Science
F.D.A.’s Accelerated Drug Approvals Come Under Scrutiny
By the point Brittany Bonds gave beginning to her third son behind an ambulance 10 weeks earlier than he was due, she not trusted the drug Makena.
The drug was meant to forestall preterm beginning and enhance the well being of a child. However it didn’t work for Mrs. Bonds, whose son Phoenix ended up in a NICU for 83 days. At 2, he nonetheless has a number of well being issues.
Makena is one other instance — just like the controversial Alzheimer’s drug Aduhelm — of a drugs fast-tracked by the Meals and Drug Administration onto the market though appreciable doubt remained about whether or not it labored.
The persevering with debate over Aduhelm’s approval has renewed consideration on the expedited pathway for medication to achieve the market. A invoice sponsored by one Republican in Congress would make it even simpler for a corporation to get a drug authorized and hold it obtainable. A proposal by a number one Democrat would give the F.D.A. extra authority to get definitive solutions about fast-tracked medication and to take away them from the market in the event that they fall quick.
However any efforts to impose limits on the fast-track course of is probably going to attract the ire of the highly effective pharmaceutical business, which was the highest U.S. sector in lobbying expenditures final 12 months and spends closely on political campaigns.
“I believe there’s going to be great resistance from the pharmaceutical business” to tightening the foundations on accelerated approvals, mentioned Dr. Michael Carome, a director at Public Citizen, a nonprofit client advocacy group.
Questions had lingered about Makena for a decade earlier than a big research confirmed the drug had the identical impact as a placebo. The F.D.A. proposed taking the drug off the market greater than a 12 months in the past. It plans to carry a listening to on Makena’s destiny that can focus scrutiny on what some critics declare is a speed-over-science drug approval course of.
Mrs. Bonds is certainly one of 13 plaintiffs in a lawsuit towards the drug’s earlier proprietor, AMAG Prescribed drugs, and desires the drug taken off the market. “It didn’t work for me and I do know it didn’t work for different folks,” she mentioned.
Covis Pharma, which now owns the drug, plans to oppose the company’s choice on the upcoming listening to, arguing that Makena is really efficient for the ladies it had initially helped: African American girls, who face a few of the highest preterm birthrates within the developed world.
Untimely infants additionally face elevated dangers of being born lifeless or disabled. “Quite a lot of emotion will get concerned on this,” mentioned Dr. Washington Hill, a Black maternal-fetal medication specialist in Sarasota, Fla. He has prescribed the drug for many years to at-risk girls and was paid $1,200 in consulting charges when he testified in its favor in 2019. “I felt this drug was efficient within the sufferers I labored with,” he mentioned in an interview.
All through the lifetime of the accelerated approval program that started 30 years in the past, the F.D.A. has needed to weigh passionate, generally determined pleas for entry to medication towards the obtainable science-based proof.
Throughout these a long time, the company issued 278 approvals underneath this system as of December. The approvals don’t show {that a} drug extends survival or improves high quality of life. As an alternative, medication might be put available on the market based mostly on a single research with a optimistic discovering — like tumor shrinkage — and saved available on the market if a follow-up research proves a profit.
This pathway, meant for critical situations and unmet medical wants, has given sufferers earlier entry to lifesaving medication, a degree of delight for business teams like BIO, the Biotechnology Innovation Group. A BIO consultant informed lawmakers final week that he supported a pending plan for drugmakers to make use of real-world proof to extra rapidly show that an accelerated approval drug works. PhRMA, which additionally represents drugmakers, mentioned it supported this system in its present type.
But critics and watchdog teams contend that Medicare has spent billions on accelerated approval medication, at the same time as drugmakers drag their toes to finish the required follow-up research which, if unfavorable, can result in withdrawal of the drug. In some circumstances, fast-tracked medication that confirmed little profit stayed available on the market anyway.
Rushing up science has lengthy been fraught: The F.D.A. was closely criticized for its actions on Vioxx, a ache drug that had been authorized underneath expedited assessment that was later withdrawn in 2004 over findings that it elevated coronary heart assaults and strokes. Much more avenues for expedited critiques had been granted underneath the twenty first Century Cures Act in 2016.
