One puzzle in question is the “Hubble tension,” which refers to a mismatch in measurements of how fast the universe is expanding. The other involves observations of numerous early, bright galaxies that existed at a time when the early universe should have been much less populated.

Now, the MIT team has found that both puzzles could be resolved if the early universe had one extra, fleeting ingredient: early dark energy. Dark energy is an unknown form of energy that physicists suspect is driving the expansion of the universe today. Early dark energy is a similar, hypothetical phenomenon that may have made only a brief appearance, influencing the expansion of the universe in its first moments before disappearing entirely.

Some physicists have suspected that early dark energy could be the key to solving the Hubble tension, as the mysterious force could accelerate the early expansion of the universe by an amount that would resolve the measurement mismatch.

The MIT researchers have now found that early dark energy could also explain the baffling number of bright galaxies that astronomers have observed in the early universe. In their new study, reported in the Monthly Notices of the Royal Astronomical Society, the team modeled the formation of galaxies in the universe’s first few hundred million years. When they incorporated a dark energy component only in that earliest sliver of time, they found the number of galaxies that arose from the primordial environment bloomed to fit astronomers’ observations.

“You have these two looming open-ended puzzles,” says study co-author Rohan Naidu, a postdoc in MIT’s Kavli Institute for Astrophysics and Space Research. “We find that in fact, early dark energy is a very elegant and sparse solution to two of the most pressing problems in cosmology.”

The study’s co-authors include lead author and Kavli postdoc Xuejian (Jacob) Shen, and MIT professor of physics Mark Vogelsberger, along with Michael Boylan-Kolchin at the University of Texas at Austin, and Sandro Tacchella at the University of Cambridge.

Big city lights

Based on standard cosmological and galaxy formation models, the universe should have taken its time spinning up the first galaxies. It would have taken billions of years for primordial gas to coalesce into galaxies as large and bright as the Milky Way.

But in 2023, NASA’s James Webb Space Telescope (JWST) made a startling observation. With an ability to peer farther back in time than any observatory to date, the telescope uncovered a surprising number of bright galaxies as large as the modern Milky Way within the first 500 million years, when the universe was just 3 percent of its current age.

“The bright galaxies that JWST saw would be like seeing a clustering of lights around big cities, whereas theory predicts something like the light around more rural settings like Yellowstone National Park,” Shen says. “And we don’t expect that clustering of light so early on.”

For physicists, the observations imply that there is either something fundamentally wrong with the physics underlying the models or a missing ingredient in the early universe that scientists have not accounted for. The MIT team explored the possibility of the latter, and whether the missing ingredient might be early dark energy.

Physicists have proposed that early dark energy is a sort of antigravitational force that is turned on only at very early times. This force would counteract gravity’s inward pull and accelerate the early expansion of the universe, in a way that would resolve the mismatch in measurements. Early dark energy, therefore, is considered the most likely solution to the Hubble tension.

Galaxy skeleton

The MIT team explored whether early dark energy could also be the key to explaining the unexpected population of large, bright galaxies detected by JWST. In their new study, the physicists considered how early dark energy might affect the early structure of the universe that gave rise to the first galaxies. They focused on the formation of dark matter halos — regions of space where gravity happens to be stronger, and where matter begins to accumulate.

“We believe that dark matter halos are the invisible skeleton of the universe,” Shen explains. “Dark matter structures form first, and then galaxies form within these structures. So, we expect the number of bright galaxies should be proportional to the number of big dark matter halos.”

The team developed an empirical framework for early galaxy formation, which predicts the number, luminosity, and size of galaxies that should form in the early universe, given some measures of “cosmological parameters.” Cosmological parameters are the basic ingredients, or mathematical terms, that describe the evolution of the universe.

Physicists have determined that there are at least six main cosmological parameters, one of which is the Hubble constant — a term that describes the universe’s rate of expansion. Other parameters describe density fluctuations in the primordial soup, immediately after the Big Bang, from which dark matter halos eventually form.

