Expressive language sampling (ELS) is a useful tool for measuring communication development in youth with Down syndrome, a new multi-site study has found.
The study, co-led by Angela Thurman and Leonard Abbeduto from the UC Davis MIND Institute and the Department of Psychiatry and Behavioral Sciences, focused on language as an outcome measure to detect meaningful changes in communication skills of individuals with Down syndrome. It successfully tested and validated ELS as a reliable set of procedures for collecting, measuring and analyzing the spoken language of participants interacting in a naturalistic setting.
Down syndrome and language delays
Down syndrome is the leading genetic cause of intellectual disability. Approximately one in every 700 babies in the United States is born with Down syndrome. Individuals with Down syndrome frequently have speech and language delays that might severely affect their independence and successful community inclusion.
“Interventions leading to improvements in language would have great impacts on the quality of life of individuals with Down syndrome,” said Abbeduto, director of the UC Davis MIND Institute, professor of psychiatry and behavioral sciences and senior author of the study. “To develop and evaluate such interventions, we need a validated measurement tool and ELS provides that.”
The ELS procedure
During the ELS procedure, researchers collect samples of participants’ speech during two types of natural interactions: conversation and narration.

Worldwide, 1 in 4 people will suffer from a depressive episode in their lifetime.
While current diagnosis and treatment approaches are largely trial and error, a breakthrough study by Indiana University School of Medicine researchers sheds new light on the biological basis of mood disorders, and offers a promising blood test aimed at a precision medicine approach to treatment.
Led by Alexander B. Niculescu, MD, PhD, Professor of Psychiatry at IU School of Medicine, the study was published today in the high impact journal Molecular Psychiatry . The work builds on previous research conducted by Niculescu and his colleagues into blood biomarkers that track suicidality as well as pain, post-traumatic stress disorder and Alzheimer’s disease.
“We have pioneered the area of precision medicine in psychiatry over the last two decades, particularly over the last 10 years. This study represents a current state-of-the-art outcome of our efforts,” said Niculescu. “This is part of our effort to bring psychiatry from the 19th century into the 21st century. To help it become like other contemporary fields such as oncology. Ultimately, the mission is to save and improve lives.”
The team’s work describes the development of a blood test, composed of RNA biomarkers, that can distinguish how severe a patient’s depression is, the risk of them developing severe depression in the future, and the risk of future bipolar disorder (manic-depressive illness). The test also informs tailored medication choices for patients.
This comprehensive study took place over four years, with over 300 participants recruited primarily from the patient population at the Richard L. Roudebush VA Medical Center in Indianapolis. The team used a careful four-step approach of discovery, prioritization, validation and testing.

Patrick Radden Keefe has investigated human smuggling, government espionage and the Northern Ireland conflict. With “Empire of Pain,” he takes on the Sackler family and the opioid crisis.Patrick Radden Keefe has always been interested in secrets.“I think I have an almost childlike suggestibility where if you tell me you know a secret and you won’t tell, I’m going to do everything I can to figure out what that secret is,” he said in a video interview from his home in Westchester County, N.Y.But if you’ve ever read something Keefe, 44, has written, you may already sense that he has a passion for unearthing what’s hidden. In his 2009 book, “The Snakehead,” he reported on a human smuggling operation run out of New York’s Chinatown, untangling the web of the enterprise and highlighting its victims and its perpetrators. In his 2019 best-seller, “Say Nothing,” he dove into the decades-long sectarian conflict in Northern Ireland, particularly the mystery surrounding Jean McConville, a young mother who was kidnapped from her home in 1972.Now he’s back with a new book, “Empire of Pain,” out from Doubleday on Tuesday, that examines the opioid crisis. It’s a byzantine topic, but Keefe focuses on the Sackler family, which owns Purdue Pharma, the maker of OxyContin.“I didn’t want to write an opioid crisis book per se,” Keefe said. “The hope is that a certain kind of reader will be interested in this book, primarily as a story about a great American dynasty, and what I would argue is the corruption of a great American dynasty.”In a statement, a lawyer for Raymond Sackler’s family, Daniel S. Connolly, said, “Documents being released in Purdue’s bankruptcy now demonstrate that Sackler family members who served on Purdue’s board of directors acted ethically and lawfully.” A representative for members of Mortimer Sackler’s family said, “Our focus is on concluding a resolution that will provide help to people and communities in need, rather than on this book.”Like the tales in his books, the saga of how Keefe came to write about the Sacklers is anything but simple. In the 2010s, he was