Released on Thursday, the HRL produced the report as part of the Conflict Observatory — a U.S. State Department-funded program that collects and analyzes evidence of atrocities using open-source data and satellite imagery.

The report identifies 223 instances of damage to power generation and transmission infrastructure over seven months in the past year. According to the research, the damage appears consistent with a “widespread and systematic effort to cripple vital power generation and transmission infrastructure across Ukraine.”

“The report is a critical first step toward accountability for Russia’s attacks on Ukraine’s energy infrastructure — attacks that have affected the lives of ordinary Ukrainians throughout the country,” Oona Hathaway, the Gerard C. and Bernice Latrobe Smith Professor of International Law and a contributor to the report, wrote to the News. “It sets out a roadmap for prosecutors, which they will be able to use as they build their cases.”

The Yale researchers focused on the period between Oct. 1, 2022, and April 30, 2023, when Russian officials claimed that a wave of attacks on Ukrainian energy infrastructure was in retaliation for an explosion at the Kerch Bridge in Russian-occupied Crimea on Oct. 8, 2022. 

Damage to civilian energy infrastructure — which controls electricity and heating for Ukrainians — is particularly dangerous to civilians during Ukraine’s cold winter months, the report says. 

According to the report, the timing and location of the attacks, along with statements from Russian public officials, are consistent with a deliberate attempt to destroy power infrastructure across Ukraine. But the attacks that the HRL report documented are not concentrated in active military zones.

Instead, the attacks on Ukrainian power infrastructure are spread across nearly all of Ukraine’s administrative regions, including in regions that are removed from the frontlines of combat. The report also determined that the Russian military had targeted power infrastructure beyond the extent needed to achieve a military advantage.

As a result, the researchers believe that Russian attacks may violate international humanitarian law, which requires combatants to take “all feasible precaution to minimize injury to civilians and damage to civilian objects,” the report says. 

The researchers also documented statements from Russian officials that described the attacks as political retaliation and intended to cause widespread civilian suffering, motives that might place the Russian attacks in violation of international law, including the terms of the Fourth Geneva Convention.

“These statements, together with the aggregate data, indicate that Russia’s attacks on Ukraine’s power generation and transmission infrastructure may constitute deliberate targeting that is inconsistent with international humanitarian law,” the report said.

To obtain the data, HRL used what they describe as a “fusion methodology,” which combines open-source data analysis and high-resolution satellite imagery to document conflict-related damage to power generation and transmission infrastructure. 

These tools use artificial intelligence models to filter through large sets of data and flag imagery that might indicate damage.

To dig through large quantities of data, the researchers feed the AI approximate parameters for imagery — like that of tanks or an explosion — that they expect to find. Attaching these general characteristics to pinpoint a target, Raymond said, is a lot like describing a stolen bike to the police.  

“Say you had your bike stolen at Claire’s Corner Copia and had to do a police report to the police department,” Raymond said. “What make or model was it? What color was it? What are other attributes about the bike? That’s going to help us find it.” 

In the two years since the start of the Russian invasion of Ukraine, the HRL has produced reports that have documented alleged Russian war crimes and humanitarian atrocities in the public eye. Their research has been cited by over 4,000 media outlets, the United States House of Representatives, the U.S. Department of State and the International Criminal Court. The ICC has used their findings as the basis of prosecutions of senior Russian officials, including Russian President Vladimir Putin.

Last February, Raymond and Kaveh Khoshnood, an associate professor of epidemiology and the faculty director of the HRL, authored a report that documented the systematic, forced transfer and deportation of thousands of Ukrainian children to Russia across a network of 43 re-education and adoption facilities. They presented their results, including that the Russian deportation network could constitute a violation of international human rights law, at a United Nations summit later that month. 

Since then, the HRL has documented the deportation of children to Belarus by the Lukashenka regime, has located detention facilities for Ukrainian civilians, assessed the destruction of Ukraine’s crop storage infrastructure and identified mass graves. Raymond’s team has documented damage to hospitals and schools, mapped torture and detention facilities and tracked the forced passportization of Ukrainians — mandating that civilians adopt Russian nationality —  in occupied areas.

Producing these reports, Raymond told the News, is a paradoxical experience. 

“If you do it right, you feel two things at once. One is an immense professional satisfaction on having achieved, hopefully the highest scientific standard of assessment of an incident or trend that can be done through these methods,” Raymond said. “The other feeling is the exact opposite: it is a mixture of horror at what happened and frustration, often about a lack of response to it.”

Raymond’s journey to the HRL began with firsthand experiences in disaster response. As an aid worker during Hurricane Katrina, he said he noticed a lack of remote data and communication networks for disaster response. The absence prompted him to begin developing fusion methodologies integrating open source and remote sensing data, just as the HRL used in Thursday’s report. 

By 2011, Raymond moved to Harvard University, where he directed the Harvard Humanitarian Initiative’s Satellite Sentinel Project, a program backed by actor George Clooney that used satellite imagery to create an early warning system against mass atrocities in Sudan and South Sudan. The next year, he helped establish Harvard’s Signal Program on Human Security and Technology, which began developing ethical and technical standards digital atrocity monitoring.

Having been at Yale since 2018, Raymond leads the HRL’s efforts to navigate a deluge of data. His team of researchers includes linguists, imagery analysts and epidemiologists to parse information and identify monitoring objectives. Developing these methodologies, Raymond said, is like being a professional golfer.

“My job is to figure out: do we use the nine wood? A putter? A five iron? And on some holes, you may use multiple golf clubs,” Raymond said. “The ability to know how to select the clubs is as important as swinging, and that comes from the experience of having tried to get a lot of different types of targets in a lot of different ways.”

For Raymond, the objective of digital atrocity monitoring is not to replace witness testimony. Instead, by cross-corroborating sources and creating a “scientifically validated” record of events with high confidence, he said he hopes to elevate witness testimony of humanitarian atrocities. 

“I am deeply grateful for their science-informed approach to action,” Megan Ranney, Dean of Yale School of Public Health, wrote in an email to the News.

The Russian invasion of Ukraine started on Feb. 24, 2022.

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Lipska is a professor of medicine at the School of Medicine who specializes in endocrinology and diabetes. On Dec. 14, she testified at the Senate Health, Education, Labor and Pensions Committee hearing titled “What is Fueling the Diabetes Epidemic?” During the hearing, she underscored the need for the federal government to negotiate with pharmaceutical companies to lower drug prices to address the root causes of diabetes and obesity. 

Many of Lipska’s patients suffering from Type I Diabetes — a chronic condition where the pancreas produces little-to-no insulin, the hormone responsible for regulating blood sugar levels — spend nearly half of their household income on insulin, which is vital for them to stay alive. Many also struggle to afford medications such as Ozempic — the brand name for semaglutide, which the FDA approved to treat Type II Diabetes — or Wegovy, another brand name for a similar drug approved for weight management. 

