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Her Sister Died of a Brain Tumor. Now She Was Having Similar Symptoms.

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Humanity has planted flags on the moon, yet a moonshot for brain cancer has yet to be realized.

I knocked and entered her room. Our patient had a few more questions about her surgery.
I introduced myself.
“This isn’t the same tall guy as before,” I recalled her joking.
“They only hire tall people,” I said.
Wearing masks in every hallway and patient room, though necessary in the time of Covid-19, had stolen the familiarity of a smile.
She was in her late 50s, wearing glasses and a light blue hospital gown, sitting up in bed. She had a full head of salt and pepper hair that was more salt than pepper really. Sprawled across her beige blankets were legal pads on which she had been taking notes.
On her right was a gingham-lined picnic basket brimming with treats, Coca-Cola and Otterbein’s Cookies, a local favorite, gifts from her co-workers.
A few weeks earlier, her life had been routine. As an information technology specialist, she had been working from home,. At some point she realized she had been experiencing weakness in her right leg, and then in her right arm.
“I noticed it late, I think, because I was sitting at my desk all the time,” she said.
Her handwriting had worsened precipitously over the previous few days. “I can’t write anymore,” she said, “and when I was lifting weights my arm felt heavy and weak.”
She had gone to the emergency room, where doctors performed a CT scan of her head. On the left side, at the top of her brain, they found a “hypodensity,” a dark area that would need further work-up. A subsequent M.R.I. scan of her brain provided more clarity.
A cystic mass was invading her left paracentral lobule, part of her primary motor cortex, a one-centimeter ribbon of brain tissue packed with the millions of neurons that allow us to voluntarily control our muscles.
I asked her if she had more questions about her surgery, which was scheduled for the next day. My attending had talked previously with her about the finding on her scan and options going forward.
“I’m just wondering what the mass is,” she said. “Hopefully you won’t find anything,” she followed up quickly.
“A scan is a representation,” I said. “We can only know for sure once we look at a piece of it under a microscope, after the surgery.”
Our concern was a tumor, but the mass could also be an infection, or an inflammatory process, or another disease, I explained. As we talked more, I learned more about the source of her anxiety.
Her sister had died of a glioblastoma a few years earlier, she told me. Glioblastoma is the most common tumor that arises from brain tissue, and one of the most lethal of human cancers. Three people in every 100,000 are diagnosed with this condition every year.
She recounted the story of her sister’s diagnosis and treatment, and the misery she had gone through. Her sister, too, had a mass on the left side of her brain, for which she had elected surgery. The surgery and mass had left her weak and unable to speak. After the diagnosis of glioblastoma was confirmed, she had undergone chemotherapy and radiation therapy, the standard of care, which can extend survival a few months. She died a year later, and had never regained her old self.
“Me and my sister have everything in common,” she said. “When I heard about this mass, I said, really, we have to have that in common too?”
I smiled at her efforts to add some humor to the situation.
“I read that glioblastoma is extremely rare, so it’s unlikely I have the same thing, right?” she asked.
I explained it was rare, but possible.
“My sister wasn’t the same after surgery,” she said. “Don’t take so much out that it causes problems.”
We talked a while longer before I left for the evening.
The next morning, the chief resident and I greeted her in her room.
“I’m ready,” she said.
Her nurses brought her down to the operating room, where the surgical nurses and technicians began their rhythms, making her comfortable on the operating table, moving equipment.
The anesthesiologist skillfully intubated her. He ferried her mind to the hinterlands.
We started by cutting a narrow furrow through her hair, as she had requested, preserving as much hair as possible. Cutting the hair before making an incision is a small part of brain surgery, but it remains our most visible maneuver. If she had what her sister had and we’d cut it all, her hair might never fully grow back in time. She would forever be marked by her disease. Cutting less mattered to her.
My attending, the chief resident and I cleaned her hair and scalp, and then, using the surgical drapes, created a window where we would work.
I made an incision down to her skull with a scalpel, and we instinctively stemmed any bleeding. After folding her scalp back and exposing her skull, I made several burr holes with a drill, then connected these using a different kind of drill to complete our craniotomy, removing a disc of skull. My chief resident and I then cut and drew back the dura, the pearly lining that protects the brain. We were now staring directly at her brain.
Using surface electrodes, and tiny jolt of electricity, we determined the boundaries of her motor cortex, the no-go zone. Compromising any part of this ribbon would result in paralysis.
My attending and chief resident started dissecting between both brain hemispheres. They met the mass from its flank. It was aberrant, alien.
We sent the first piece of it to the pathologist for analysis.
They methodically resected the mass, working from within the abnormal tissue itself; better to damage the mass than to harm healthy brain tissue. They peeled it away from her brain, bit by bit. It was deliberate work.
The phone rang, interrupting the sound of buzzing electrocautery forceps and whirring suction tips. It was the pathologist.
“The specimen is consistent with glioblastoma,” her voice rang on speakerphone, to a change of tenor in the room.
Like her sister, I thought to myself.
Two years earlier, I had seen Damien Chazelle’s “First Man,” a biopic of Neil Armstrong. There was a moment in the film when the astronaut stood at the rim of a baby crater on the moon. He had spent 10 minutes at that crater, but what he did there remains a mystery. The filmmakers had suggested he left a bracelet there, a bracelet that had belonged to his daughter Karen, who had died seven years earlier, in 1962, at age 2.