reporting on El Chapo, and wrote about the drug lord for The New York Times Magazine in 2012 and The New Yorker in 2014.During his research, he noticed the uptick in heroin usage in the United States. As he learned more about soaring opioid abuse, he stumbled on the Sackler name. He had heard of the family because the name is displayed at the Metropolitan Museum of Art, but he didn’t know much about them.So he began reporting. His first article about the Sacklers and the opioid crisis was published in The New Yorker in 2017. In 2018, Maura Healey, the attorney general of Massachusetts, sued Purdue Pharma, and in January 2019, court filings from the lawsuit were released. Sitting in his home office, Keefe read the documents and tweeted what he found.The documents gave him what he felt he needed to transform his reporting into a compelling book. “It was important for me to include the point of view of the Sacklers, even if they wouldn’t talk to me,” he said. “The stories the Sacklers tell themselves are really important.”In his statement, Connolly said Keefe “has refused to correct errors in his past reporting and also blatantly violated journalistic ethics by refusing to meet with representatives for the Sackler family during the reporting of his book.” In response, Daniel Novack, a lawyer for Doubleday, said, “Representatives for members of the Raymond and Mortimer Sackler family have attempted to disrupt this book from the outset with legal threats and unfounded attacks on Mr. Keefe’s professionalism. They refused to be interviewed or to substantively engage with Mr. Keefe’s request for comment.”By the time Keefe was ready to begin writing “Empire of Pain,” he was busy promoting “Say Nothing” and working on a Cold War podcast, “Wind of Change,” while also on staff at The New Yorker. Then the coronavirus pandemic struck, and cleared his calendar. “There was nothing left to do but write the damn book,” he said.He spent much of last year working on it while sitting on his bed, because he didn’t have access to his desk at work, and his wife, Justyna Gudzowska, a lawyer, was using their home office.Keefe working on “Empire of Pain” from his home during Covid lockdown.Justyna GudzowskaKeefe grew up as the oldest of three siblings in Boston. His mother was a philosophy professor at the University of Massachusetts, Boston, and his father worked in state government before becoming a real estate developer. He studied history at Columbia, followed by a master’s degree in international studies from Cambridge and a second master’s in new media and informations systems from the London School of Economics. When he returned to the United States, he enrolled in law school at Yale.Throughout his studies, he was pitching stories to The New Yorker and other publications, but he wasn’t getting assignments. (He framed a 1998 rejection letter from The New Yorker and hung it in his home office.) Eventually, Keefe took a year off from law school and worked on “Chatter,” a book about government eavesdropping, on a New York Public Library fellowship that was directed by the biographer Jean Strouse.“He just tunneled in and really worked,” Strouse said of Keefe. “He just finds these great, complicated stories and dives in.”She became a mentor, and Keefe began writing for The New York Review of Books, Slate and Legal Affairs. But he still wasn’t sure if he could be a full-time writer. He returned to Yale, finished his degree and in 2005 started studying for the New York bar exam. In the process, he became fascinated by the trial of Sister Ping, a woman accused of smuggling in Chinatown. Once again, he pitched The New Yorker. This time, Daniel Zalewski, the features director, said yes.“There is, I think, a prosecutorial zeal to his work,” Zalewski said. He has been Keefe’s primary editor ever since.“When he walks in my office door and begins to tell me something he’s excited about, it’s incredibly infectious,” Zalewski added. “He kind of chuckles to himself constantly, not because he’s self-impressed but because the story is delighting him so much.”Still, Keefe juggled writing and other jobs, including at the progressive think tank the Century Foundation and the Pentagon, before he was hired full-time at The New Yorker in 2012. Those experiences helped his reporting, he said. “I love legal documents, probably more than the next reporter.”Law school also “demystified the law for me a little bit. So when I get a threatening legal letter, I’m not as easily terrified,” he said. Even before he began working on “Empire of Pain,” he received such letters from a lawyer for the Sacklers.The pressure made him more determined to finish the book, he said. But he knows its ending may be unrewarding for readers. There’s no neat conclusion. Litigation over the opioid crisis is still ongoing, and Purdue Pharma filed for bankruptcy protection in 2019. But for Keefe, his book is a step.“The small thing that I can do is tell the story that is hopefully rigorous and compelling and creates a record for people who want to know what really happened,” he said. “And a kind of record that the family, as much as they might try, cannot really expunge. That’s not the accountability anybody wants, but it’s not nothing.”Follow New York Times Books on Facebook, Twitter and Instagram, sign up for our newsletter or our literary calendar. And listen to us on the Book Review podcast.