“I see patients in clinic who struggle paying for the medicines and often don’t take their medicines because they cost too much — and I see the consequences,” Lipska said in an interview with the News. “I get very upset about this, and I get very angry at our healthcare system because people suffer when they cannot afford the medications they need.”

On the stand, Lipska presented evidence from a 2017 survey conducted at the Yale Diabetes Center which showed that one in four diabetes patients who were prescribed insulin had to ration the medication due to cost. According to Lipska, though recent advocacy efforts have led to a decrease in insulin prices, the medication remains expensive.

These novel medications are not cheap. Patients with Type II Diabetes — a condition in which insulin is unable to lower a patient’s blood sugar — often pay over $900 per month for Ozempic. Similarly, patients suffering from obesity have to pay $1,300 a month for Wegovy. Patients must take these medications continuously for an indefinite period in order to maintain their ongoing effects. 

“Patients are looking at a potentially lifelong treatment and could be facing the most expensive subscription service in the history of medicine,” Lipska told the News.

In the hearing, Lipska noted that if Medicare were to cover Wegovy for its beneficiaries with obesity, American taxpayers would have to pay $268 billion. 

Further, according to a study conducted by Luan Yu, a cardiologist and assistant professor of medicine at the School of Medicine, the populations least able to afford these treatments are the ones who need them the most.

“We found that these minority populations who have higher prevalence of obesity also have more financial barriers, in terms of accessing healthcare and afford[ing] the medications,” Lu told the News.

However, other countries are avoiding these steep costs. Lipska testified that Ozempic costs $100 per month in Sweden and just $80 in Australia and France.

In contrast, patients in the U.S. must pay 10 times that amount. For Lipska, the lessons learned from insulin affordability should inform how the government negotiates prices with pharmaceutical companies for novel medications like Ozempic.

“The Inflation Reduction Act already authorizes the Secretary of the Department of Health and Human Services to negotiate prices with pharmaceutical companies under specific provisions, and for a limited set of drugs,” Lipska told the Senate.

According to Lipska, this process involves aligning the launch price with the drug’s value and what patients can afford. She argued the government should sit at the negotiating table with pharmaceutical companies such as Novo Nordisk, the developer of Ozempic which has a market value higher than Denmark’s GDP. 

Still, Lipska emphasized the need to tackle diabetes and obesity upstream, instead of relying on drugs. For her, more long-term preventative solutions, such as reducing food deserts, are more favorable than using weight-loss medications. 

“In cardiovascular disease prevention, we always talk about prevention being more cost-effective than management or treatment,” Lu told the News. “It’s better to prevent people from becoming obese. Then, if they become obese, you treat them.”

In the hearing, Senator Bernie Sanders — chair of the Senate Health, Education, Labor and Pensions Committee — underscored Lipska’s call to action. 

“Nearly 30 years ago as I think we all know and the American people know, Congress had the extraordinary courage to take on the tobacco industry whose products killed nearly 400,000 Americans every year including my father,” he said. “Now is the time for us to seriously combat the Type II Diabetes and obesity epidemics in America.” 

Over one in 10 people in the United States suffer from diabetes.

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Led by Dr. Hong-Bo Zhao, professor of otolaryngologic surgery at the School of Medicine, the research explores the link between hearing loss and developing Alzheimer’s, the progressive brain disease that results in memory loss and cognitive impairment.

According to Zhao, many scientists in the field recognize that hearing loss can preempt cognitive decline. How exactly hearing dysfunction may be linked to Alzheimer’s, though, is still unclear — a topic that Zhao aims to study through a new $2.4 million grant from the National Institute on Aging announced earlier this month. 

“They encouraged us to perform this kind of study because early diagnosis is crucial for the disease,” Zhao said. “Now maybe we can find a way to block such a degenerative process.”

Currently, there is no effective method to treat or prevent Alzheimer’s disease, and existing treatments depend on detecting the disease as early as possible, Zhao said. An early Alzheimer’s diagnosis and corresponding intervention that delays dementia — the progressive decline of cognitive capability — by just one year could decrease the amount of dementia worldwide by 10 percent.

Zhao believes that even before dementia and other Alzheimer’s symptoms arise, changes in the way the brain processes sound might be an early warning sign for Alzheimer’s disease. His new research aims to explore the link between auditory processing and Alzheimer’s, especially since hearing loss commonly occurs 5-10 years before dementia symptoms show up in patients.

“Very few people study the auditory system changes in Alzheimer’s disease,” Zhao told the news. “Our lab is one of the few labs to perform such a study in the United States.”

With the new grant, Zhao’s lab plans to use mouse models in which researchers modify mouse genes to increase the number of times they are expressed. When the mice overexpress these genes, they show dementia symptoms — effectively guaranteeing that the mice will develop Alzheimer’s.

As the mice grow, Zhao’s team plans to perform RNA sequencing tests on the parts of the mice’s brains linked to auditory processing. The sequencing tests measure genetic changes in the brain areas linked to hearing.

If these changes happen in consistent patterns before the mice exhibit dementia symptoms, the gene changes could be an early indicator for Alzheimer’s — a “biomarker,” Zhao said. 

And just as human patients often have hearing loss before developing Alzheimer’s symptoms, Zhao’s team also plans to evaluate the mice’s hearing before they display signs of dementia, measuring changes in the mice’s brain activity in response to external sounds.

“We basically conduct hearing tests. said Dr. Yang Yang, a postdoctoral associate in Zhao’s lab. “And we do testing like the EEG [electroencephologram] … and try to see if there is any difference.”

One of the challenges the researchers face, though, is to distinguish the symptoms of Alzheimer’s from those of natural aging. According to Yang, age-related hearing loss is difficult to distinguish from hearing loss linked to Alzheimer’s, making it difficult to pinpoint a precise relationship between the two conditions.

For the researchers, overcoming that confounding variable was one reason to opt for the mouse model, where young mice can be evaluated for hearing and memory loss before the symptoms of age set in. 

Even in genetically modified mice as young as three months old, Zhao’s team has observed hearing loss. Their onset of Alzheimer’s occurred at nine months, indicating that dementia — not age — was tied to hearing loss.

Identifying Alzheimer’s biomarkers through auditory pathways may pave the way for advancements in early detection and intervention strategies, Zhao explained. Even if doctors can’t cure the disease, creating reliable ways to detect Alzheimer’s earlier — in this case, through changes in the hearing pathway — could help patients better manage their symptoms and slow the progression of dementia. 

For Zhao’s peers, it’s a promising goal.

“Our Department is very excited that his work may offer breakthrough understanding of Alzheimer’s, a devastating disease that definitely involves the auditory system,” Dr. Joseph Santos-Sacchi, a professor of otolaryngologic surgery, cellular and molecular physiology and neuroscience, wrote to the News.