Karen had succumbed to what is believed to have been diffuse intrinsic pontine glioma, a rare childhood cancer of the brainstem that shares some similarities to glioblastoma. His daughter had undergone radiation therapy, which reduces symptoms from the tumor, but only for a short while. It remains the only available treatment for this devastating disease, which today, as then, is almost universally fatal.
Humanity has planted flags on the moon, yet a moonshot for brain cancer has yet to be realized.
Diagnosis known, we gradually stopped removing more tumor. The more tumor you remove, the longer the average survival, meager though it may be. But the quest for surgical perfection sometimes comes with a cost. In the brain, where critical human functions are packed into mere millimeters of tissue, removing more tumor and possibly damaging healthy tissue risks the loss of strength, speech, vision, memory and more. In glioblastoma, tumor cells that have traveled centimeters away from the bulk of the tumor, far out of reach of any forceps, almost guarantee the cancer’s recurrence. Surgical perfection is imperfect. She wanted to preserve her strength.
We sutured the dura closed, and then plated her bone back on. With care, we closed the layers of her skin. In a short while, she was extubated, and we brought her up to our neurological intensive care unit to recover.
“I have seven years on my sister, and a lot of young people are dying these days, so I’m trying to be pragmatic,” she had said to me the day before. Bargaining.
Forty years ago, the median survival time for glioblastoma was four-and-a-half months. Since then, researchers have characterized the genetics of glioblastoma and studied various vaccines, chemotherapies, immunotherapies, cell therapies, new imaging modalities, targeted radiation therapies and innovative forms of drug delivery to treat the disease. Many steps.
The median survival time today is about 15 months. Only a small percentage of patients survive more than five years.
Defeatism is a common feeling among neurosurgeons, but you maintain resolve, for your patients, and for yourself. The next morning, our patient was in good spirits, recovering well, with good strength. We delicately shared the diagnosis with her.
“Just my luck,” she said with a smile. She seemed to be expecting it.
Some cancers in siblings can be explained by genetics. But that’s not the case for glioblastoma. As for her sister, and many others, it really was just bad luck.
Our surgical team, along with our colleagues in neuro-oncology and radiation oncology, recommended the standard treatment of chemotherapy and radiation therapy. But she declined treatment multiple times and chose palliative care.
“I don’t want to drag it out,” she said.
She died peacefully four months later, surrounded by her family, listening to “The Sound of Music,” her favorite musical.
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C.D.C. Advisers to Discuss Rare Heart Problems in Vaccinated Youth

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Advisers to the Centers for Disease Control and Prevention are meeting on Wednesday to address reports of rare heart problems in young people immunized with the coronavirus vaccines made by Pfizer-BioNTech and Moderna.
The reports involve conditions called myocarditis, inflammation of the heart muscle; and pericarditis, inflammation of the membrane surrounding the heart. Most cases have been mild, with symptoms like fatigue, chest pain and disturbances in heart rhythm that quickly clear up. The agency is tracking nearly 800 reports, although not all have definitively been linked to the vaccines.
The C.D.C. advisers’ meeting comes as the Biden administration publicly acknowledges that it expects to fall short of its goal of getting 70 percent of Americans partly vaccinated by July 4. The shortfall, officials said on Tuesday, results in part from reluctance among younger Americans to be immunized.
Experts have said that the benefits of immunization far outweigh the risk of the possible problems, but they are expected to revisit that debate, particularly for adolescents and young adults.
More than half of the heart problems were reported in Americans ages 12 to 24, while that age group accounted for only 9 percent of the millions of doses administered. The numbers are higher than would be expected for those ages.
As of May 31, 216 people had experienced myocarditis or pericarditis after one dose of either vaccine, and 573 after the second dose. While most cases were mild, 15 patients remained in hospitals at that time. The second dose of the Pfizer-BioNTech vaccine was linked to about twice as many cases as the second dose of the vaccine made by Moderna.
“We look forward to more clarity regarding the potential risk of myocarditis after mRNA vaccines to increase vaccine confidence and vaccination rates,” said Dr. Yvonne Maldonado, chair of the Committee on Infectious Diseases at the American Academy of Pediatrics.
Recommendations from the C.D.C. advisers after Wednesday’s meeting may also influence decisions to immunize children younger than 12 when vaccines become available for that age group. Some experts have questioned whether the benefits to children outweigh the potential risks, given the low odds of serious illness in young children.
The C.D.C. strongly recommends Covid-19 vaccines for Americans ages 12 and older. The agency reported this month that the number of hospitalizations related to Covid-19 among adolescents in the United States was about three times higher than hospitalizations linked to influenza over three recent flu seasons.
As of June 10, nearly 17,000 children in 24 states had been hospitalized for Covid-19 and 330 children had died, according to data collected by the American Academy of Pediatrics.
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With Mass Vaccination Sites Winding Down, It’s All About the ‘Ground Game’

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The shift away from high-volume centers is an acknowledgment of the harder road ahead: a highly targeted push, akin to get-out-the-vote efforts, to persuade the reluctant to get shots.

NEWARK — There were only six tiny vials of coronavirus vaccine in the refrigerator, one Air Force nurse on duty and a trickle of patients on Saturday morning at a federally run mass vaccination site here. A day before its doors shut for good, this once-frenetic operation was oddly quiet.
The post-vaccination waiting room, with 165 socially distanced chairs, was mostly empty. The nurse, Maj. Margaret Dodd, who ordinarily cares for premature babies at Brooke Army Medical Center at Fort Sam Houston in San Antonio, had already booked her flight home. So had the pharmacist, Heather Struempf, who was headed back to nursing school in Wyoming.