A pharmacist whose brother died after having the AstraZeneca vaccine has told the BBC she still feels strongly that people should continue have their jabs. Alison Astles’ brother Neil, 59, died of a blood clot on the brain on Sunday, after having the vaccination on 17 March.She said he was “extraordinarily unlucky” and that “more lives will be saved by people having the vaccine than not.”

Hundreds of sellers are offering false and stolen vaccine cards, as businesses and states weigh proof of vaccinations for getting people back to work and play.SAN FRANCISCO — On Etsy, eBay, Facebook and Twitter, little rectangular slips of paper started showing up for sale in late January. Printed on card stock, they measured three-by-four inches and featured crisp black lettering. Sellers listed them for $20 to $60 each, with a discount on bundles of three or more. Laminated ones cost extra.All were forgeries or falsified copies of the Centers for Disease Control and Prevention vaccination cards, which are given to people who have been inoculated against Covid-19 in the United States.“We found hundreds of online stores selling the cards, potentially thousands were sold,” said Saoud Khalifah, the founder of FakeSpot, which offers tools to detect fake listings and reviews online.The coronavirus has made opportunists out of many people, like those who hoarded bottles of hand sanitizer at the start of the pandemic or those who cheated recipients out of their stimulus checks. Now online scammers have latched onto the latest profit-making initiative: the little white cards that provide proof of shots.Online stores offering counterfeit or stolen vaccine cards have mushroomed in recent weeks, Mr. Khalifah said. The efforts are far from hidden, with Facebook pages named “vax-cards” and eBay listings with “blank vaccine cards” openly hawking the items.A screenshot of a “vax cards” page on  Facebook. Selling fake vaccination cards could break federal laws that forbid copying the C.D.C. logo, legal experts said. If the cards were stolen and filled out with false numbers and dates, they could also violate identity theft laws, they said.But profiteers have pressed ahead as demand for the cards has grown from anti-vaccine activists and other groups. Airlines and other companies have recently said they may require proof of Covid-19 immunization so that people can safely travel or attend events.The cards may also become central to “vaccine passports,” which offer digital proof of vaccinations. Some tech companies developing vaccine passports ask people to upload copies of their C.D.C. cards. Los Angeles also recently began using the C.D.C. cards for its own digital proof of immunization.Last week, 45 state attorneys general banded together to call on Twitter, Shopify and eBay to stop the sale of false and stolen vaccine cards. The officials said they were monitoring the activity and were concerned that unvaccinated people would misuse the cards to attend large events, potentially spreading the virus and prolonging the pandemic.“We’re seeing a huge market for these false cards online,” said Josh Shapiro, Pennsylvania’s attorney general, whose office has investigated fraud related to the virus. “This is a dangerous practice that undermines public health.”The C.D.C. said it was “aware of cases of fraud regarding counterfeit Covid-19 vaccine cards.” It asked people not to share images of their personal information or vaccine cards on social media.Facebook, Twitter, eBay, Shopify and Etsy said that the sale of fake vaccine cards violated their rules and that they were removing posts that advertised the items.The C.D.C. introduced the vaccination cards in December, describing them as the “simplest” way to keep track of Covid-19 shots. By January, sales of false vaccine cards started picking up, Mr. Khalifah said. Many people found the cards were easy to forge from samples available online. Authentic cards were also stolen by pharmacists from their workplaces and put up for sale, he said.Many people who bought the cards were opposed to the Covid-19 vaccines, Mr. Khalifah said. In some anti-vaccine groups on Facebook, people have publicly boasted about getting the cards.