, as 25 per cent of the population is already doing it.  

“It can be any type of exercise but would roughly be the equivalent of just under three hours of walking per day.” 

The research team suggested low levels of physical activity could even rival the negative effects of smoking, with other research finding each cigarette could take 11 minutes from a smoker’s life.  

By extension, a more active lifestyle could also offer protective effects against heart disease, stroke, certain cancers and other chronic illnesses, with the study’s findings highlighting a need for national physical activity guidelines to be revisited using these methods.  

Dr Veerman said physical activity had been vastly underestimated in its capacity to improve health outcomes, suggesting even modest increases in movement could lead to significant life-extension benefits.  

“If there's something you could do to more than halve your risk of death, physical activity is enormously powerful,” he said.  

“If we could increase investment in promoting physical activity and creating living environments that promote it such as walkable or cyclable neighbourhoods and convenient, affordable public transport systems, we could not only increase longevity but also reduce pressure on our health systems and the environment.”  

 

 

Are health care disparities tied to worse outcomes for kids with MS?



American Academy of Neurology




MINNEAPOLIS – People who develop multiple sclerosis (MS) as children and grow up in less advantaged neighborhoods may have a larger volume of inflammation and brain tissue loss on imaging than those who grow up in more advantaged neighborhoods, according to a study published in the November 27, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology.

MS rarely develops in children. About 5% of people with MS are diagnosed before age 18.

In addition to neighborhood location, worse brain imaging outcomes were also seen among people who self-identified as Black or Latino, those from families where the parents had lower education levels, and those who had public health insurance, which is used as a marker of low household income.  

“Our findings suggest that social disadvantage in childhood can have lasting effects on MS severity,” said study author Kimberly A. O’Neill, MD, of New York University Grossman School of Medicine. “Childhood is a critical time for exposure to environmental factors associated with increased susceptibility to MS, such as passive smoke, pollution and low sunlight exposure. More studies are needed to understand which and how factors in disadvantaged neighborhoods increase the risk for MS severity in young people.”

The study involved 138 people with an average age of 20 who were diagnosed with MS before age 18, known as pediatric onset MS. They had been diagnosed with MS for an average of four years.

All had brain scans to measure areas of brain inflammation and injury due to MS and brain volume loss. Researchers collected information on social factors that may impact a person’s health, including self-reported race and ethnicity, type of health insurance, parents’ education level, and the degree of neighborhood advantage or disadvantage.

Social factors associated with disadvantage correlated with greater volume of inflammatory lesions in the white matter of the brain and also with greater black hole volume, which is a sign of irreversible loss of brain tissue. Together, the identified social factors accounted for 26% of the difference in white matter lesion volume and 23% of the difference in black hole volume among participants.

Once all factors were taken into account, having public health insurance was the strongest predictor of having greater amounts of inflammation and tissue loss. People with public health insurance had average white matter lesion volume that was larger than people with private insurance. They also had average black hole volumes larger than those with private insurance.

The researchers found that the differences were not explained by how soon children were seen by a neurologist, how quickly they were started on medication for MS or how effective their medications were at slowing their disease progress.

“This suggests that access to health care does not explain the more severe disease burden shown in the brain scans of people in disadvantaged groups in our study,” O’Neill said. “While these are associations and not causes, many of these groups have historically been underrepresented in MS research and our work here is just beginning.”  

A limitation of the study is that researchers used the address of the children at the time of their diagnosis but did not have information on any prior addresses. Additionally, only a few types of social factors were studied.

The study was supported by the Lourie Foundation.

Learn more about brain health at BrainandLife.org home of the American Academy of Neurology’s free patient and caregiver magazine focused on the intersection of neurologic disease and brain health. Follow Brain & Life® on FacebookX and Instagram.

When posting to social media channels about this research, we encourage you to use the hashtags #Neurology and #AANscience.

The American Academy of Neurology is the world's largest association of neurologists and neuroscience professionals, with over 40,000 members. The AAN’s mission is to enhance member career fulfillment and promote brain health for all. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer's disease, stroke, concussion, epilepsy, Parkinson's disease, multiple sclerosis, headache and migraine.

For more information about the American Academy of Neurology, visit AAN.com or find us on FacebookXInstagramLinkedIn and YouTube.

 

Clinical trial at Emory University reveals twice-yearly injection to be 96% effective in HIV prevention




Emory Health Sciences

Colleen Kelley, MD, lead author of the study, professor at Emory University's School of Medicine, and co-director of the Emory Center for AIDS Research 

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Colleen Kelley, MD, lead author of the study, professor at Emory University's School of Medicine, and co-director of the Emory Center for AIDS Research

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Credit: Emory




For oral medications that prevent new HIV infection to be effective, the patient must take certain actions, including attending doctor’s visits every three months and – most importantly – consistency. 