Across the country, one by one, mass vaccination sites are shutting down. The White House acknowledged for the first time on Tuesday that it would not reach President Biden’s goal of getting 70 percent of American adults at least partly vaccinated by July 4. The setback stems from hesitancy in certain groups, slow acceptance by young adults and a swirl of other complex factors.
The Newark site, which closed on Sunday, was the last of 39 federally operated mass vaccination centers that administered millions of shots over five months in 27 states — a major turning point in the effort Mr. Biden described last week as “one of the biggest and most complicated logistical challenges in American history.” Many state-run sites are also closed or soon will be.
The nation’s shift away from high-volume vaccination centers is an acknowledgment of the harder road ahead, as health officials pivot to the “ground game”: a highly targeted push, akin to a get-out-the-vote effort, to persuade the reluctant to get their shots.
Mr. Biden will travel to Raleigh, N.C., on Thursday to spotlight this time-consuming work. It will not be easy — as Dr. Anthony S. Fauci, the president’s coronavirus response coordinator, discovered last weekend, when he went door-knocking in Anacostia, a majority-Black neighborhood in Washington, with Mayor Muriel E. Bowser.
In an interview on Tuesday, Dr. Fauci said he and the mayor spent 90 minutes talking to people on their front porches. But even with a celebrity doctor at the door and the prospect of giveaways at the vaccination center in a high school a few blocks away, many remained hesitant. Dr. Fauci said he persuaded six to 10 people to get their shots, though he did encounter some flat refusals.
“We would say, ‘OK, come on, listen: Get out, walk down the street, a couple of blocks away. We have incentives, a $51 gift certificate, you can put yourself in a raffle, you could win a year’s supplies of groceries, you could win a Jeep,’” Dr. Fauci said. “And several of them said, ‘OK, I’m on my way and I’ll go.’”
But in Newark, where more than three-quarters of the population is Black or Latino, the numbers tell the story. In Essex County, N.J., which includes Newark, 70.2 percent of adults have been vaccinated. But Essex also includes wealthy suburbs; in Newark, the figure is 56 percent, Judith M. Persichilli, the state’s health commissioner, said in an interview.
The Newark vaccination site, in a converted athletic facility at the New Jersey Institute of Technology that is ordinarily home to the school’s tennis teams, was set up and run by the Federal Emergency Management Agency in conjunction with the Defense Department and other federal agencies. It opened on March 31; when it was operating at full tilt, its medical staff administered as many as 6,700 shots a day.
By Saturday, the daily tally was down to about 300. The long, corridorlike tents that had once shielded lines of patients from cold weather were empty. Of 18 registration desks, only four were in use, and most of the vaccination cubicles were unoccupied.
Most of the patients, including some teenagers brought by their parents, were there for their second dose of the Pfizer-BioNTech vaccine. Many — like Abdullah Heath, 19, who took a year off after high school and will attend Rutgers University in the fall — said they were hesitant. But Rutgers requires vaccination, so Mr. Heath had little choice.
“I wanted to wait to see how other people were when they took the shot,” he said.
Alfredo Sahar, 36, a real estate agent originally from Argentina, said he had received his first dose on the spur of the moment, without an appointment, when he tagged along with his wife to the Newark site. The couple showed up for their second doses on Saturday with a young friend, Federico Cuadrado, 19, who was visiting from Argentina and received his first shot.
“Relax this arm,” Major Dodd said as Mr. Cuadrado rolled up his sleeve. But she will not be administering his second shot; with the site now closed, he will have to go elsewhere.
At the height of its vaccination drive, New Jersey had seven mass sites: six run by the state, plus the FEMA site in Newark. Two of the state sites have closed, another will shut down this week, and the last three are expected to do so in mid-July, said Ms. Persichilli, a nurse and former hospital official. She called the FEMA site, which vaccinated 221,130 people in all, “invaluable.”
Mr. Biden has said repeatedly that equity — making sure people of all races and incomes have the same access to care and vaccines — is crucial to his coronavirus response. FEMA determined the locations for its mass vaccination sites using the Centers for Disease Control and Prevention’s “social vulnerability index” to identify communities most in need, Deanne Criswell, the FEMA administrator, said in an interview.
It was a learning experience for the agency, she said, adding that 58 percent of the roughly six million shots administered at the mass vaccination sites were given to people of color.
“We didn’t have a playbook for this type of an operation,” Ms. Criswell said. (The agency now has one that is 44 pages long.)
In New Jersey, traffic at the mass vaccination sites started tapering off about six weeks ago, Ms. Persichilli said. At about that time, the state moved to a “hub and spoke” strategy, creating pop-up sites in churches, barbershops and storefronts surrounding existing vaccination centers that could store and supply the vaccines.
The state also has 2,000 canvassers — 1,200 paid, partly with federal taxpayer dollars, and 800 volunteers — who have knocked on 134,000 doors in areas with low vaccination rates to direct people to nearby clinics. And the Health Department is planning vaccine clinics at a rock music festival, a balloon festival and a rodeo in Atlantic City.
Overall, New Jersey is way ahead of most states: 78 percent of adults have had at least one dose of a vaccine. In four states — Mississippi, Alabama, Louisiana and Wyoming — the figure is lower than 50 percent.