“My body my choice,” wrote one commenter in a Facebook post last month. Another person replied, “can’t wait to get mine too, lol.”Other buyers want to use the cards to trick pharmacists into giving them a vaccine, Mr. Khalifah said. Because some of the vaccines are two-shot regimens, people can enter a false date for a first inoculation on the card, which makes it appear as if they need a second dose soon. Some pharmacies and state vaccination sites have prioritized people due for their second shots.The tweet linked to a now-defunct Etsy shop that sold fake vaccine cards. One Etsy seller, who declined to be identified, said she had sold dozens of fake vaccine cards for $20 each recently. She justified her actions by saying she was helping people evade a “tyrannical government.” She added that she did not plan to get inoculated.Vaccine proponents say they have been troubled by the proliferation of forged and stolen cards. To hold those people accountable, Savannah Sparks, a pharmacist in Biloxi, Miss., began posting videos on TikTok last month naming the sellers of falsified vaccine cards.In one video, Ms. Sparks explained how she had tracked down the name of a pharmacy technician in Illinois who had nabbed several cards for herself and her husband and then posted about it online. The pharmacy technician had not disclosed her identity, but had linked the post to her social media accounts, where she used her real name. The video has 1.2 million views.“It made me so mad that a pharmacist was using her access and position this way,” Ms. Sparks said. The video drew the attention of the Illinois Pharmacists Association, which said it reported the video to a state board for further investigation.Ms. Sparks said her work had drawn detractors and vaccine opponents, who have threatened her and posted her home phone number and address online. But she was undeterred.“They should be first in line advocating for people to get vaccinated,” she said of pharmacists. “Instead, they’re trying to use their positions to spread fear and help people circumvent getting the vaccine.”Mr. Shapiro, the Pennsylvania attorney general, said in addition to violating federal copyright laws, the sale of counterfeit and stolen cards most likely broke civil and consumer protection laws that mandate that an item can be used as advertised. The cards could also violate state laws regarding impersonation, he said.“We want to see them stop immediately,” Mr. Shapiro said of the fraudsters. “And we want to see the companies take serious and immediate action.”

Music therapy is increasingly used to help patients cope with stress and promote healing.“Focus on the sound of the instrument,” Andrew Rossetti, a licensed music therapist and researcher said as he strummed hypnotic chords on a Spanish-style classical guitar. “Close your eyes. Think of a place where you feel safe and comfortable.”Music therapy was the last thing that Julia Justo, a graphic artist who immigrated to New York from Argentina, expected when she went to Mount Sinai Beth Israel Union Square Clinic for treatment for cancer in 2016. But it quickly calmed her fears about the radiation therapy she needed to go through, which was causing her severe anxiety.“I felt the difference right away, I was much more relaxed,” she said.Ms. Justo, who has been free of cancer for over four years, continued to visit the hospital every week before the onset of the pandemic to work with Mr. Rossetti, whose gentle guitar riffs and visualization exercises helped her deal with ongoing challenges, like getting a good night’s sleep. Nowadays they keep in touch mostly by email.The healing power of music — lauded by philosophers from Aristotle and Pythagoras to Pete Seeger — is now being validated by medical research. It is used in targeted treatments for asthma, autism, depression and more, including brain disorders such as Parkinson’s disease, Alzheimer’s disease, epilepsy and stroke.Live music has made its way into some surprising venues, including oncology waiting rooms to calm patients as they wait for radiation and chemotherapy. It also greets newborns in some neonatal intensive care units and comforts the dying in hospice.While musical therapies are rarely stand-alone treatments, they are increasingly used as adjuncts to other forms of medical treatment. They help people cope with their stress and mobilize their body’s own capacity to heal.“Patients in hospitals are always having things done to them,” Mr. Rossetti explained. “With music therapy, we are giving them resources that they can use to self-regulate, to feel grounded and calmer. We are enabling them to actively participate in their own care.”The Healing Power of Music“A Song for Wayne,” performed by Edie Elkan and written as she played at the bedside of a student who was dying.Even in the coronavirus pandemic, Mr. Rossetti has continued to perform live music for patients. He says that he’s seen increases in acute anxiety since the onset of the pandemic, making musical interventions, if anything, even more impactful than they were before the crisis.Mount Sinai has also recently expanded its music therapy program to include work with the medical staff, many of whom are suffering from post-traumatic stress from months of dealing with Covid, with live performances offered during their lunch hour.It’s not just a mood booster. A growing body of research suggests that music played in a therapeutic setting has measurable medical benefits.