According to the World Health Organization, one in ten people will have disabling hearing loss by 2050.

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In middle school, Hereen said, a classmate followed her around and threw paper at her, calling her “a whale.” Heeren said that during a doctor’s visit, one health provider told Heeren’s mom, “just don’t feed her cookies for dinner.” 

Hereen told the News that ever since she can remember, she has consistently measured in the 99th percentile for her weight. 

Heeren’s family implemented dietary changes — she avoided foods with additives and preservatives and packed healthy snacks whenever she went to social events — but, she said, the weight never seemed to come off. 

Things reached a breaking point when she attended her brother’s science olympiad tournament, Heeren said. Sitting in the crowd, she said she felt the sides of the chairs pushing into her thighs.

 “It felt like me and my body were at war,” Heeren told the News. 

Though Heeren and her family thought they had already done everything they could, Heeren said they decided that she needed a more dramatic intervention: bariatric surgery. 

Following her surgery, Heeren founded OCEANS Lifestyles — a support group for teens who have received a gastric bypass surgery. She now advocates for teens’ right to make their own decisions and to be fully informed about their treatment options for obesity.

Bariatric surgery describes various medical procedures that help manage obesity. Sleeve gastrectomy — one of the most common types — permanently reduces the size of a patient’s stomach, restricting how much food they can eat in one sitting. The surgery also reduces the amount of hunger hormones the stomach produces. 

This January, the American Academy of Pediatrics included bariatric surgery in their clinical guidelines for treating children with obesity, which emphasized providing immediate, intensive obesity treatment shortly after a diagnosis. 

Previously the AAP advocated for a policy of “watchful waiting,” which some experts have said failed to recognize obesity as a chronic illness. The new policies state that pediatric healthcare specialists should refer adolescents 13 years of age or older with severe obesity — referring to a BMI greater than or equal to 120 percent of the 95th percentile — for evaluation for bariatric surgery. 

Surgery and recovery process

Since the AAP released the guidelines, Alan Hornick, an assistant professor of surgery in pediatrics at the Yale School of Medicine, told the News he has seen an uptick in adolescents and parents interested in bariatric surgery — especially in younger patients. 

“I think people are now more inclined to think of surgery as a kind of a first line in slightly younger patients,” Hornick said.

According to John Morton, the medical director for bariatric surgery at Yale New Haven Health System, the most common bariatric surgeries performed on adolescents is a sleeve gastrectomy.

At Yale, adolescents seeking bariatric surgery first enter the adolescent weight loss program, supervised by Michelle Van Name, an assistant professor of pediatrics in endocrinology, and her team. In this program, Van Name said, the patients undergo a comprehensive evaluation, including nutrition, psychological assessment and physical and emotional maturation. 

Van Name and her team refer the patient to bariatric surgery only if all the criteria are met and there is full family and patient support. The patient or their family can opt out of the surgery at any point during this process, she added.

“We want our patients and their families to be making an informed decision,” Van Name told the News. “It’s also important for them to know what medications are currently approved to treat the disease of obesity, and make sure everybody has up to date information so that they can decide if this is the right time in this adolescent’s life for them to follow this treatment path.”

After the initial evaluation, Morton and Hornick conducted further observation, typically meeting with the patient six times before the surgery to offer habit-change encouragement and ensure rigorous preparation, Morton told the News. 

According to Morton, he will choose not to perform the surgery if the patient has an active substance abuse or an untreated mental illness, or if the family is not willing to implement lasting changes in the household.

“Otherwise, it’s a very difficult problem,” Morton said. “It would be like sending home an asthmatic child to smokers.”

Morton said that before the surgery some patients are prescribed weight-loss drugs, such as Wegovy or Mounjaro, to lower the patient’s weight before surgery. Two weeks before surgery, patients adhere to a liquid diet, which he said helps shrink the patient’s liver and kick starts weight loss in the patient.

According to Morton, the procedure takes roughly 45 minutes. He said that he makes four incisions, each less than three-quarters of an inch. Morton said that he then takes the stomach —  roughly the size of a football — and uses a surgical stapler to remove two-thirds of the stomach, leaving it about the size of a banana.

“The portion of the stomach we removed is not essential for digestion,” Morton said. “Its main role is to allow us to eat more. That rendered an evolutionary advantage to us many years ago, when we weren’t sure where our next meal was coming from. Now with all the food availability, we don’t need it.”

After the surgery, patients recover in the hospital for one or two days, he said. 

Then, according to Morton, they are put on a gradual diet escalation. For two weeks, he said, the patients only consume liquids and go on a puréed diet for a couple of weeks. Morton said that once patients return to regular eating, physicians recommend that they exercise and consume more protein and fewer carbohydrates and sugars.

“Once they are discharged from the hospital, we talk to them nearly daily, once they are discharged from the hospital, and then we see them monthly,” Van Name said. “Adolescents tend to need support.” 

According to the AAP guidelines, bariatric surgery can result in weight loss and improvements in multiple conditions associated with obesity, such as hypertension, Type 2 Diabetes and cardiovascular disease.

Morton said he has also conducted a study that found that the surgery produces a “halo effect,” where family members tend to lose weight when a patient undergoes the surgery.

Weight loss, transformations, and criticisms

Heeren said the surgery transformed her relationship with her body. 

“Afterwards, I finally was able to live my life in a healthy way and have my body be able to go on runs and be able to play tennis,” Heeren said. “It felt like we were a little bit more at peace.”

Heeren said that she had to overcome several hurdles during her surgery journey. She said that had to miss school days, and her mother had to miss work so she could attend pre-operative visits that took up multiple hours.

Heeren said that some people in her community criticized her parents for allowing her to have the surgery.

“There’s a lot of people who thought that [my parents] were doing something that was going to be putting me in danger instead of helping me,” Heeren said. “A lot of times, people criticize parents of kids living with obesity and blame them for why their children are struggling. My parents had it coming from a bunch of different directions growing up.”

Many patients also struggle to receive insurance coverage for bariatric surgery, forcing patients to pay for the surgery out of pocket, which limits access to the surgery. 

Balancing benefits and concerns 

Potential complications that come with the surgery include bleeding, infection, reflux for sleeve procedures, blood clots and nutritional deficiencies, according to Morton. Yet, he said the surgery is as safe as a knee or hip replacement.

“I’ve had the good fortune of, over the last 22 years, not having any operative mortality, and that’s been over 6,000 cases,” Morton told the News.

Despite the relatively safe track record for bariatric surgery that Morton described, some people have criticized the AAP for including it in their guidelines. After they first released the guidelines, both the New York Times and Mental Health America published opinion articles that expressed concern about the surgery. 