“We’re running a marathon, and we’re in the last couple of miles, and we’re exhausted, and they’re going to be the most difficult ones,” Ms. Persichilli said. “But they are also going to be the most satisfying ones.”
Public health officials know that the last mile of any vaccination campaign is indeed the hardest. The eradication of smallpox, considered the greatest public health triumph of the 20th century, came after a highly targeted global campaign that lasted two decades. Polio has still not been eradicated in some countries, Dr. Fauci said, because of vaccine hesitancy, including among women who express unfounded fears of infertility.
“We should have eradicated polio a long time ago,” he said.
The federal effort has been enormous, involving more than 9,000 people from across the government, as well as 30,000 National Guard members supporting Covid-19 vaccination in 58 states and territories, according to Sonya Bernstein, a senior policy adviser for the White House.
With the large vaccination sites winding down, FEMA is also pivoting. The agency still supports more than 2,200 community vaccination centers and mobile vaccination units. Now FEMA is rolling out a new pilot program to offer shots at or near recovery centers that it sets up after hurricanes and other natural disasters. The first of these opened this week in St. Charles Parish, La., which has a large minority population and was devastated by Hurricane Laura last summer. Only 51 percent of the adult population in St. Charles Parish has had at least one shot, according to data from the C.D.C.
In Newark, the mood on Saturday was bittersweet. People like Major Dodd and Ms. Struempf, thrown together in a crisis, were exchanging phone numbers with newfound friends and colleagues as they planned to go their separate ways. After living in hotels for more than two months, they were both eager to depart and wistful about the prospect.
Michael Moriarty, the FEMA official in charge of vaccination operations in the New York-New Jersey region, surveyed the scene: the vacant cubicles and chairs, the boxes of unused latex gloves, the brown paper taped to the floor to cover the tennis courts. It would not take long to undo, he said, adding, “They’ll be playing tennis here at the end of the week.”
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They Relied on Chinese Vaccines. Now They’re Battling Outbreaks.

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More than 90 countries are using Covid shots from China. Experts say recent infections in those places should serve as a cautionary tale in the global effort to fight the disease.

Mongolia promised its people a “Covid-free summer.” Bahrain said there would be a “return to normal life.” The tiny island nation of the Seychelles aimed to jump-start its economy.
All three put their faith, at least in part, in easily accessible Chinese-made vaccines, which would allow them to roll out ambitious inoculation programs when much of the world was going without.
But instead of freedom from the coronavirus, all three countries are now battling a surge in infections.
China kicked off its vaccine diplomacy campaign last year by pledging to provide a shot that would be safe and effective at preventing severe cases of Covid-19. Less certain at the time was how successful it and other vaccines would be at curbing transmission.
Now, examples from several countries suggest that the Chinese vaccines may not be very effective at preventing the spread of the virus, particularly the new variants. The experiences of those countries lay bare a harsh reality facing a postpandemic world: The degree of recovery may depend on which vaccines governments give to their people.
In the Seychelles, Chile, Bahrain and Mongolia, 50 to 68 percent of the populations have been fully inoculated, outpacing the United States, according to Our World in Data, a data tracking project. All four ranked among the top 10 countries with the worst Covid outbreaks as recently as last week, according to data from The New York Times. And all four are mostly using shots made by two Chinese vaccine makers, Sinopharm and Sinovac Biotech.
“If the vaccines are sufficiently good, we should not see this pattern,” said Jin Dongyan, a virologist at the University of Hong Kong. “The Chinese have a responsibility to remedy this.”
Scientists don’t know for certain why some countries with relatively high inoculation rates are suffering new outbreaks. Variants, social controls that are eased too quickly and careless behavior after only the first of a two-shot regimen are possibilities. But the breakthrough infections could have lasting consequences.
In the United States, about 45 percent of the population is fully vaccinated, mostly with doses made by Pfizer-BioNTech and Moderna. Cases have dropped 94 percent over six months.
Israel provided shots from Pfizer and has the second-highest vaccination rate in the world, after the Seychelles. The number of new daily confirmed Covid-19 cases per million in Israel is now around 4.95.
In the Seychelles, which relied mostly on Sinopharm, that number is more than 716 cases per million.
Disparities such as these could create a world in which three types of countries emerge from the pandemic — the wealthy nations that used their resources to secure Pfizer-BioNTech and Moderna shots, the poorer countries that are far away from immunizing a majority of citizens, and then those that are fully inoculated but only partly protected.
China, as well as the more than 90 nations that have received the Chinese shots, may end up in the third group, contending with rolling lockdowns, testing and limits on day-to-day life for months or years to come. Economies could remain held back. And as more citizens question the efficacy of Chinese doses, persuading unvaccinated people to line up for shots may also become more difficult.
One month after receiving his second dose of Sinopharm, Otgonjargal Baatar fell ill and tested positive for Covid-19. Mr. Otgonjargal, a 31-year-old miner, spent nine days in a hospital in Ulaanbaatar, the capital of Mongolia. He said he was now questioning the usefulness of the shot.
“People were convinced that if we were vaccinated, the summer will be free of Covid,” he said. “Now it turns out that it’s not true.”
Beijing saw its vaccine diplomacy as an opportunity to emerge from the pandemic as a more influential global power. China’s top leader, Xi Jinping, pledged to deliver a Chinese shot that could be easily stored and transported to millions of people around the world. He called it a “global public good.”