On the heels of the Aduhelm approval debate, the F.D.A. faces one other spherical of scrutiny subsequent week when its advisory panel critiques a brand new drug, Amylyx, for amyotrophic lateral sclerosis, a deadly neurological dysfunction. Whereas the drug meets one bar for accelerated approval — the addressing a critical illness with unmet wants — its maker is looking for conventional approval.
As for the present state of accelerated approvals, April Grant, a spokeswoman for the F.D.A., mentioned the company was working to make sure that drugmakers accomplished follow-up research of the medication in a well timed method. If it finds gaps in its authority, “then the company will work with Congress to shut these gaps,” Ms. Grant mentioned.
The accelerated program traces its historical past to a raucous 1988 protest on the F.D.A.’s entrance steps, when AIDS activists stormed the company headquarters, enraged that it had performed so little as 1000’s of younger males had been dying.
They outlined one another’s our bodies with sidewalk chalk. The police cuffed them in zip ties and dragged them away.
Mark Harrington, who helped set up the 1988 demonstration, is government director of the Therapy Motion Group, which advocates entry to medical therapies. He mentioned the rowdy protest led to discussions for expediting entry to new medication.
Whereas medication that originally appeared promising fell quick, by the mid-90s, protease inhibitors slashed virus ranges and delivered a medical miracle.
“So the underside line is that the accelerated approval rules labored,” Mr. Harrington mentioned. “They helped draw extra corporations into the area. They led to the invention of efficient therapies.”
But Mr. Harrington and others have watched with concern as researchers have recognized accelerated approval medication that delivered minimal, if any, positive factors for sufferers.
Of the 253 medication approved underneath accelerated approval since 1992, almost half — 112 — haven’t been confirmed to increase survival or enhance high quality of life, in line with an investigation within the The BMJ printed final 12 months. Two dozen of the medication had been available on the market for 5 years or extra.
One other research confirmed that 20 p.c of 93 most cancers drug therapies cleared since 1992 had been confirmed to increase total survival, whereas others remained available on the market after follow-up research confirmed extra modest positive factors, like delaying tumor development. The F.D.A. mentioned total survival enchancment might be exhausting to evaluate, because it takes years to realize.
That research reported that one drug, Avastin, bought accelerated approval to deal with glioblastoma, a mind most cancers. Despite the fact that a follow-up research didn’t present prolonged survival or improved high quality of life, Avastin nonetheless acquired full approval for that use in 2017.
The identical drug was used to deal with breast most cancers and is the one instance of the F.D.A. revoking accelerated approval for one use of a drug — regardless of emotional pleas to permit it for most cancers sufferers in 2011.
In 2010, the F.D.A. backed off its choice to withdraw Midodrine for sufferers with dangerously low blood stress, only a month after telling the drugmaker it had “not been capable of present proof of the drug’s profit.”
Actually, the makers of Makena cited that precedent in arguing that their preterm-birth drug ought to stay obtainable. The company altered course on the blood stress drug “prompted by the outpouring of help for the drug and concern over dropping entry,” Makena’s maker reminded the F.D.A.
Covis, the drug’s present proprietor, funded a affected person group referred to as the Preterm Beginning Prevention Alliance, whose members could testify on the listening to over the drug’s destiny.
The story of Makena begins with a medical thriller: Scientists aren’t sure what triggers the method of giving beginning in people. A clue to forestalling it appeared to emerge in 2003 with the outcomes of a research on the drug’s energetic ingredient, a type of the hormone progesterone.
The research, which included many high-risk Black girls, confirmed that these on the medicine noticed a 34 p.c discount of their danger of getting a preterm beginning in contrast with these in a management group.
An F.D.A. statistical assessment of the research concluded that the information does “not present convincing proof” of effectiveness. Of principal concern, the report mentioned, was that the drug appeared simplest when began at or earlier than 18 weeks of the being pregnant, when the charges of fetal or new child loss of life was additionally “most pronounced.”
Nonetheless, the F.D.A. granted the drug accelerated approval in 2011, and it stays the one authorized drug meant to scale back the chance of recurrent preterm beginning. High medical societies, which have accepted funding from the drug’s maker, endorsed its use, and Makena grew to become so routinely prescribed that it was tough to check in the USA.
By 2019, although, outcomes of a big research performed principally in Europe had been in. They instructed that the drug had no impact: The share of ladies who gave beginning preterm whereas on the drug was about the identical as these given a placebo.