Mona Sharifi, an associate professor of pediatrics and biostatistics at the Yale School of Medicine, helped write the AAP’s guidelines. According to Sharifi, to produce the guidelines, a team of clinicians sifted through thousands of scientific articles and generated a summary of the results, which they translated into policy. 

Sharifi said she felt that some of the initial criticisms focused too much on the medication and surgery recommendations, failing to recognize that the AAP also promoted various weight treatments within the context of a family’s preferences and options.

“We very carefully placed the recommendation on making a referral or connecting families with a program — not that surgery should be done,” said Sharifi. “They don’t necessarily mean that when you’re referred, you’re gonna have bariatric surgery.”

About 2,000 adolescents receive gastric bypass surgeries every year in the United States.

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Loved ones, medical staff, and the patients themselves doubt the reality of their symptoms. Doctors struggle to offer them explanations.  

At the Yale Multidisciplinary Long Covid Clinic, however, medical workers try to unravel the mystery of long COVID. The center is directed by Lisa Sanders, associate professor of general medicine, who is no stranger to medical mysteries like long COVID. She currently writes the “Diagnosis” and “Think Like a Doctor” columns for the New York Times, and she previously published two medical books,“Every Patient Tells a Story: Medical Mysteries and the Art of Diagnosis” and “Diagnosis: Solving the Most Baffling Medical Mysteries.” 

In her role as director, Sanders is essentially a detective in a white coat. When a patient is referred to the clinic, Sanders first investigates whether the culprit is long COVID. This process involves ruling out other factors that may cause similar symptoms. For example, if a patient reports feeling fatigued, she checks that the patient does not have sleep apnea. According to Sanders, by repeating this process, the researchers remove some uncertainty from a long COVID diagnosis. 

From there, Sanders told the News, she tackles the downstream effects of the disease. Because the symptoms of long COVID are known and treatable, Sanders said she can treat the effects, despite not understanding the root cause.

“If you can’t treat the actual disease, just treat the symptoms that are tormenting people and reassure them that at least some people get better,” Sanders said. “Depending on who you read, 80-plus percent of people don’t have symptoms after a year.”

The Yale Multidisciplinary Long Covid Clinic is on the third floor of Yale New Haven Hospital’s St. Raphael Campus. Patients enter a waiting room adorned with long COVID support group flyers and prints of beach paintings. A narrow hallway connects Sanders’ office, an examination room and a physical therapy room.

Sanders said that next month the Center will move to a larger space.

“Our patients say ‘oh my god, this is such a small room, this is such a small space.’ Like really?” Sanders said. “It’s gonna be so luxurious.”

Despite its small size, the Center provides each patient with help from social workers, physical therapists and Sanders. 

Early in the pandemic, this level of treatment was not available to long-haulers, a colloquial term for people with long COVID. Instead, patients in New Haven with long COVID symptoms had to seek out specialists in separate departments that best aligned with their symptoms, Sanders said. Sanders said that eventually, specialists realized that the best way to help people with long COVID was not with specialty care, rather, it was with a specialized long COVID Center. Sanders was immediately interested in leading the center.

“The thought that I could learn about this, and maybe help people with it seemed appealing,” Sanders told the News.

Part of this learning is trying to define long COVID. 

Characterized by persistent symptoms long after initial infection, long COVID remains a puzzling challenge for patients, healthcare professionals and researchers. However, common symptoms include fatigue, brain fog, cough and shortness of breath after their initial COVID-19 infection, Sanders told the News. For many patients, these symptoms can become physically and emotionally debilitating, Sanders said.

“You had COVID, and then something bad happened,” Sanders said. “But that’s all we can say now because we have no idea what the pathophysiology is.”

Parallels to polio

COVID-19 is not the first epidemic to leave a wake of people experiencing lingering symptoms, said Naomi Rogers, a history professor at Yale who studies 20th and 21st-century medicine and disability. 

In the middle of the 20th century, the United States weathered a series of polio outbreaks, a virus that primarily affects children and can, in rare cases, cause long-term paralysis. One 1955 polio epidemic infected 3,950 people in Massachusetts. Of those infected, 2,771 were paralyzed, some for a few weeks or months and some permanently.

“Polio was seen as a really scary disease because of its disabling effects,” Rogers said. “Everybody feared that if their child got it, they would never be able to work independently or live independently.” 

According to Rogers, some patients with polio also developed “post-polio” syndrome. These people had polio as children and fully recovered, but then, decades after their illness, became paralyzed.

Rogers pointed to similarities between post-polio syndrome and long COVID. Like patients with long COVID, people with post-polio syndrome continued to have symptoms of the disease long after the actual infection had passed, Rogers said. Some patients with post-polio were dismissed by their doctors because the doctors had never heard of the disease, according to Rogers. People with post-polio syndrome, like those with long COVID, Rogers said, had to advocate for themselves in medical settings and seek ways to alleviate their symptoms outside of traditional medicine. 

Rogers also highlighted similarities between long COVID and diseases such as chronic Lyme and Chronic Fatigue Syndrome. For people with these conditions, she said, it is difficult to make friends, family or doctors aware that there is an actual disease behind what she said are relatively vague symptoms. 

“You can’t see pain. You can’t see weakness. There are a lot of chronic responses that are not visible,” Rogers said.

In addition to vague symptoms, Rogers said that long COVID is complicated because nobody knows exactly what it is or how to think about it. 

Unlike other chronic diseases such as cancer or AIDS, she explained, long COVID is too recent for the public to have a clear picture of what it is like. 

“When we say long COVID, we don’t have in our minds what long COVID looks like,” Rogers said. 

Studying Long Covid

A group of interdisciplinary researchers at Yale are working to uncover what long COVID is and how it can be treated. 

During the pandemic, researchers at Yale, including Akiko Iwasaki, Sterling Professor of immunobiology at the School of Medicine, noticed that some patients who had COVID-19 developed chronic symptoms that lasted for a long time after their infection. Iwasaki and her lab also noted that some people who got the COVID-19 vaccine had an immune response.

As the pandemic progressed, Iwasaki established a network of researchers studying COVID-19 who also wanted to understand the unusual immune responses caused by COVID-19. This collaboration became the Center for Infection and Immunity, or CII, which opened in August 2023. 

The center, which Iwasaki directs, seeks to understand how chronic diseases develop and uncover links between infection and chronic disease. It also tries to connect immune responses to factors such as sex, genetics, age and environment, and develop therapies for treating chronic disease.

Iwasaki said that, because post-acute syndromes, such as long COVID, are difficult to understand and quantify, studying them requires an interdisciplinary approach.

Patient-centered approach

In studying chronic disease, the CII seeks to include patients as full participants in their research. CII partners with the Center for Outcomes Research and Evaluation, or CORE, to enhance their patient-centered research approach.

“We’re trying to create a different spirit around the research,” Harlan Krumholz, a professor at the School of Medicine and the director of CORE told the News. Krumholz is also on the CII leadership team. 