The MIT team reasoned that if early dark energy affects the universe’s early expansion rate, in a way that resolves the Hubble tension, then it could affect the balance of the other cosmological parameters, in a way that might increase the number of bright galaxies that appear at early times. To test their theory, they incorporated a model of early dark energy (the same one that happens to resolve the Hubble tension) into an empirical galaxy formation framework to see how the earliest dark matter structures evolve and give rise to the first galaxies.

“What we show is, the skeletal structure of the early universe is altered in a subtle way where the amplitude of fluctuations goes up, and you get bigger halos, and brighter galaxies that are in place at earlier times, more so than in our more vanilla models,” Naidu says. “It means things were more abundant, and more clustered in the early universe.”

“A priori, I would not have expected the abundance of JWST’s early bright galaxies to have anything to do with early dark energy, but their observation that EDE pushes cosmological parameters in a direction that boosts the early-galaxy abundance is interesting,” says Marc Kamionkowski, professor of theoretical physics at Johns Hopkins University, who was not involved with the study. “I think more work will need to be done to establish a link between early galaxies and EDE, but regardless of how things turn out, it’s a clever — and hopefully ultimately fruitful — thing to try.”

“We demonstrated the potential of early dark energy as a unified solution to the two major issues faced by cosmology. This might be an evidence for its existence if the observational findings of JWST get further consolidated,” Vogelsberger concludes. “In the future, we can incorporate this into large cosmological simulations to see what detailed predictions we get.”

This research was supported, in part, by NASA and the National Science Foundation.

Dr. Mohammadi, an Associate Professor with the School of Engineering, says their latest work, dubbed the iValve, is their most advanced yet and combines the best of both technologies — mechanical and tissue — when it comes to replacement heart valves.

“Tissue valves generally perform better than mechanical valves because of their shape, but last only 15 to 20 years on average, which would require another replacement. Mechanical valves can last a lifetime, but do not perform as well as tissue valves, requiring patients to take daily anticoagulants,” says Dr. Mohammadi.

“We have produced a new mechanical heart valve that combines the best of both worlds — offering the performance of tissue valves with the long-lasting durability of mechanical valves. We believe this valve could make life easier and safer for patients,” he adds.

The breakthrough valve was made possible through an international collaboration with ViVitro Labs and independent consultants Lawrence Scotten and Rolland Siegel. The research was funded by Angeleno Medical and published this month in the Journal of Biomechanics.

“This is the only valve of its kind to be designed and built in Canada,” notes Dr. Mohammadi. “We are incredibly proud of this valve as an example of the engineering innovation coming from UBC and Canada.”

Dr. Mohammadi also says while mechanical heart valve replacements have long been in use, the long-standing challenge has been to perfect the technology for the smallest hearts — tiny infants.

“What is particularly exciting about the iValve, is that it was specifically designed for high-heart-rate applications, such as in pediatric patients,” explains Dr. Mohammadi.

Now that their prototype performs well in mechanical lab tests, the researchers will bring it to animal and clinical trials. If all goes well, they hope the iValve could be ready for those trials within two years.

In the meantime, they will also be using the technology and techniques to develop new valves.

“This valve is designed to allow blood flow to the aorta, which is the body’s largest artery, and the blood vessel that carries oxygen-rich blood away from the heart throughout your body,” explains Mohammadi. “Next, we will take what we have learned and develop one for the mitral valve. That valve is responsible for making sure that blood flows from your left atrium to your left ventricle. It also ensures that blood doesn’t flow backward between those two chambers.”

Heart Valve Performance Lab Manager Dr. Dylan Goode is excited about what the future holds for the iValve — and for the benefits it could bring to patients.

Dr. Goode began working with Dr. Mohammadi in 2018 while completing his Master of Applied Science in Mechanical Engineering. Recently, he successfully defended his doctoral dissertation, which documents his design work, fabrication and testing of the iValve.

“We have shown that the iValve can provide the structural benefits of a mechanical heart valve and last a patient’s lifespan while providing improved hemodynamic performance, meaning an improvement of the way in which blood flows through vessels.”

Dr. Goode notes the new iValve could also mean a major improvement in lifestyle for these patients who endure a routine of regular anticoagulant therapy — blood thinners — which can increase their risk of severe bleeding, blood clots or damage to tissues and organs if blood flow is impeded.