The F.D.A. examined the information to see if there was a subgroup of sufferers in the USA, together with 113 Black girls, who benefited. It couldn’t discover one. In October 2020, the F.D.A. introduced it wished to discontinue use of the drug.
The drug’s maker, then AMAG Prescribed drugs, requested for a listening to, arguing partly that the research left open the query of whether or not their drug benefited high-risk Black girls. “Our view is that given the outcomes of each of those trials, extra analysis is merited,” mentioned Francesco Tallarico, normal counsel for Covis Pharma.
It’s a priority shared by others who haven’t any monetary stake, together with Dr. Michael Greene, a professor emeritus at Harvard’s medical college. He and colleagues mentioned the second research was “underpowered” as a result of it included few Black girls.
“Is it actually truthful and equitable to yank the labeled indication for a drug that’s useful to a minority, simply because it’s not useful to the bulk?” mentioned Dr. Greene, who’s an affiliate editor of the New England Journal of Medication. “That didn’t actually appear truthful to us.”
Debate over the drug has divided the maternal-fetal medical care group, Dr. Hill, the maternal-fetal specialist in Sarasota, mentioned. He desires the drug to stay authorized, however is unsure that can occur. “My intestine response can be it’s going to take a variety of convincing.”
Even those that are skeptical of the drug need to know extra. “I believe there must be extra research,” mentioned Olivette Bennett, a pregnant Baltimore girl, who’s Black, who lately stopped taking the drug as a result of she didn’t suppose it was working. “The place is the voice for the African American girls who mentioned it labored for them?”
Within the federal lawsuit towards AMAG Prescribed drugs, Mrs. Bonds of Missouri, who’s white, and different plaintiffs declare the corporate leaders did periodic critiques of the 2019 research, however continued to market the drug as one thing that would assist girls. AMAG mentioned the lawsuit must be dismissed, arguing it amounted to an assault on a drugmaker’s proper to promote an F.D.A.-approved drug.
In an interview, Mrs. Bonds mentioned she started taking Makena throughout every of three pregnancies after a stillbirth in 2011. Her first two sons had been born at 36 weeks, a number of weeks wanting full-term.
She mentioned she reluctantly took the drug whereas pregnant along with her third son. She was dispirited that his beginning got here earliest of all. She mentioned the drug ought to have been studied extra earlier than approval. “I believe it will have helped stop a variety of false hope,” Mrs. Bonds mentioned.
Science
How to protect yourself from the smoke caused by L.A. wildfires
You don’t have to live close to a wildfire to be affected by its smoke. With severe winds fanning the fires in and around Pacific Palisades, the Pasadena foothills and Simi Valley, huge swaths of the Southland are contending with dangerous air quality.
Wildfire smoke can irritate your eyes, nose, throat and lungs. The soot may contain all kinds of dangerous pollutants, including some that may cause cancer. The tiniest particles in smoke can travel deep into your lungs or even enter your bloodstream.
Conditions like these aren’t good for anyone, but they’re particularly bad for people in vulnerable groups, including children, those with asthma or other respiratory conditions, people with heart disease and those who are pregnant.
Here’s what you should know to keep yourself safe.
Stay indoors
Minimize your exposure to unhealthy air by staying inside and keeping your doors and windows shut.
If you have a central heating and air conditioning system, you can keep your indoor air clean by turning it on and keeping it running. Make sure the fresh-air intake is closed so that you’re not drawing in outdoor air.
Keep your pets inside
They shouldn’t breathe the unhealthy air either.
Check your air filters
Clean filters work better than dirty ones, and high-efficiency filters work better than regular ones. The California Air Resources Board and the South Coast Air Quality Management District recommend filters with a MERV rating of 13 or higher.
You might consider using portable high-efficiency air cleaner in a room where you spend the most time. The U.S. Environmental Protection Agency has information about them here, and CARB has a list of certified cleaning devices here.
Don’t pollute your indoor air
That means no burning candles or incense. If your power is out and you need to see in the dark, you’re much better off with a flashlight or headlamp.
If you’re cold, bundle up. This is not the time to start a cozy fire in the fireplace. Don’t use a gas stove or wood-fired appliances, since these will make your indoor air quality worse, not better, the AQMD says.
The CDC also advises against vacuuming, since it can stir up dust and release fine particles into the air.