Krumholz said patients with post-acute syndromes are “desperate for answers.” 

But because chronic syndromes like long COVID are poorly understood, he said many patients feel “abandoned” by doctors, caregivers and the medical system. 

“There’s not one evidence-based therapy,” Krumholz said. “We even have trouble defining the condition, because there aren’t any diagnostics.”

To combat this feeling of neglect, CORE and CII developed a new model for doing patient research which Krumholz called “highly participant-centric.”

One way the researchers study long COVID is through the Yale LISTEN study, which stands for Listen to Immune, Symptom and Treatment Experiences Now. The LISTEN study follows a pool of participants with long COVID who share health data and specimens like blood or saliva with researchers. 

People participating in the LISTEN study can opt to participate in different research projects. For example, the CII is also conducting a trial on the effect of Paxlovid — an antiviral drug used to treat COVID-19 — on long COVID. 

The trial is being conducted virtually, to make it easy for people to participate in research. Patients involved in the study receive drugs or placebo pills by mail, then fill out surveys online and electronically transmit their data to researchers. 

The trial organizers also hold regular town hall meetings, where study participants can ask questions and suggest changes. When researchers learn new information through their research, they share it with the participants. 

New long COVID study gives hope to researchers, patients 

In September, researchers from the CII and Mount Sinai Hospital published a paper in Nature that identified biological markers associated with long COVID. By analyzing blood samples, the researchers found that hormonal dysfunction, exhaustion of certain immune cells and the reactivation of latent viruses are key factors in long COVID. 

“To us, that means that there is an immunological underpinning to this disease,” Iwasaki said. 

According to Iwasaki, the evidence that long COVID is a biological disease is an important discovery not only to understand the disease but also to validate patients’ struggles. People suffering from long COVID and other chronic diseases are often perceived as inventing or exaggerating their illness, Iwasaki said. 

The idea that patients are making up their symptoms, Iwasaki said, is one of the major misconceptions that the CII seeks to debunk. Iwasaki added that the identification of biological markers helps dispel the belief that long COVID is only a psychiatric illness. 

Sanders said she believes there should have never been a need to prove long COVID patients had an actual disease. 

“I never thought they needed any validation. I thought that people who saw it as psychiatric alone were nuts,” Sanders told the News. “Eleven million people have long COVID in the United States alone, and there’s so many more than that in the world. Over a million people don’t just come up with the same problem.” 

Long COVID is not the CII’s only focus. Researchers at the Center also study diseases such as chronic Lyme disease, which is a disease spread by ticks, and myalgic encephalomyelitis chronic fatigue syndrome, or ME/CFS.

While post-acute syndromes are complex and tricky to study, long COVID provides a unique research opportunity, Iwasaki said. People with the disease became ill around the same time and from the same virus, which allows researchers to simultaneously study a large number of people who have a similar chronic illness. 

Iwasaki said that it is difficult to find this kind of continuity with other post-acute viral syndromes because most chronic diseases occur in small numbers and at different times. 

Research developments often come up in conversation during visits to the Long COVID Clinic. Patients frequently tell Sanders about new research they have encountered, and Sanders will follow up on it. Sanders even has a Google alert that sends her every online publication that has to do with long COVID.

Like Iwasaki, Sanders views long COVID as a unique opportunity to develop our understanding of chronic illness.

“It would be terrible to waste this and not learn anything from it, like we have done with so many other infections,” Sanders said. “We have the technology and the curiosity. God only knows what other factors allowed this to be an active area of research, but I’m so glad it is.”

Adults aged between 35 and 49 exhibited the highest prevalence of experiencing long COVID.

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Before becoming Yale’s president, Salovey spent much of his research career investigating topics including jealousy, self-awareness and emotional intelligence. 

Salovey told the News that after he steps down, he intends join psychologists John Mayer and David Caruso to update the Mayer, Salovey, Caruso Emotional Intelligence Test — an the emotional intelligence test the trio developed in 2002. 

“Just a week or so before we knew he was stepping down, he agreed to participate in a research project,” Caruso, senior advisor to the dean of Yale College, said. “And we were both a little surprised. A week later, he announced he was stepping down. I think he’s now thinking about returning to his roots.”

Salovey’s former colleagues said that Salovey agreed to collaborate with them again just one week before announcing his plans to step down from the presidency.

The Mayer, Salovey, Caruso Emotional Intelligence Test — also known as the MSCEIT  — assesses emotional intelligence through a series of tasks and scenarios that measure different facets of emotional intelligence, such as recognizing others’ emotions, understanding the causes of emotions, effectively managing emotions and utilizing emotional information for problem-solving and decision-making. According to Caruso, the MSCEIT is unique because unlike other assessments that rely on self-reporting, their test has definitive right and wrong responses.

Some MSCEIT questions ask test-takers to analyze emotions in people’s faces or landscapes, while others ask participants to predict how someone would emotionally react based on a given scenario. The test takes 30 to 45 minutes for a participant to complete. 

Salovey and his collaborators told the News that they plan to update the MSCEIT to make it shorter and more interactive than previous iterations, Mayer said. The test will also adopt a new analytical method called “veritical judging” to determine the most “emotionally-intelligent” answer to a question. 

Their new method, according to Mayer, would rely on a panel of emotional experts and judges to answer the prospective questions that the researchers develop. If the experts and judges cannot agree on the most emotionally intelligent response to a question, Mayer said that question will not be included in the test.

Salovey’s early research on jealousy, joy and sorrow 

Before studying emotional intelligence, Salovey was first interested in jealousy research. This interest in studying jealousy and envy grew during his time working in Stanford University Psycology and Law Professor David Rosenhan’s laboratory while he was an undergraduate in the late 1970s. 

“I’ve always been interested in complex social emotions and their impact on thinking and behavior,” Salovey wrote to the News. 

Salovey pursued a doctoral degree in psychology under Judith Rodin, a former Yale provost and professor of psychology. In 1986, Salovey published three separate studies that analyzed the distinctions between social-comparison jealousy and romantic jealousy. 

In one of these studies, Salovey found that, on average, Yale undergraduates reported feeling more jealous during instances of social comparison — such as when “someone else gets a job that you want” — compared to instances of romantic envy, like when a romantic partner has an affair.

While he was working on publishing his research on jealousy, Salovey was also seeking to explore the connections between emotions, self-awareness and behavior in his dissertation. His research studied how fleeting emotional states — like positive and negative moods — can shape self-perception and influence an individual’s actions. 

“My PhD dissertation research was an attempt to figure out the connections between positive and negative emotions on helping behavior by studying in particular the thinking patterns that linked them,” Salovey wrote to the News. “I was especially interested in the way in which joy or sorrow changed what one thought about oneself.” 