The investigational mRNA cancer immunotherapy is targeted for patients with lung cancer, melanoma and other solid tumours. Nineteen patients with advanced stage cancers received between one and nine doses of the immunotherapy treatment. Scientists have found the immunotherapy created an immune response against cancer and was well tolerated, with adverse events including fatigue, injection site pain and fever.

Results from the Phase I trial, also the first-in-human study of the therapy, are being presented on Saturday, 14^th September at the European Society of Medical Oncology conference in Barcelona by the UK Chief Investigator of the trial from King’s College London and Guy’s and St Thomas’ NHS Foundation Trust. The trial is sponsored by Moderna.

The mRNA immunotherapy is just one of many cancer vaccines entering clinical trials around the world. The therapy works by presenting common markers of tumours to patients’ immune systems, training them to recognise and fight cancer cells that express them and potentially eliminate cells that could supress the immune system.

The Phase I trial was designed to test the safety and tolerability of the immunotherapy, and secondary and tertiary objectives were to assess the radiographic and immunological responses.

Eight out of sixteen patients who could have their responses evaluated were able to demonstrate their tumour size did not grow and no new tumours appeared.

Data also showed the mRNA immunotherapy could activate the immune system in many patients, generating immune cells in the blood that could recognise the two proteins of interest (PD-L1 and IDO1). Researchers were able to show in some patients that the immunotherapy can increase levels of important immune cells that can kill cancer cells as well as reduced levels of other immune cells that can prevent the immune system from fighting cancer.

The results should be treated with caution, say the study authors, as the sample size was small and the primary objective of the study was to test for safety and determine the optimal dose of the immunotherapy. However, these promising early results support further research into mRNA-4359.

The trial continues to recruit patients with melanoma and lung cancer in combination with the immunotherapy drug pembrolizumab to provide more information on the safety and efficacy of the therapy.

The UK’s Chief Investigator of the trial Dr Debashis Sarker, a Clinical Reader in Experimental Oncology at King’s College London and a consultant in medical oncology at Guy’s and St Thomas’ NHS Foundation Trust, said: “This study evaluating an mRNA cancer immunotherapy is an important first step in hopefully developing a new treatment for patients with advanced cancers.

“We have shown that the therapy is well tolerated without serious side effects and can stimulate the body’s immune system in a way that could help to treat cancer more effectively. However, as this study has only involved a small number of patients to date, it’s too early to say how effective this could be for people with advanced stage cancer.

“The trial continues to recruit patients with melanoma and lung cancers and is a huge international effort across the UK, USA, Spain and Australia.”

Kyle Holen, M.D., Moderna’s Senior Vice President and Head of Development, Therapeutics and Oncology, said: “We are encouraged by the Phase 1 results of mRNA-4359, which demonstrate its potential to elicit strong antigen-specific T-cell responses while maintaining a manageable safety profile.

“This novel approach could be a key component in shifting the tumour microenvironment toward a more immune-permissive state, offering potential hope for patients with advanced solid tumours.”

“In patients with obesity who were prescribed semaglutide or liraglutide, we found that long-term weight reduction varied significantly based on the medication’s active agent, treatment indication, dosage and persistence with the medication,” said Hamlet Gasoyan, Ph.D., lead author of the study and a researcher with Cleveland Clinic’s Center for Value-Based Care Research.

Semaglutide (sold under the brand names Wegovy and Ozempic) and liraglutide (sold under the brand names Saxenda and Victoza) are glucagon-like peptide-1 receptor agonists, or GLP-1 RA medications. Those FDA-approved medications help lower blood sugar levels and promote weight loss.

Obesity is a complex chronic disease that affects more than 41% of the U.S. adult population. Clinical trials have shown that anti-obesity medications are effective; however, there is limited data in real-world settings regarding the factors associated with long-term weight change and clinically significant weight loss.

In this study, the researchers identified key factors that were associated with long-term weight loss of patients with obesity. They also indicated the elements that were linked to the probability of achieving 10% or more weight loss.

This retrospective cohort study included 3,389 adult patients with obesity who initiated treatment with injectable semaglutide or liraglutide between July 1, 2015, and June 30, 2022. Follow-up ended in July 2023.