Take care when cleaning up
You don’t want your skin to come into contact with wildfire ash. That means you should wear long sleeves, pants, gloves, socks and shoes. The AQMD even wants you to wear goggles.
If you’re sweeping up ash outdoors, get a hose and mist it with water first. That will keep it from flying up in the air as you move it around. Once the ash is wet, sweep it up gently with a broom or mop. Bag it up in a plastic bag and throw it away.
It’s a good idea to wash your vehicles and outdoor toys if they’re covered in ash. Try not to send ashy water into storm drains. Direct the dirty water into ground areas instead, the AQMD advises.
Those with lung or heart problems should avoid clean-up activities.
Discard spoiled food…
If you lost power for a significant length of time, the food in your refrigerator or freezer may be spoiled.
Food kept in a fridge should stay safe for up to four hours if you’ve kept the door closed. If you’ve been without power for longer than that, you’ll need to toss all perishable items, including meat, poultry, fish, eggs, milk and cut fruits and vegetables. Anything with “an unusual smell, color, or texture” should be thrown out as well, according to the U.S. Centers for Disease and Control Prevention.
Refrigerated medicines should be OK unless the power was out for more than a day. Check the label to make sure.
…even if it was in the freezer
Your freezer may be in better shape, especially if it’s well-stocked. Items in a full freezer may be safe for up to 48 hours if it’s been kept shut, and a half-full freezer may be OK for up to 24 hours. (The frozen items help keep each other cold, so the more the better.)
If items have remained below 40 degrees Fahrenheit (4 degrees Celsius) or you can still see ice crystals in them, they may be OK to use or refreeze, according to the federal government’s food safety website.
Ice cream and frozen yogurt should be thrown out if the power goes out for any amount of time. Meat, poultry, seafood, eggs, milk and most other dairy products need to go if they were exposed to temperatures above 40 degrees F for two hours or longer. The same goes for frozen meals, casseroles, soups, stews and cakes, pies and pastries with custard or cheese fillings.
Fruit and fruit juices that have started to thaw can be refrozen unless they’ve started to get moldy, slimy or smell like yeast. Vegetables and vegetable juices should be discarded if they’ve been above 40 degrees F for six hours or more, even if they look and smell fine.
Breakfast items like waffles and bagels can be refrozen, as can breads, rolls, muffins and other baked goods without custard fillings.
Consider alternative shelter
If you’ve done everything you can but your eyes are still watering, you can’t stop coughing, or you just don’t feel well, seek alternative shelter where the air quality is better.
Hold off on vigorous exercise
Doing anything that would cause you to breathe in more deeply is a bad idea right now.
Mask up outdoors
If you need to be outside for an extended time, be sure to wear a high-quality mask. A surgical mask or cloth mask won’t cut it — health authorities agree that you should reach for an N95 or P-100 respirator with a tight seal.
Are young children at greater risk of wildfire smoke?
Very young children are especially vulnerable to the effects of wildfire smoke because their lungs are still rapidly developing. And because they breathe much faster than adults, they are taking in more toxic particulate matter relative to their tiny bodies, which can trigger inflammation, coughing and wheezing.
Any kind of air pollution can be dangerous to young children, but wildfire smoke is about 10 times as toxic for children compared to air pollution from burning fossil fuels, said Dr. Lisa Patel, clinical associate professor of pediatrics at Stanford Children’s Health. Young children with preexisting respiratory problems like asthma are at even greater risk.
Patel advises parents to keep their young children indoors as much as possible, create a safe room in their home with an air purifier, and try to avoid using gas stoves to avoid polluting the indoor air.
Children over the age of 2 should also wear a well-fitting KN95 mask if they will be outdoors for a long period of time. Infants and toddlers younger than that don’t need to mask up because it can be a suffocation risk, Patel said.
What are the risks for pregnant people?
Pregnant people should also take extra precautions around wildfire smoke, which can cross the placenta and affect a developing fetus. Studies have found that exposure to wildfire smoke during pregnancy can increase the risk of premature birth and low birth weight. Researchers have also linked the toxic chemicals in smoke with maternal health complications including hypertension and preeclampsia.
What about other high-risk populations?