Salovey found that participants who reported being in positive moods tended to report feeling higher levels of self-esteem at that moment. These participants were also more likely to attribute positive traits to external circumstances. Participants who reported being in negative moods reported having a lower sense of self-esteem. According to Salovey, these experiments were only partly successful, though he published a paper based on these findings five years later. 

The foundations of emotional intelligence 

In 1990, Salovey and Mayer, then an assistant professor of psychology at Yale, published a paper that laid the foundation for the concept of emotional intelligence, or EI. The duo defined emotional intelligence as the ability to recognize, understand, manage and utilize emotions effectively. Additionally, they argued that EI is distinct from cognitive intelligence or an IQ. 

Despite receiving pushback against their initial article, Mayer’s said that this criticism was crucial for improving their research. 

“We were fortunate enough to have really helpful smart colleagues who didn’t like what we were doing and expressed their criticism very clearly,” Mayer said. 

After Caruso joined Mayer and Salovey in their research, the team developed the MSCEIT in 2002. In response to scholarly criticisms and challenges since creating the MSCEIT, Mayer and Salovey said they have worked to refine their approach.  

According to his colleagues, Salovey played a crucial role in making these adjustments, even during his time as Univversity president. Caruso said that Salovey is a skilled science writer who often looked over research papers while they were in progress to ensure that they were communicating the findings in a clear and concise manner.

Alexander Rothman, a psychology professor at the University of Minnesota and one of Salovey’s earliest graduate students, said that Salovey has been dedicated to impacting science with a “balance of passion and humility” throughout his career.  

“He’s incredibly committed and focused to do the best work that you can do and to ensure that the work he does has the impact that he wants to have,” Rothman said. “He does it with a tremendous amount of humility.” 

Peter Salovey is the 23rd president of Yale University.

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Koskoff Koskoff & Bieder, the same law firm that represents the 68 other patients, filed the new complaint Tuesday, which highlights claims that the University failed to use proper safeguards to prevent siphoning of the clinic’s fentanyl supply. The complaint also claims Yale failed to notify previous patients who recieved treatment at the old New Haven location that investigators uncovered evidence of drug diversion in 2020. 

A November 2020 Drug Enforcement Agency, or DEA, inspection revealed that one nurse at the Orange facility, named Donna Monticone, had been stealing fentanyl for her own use and replacing it with saline, from June to October 2020. Monticone admitted to swapping fentanyl for saline during fertility procedures and was sentenced to four weekends in prison, three months of home confinement and three years of supervised release in 2021. 

The University agreed to pay $308,250 to the Department of Justice last October over allegations that Yale did not maintain accurate records and procedures to prevent the theft of narcotics.  

“The true scale of the mass diversion of fentanyl at Yale University remains unknown,” the Tuesday complaint claims.

The patients involved in the complaint allege that while they all but onethey received treatment at the clinic’s New Haven location in 2019, they experienced excruciating pain that was similar to that of the other 68 patients involved in suing Yale. 

According to a press release on Tuesday from Koskoff Koskoff & Bieder, the new plaintiffs began to suspect their cases were linked to those they heard about in, “The Retrievals,” the New York Times podcast that dropped this summer detailing Monticone’s fentanyl swapping. 

“When I learned years later that the excruciating pain I experienced was a direct result of the institution’s failure to properly manage controlled substances, and that nobody on my care team or administrators at Yale had reached out to tell me about this, I felt betrayed,” plaintiff Kaitlin O’Connor wrote in the law firm’s press release.

Meanwhile, the University maintains that the drug diversions were limited to the timeframe and facility in Orange that Monticone admitted to being responsible for. 

In a written statement to the News addressing the plaintiff’s claims on Tuesday evening, Karen Peart, a spokesperson from the University, emphasized that the Department of Justice’s investigation, which was connected to the DEA’s inspection, was thorough. 

“They concluded that the diversions took place specifically from June through October 2020,” Peart said.

In December 2020, Yale mailed a letter to patients who were treated at the Orange clinic, informing them of the drug diversion. According to the complaint, the complaint stated there to be “no reason to believe that this event has had any negative effect on your health or the outcome of the care that you received.”

According to the complaint, Yale’s letter told patients they would not be able to know if they were given saline instead of fentanyl during procedures. 

“The question and answer page accompanying the letter further stated that, ‘discomfort after a procedure [would not] indicate that I didn’t receive fentanyl,’ and that fentanyl ‘doesn’t play a role in reducing pain after the procedure,” the plaintiff’s attorneys wrote in the complaint. 

The plaintiffs argue that the letter did not mention that Yale violated the Controlled Substances Act, as the DEA investigation included several discoveries of loose caps on fentanyl vials. The lawsuit also claims that a Yale administrator determined the security processes at the REI clinic were inadequate.

“This is a case of staggering neglect and betrayal by Yale University,” Josh Koskoff, an attorney for the plaintiffs at Koskoff Koskoff & Bieder, said in the press release. “There is now overwhelming evidence that the University’s cavalier dismissal of women’s pain extended to both the Orange and Long Wharf REI clinics, meaning the painkiller diversion went on for a matter of years, during which they ignored evidence of diversion and left countless patients in the dark about the truth of what had happened to them.” 

Koskoff also sent an email to the University on April 7, 2021 requesting that Yale notify any patients who Monticone treated while she worked at Yale that she had swapped fentanyl for saline during patient procedures, according to the complaint. 

In the email, Koskoff asserted that Monticone may have been engaged in diverting fentanyl before 2020, when the clinic moved to Orange. 

The Yale Fertility Center is located at 200 West Campus Dr. in Orange.

Tristan Hernandez contributed reporting.

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The Yale team joins groups from Harvard, Stanford and the New York Genome Editing Center in receiving funding from fund BD²: Breakthrough Discoveries for Thriving with Bipolar Disorder. The Yale group is led by psychiatric neuroscience professor Hilary Blumberg and will focus on how mitochondria, the parts of the cell that turn food into cellular fuel, generate energy and on how differences in mitochondrial structures and energy productions pathways might play a role in bipolar disorder.

“Researching bipolar disorder has been my life’s work, motivated by wanting to reduce the suffering and high rates of suicide associated with the disorder,” said Blumberg, who is also the director of Yale’s Mood Disorders Research Program. “The field has made great progress, but it’s been very challenging to try to understand the causes of bipolar disorder when disciplines research pieces of the puzzle separately.”

According to Blumberg, many individuals with bipolar disorder report symptoms related to energy levels and their sleep — which are often linked to mitochondrial function. Genetic studies and other previous research have also suggested that mitochondria are key players in the disorder’s biological underpinnings. The Yale researchers believe that disrupted pathways in the mitochondria could play a major role in the development of bipolar disorder.