“Those who undergo the therapy seem to need less anxiety medicine, and sometimes surprisingly get along without it,” said Dr. Jerry T. Liu, assistant professor of radiation oncology at the Icahn School of Medicine at Mount Sinai.A review of 400 research papers conducted by Daniel J. Levitin at McGill University in 2013 concluded that “listening to music was more effective than prescription drugs in reducing anxiety prior to surgery.”“Music takes patients to a familiar home base within themselves. It relaxes them without side effects,” said Dr. Manjeet Chadha, the director of radiation oncology at Mount Sinai Downtown in New York.It can also help people deal with longstanding phobias. Mr. Rossetti remembers one patient who had been pinned under concrete rubble at Ground Zero on 9/11. The woman, who years later was being treated for breast cancer, was terrified by the thermoplastic restraining device placed over her chest during radiation and which reawakened her feelings of being entrapped.“Daily music therapy helped her to process the trauma and her huge fear of claustrophobia and successfully complete the treatment,” Mr. Rossetti recalled.Some hospitals have introduced prerecorded programs that patients can listen to with headphones. At Mount Sinai Beth Israel, the music is generally performed live using a wide array of instruments including drums, pianos and flutes, with the performers being careful to maintain appropriate social distance.“We modify what we play according to the patient’s breath and heart rate,” said Joanne Loewy, the founding director of the hospital’s Louis Armstrong Center for Music & Medicine. “Our goal is to anchor the person, to keep their mind connected to the body as they go through these challenging treatments.”Edie Elkan plays the harp as part of the music therapy program at Robert Wood Johnson Hospital in New Jersey.Edie ElkanDr. Loewy has pioneered techniques that use several unusual instruments like a Gato Box, which simulates the rhythms of the mother’s heartbeat, and an Ocean Disc, which mimics the whooshing sounds in the womb to help premature babies and their parents relax during their stay in noisy neonatal intensive care units.Dr. Dave Bosanquet, a vascular surgeon at the Royal Gwent Hospital in Newport, Wales, says that music has become much more common in operating rooms in England in recent years with the spread of bluetooth speakers. Prerecorded music not only helps surgical patients relax, he says, it also helps surgeons focus on their task. He recommends classical music, which “evokes mental vigilance” and lacks distracting lyrics, but cautions that it “should only be played during low or average stress procedures” and not during complex operations, which demand a sharper focus.Music has also been used successfully to support recovery after surgery. A study published in The Lancet in 2015 reported that music reduced postoperative pain and anxiety and lessened the need for anti-anxiety drugs. Curiously, they also found that music was effective even when patients were under general anesthesia.None of this surprises Edie Elkan, a 75-year-old harpist who argues there are few places in the health care system that would not benefit from the addition of music. The first time she played her instrument in a hospital was for her husband when he was on life support after undergoing emergency surgery.“The hospital said that I couldn’t go into the room with my harp, but I insisted,” she said. As she played the harp for him, his vital signs, which had been dangerously low, returned to normal. “The hospital staff swung the door open and said, ‘You need to play for everyone.’”Ms. Elkan took these instructions to heart. After she searched for two years for a hospital that would pay for the program, the Robert Wood Johnson University Hospital in Hamilton, N.J., signed on, allowing her to set up a music school on their premises and play for patients at all stages in their hospitalization.Ms. Elkan and her students have played for over a hundred thousand patients in 11 hospitals that have hosted them since her organization, Bedside Harp, was started in 2002.In the months since the pandemic began, the harp players have been serenading patients at the entrance to the hospital, as well as holding special therapeutic sessions for the staff outdoors. They hope to resume playing indoors later this spring.For some patients being greeted at the hospital door by ethereal harp music can be a shocking experience.Recently, one woman in her mid-70s turned back questioningly to the driver when she stepped out of the van to a medley of familiar tunes like “Beauty and the Beast” and “Over the Rainbow” being played by a harpist, Susan Rosenstein. “That’s her job,” the driver responded, “to put a smile on your face.”While Ms. Elkan says that it is hard to scientifically assess the impact — “How do you put a number on the value of someone smiling who has not smiled in six months?”