Mongolia was a beneficiary, jumping at the chance to score millions of Sinopharm shots. The small country quickly rolled out an inoculation program and eased restrictions. It has now vaccinated 52 percent of its population. But on Sunday, it recorded 2,400 new infections, a quadrupling from a month before.
In a statement, China’s Foreign Ministry said it did not see a link between the recent outbreaks and its vaccines. It cited the World Health Organization as saying that vaccination rates in certain countries had not reached sufficient levels to prevent outbreaks, and that countries needed to continue to maintain controls.
“Relevant reports and data also show that many countries that use Chinese-made vaccines have expressed that they are safe and reliable, and have played a good role in their epidemic prevention efforts,” the ministry said. China has also emphasized that its vaccines target severe disease rather than transmission.
No vaccine fully prevents transmission, and people can still fall ill after being inoculated, but the relatively low efficacy rates of Chinese shots have been identified as a possible cause of the recent outbreaks.
The Pfizer-BioNTech and Moderna vaccines have efficacy rates of more than 90 percent. A variety of other vaccines — including AstraZeneca and Johnson & Johnson — have efficacy rates of around 70 percent. The Sinopharm vaccine developed with the Beijing Institute of Biological Products has an efficacy rate of 78.1 percent; the Sinovac vaccine has an efficacy rate of 51 percent.
The Chinese companies have not released much clinical data to show how their vaccines work at preventing transmission. On Monday, Shao Yiming, an epidemiologist with the Chinese Center for Disease Control and Prevention, said China needed to fully vaccinate 80 to 85 percent of its population to achieve herd immunity, revising a previous official estimate of 70 percent.
Data on breakthrough infections has not been made available, either, though a Sinovac study out of Chile showed that the vaccine was less effective than those from Pfizer-BioNTech and Moderna at preventing infection among vaccinated individuals.
A representative from Sinopharm hung up the phone when reached for comment. Sinovac did not respond to a request for comment.
William Schaffner, medical director of the National Foundation for Infectious Diseases at Vanderbilt University, said the efficacy rates of Chinese shots could be low enough “to sustain some transmission, as well as create illness of a substantial amount in the highly vaccinated population, even though it keeps people largely out of the hospital.”
Despite the spike in cases, officials in both the Seychelles and Mongolia have defended Sinopharm, saying it is effective in preventing severe cases of the disease.
Batbayar Ochirbat, head researcher of the Scientific Advisory Group for Emergencies at Mongolia’s Ministry of Health, said Mongolia had made the right decision to go with the Chinese-made shot, in part because it had helped keep the mortality rate low in the country. Data from Mongolia showed that the Sinopharm vaccine was actually more protective than the doses developed by AstraZeneca and Sputnik, a Russian vaccine, according to the Health Ministry.
The reason for the surge in Mongolia, Mr. Batbayar said, is that the country reopened too quickly, and many people believed they were protected after only one dose.
“I think you could say Mongolians celebrated too early,” he said. “My advice is the celebrations should start after the full vaccinations, so this is the lesson learned. There was too much confidence.”
Some health officials and scientists are less confident.
Nikolai Petrovsky, a professor at the College of Medicine and Public Health at Flinders University in Australia, said that with all of the evidence, it would be reasonable to assume the Sinopharm vaccine had minimal effect on curbing transmission. A major risk with the Chinese inoculation is that vaccinated people may have few or no symptoms and still spread the virus to others, he said.
“I think that this complexity has been lost on most decision makers around the world.”
In Indonesia, where a new variant is spreading, more than 350 doctors and health care workers recently came down with Covid-19 despite being fully vaccinated with Sinovac, according to the risk mitigation team of the Indonesian Medical Association. Across the country, 61 doctors died between February and June 7. Ten of them had taken the Chinese-made vaccine, the association said.
The numbers were enough to make Kenneth Mak, Singapore’s director of medical services, question the use of Sinovac. “It’s not a problem associated with Pfizer,” Mr. Mak said at a news conference on Friday. “This is actually a problem associated with the Sinovac vaccine.”
Bahrain and the United Arab Emirates were the first two countries to approve the Sinopharm shot, even before late-stage clinical trial data was released. Since then, there have been extensive reports of vaccinated people falling ill in both countries. In a statement, the Bahraini government’s media office said the kingdom’s vaccine rollout had been “efficient and successful to date.”
Still, last month officials from Bahrain and the United Arab Emirates announced that they would offer a third booster shot. The choices: Pfizer or more Sinopharm.
Reporting was contributed by Khaliun Bayartsogt, Andrea Kannapell, Ben Hubbard, Asmaa al-Omar and Muktita Suhartono. Elsie Chen and Claire Fu contributed research.
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Ei-ichi Negishi, Nobel Prize Winner in Chemistry, Dies at 85

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His work in creating a method to build complex organic molecules applied to everything from pharmaceutical manufacturing to electronics.

Ei-ichi Negishi, who shared the Nobel Prize in Chemistry in 2010 for developing techniques now ubiquitous in the manufacture of pharmaceuticals, died on June 6 in Indianapolis. He was 85.
His death, at a hospital, was announced by Purdue University, where Dr. Negishi was a professor for four decades. No cause was given.
Dr. Negishi’s Nobel-winning research involved chemical reactions that produce complex organic compounds — large carbon-based molecules used in drugs, plastics and many other industrial materials. Coaxing one carbon atom to bond to another can be difficult, but Dr. Negishi and other chemists figured out that metals, palladium in particular, could be used as intermediary matchmakers.