“What I think is really exciting and important, and is being facilitated by BD², is that pieces of a puzzle are now being brought together,” Blumberg said, “so now we can start to be asking the important questions like, what are the genetic and molecular mechanisms that underlie cellular changes and contribute to brain changes, and identify new treatment targets across these levels of scientific translation.”

Blumberg explained that the Yale team hopes to connect those puzzle pieces from different scientific fields to generate a multi-level understanding of bipolar disorder; she added that their research is divided into four aims.

Blumberg will lead the first aim, which focuses on the clinical features, symptoms, behaviors and brain circuitry of individuals diagnosed with bipolar disorder. Employing several brain scanning techniques, the researchers plan to examine differences in brain circuitry functioning and how mitochondria may be involved. 

Using a combination of magnetic resonance imaging techniques, including functional MRI, and a new imaging technology called broadband near infrared spectroscopy — or bNIRS — the researchers will be able to observe brain activity and mitochondrial activation in the same patient. 

In the second aim of the study, genetics professor and stem cell expert In-Hyun Park, will analyze blood samples collected from the participants who were scanned. Park’s lab will use these samples to generate cells called induced pluripotent stem cells (iPSCs), which can be used to create brain organoid models consisting of real neurons and other brain cells. 

This approach, Park said, provides a unique opportunity to explore the functioning of live brain cells and how they respond to medications.

 “From the stem cell, we can generate a brain-like structure called the brain organoid, which mimics the structure and function of the human brain,” said Park. “Using this model, we can compare the overall structure and neural activity and total gene expression and function between the healthy control and [bipolar disorder] patient.”

Directed by medicine and neuroscience professor Elizabeth Jonas, the study’s third aim will take a deep dive into the biochemistry of mitochondria using Park’s brain organoid models. Jonas’s research focuses on a protein in the mitochondria called ATP synthase, which contains a channel that ordinarily carries small charged particles — ions — across the mitochondria’s membrane during the process of generating cellular energy.

However, through her research, Jonas discovered a leak in the ATP synthase channel — one that lets ions escape. That leak can disrupt the delicate balance of ion concentrations on both sides of the mitochondria’s membrane — a balance that mitochondria use to moderate their energy production. As a result, Jonas explained, brain cells with the ATP synthase leak can be “hyperexcitable.”

Jonas’s research has previously shown evidence of this leak in the cells of individuals with bipolar disorder. Their brain cells, she’s also found, can be hyperexcitable. Through the new grant, Jonas hopes to tie everything together: understanding how the ATP synthase leak can play a role in causing bipolar disorder.

Cellular and molecular physiology professor Hongying Shen and psychiatry professor Kristen Brennand will oversee the study’s final aim. This research phase will focus on genetics of bipolar disorder, using advanced gene-editing tools like CRISPR Cas-9. The team aims to replicate earlier findings about bipolar disorder at the genetic and molecular levels. 

“What is especially powerful is performing this combination of research and integrating the work across the aims; for example, being able to look at someone’s brain scanning and in that same person studying their neurons,” said Blumberg, “And still more powerful will be performing the research in the context of the highly collaborative overall BD² research network.”

While the scientists are optimistic about their four-fold approach to studying bipolar disorder, they still face challenges during the research process. 

According to Jonas, one major complication stems from the limitations of brain organoids, which cannot fully replicate the intricacies of the human brain. The process of translating information from these organoids to the human brain is a complex endeavor, Jonas said.

“They’re not real brains,” said Jonas, “so we know that the brain organoids may tell us something about which cells in the real brain are abnormal, but they won’t tell us everything.”

But Blumberg said she remains hopeful about what the research represents and what it can produce.

She told the News that the grant they received represents growing support for new and highly collaborative efforts to study bipolar disorder. 

“We’re going to find out new things about bipolar disorder that will bring better help to people who are suffering with it,” Blumberg said. 

The Yale School of Medicine is located at 333 Cedar St.

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The National Suicide Prevention Lifeline is a hotline for individuals in crisis or for those looking to help someone else. To speak with a certified listener, call 988. 

Crisis Text Line is a texting service for emotional crisis support. To speak with a trained listener, text HELLO to 741741. It is free, available 24/7 and confidential.

To talk with a counselor from Yale Mental Health and Counseling, schedule a session here. On-call counselors are available at any time: call (203) 432-0290.  Appointments with Yale College Community Care can be scheduled here.

Students who are interested in taking a medical leave of absence should reach out to their residential college dean.

Additional resources are available in a guide compiled by the Yale College Council here.

As Alexis Joy D’Achille was about to give birth, a complication temporarily cut off her then-unborn daughter’s breathing. Though her daughter survived the birth without complications, Alexis blamed herself. 

Like one in seven new mothers across the nation, Alexis began suffering from postpartum depression. This is the most common complication associated with pregnancy, said Katrina Furey, a psychiatrist at the Yale School of Medicine. It is also undertreated. 

“Almost immediately, things were different,” said Steven D’Achille, Alexis’s husband. “She started to become very anxious. She couldn’t shake the thought that her very first act of motherhood was harming our daughter.”

Doctors prescribed Alexis the medication Zoloft, which is intended for major depressive disorder. But after starting on the medication, her condition worsened dramatically. Instead of switching her medication, her doctors doubled the dose.

For Alexis, though, the common treatments for major depressive disorders did not help with postpartum depression. In 2013, just six weeks after giving birth to her daughter, Alexis died by suicide.

Her husband hopes that the Food and Drug Administration’s recent approval of zuranolone — the first oral medication to specifically target postpartum depression — could prevent more stories like this one.

“I’m so excited for it because at least someone’s trying to do better,” said Steven D’Achille. “I’m sure there’s women that are alive today because of that drug.”

Postpartum depression manifests in the weeks and months after childbirth, Furey said, and it can be debilitating. The condition can lead to a loss of interest or pleasure, difficulty sleeping, feelings of worthlessness or guilt, fatigue, impaired concentration or indecisiveness, suicidal ideation and changes in weight or appetite. 

Unlike brexanolone, the alternative treatment for postpartum depression, zuranolone is typically taken orally for two weeks, Furey told the News. Patients can take the pill at home, whereas brexanolone requires patients to recieve doses intravenously for 60 hours in a hospital. During clinical trials, zuranolone showed promising results in treating symptoms in as few as three days.

According to Furey, zuranolone reduces symptoms of postpartum depression by tapping into the biology that causes the condition. 

During the third trimester of pregnancy, estrogen and progesterone levels are at their peak. When labor begins, and the baby is delivered, these hormone levels drop significantly and cause a major shift in the body’s chemistry. Some women are sensitive to this hormonal shift, which can lead to postpartum depression and other mental health issues.

  Zuranolone acts like a synthetic version of the hormone allopregnanolone, a byproduct of the hormone progesterone that is known for its calming effects. Women with postpartum depression tend to have lower allopregnanolone levels in their blood, so zuranolone is designed to supplement allopregnanolone levels in mothers with postpartum depression.