— studies suggest that harp therapy helps calm stress and put both patients and hospital staff members at ease.Ms. Elkan is quick to point out that she is not doing music therapy, whose practitioners need to complete a five-year course of study during which they are trained in psychology and aspects of medicine.“Music therapists have specific clinical objectives,” she said. “We work intuitively — there’s no goal but to calm, soothe and give people hope.”“When we come onto a unit, we remind people to exhale,” Ms. Elkan said. “Everyone is kind of holding their breath, especially in the E.R. and the I.C.U. When we come in, we dial down the stress level several decibels.”Ms. Elkan’s harp can do more than just soothe emotions, says Ted Taylor, who directs pastoral care at the hospital. It can offer spiritual comfort to people who are at a uniquely vulnerable moment in their lives.“There is something mysterious that we can’t quantify,” Mr. Taylor, a Quaker, said. “I call it soul medicine. Her harp can touch that deep place that connects all of us as human beings.”

An Operation Warp Speed report last June flagged staffing and quality control concerns at Emergent BioSolutions’ factory in Baltimore. The troubled plant recently had to throw out up to 15 million doses.WASHINGTON — A top federal pandemic official warned last June that Emergent BioSolutions, the government contractor that last month threw out millions of doses of Covid-19 vaccines because of contamination, lacked enough trained staff and had a record of problems with quality control.A copy of the official’s assessment, obtained by The New York Times, cited “key risks” in relying on Emergent to handle the production of vaccines developed by both Johnson & Johnson and AstraZeneca at Emergent’s Bayview plant in Baltimore.The assessment, which has not been released publicly, was based in part on a visit to the plant just days after the government awarded Emergent a contract worth up to $628 million, mostly to prepare its factories to make coronavirus vaccines as part of Operation Warp Speed.Addressing the problems “will require significant effort,” and the company “will have to be monitored closely,” said the report, which was written by Carlo de Notaristefani, a manufacturing expert who has overseen production of Covid-19 vaccines for the federal government since last May. Though marked as a draft, federal officials said the report was considered to be final.Ten months after his report, the plant has become a major headache for the team named by President Biden to oversee the pandemic response. The Times reported on Tuesday on a host of quality control problems, flagged in audits and investigations by AstraZeneca, Johnson & Johnson, two federal agencies and Emergent’s own quality evaluators.Federal officials ordered major changes to the plant after revelations late last month that Emergent had to jettison between 13 million and 15 million doses of Johnson & Johnson’s vaccine. It is not clear what will happen to another 62 million doses of the vaccine produced at the plant, or whether Johnson & Johnson will be able to deliver the 24 million doses it has promised to the federal government by the end of the month.So far, the Food and Drug Administration has not certified the factory to distribute any doses for public use, and the agency is not expected to do so until it conducts a thorough review, which can take weeks.Asked about the June report, a company spokesman said on Wednesday night: “Emergent’s top priority continues to be the strengthening of the supply chain for Johnson & Johnson’s vitally needed Covid-19 vaccine.”Biden administration officials insist that the government has enough doses from the other two federally authorized vaccine makers — Pfizer-BioNTech and Moderna — to cover the vast majority of the nation’s roughly 260 million adults. But federal officials are still concerned about Emergent’s problems, not only because the federal government has invested heavily in the plant, but because there may be implications for the world’s vaccine supply if the issues are not resolved.AstraZeneca was expected to fulfill the majority of the global need, but safety concerns have upended those plans. British officials said on Wednesday that people under 30 should not take the AstraZeneca vaccine, and authorities in the European Union said they had found a “possible link” between the vaccine and rare but worrisome blood clots. That makes Johnson & Johnson’s vaccine more important, experts say.Emergent was forced to discard the Johnson & Johnson doses after checks revealed contamination with a virus used in the production of the AstraZeneca vaccine. An