In these reactions, two carbon-based molecules first stick to the palladium. The palladium then disconnects from them, and the two carbons attach to each other, forming a new, larger molecule. With the palladium working as a catalyst, the organic chemistry reactions can run at lower temperatures with fewer steps, reducing cost and waste.
“It just allows this enormous selectivity,” said James M. Tour, a professor of chemistry at Rice University in Houston, who was a graduate student of Dr. Negishi’s. “When you build molecules, you have to be able to work on one part of the molecule without destroying the other part.”
Chemists had discovered the magic of palladium earlier, and in 1977 Dr. Negishi built on that work by using zinc compounds to ease the mingling of carbon atoms on palladium. That made the process more applicable to a wider range of reactions.
“Without organic compounds, none of us can live,” Dr. Negishi said in a news conference on the day the Nobel was announced. “One of our major dream goals is to be able to synthesize any organic compounds in high yield, high efficiency.”
He gave as an analogy the creating of elaborate Lego formations. “That is a pretty accurate description of what we have been trying to do,” he said.
Traditionally, organic chemists largely limited themselves to molecules using the 10 or so elements found in organic compounds. Dr. Negishi said that he and others had “realized that we should make sure of the entire periodic table.”
By expanding to other elements like palladium, chemists in effect increased the number of Lego pieces they could use, and that opened new avenues to synthesize the molecules they wanted to make.
Dr. Negishi shared the 2010 Nobel in Chemistry with Richard F. Heck of the University of Delaware and Akira Suzuki of Hokkaido University in Sapporo, Japan.
Unlike many Nobelists who say they never expected to receive the highest honor in the science world, Dr. Negishi said it was “not a major surprise” to receive an early morning phone call on Oct. 6, 2010, from the Royal Swedish Academy of Sciences, which administers the Nobels.
Dr. Tour said Dr. Negishi had pursued research that he thought was Nobel-worthy. “He dreamed about it,” Dr. Tour said. “He often discussed the Nobel Prize. And what would have to be done to win this.”
To that end, Dr. Negishi could be relentless. “He was extremely exacting,” Dr. Tour said. “He had no trouble pushing people to the point of tears at a blackboard.”
Dr. Tour said Dr. Negishi also had a generous side. “If anybody would walk up to his office door and knock, his door was always open,” Dr. Tour said. “And you’d usually sit down for much longer than you bargained for, because he analyzed the whole project you’re working on, not just the question that you’re asking.”
Ei-ichi Negishi was born on July 14, 1935, in Changchun, China, then known as Hsinking, the capital of the Japanese-controlled part of the country, in the northeast. His family moved to Tokyo after World War II and then to a rural area outside Tokyo, where his father farmed and his mother took care of the family’s five children.
After graduating from the University of Tokyo in 1958 with a bachelor of engineering degree, he worked as a research chemist at the Iwakuni Research Laboratories in Japan. By his account, he realized that he needed more academic training but felt that graduate school was financially out of reach.
His fortunes changed in 1960, however, when he won a Fulbright scholarship to attend the University of Pennsylvania. After finishing his doctorate in 1963, he joined the laboratory of Herbert C. Brown at Purdue. Dr. Brown became the first Purdue faculty member to win a Nobel Prize, in 2004; Dr. Negishi was the second.
“In terms of research, he is my only mentor” Dr. Negishi said of Dr. Brown in an interview after the Nobel announcement. “I have had other professors, but he taught me just about everything as to how to do research.”
Dr. Negishi moved to Syracuse University as an assistant professor in 1972 and returned to Purdue in 1979 as a professor. He retired in 2019, having been an author of more than 400 scientific papers.
In 2010, Dr. Negishi, who remained a Japanese citizen, received the Order of Culture from Emperor Akihito. He was elected to the National Academy of Sciences in 2014.
Survivors include two daughters, four grandchildren and one great-granddaughter. His wife of 58 years, Sumire, died in 2018.
“When he got his Nobel Prize, he became nicer,” Dr. Tour said. “He’d take his wallet out of his pocket, and protruding from his wallet was the Nobel Prize medallion.”
Dr. Tour said Dr. Negishi would pass the medal around and wouldn’t mind if someone dropped it. “You could see the ding in one side of it,” Dr. Tour said. “And he just laughed about it.”
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New Alzheimer’s Drug Could Cost the Government as Much as It Spends on NASA

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The Alzheimer’s treatment will cost $56,000 per patient, and millions may use it. The result: “crazy numbers” for Medicare.
Josh KatzSarah Kliff and
A newly approved drug to treat Alzheimer’s disease is expected to become a multibillion dollar expense for Medicare. By one projection, spending on the drug for Medicare’s patients could end up being higher than the budgets for the Environmental Protection Agency or NASA.
There’s little evidence that the drug, Aduhelm, slows the progression of dementia, but the Food and Drug Administration approved it this month. Analysts expect that Medicare and its enrollees, who pay a share of their prescription drug costs, will spend $5.8 billion to $29 billion on the drug in a single year.
“It’s unfathomable,” said Tricia Neuman, executive director of the Kaiser Family Foundation’s program on Medicare policy. “These are crazy numbers.”
Plenty of other drugs cost more than Aduhelm, which is made by Biogen and will be priced at $56,000 annually. What makes it different is that there are millions of potential customers, and the drug is expected to be taken for years.