However, zuranolone was ineffective in people with major depressive disorder. 

“When they took pregnancy out of it, they didn’t see that effect,” Furey said. “It suggests there’s something unique about postpartum depression’s biology.”

As in Alexis’s case, doctors often prescribe medications for major depressive disorder to mothers with postpartum depression — but the results can be mixed. 

While Zoloft may have been ineffective for Alexis, it was difficult for her to receive treatment at all. After calling mental healthcare professionals for weeks while she was alive, Steven received calls back as late as two months after Alexis’s funeral. And when she talked to providers, Steven added, they often dismissed the idea Alexis was suffering from postpartum depression.

That situation is not unique to Alexis, Forey said. Only about 25 percent of women who are positively screened for postpartum depression receive treatment. In comparison, 61 percent of people who screened positive for major depressive disorder received treatment.

Some experts believe that developing an accessible drug that targets postpartum depression might help validate mothers’ experiences with the condition. 

“It will destigmatize things because there’s a medication that validates that experience,” said Dr. Joan Combellick ’91, an assistant professor of nursing at the Yale School of Nursing. “In a way, there’s part of me that is discouraged that we rely on a medication to validate something like a mental health condition.”

Zuranolone, however, might not be a panacea. There are still concerns surrounding the drug, Furey said.

None of the studies on zuranolone so far have looked at their safety for nursing mothers. While Furey would still recommend it to women, she acknowledged that some providers might be hesitant to prescribe it given the lack of testing on nursing mothers.

Still, Steven believes that zuranalone will offer a long-term net positive, even if it does not become a leading treatment.

“If it’s not zuranalone, there’s something good that’s going to come from it,” Steven said. “There are a lot of moms in the crowd that it did help.”

Zuranolone was developed by the biotechnology company Biogen.

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Harvey Kliman, a research scientist in obstetrics, gynecology and reproductive sciences and senior author of the study, developed a new classification system for pregnancy losses based on examining the placentas of babies who passed away. Of the millions of pregnancy losses each year, 40 percent are classified as “unexplained,” leaving families uncertain about the cause. Kliman said he seeks to use his research to help families understand what caused their loss.

“If you don’t know why it happened, invariably, these women feel that they must be responsible,” Kliman said. “Guilt is an understatement. They feel devastatingly responsible for the loss. They are already the mother of this child, and they feel they failed their child.”

The researchers found that the causes of pregnancy loss depend on the phase of the pregnancy, according to Parker H. Holzer GRD ’21, a Yale data science doctoral student and an author of the paper, wrote to the News. With the study, Holzer said the authors hope that doctors can now know what signals to look for at each stage of pregnancy, allowing doctors to hopefully further decrease the rate of pregnancy loss.

To uncover these signals, the researchers analyzed 1,256 placentas from 922 patients. All of these patients’ pregnancies had ended in loss and were referred to Yale’s consult service for evaluation. Of the pregnancies, 70 percent were miscarriages, while 30 percent were stillbirths. 

The researchers attributed the deaths to placental complications including cord accidents, abruptions, thrombotic issues and infections. They attributed other cases to two new categories, which they introduced — “placenta with abnormal development” and “small placenta,” which are placentas below the 10th percentile for gestational age.

  As director of volunteer organization Measure the Placenta, Ann O’Neill works to promote using the Estimated Placental Volume test placenta in prenatal care. The organization is comprised of parents who experienced stillbirths due to an undetected very small or large placenta. She told the News about the guilt she experienced when her baby, Elijah, was born still in 2018. 

“The pressing question that at first I was terrified to ask was ‘Why did he die?’” O’Neill said. “How could this seemingly healthy baby out of nowhere just die?”

When O’Neill turned to pathologists to find answers, she said they provided little help. They labeled Elijah’s passing as unexplained, but his pathology report had one oddity: Elijah, a large baby, had a small placenta. The size difference was so pronounced, according to O’Neill, that pathologists told her the placenta might not be Elijah’s. Though later genetic tests revealed it was his, O’Neill told the News that the pathologists initially wondered whether it might have accidentally been swapped with another placenta. 

O’Neill said she left the meeting with the pathologist feeling disappointed and still seeking answers. Later, O’Neill listened to a podcast in which Kliman discussed the possibility that a small placenta may cause stillbirths. Hoping to find an answer, O’Neill sent Elijah’s physical placenta to Kliman, who attributed Elijah’s death to his small placenta.

“Getting an answer from Kliman was huge in so many ways,” O’Neill said. “Number one, the self-blaming doesn’t happen.”

The study offers additional findings on a larger scale. The study suggests that placental examination can identify the cause behind approximately 99 percent of stillborn cases. The researchers noted that over 60 percent of unexplained stillbirths are due to “placental insufficiency,” or that the placenta is too small in proportion to the baby’s size. Another cause is placental dysmorphia, which describes the placenta’s shape or weight. 

Though the research may help provide closure to these families, Kliman said it will be difficult to translate into clinical changes. The American College of Obstetricians and Gynecologists sets clinical practices in this field. The ACOG requires direct scientific proof that changes to standard treatment, such as measuring the placenta, will result in different outcomes. 

In this case, Kliman said, it is nearly impossible to meet ACOG’s standards. Scientists can never be certain that a treatment will prevent a stillbirth, according to Kliman. Further, he said, it is difficult to change clinical practices because healthcare professionals are not trained in using the EPV test during their residency and fellowship programs. Consequently, Kliman said, some doctors might question the need to incorporate the EPV into their established routines. 

The study encourages clinicians to adopt the EPV tests to manage high-risk pregnancies and make informed decisions about the timing of delivery. If they identify a small placenta, along with other factors, early delivery may mitigate the risk of fetal loss before birth.

Still, the researchers said that the study has limitations. The study lacked comprehensive data on maternal demographics, such as race or ethnicity. Nevertheless, the researchers told the News they recognized that this could be an important point for further research. 

“This study will need to be confirmed by others, however it is likely to change our ability to diagnose the cause of pregnancy loss and potentially help to prevent this tragedy,” Hugh Taylor ’83, a professor of obstetrics, gynecology and reproductive science, wrote to the News. 

Following the study, Kliman said he hopes to explore the genomics underlying pregnancy losses and to delve deeper into the mechanisms that link dysmorphic placentas to pregnancy complications. 

Kliman and Taylor are now conducting an NIH-funded trial that sequences the entire genome of patients who have experienced more than one miscarriage. 

“It’s terrifying to find an answer, but when you do, the emotional guilt is relieved,” O’Neill said. “You have the weight off your shoulders. For future medical care, it’s crucial to understand what caused the previous loss so that in any future pregnancies you can be monitored for those things.”

Stillbirth affects one of every 175 births in the United States.

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