investigation is now underway, but federal and former company officials suspect the lot was tainted because an employee moved from AstraZeneca’s section of the plant to Johnson & Johnson’s without showering and taking other precautions.Between October and January, Emergent threw away five lots of the AstraZeneca vaccine — each the equivalent of two million to three million doses — because of contamination or suspected contamination, The Times reported on Tuesday.By giving Emergent a key role in its coronavirus response, the government was counting on the company to deliver on a promise made more than eight years earlier. To ensure a domestic supply of vaccines in a pandemic, the government had awarded Emergent a $163 million contract in 2012 to ready the Baltimore plant for mass production in a crisis.But Mr. de Notaristefani wrote that Emergent had used the site primarily for smaller development projects. To make large amounts of Covid-19 vaccines, the company “will have to strengthen” its quality controls, requiring “significant resources and commitment,” he wrote.His report was based in part on a visit to the plant on June 4 last year, as well as information provided by the company and conversations with the Biomedical Advanced Research and Development Authority, the federal agency that awarded Emergent the manufacturing contract.It is unclear what action, if any, the Trump administration took in response, or whether the Biden administration reviewed the findings before the recent problems arose.Mr. de Notaristefani, a former top executive at two major pharmaceutical companies, cited “significant” personnel problems, writing that plans to increase staffing seemed “inadequate to enable the company to manufacture at the required rate.”He also noted that audits by the F.D.A. and individual companies that had hired Emergent “highlighted the need for extensive training of personnel, and strengthening of the quality function.”Nonetheless, he wrote, “the organization has the necessary experience/competence” to scale up its manufacturing. He wrote that “management is knowledgeable and appears self-confident,” and with enough government oversight, “risks can be mitigated.”At the time of the visit, Emergent also planned to make a third Covid-19 vaccine, developed by Novavax, but that company has since partnered with another manufacturer in a government-backed deal. “Offloading the Novavax program to a different facility will also help reduce the load on Emergent Bayview,” Mr. de Notaristefani wrote.Emergent is a longtime federal contractor in the area of biodefense. Sales of its anthrax vaccines accounted for nearly half the Strategic National Stockpile’s half-billion-dollar annual budget through most of the last decade, The Times reported last month. That left the government with less money for items needed in a pandemic, and last year, the stockpile’s shortage of basic medical supplies became a symbol of the government’s bungled coronavirus response.Though the original federal contract for the Baltimore plant required Emergent to demonstrate large-scale manufacturing of a pandemic influenza vaccine — envisioned by health officials as a pressure test of its abilities — Emergent had yet to do so, The Times reported on Tuesday. The company risked defaulting on the original deal, which had set a deadline of June 2020. The company also has separate agreements with the two vaccine makers worth more than $875 million.In the effort to resolve the factory’s troubles, federal officials have simplified Emergent’s mission, limiting it to only producing Johnson & Johnson’s vaccine and forcing AstraZeneca to move its production lines elsewhere. Johnson & Johnson is also now asserting direct control over the manufacturing, although the work force at the plant in southeast Baltimore remains Emergent’s.The existence of Mr. de Notaristefani’s assessment was reported earlier by Politico, but its details were not previously known. Asked about the report on Wednesday, the White House spokeswoman, Jen Psaki, said she “would have to check on the specifics.”Mr. de Notaristefani’s concerns were echoed by two former plant supervisors, who spoke on the condition of anonymity for fear of career repercussions. In interviews with The Times, they cited crushing workloads and shortcuts taken to meet unrealistic timetables.Mr. de Notaristefani noted that Emergent planned to boost the factory’s work force to nearly 300. It now has 600 workers, according to the company’s spokesman. Even so, the ex-supervisors said, employees are overwhelmed, and some are often forced to work more than 70 hours a week.A review of months of company logs obtained by The Times showed that employees repeatedly said they deviated from manufacturing standards because of a lack of manpower and shortened production times.