At the start of the study, the median baseline body mass index among study participants was 38.5; 82.2% had type 2 diabetes as treatment indication. Among the patients, 68.5% were white, 20.3% were Black, and 7.0% were Hispanic. More than half of the participants were female (54.7%). Most of the patients received treatment for type 2 diabetes. Overall, 39.6% were prescribed semaglutide for type 2 diabetes, 42.6% liraglutide for type 2 diabetes, 11.1% semaglutide for obesity, and 6.7% liraglutide for obesity.

Results show that one year after the initial prescription’s fill, weight change was associated with the following factors:

• Persistence with medication. On average, patients who were persistent with the medication at one year experienced -5.5% weight change versus -2.8% among patients who had 90-275 medication coverage days within the first year and -1.8% among those with less than 90 covered days.

Researchers found that four in 10 patients (40.7%) were persistent with their medication one year after their initial prescription’s fill. The proportion of patients who were persistent with semaglutide was 45.8% versus 35.6% in patients receiving liraglutide.

Among patients who persisted with their medication at 12 months, the average reduction in body weight was -12.9% with semaglutide for obesity, compared to -5.9% with semaglutide for type 2 diabetes. The reduction in body weight was -5.6% with liraglutide for obesity, compared to -3.1% with liraglutide for type 2 diabetes.

Studies have shown that achieving sustained weight loss of 10% or more provides clinically significant health benefits. With that in mind, Dr. Gasoyan and colleagues looked at the proportion of patients who achieved 10% or more weight reduction.

Overall, 37.4% of patients receiving semaglutide for obesity achieved 10% or more body weight reduction compared to 16.6% of patients receiving semaglutide for type 2 diabetes. In comparison, 14.5% of those receiving liraglutide for obesity achieved 10% or more body weight reduction versus 9.3% of those receiving liraglutide for type 2 diabetes.

Among patients who persisted with their medication one year after their initial prescriptions, the proportion who achieved 10% or more weight reduction was 61% with semaglutide for obesity, 23.1% with semaglutide for type 2 diabetes, 28.6% with liraglutide for obesity, and 12.3% with liraglutide for type 2 diabetes.

Based on the study’s multivariable analysis that accounted for relevant socio-demographic and clinical variables, the following factors were associated with higher odds of achieving 10% or more weight reduction one year after the initial prescriptions:

“Our findings could help inform patients and providers regarding some of the key factors that are associated with the probability of achieving sustained weight loss of a magnitude large enough to provide clinically significant health benefits,” said Dr. Gasoyan. “Having real-world data could help manage expectations regarding weight reduction with GLP-1 RA medications and reinforce that persistence is key to achieve meaningful results.”

In a previous study, Dr. Gasoyan and colleagues looked at the factors influencing the long-term use of anti-obesity medications. Future research will continue to explore patients’ persistence and health outcomes with GLP-1 RA medications. ?

Dr. Gasoyan is supported by a grant from the National Cancer Institute.

The results of the trial, dubbed the DESTINY-Breast12 study, were presented today at the European Society of Medical Oncology (ESMO) Congress 2024 in Barcelona, Spain, and published simultaneously in a paper in the journal Nature Medicine.

The findings point to T-DXd as a valuable new treatment option for patients with a particularly challenging form of cancer, researchers say. “As many as half of patients with HER2-positive breast cancer develop brain metastases, which often has a poorer prognosis than breast cancer that hasn’t spread to the brain,” says Nancy Lin, MD, leader of the trial and senior author of the study in Nature Medicine. Lin is the associate chief of the Division of Breast Oncology, Dana-Farber, Susan F. Smith Center for Women’s Cancers, and the director of the Metastatic Breast Cancer Program. Localized therapies such as surgery, radiosurgery, and radiation therapy to the brain, are used to treat brain metastases, but the disease usually progresses in the central nervous system — the brain and spinal cord — within six to 12 months of treatment.

Trastuzumab deruxtecan consists of the drug deruxtecan — a chemotherapy agent — linked to an antibody that targets the HER2 protein on breast cancer cells. Trastuzumab itself is a mainstay treatment of HER2-positive breast cancer that has spread to other parts of the body, including the brain. But as with treatments directed specifically at the brain, patients receiving trastuzumab usually have their disease progress, often in the central nervous system.