Certain chronic diseases including asthma, chronic obstructive pulmonary disease or other respiratory conditions can also make you particularly vulnerable to wildfire smoke. People with heart disease, diabetes and chronic kidney disease should take extra care to breathe clean air, the CDC says. The tiny particles in wildfire smoke can aggravate existing health problems, and may make heart attacks or strokes more likely, CARB warns.
Get ready for the next emergency
Living in Southern California means another wildfire is coming sooner or later. To prepare for the bad air, you can:
- Stock up on disposable respirators, like N95 or P-100s.
- Have clean filters ready for your A/C system and change them out when things get smoky.
- Know how to check the air quality where you live and work. The AQMD has an interactive map that’s updated hourly. Just type in an address and it will zoom in on the location. You can also sign up to get air quality alerts by email or on your smartphone.
- Know where your fire extinguisher is and keep it handy.
- If you have a heart or lung condition, keep at least five days’ worth of medication on hand.
Times staff writer Karen Garcia contributed to this report.
Science
Punk and Emo Fossils Are a Hot Topic in Paleontology
Mark Sutton, an Imperial College London paleontologist, is not a punk.
“I’m more of a folk and country person,” he said.
But when Dr. Sutton pieced together 3-D renderings of a tiny fossil mollusk, he was struck by the spikes that covered its wormlike body. “This is like a classic punk hairstyle, the way it’s sticking up,” he thought. He called the fossil “Punk.” Then he found a similar fossil with downward-tipped spines reminiscent of long, side-swept “emo” bangs. He nicknamed that specimen after the emotional alt-rock genre.
On Wednesday, Dr. Sutton and his colleagues published a paper in the journal Nature formally naming the creatures as the species Punk ferox and Emo vorticaudum. True to their names, these worm-mollusks are behind something of an upset (if not quite “anarchy in the U.K.”) over scientists’ understanding of the origins of one of the biggest groups of animals on Earth.
In terms of sheer number of species, mollusks are second only to arthropods (the group that contains insects, spiders and crustaceans). The better-known half of the mollusk family tree, conchiferans, contains animals like snails, clams and octopuses. “The other half is this weird and wacky group of spiny things,” Dr. Sutton said. Some animals in this branch, the aculiferans, resemble armored marine slugs, while others are “obscure, weird molluscan worms,” he said.
Punk and Emo, the forerunners of today’s worm-mollusks, lived on the dark seafloor amid gardens of sponges, nearly 200 million years before the first dinosaurs emerged on land. Today, their ancient seafloor is a fossil site at the border between England and Wales.
The site is littered with rounded rocky nodules that “look a bit like potatoes,” Dr. Sutton said. “And then you crack them open, and some of them have got these fossils inside. But the thing is, they don’t really look like much at first.”
While the nodules can preserve an entire animal’s body in 3-D, the cross-section that becomes visible when a nodule is cracked open can be difficult to interpret “because you’re not seeing the full anatomy,” Dr. Sutton said.
Paleontologists can use CT scans to see parts of fossils still hidden in rock, essentially taking thousands of X-rays of the fossil and then stitching those X-ray slices together into one digital 3-D image. But in these nodules, the fossilized creatures and the rock surrounding them are too similar in density to be easily differentiated by X-rays. Instead, Dr. Sutton essentially recreated this process of slicing and imaging by hand.
“We grind away a slice at a time, take a photo, repeat at 20-micron intervals or so, and basically destroy but digitize the fossil as we go,” Dr. Sutton said. At the end of the process, the original fossil nodule is “a sad-looking pile of dust,” but the thousands of images, when painstakingly digitally combined, provide a remarkable picture of the fossil animal.
Punk and Emo’s Hot Topic-worthy spikes set them apart from other fossils from the aculiferan branch of the mollusk family. “We don’t know much about aculiferans, and it’s unusual to find out we’ve suddenly got two,” Dr. Sutton said.
Stewart Edie, the curator of fossil bivalves at the Smithsonian National Museum of Natural History, said that Punk and Emo’s bizarre appearances shook up a long-held understanding of how mollusks evolved. Traditionally, scientists thought that the group of mollusks containing snails, clams and cephalopods “saw all of the evolutionary action,” said Dr. Edie, who was not involved with the new discovery. “And the other major group, the aculiferans, were considerably less adventurous.” But Punk and Emo “buck that trend,” he said.