The drug’s approval has aroused criticism from health policy experts and pharmaceutical researchers for its lack of proven effectiveness. Effective or not, if widely prescribed, it could have an overwhelming impact on Medicare’s budget because the public program covers the vast majority of the nearly six million Americans with an Alzheimer’s diagnosis.
There is little precedent for a sudden spending jolt of this size. Even at the low end of projections, Aduhelm would become one of Medicare’s most expensive drugs.
At the high end, analysts say the new drug could cause a 50 percent increase in Medicare’s annual spending on drugs delivered in hospitals and doctor’s offices (as Aduhelm, which is given intravenously, would need to be).
The comparisons here are approximate: A third of Medicare enrollees are covered through private Medicare Advantage plans that do not release detailed information on the drugs provided in doctor’s offices. To estimate that spending, we used the drug spending data for Medicare enrollees in the traditional public program and increased it to account for the missing share.
Spending on this scale, so suddenly, could have far-reaching impacts for Medicare, its users and taxpayers. The addition of $29 billion a year to Medicare’s budget would be paid for by increases in both taxpayer spending and in the premiums paid by all Medicare users. Premiums might also go up for supplemental plans many Medicare beneficiaries buy to offset costs the program doesn’t pay directly. And the costs are likely to spill over into state budgets, where Medicaid pays premiums for low-income Medicare enrollees.
Congress, budget experts and several White Houses have spent years suggesting ways to trim spending in Medicare, a large and growing share of the federal budget. But many of these proposals are politically difficult to achieve — and most would save less than the projected cost of Aduhelm.
“It’s so much work to get savings that are really much smaller than this one drug would cost,” said Joshua Gordon, the director of health policy at the Committee for a Responsible Federal Budget, who says he has found himself thinking nonstop about the challenges raised by Aduhelm since its approval.
Cost predictions vary because analysts aren’t sure how many patients will ultimately use the new drug. The F.D.A.’s approval could apply to everyone diagnosed with Alzheimer’s disease. But the drug was developed for a smaller group of around 1.5 million patients who are in the early stages of the disease. Analysts aren’t yet sure whom doctors will recommend the treatment for, and which families will want to try it. The F.D.A. has asked Biogen to continue studying the drug until 2030, but prescribing could become widespread before there are any further public results on how well it works.
Allison Parks, a Biogen spokeswoman, said in an email that the company would focus on reaching the type of patients who were studied in the company’s clinical trials, “in the early symptomatic stage of the disease.”
The range reflects a variety of reasonable expert estimates. The high estimate, drawing on a Kaiser paper, assumes that about a quarter of the two million Medicare enrollees who currently take an Alzheimer’s treatment will take this one. The low one is based on a Cowen and Company analyst estimate of $7 billion in total sales by 2023.
Estimating how many patients will use the drug is challenging. Aduhelm is not just expensive, but also somewhat hard to take, requiring monthly in-person visits to an infusion center for treatment. Patients who take it will be required to get multiple brain scans during their treatments to look for side effects.
And the side effects themselves — about 40 percent of patients in one clinical trial showed signs of brain swelling — may discourage some patients from trying the drug, and prompt others to stop taking it. (The many scans — and treatments for more serious side effects — would also be covered by Medicare.)
There are six million Medicare enrollees who do not purchase supplemental coverage who could have to pay 20 percent of the drug’s cost, in this case $11,200 a year.
Demand may nevertheless be high from families who see an opportunity to intervene when faced with a devastating diagnosis. Until now, there have been few treatment options available for patients hoping to forestall cognitive decline from the disease.
“There is something intrinsically hard about having a loved one, seeing the clock ticking, and saying, Well, let’s just wait,” said Dr. Steven Pearson, a primary care physician and the president of the Institute for Clinical and Economic Review (ICER). “It’s very hard to ignore the drive to do something.”
Doctors, who would administer this drug and be paid a percentage of the drug’s high price by Medicare for that work, may face financial incentives to say yes when patients ask for it.
“The implications of this one drug and the associated set of procedures are enormous,” said Rachel Sachs, a law professor at Washington University in St. Louis and an author of a recent essay in The Atlantic asserting that the drug could “break American health care.”
Private insurers may erect roadblocks to treatment, requiring patients to get additional tests or prove that other options haven’t worked. But in normal circumstances, Medicare covers drugs that are approved by the F.D.A. Medicare decides what drugs to cover based on whether they are “reasonable and necessary,” not on how much they cost.
Medicare is initially required to pay for this type of drug at its list price in addition to a 3 percent fee to the doctor who gives it. And then, after about a year on the market, it pays the average sales price plus 6 percent. For drugs with competition, that average price can be substantially lower than the sticker price. But for a drug like Aduhelm, which is the first of its kind, the drugmaker may not offer doctors discounts.
Medicare, which covers 61 million Americans 65 and over, does have some tools to contain costs. It could decide to cover the drug in a way that is more limited than the F.D.A. approval, a break from its normal practice.
Or it could do something even more unusual: An unexpected alliance of advocates has suggested that Medicare put the drug into a randomized experiment to evaluate how well it works — paying to cover the drug in some parts of the country, but not others. Such policy experiments were authorized under the Affordable Care Act, but one has never been used to limit coverage of a drug in this way.
Other countries will most likely control the cost of Aduhelm by negotiating with Biogen for a lower price, or simply decline to buy it at all. Most will consider the drug’s effectiveness when deciding what they are willing to pay. So far, the drug has not been approved for use anywhere else in the world.