“Additional systemic therapies for patients with brain metastases are urgently needed,” Lin remarks.

The DESTINY-Breast12 trial involved 504 patients with HER-2 positive breast cancer treated at 78 cancer centers in Western Europe, Japan, Australia, and the U.S. Two hundred sixty-three participants had active or stable brain metastases and 241 had no brain metastases. All had received at least one therapy before enrolling in the trial.

After a median follow-up of 15.4 months, progression-free survival of participants with brain metastases — the length of time patients lived with the cancer before it worsened — was a median of 17.3 months, investigators found. 12- month progression-free survival was 61.6%. Seventy-one percent of participants had an intracranial objective response — a measurable decrease of their cancer in the central nervous system. As expected, there was also a high rate of response in tumors outside of the central nervous system in patients with or without brain metastases. Ninety percent of patients in both groups were alive a year after beginning T-DXd treatment.

The side effects associated with T-DXd were consistent with those reported in previous studies and included nausea, constipation, neutropenia (low levels of a type of white blood cells), fatigue, and anemia. Interstitial lung disease (ILD), a known risk of T-DXd, was observed at similar rates to prior studies, and vigilance to this potentially fatal side effect remains critical.

“Our data show that T-DXd has substantial and durable activity within the brain in patients with HER2-positive breast cancer that has metastasized there,” Lin says. “These results support the use of the drug going forward in this patient population.”

That’s the groundbreaking finding from a new study published in the Journal of Physiology that shows for the first time that maternal obesity alters a critical thyroid hormone in the fetal heart, disrupting its development.

Consuming a high-fat, sugary diet during pregnancy also increases the likelihood of the unborn baby becoming insulin resistant in adulthood, potentially triggering diabetes and causing cardiovascular disease. This is despite babies being a normal weight at birth.

University of South Australia researchers identified the link by analysing tissue samples from the fetuses of pregnant baboons fed a high-fat, high-energy diet in a biomedical research institute in the United States. They then compared this to fetuses from baboons on a control diet.

Lead author, University of South Australia PhD candidate Melanie Bertossa, says the findings are significant because they demonstrate a clear link between an unhealthy diet high in saturated fats and sugar, and poor cardiovascular health.

“There has been a long-standing debate as to whether high-fat diets induce a hyper- or hypothyroid state in the fetal heart. Our evidence points to the latter,” Bertossa says.

“We found that a maternal high-fat, high-energy diet reduced concentrations of the active thyroid hormone T3, which acts like a switch around late gestation, telling the fetal heart to start preparing for life after birth. Without this signal, the fetal heart develops differently.”

Bertossa says that diets high in fat and sugar can alter the molecular pathways involved in insulin signalling and critical proteins involved in glucose uptake in the fetal heart. This increases the risk of cardiac insulin resistance, often leading to diabetes in adulthood.

“You’re born with all the heart cells you will ever have. The heart doesn’t make enough new heart muscle cells after birth to repair any damage, so changes that negatively impact these cells before birth could persist for a lifetime.

“These permanent changes could cause a further decline in heart health once children reach adolescence and adulthood when the heart starts to age.”

Senior author, UniSA Professor of Physiology Janna Morrison, says the study demonstrates the importance of good maternal nutrition in the leadup to pregnancy, not only for the mother’s sake but also for the health of the baby.

“Poor cardiac outcomes were seen in babies that had a normal birth weight — a sign that should guide future clinical practice,” Prof Morrison says.

“Cardiometabolic health screening should be performed on all babies born from these types of pregnancies, not just those born too small or too large, with the goal being to detect heart disease risks earlier.”

Prof Morrison says that if rising rates of high-fat sugary diets are not addressed, more people will develop health complications such as diabetes and cardiovascular disease, which could result in shorter life spans in the decades ahead.

“Hopefully, with the knowledge we have now about the negative health impacts of obesity, there is potential to change this trajectory.”

The researchers are currently undertaking long-term studies of babies born to women on high- fat high-energy diets to track their health over decades.