These daily oral antiretrovirals, more commonly referred to as PrEP (pre-exposure prophylaxis), such as Truvada®, are extremely effective at HIV prevention, but only if they are taken daily as directed. Truvada’s efficacy is greatly compromised when taken inconsistently. 

However, results from a recent Gilead-funded clinical trial (Purpose-2) led by physicians at Emory University and Grady Health System indicate that a twice-yearly injection of Lenacapavir offers a 96% reduced risk of infection overall, making the injection significantly more effective than the daily oral PrEP. The findings were recently published in the New England Journal of Medicine.

“Seeing these high levels of efficacy – at almost 100% -- in an injectable that people only have to take every six months is incredible,” says Colleen Kelley, MD, lead author of the study and professor in the School of Medicine at Emory University. “This is a considerable and profound advancement in medicine, especially for people whose circumstances don’t allow them to take a daily oral medication, and for those among populations disproportionately impacted by HIV.”  

In the randomized, double-blind, Phase III clinical trial comparing the efficacy of the two medications, 99% of the participants in the Lenacapavir group did not acquire an HIV infection. During the trial, only two participants in the Lenacapavir group, comprised of 2,179 people, acquired HIV. This compares to nine new HIV infections in the Truvada®group, which had 1,086 people. The trial showed that adherence to the injectable was higher than of the daily oral pill. 

Kelley, also the co-director of the Emory Center for AIDS Research, and Associate Dean for Research for Emory at Grady adds that while PrEP is incredibly effective at preventing infection, part of what made the injection more effective in the clinical trial was the challenges associated with adherence to a daily oral pill. 

“What we see over time is that about half of people who start taking daily oral PrEP stop within a year due to various factors,” says Kelley, referencing healthcare disparities in general. “Having an effective injectable that is only needed twice annually is very significant for people who have trouble accessing healthcare or staying adherent to daily, oral pills.” 

The inclusion of racially, ethnically, and gender-diverse participants in the clinical trial was notable because it was representative of populations disproportionately impacted by HIV in real time. For example, the trial groups were comprised of cisgender men and gender-diverse people at 88 sites in Peru, Brazil, Argentina, Mexico, South Africa, Thailand, and the U.S. 

According to the study, the same populations that are disproportionately impacted by HIV are the same populations that have limited access to PrEP – or may have difficulty consistently taking the oral antiretroviral medication – ultimately highlighting the need for more options. The study also indicates that more than half of the new HIV infections nationwide in 2022 were among cisgender gay men, and 70% of those were among Black or Hispanic individuals. 

Valeria Cantos, MD, associate professor in the School of Medicine at Emory University, physician at Grady Memorial Hospital, and the principal investigator for the clinical trial at the Grady research site, emphasized the importance of having trials that include populations truly representative of the patients that Grady serves. 

“At Grady, our focus is on increased representation of underserved and vulnerable populations, acknowledging and addressing the distrust towards research held by some community members due to prior abuses or neglect of these populations by research institutions in the past,” Cantos says. “Grady is an established, trusted research site because of its commitment to equity.”

At the Grady clinical trial site, medical materials were available in Spanish, and bilingual staff members recruited and enrolled trial participants who only spoke Spanish. Cantos also indicated that the site enrolled participants who are representative of the populations that would benefit the most from Lenacapavir. In addition to Grady, the Hope Clinic and Emory Midtown Hospital were among the 88 sites supporting the clinical trial. 

“We are not reaching everyone we need to reach with our current HIV prevention interventions, such as those who are disproportionately impacted by HIV and health care disparities,” says Kelley. “For people that are unable to take the daily oral pills, the injectable agents can really give incredible efficacy and be a game changer in helping them stay HIV negative.”

Since the Phase III clinical trial has been completed and submitted by the FDA for consideration, Kelley is hopeful that Lenacapavir may be approved by 2025 for commercial use. 

““The results of this study add to the armamentarium of novel tools for HIV prevention. Long acting antiretrovirals offer new hope for those who are not able to take oral medications,” says Carlos del Rio, MD, chair of the Department of Medicine at Emory University School of Medicine. “The challenge is now to roll out and make these tools available and accessible in an equitable way— only then we will see new HIV infections dramatically decreased locally and globally,” adds del Rio, also co-director of the Emory Center for AIDS Research.  

CITATION: Colleen Kelley, et al. Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons. New England Journal of Medicine. Nov. 27, 2024. 10.1056/NEJMoa2411858