In an article published in the April 8 issue of Nature, the National Institutes of Health’s Somatic Cell Gene Editing Consortium provided a detailed update on the progress of their nationwide effort to develop safer and more effective methods to edit the genomes of disease-relevant somatic cells and reduce the burden of disease caused by genetic changes.
Gene editing allows scientists to modify sections of an organism’s DNA and is considered a promising treatment for a number of genetic diseases. There have been numerous advances in the laboratory over the last few decades, but there are still many challenges to overcome before gene editing can be widely used in the patient population. Launched in 2018, the Somatic Cell Gene Editing Consortium (SCGE) has brought together some of the leading researchers in the field to advance discovery and accelerate the translation of somatic gene editing advances in the lab to the clinical setting.
Over six years, the NIH will allocate approximately $190 million to SCGE to realize gene editing’s potential. The end result will be a freely available toolkit that will provide the biomedical research community with rigorously evaluated information about genome editors and methods for delivering and tracking gene editing molecules.
“NIH realized it was important for all of us who are investigating gene editing to work together toward a common goal,” said Carnegie Mellon University Professor of Chemistry Danith Ly who joined the consortium in 2019. “We’re designing molecules that can go into the cell and we’re cataloging each and every one. What we’ll end up with is a very valuable, rigorously evaluated resource for those who want to bring gene editing to patients.”
While much of the consortium’s work focuses on CRISPER-Cas related systems, the SCGE points out that it’s important to continue to develop other systems. They specifically single out the peptide nucleic acid-based gene editing technique developed by Carnegie Mellon’s Ly and Yale University’s Peter Glazer.
“Although there is a significant focus on CRISPR-Cas related systems within the SCGE, it is crucial to continue to explore alternate systems, in part because they may differ in both their potential for delivery and their biological or immunological responses,” the consortium wrote in Nature.
While CRISPR-Cas edits genes in cells that have been removed from the body, Ly and Glazer’s peptide nucleic acid (PNA) system is administered intravenously and edits cells in vivo. Using nanoparticles, a PNA molecule paired with a donor strand of DNA is delivered directly to a malfunctioning gene. Ly, a leading researcher in synthetic nucleic acid technology, has programmed PNA molecules to open double stranded DNA at the site of a targeted mutation. The donor DNA from the complex binds to the cell’s faulty DNA and triggers the DNA’s innate repair mechanisms to edit the gene. The team has used the technique to cure beta thalassemia in adult mice and in fetal mice in utero.
The PNA gene editing system doesn’t have the high-yield of CRISPER-Cas systems, but it does have the advantage of being less likely to make off-target modifications. According to Ly, that means their technique might be better for genetic diseases that only need to have a small percentage of cells corrected to make a therapeutic difference. For example, in the beta thalassemia studies, Ly and Glazer found that editing only six to seven percent of cells was curative.
Ly and Glazer plan to further refine and improve their technique through their participation in SCGE, and they look forward to sharing their results with the consortium and the greater biomedical community.
Story Source:
Materials provided by Carnegie Mellon University. Original written by Jocelyn Duffy. Note: Content may be edited for style and length.