The new alt-rock aculiferans reveal the hidden diversity of their group in the distant past and raise questions about why their descendants make up such a small part of the mollusk class today. “This is really giving us an almost unprecedented window into the sorts of things that were actually around when mollusks were getting going,” Dr. Sutton said. “It’s just this little weird, unexpected, really clear view of what was going on in the early history of one of the most important groups of animals.”
Science
FDA sets limits for lead in many baby foods as California disclosure law takes effect
The U.S. Food and Drug Administration this week set maximum levels for lead in baby foods such as jarred fruits and vegetables, yogurts and dry cereal, part of an effort to cut young kids’ exposure to the toxic metal that causes developmental and neurological problems.
The agency issued final guidance that it estimated could reduce lead exposure from processed baby foods by about 20% to 30%. The limits are voluntary, not mandatory, for food manufacturers, but they allow the FDA to take enforcement action if foods exceed the levels.
It’s part of the FDA’s ongoing effort to “reduce dietary exposure to contaminants, including lead, in foods to as low as possible over time, while maintaining access to nutritious foods,” the agency said in a statement.
Consumer advocates, who have long sought limits on lead in children’s foods, welcomed the guidance first proposed two years ago, but said it didn’t go far enough.
“FDA’s actions today are a step forward and will help protect children,” said Thomas Galligan, a scientist with the Center for Science in the Public Interest. “However, the agency took too long to act and ignored important public input that could have strengthened these standards.”
The new limits on lead for children younger than 2 don’t cover grain-based snacks such as puffs and teething biscuits, which some research has shown contain higher levels of lead. And they don’t limit other metals such as cadmium that have been detected in baby foods.
The FDA’s announcement comes just one week after a new California law took effect that requires baby food makers selling products in California to provide a QR code on their packaging to take consumers to monthly test results for the presence in their product of four heavy metals: lead, mercury, arsenic and cadmium.
The change, required under a law passed by the California Legislature in 2023, will affect consumers nationwide. Because companies are unlikely to create separate packaging for the California market, QR codes are likely to appear on products sold across the country, and consumers everywhere will be able to view the heavy metal concentrations.
Although companies are required to start printing new packaging and publishing test results of products manufactured beginning in January, it may take time for the products to hit grocery shelves.
The law was inspired by a 2021 congressional investigation that found dangerously high levels of heavy metals in packaged foods marketed for babies and toddlers. Baby foods and their ingredients had up to 91 times the arsenic level, up to 177 times the lead level, up to 69 times the cadmium level, and up to five times the mercury level that the U.S. allows to be present in bottled or drinking water, the investigation found.
There’s no safe level of lead exposure for children, according to the U.S. Centers for Disease Control and Prevention. The metal causes “well-documented health effects,” including brain and nervous system damage and slowed growth and development. However, lead occurs naturally in some foods and comes from pollutants in air, water and soil, which can make it impossible to eliminate entirely.
The FDA guidance sets a lead limit of 10 parts per billion for fruits, most vegetables, grain and meat mixtures, yogurts, custards and puddings and single-ingredient meats. It sets a limit of 20 parts per billion for single-ingredient root vegetables and for dry infant cereals. The guidance covers packaged processed foods sold in jars, pouches, tubs or boxes.
Jaclyn Bowen, executive director of the Clean Label Project, an organization that certifies baby foods as having low levels of toxic substances, said consumers can use the new FDA guidance in tandem with the new California law: The FDA, she said, has provided parents a “hard and fast number” to consider a benchmark when looking at the new monthly test results.
But Brian Ronholm, director of food policy for Consumer Reports, called the FDA limits “virtually meaningless because they’re based more on industry feasibility and not on what would best protect public health.” A product with a lead level of 10 parts per billion is “still too high for baby food. What we’ve heard from a lot of these manufacturers is they are testing well below that number.”
The new FDA guidance comes more than a year after lead-tainted pouches of apple cinnamon puree sickened more than 560 children in the U.S. between October 2023 and April 2024, according to the CDC.
The levels of lead detected in those products were more than 2,000 times higher than the FDA’s maximum. Officials stressed that the agency doesn’t need guidance to take action on foods that violate the law.
Aleccia writes for the Associated Press. Gold reports for The Times’ early childhood education initiative, focusing on the learning and development of California children from birth to age 5. For more information about the initiative and its philanthropic funders, go to latimes.com/earlyed.
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