Medicare can’t do that. Because of the way it pays for drugs under current law, it has no way to bargain down the price. Democrats increasingly support legislation to change that. The House passed legislation in 2019 that would give Medicare the authority to negotiate some prices, but it died in the Senate. Legislators reintroduced the same bill in the House in April.
President Biden supports allowing Medicare to negotiate drug prices but did not include the policy in his proposed American Families Plan.
Dr. Pearson of ICER has estimated that if the new drug’s effectiveness were taken into account, a fair price would be $2,500 to $8,300.
“It will be interesting to see if this starts a discussion about fair pricing in the United States,” he said. “To most people’s eyes, this looks like an outstanding example of a price that just does not match up with the evidence.”
Methodology: Estimated current spending on Medicare Part B drugs was drawn from the Centers for Medicare and Medicaid Services Part B Drug Spending Dashboard, and adjusted up by 54 percent to account for Medicare beneficiaries enrolled in Medicare Advantage plans. Because of the demographics of who is in which program, this assumption may overestimate current drug spending.)
Medicare Part D drug spending was drawn directly from the C.M.S. Part D Drug Spending Dashboard, and may represent an overestimate because those numbers do not include all rebates paid to drug plans.
The high Aduhelm spending estimate comes from a Kaiser Family Foundation paper. The low estimate is derived from a total sales estimate from Cowen and Company, and adjusted to account for an estimated 80 percent of Alzheimer’s patients early in their disease enrolled in Medicare — and Medicare’s initial 3 percent payment to doctors for overhead and administration.
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Medicaid Enrollment Surpassed 80 Million, a Record, During the Pandemic

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The increase points to the program’s growing role not just as a safety net, but also as a foundation of U.S. health coverage.

Medicaid enrollment rose sharply during the pandemic, with nearly 10 million Americans joining the public health program for the poor, a government report released Monday showed.
Eighty million people were covered under Medicaid, a record. It reflected an increase of nearly 14 percent over the 12-month period ending Jan. 31. The figure also includes enrollment in the Children’s Health Insurance Program, which covers children whose parents earn too much for Medicaid, but too little to afford other coverage.
The spike in enrollment demonstrates Medicaid’s increasingly important role not just as a safety net, but also as a pillar of the American health system, with fully a quarter of the population getting coverage through it.
“This tells us that Medicaid is a critical program for American families,” said Chiquita Brooks-LaSure, the Biden administration official who oversees Medicaid. “What we’ve seen during this pandemic is that people want access to affordable health insurance, and how important it is during a public health crisis.”
The Affordable Care Act transformed Medicaid from a targeted health care benefit meant to help certain groups — expectant mothers, for example, and those with disabilities — to a much wider program providing largely free coverage to most people below a certain income threshold. A notable exception is the 12 states — mostly in the South — that have declined to expand Medicaid under the A.C.A.
Medicaid, in which states and the federal government share the cost, covers all adults with income up to 138 percent of the poverty level, which would be about $17,420 for an individual to qualify this year.
The expansion of Medicaid in most states since the bulk of the A.C.A. took effect in 2014 provided a public source of coverage for the newly unemployed that did not exist a decade ago. Adult enrollment in Medicaid grew twice as fast as child enrollment, suggesting that widespread job loss related to the pandemic created a huge group of newly eligible adults.
“In past economic downturns, there has been substantial growth in Medicaid enrollment, but it was concentrated among children,” said Rachel Garfield, co-director of the Kaiser Family Foundation’s program on Medicaid and the uninsured. “This time, it’s interesting we’re seeing much of the enrollment happening among adults.”
She also noted that Medicaid enrollment has increased much faster during the pandemic economic contraction than in previous downturns. Fewer than four million Americans joined the program in 2009, at the beginning of the Great Recession.
There may also have been increased interest among uninsured Americans who were already eligible for Medicaid, but who decided to enroll only because of heightened health concerns during the pandemic.
“When we look at who remains uninsured, so many times it’s people who are eligible but unenrolled,” Ms. Brooks-LaSure, the Medicaid official, said. “Right now, we’re seeing that when we make it easy for people to enroll, they do it.”
Medicaid enrollment had been declining in the years leading up to the pandemic. More than a million children lost coverage between December 2017 and June 2019, a trend that rattled health care advocates. Many attributed the changes to new rules during the Trump administration that made it harder to sign up and remain signed up.
That changed last spring, as the pandemic took hold and Congress gave states extra money to fund their Medicaid programs. Congress gave a 6.2 percent spending bump on the condition that states not disenroll patients or tighten eligibility requirements.
A woman who gave birth, for example, would normally have lost coverage 60 days after delivery, but because of the legislation, she could stay on Medicaid for the length of the pandemic. Those rules remain in effect until the federal government declares the public health emergency over.
Three states — Utah, Idaho and Nebraska — expanded Medicaid last year after voters approved ballot initiatives; those states saw especially large enrollment surges. A fourth, Oklahoma, will expand Medicaid to most low-income adults starting next month.
Even after its growth under the Affordable Care Act, the Medicaid program has holes that are hard to fix. The 2012 Supreme Court decision that upheld the law’s individual insurance mandate also made expanding Medicaid optional for states.
As a result, millions of low-income adults in the 12 holdout states, which include Florida and Texas, still have no coverage. A recent study in JAMA found that Medicaid enrollment increased faster during the pandemic in the states that participated in the expansion, most likely because many more people were eligible for coverage.
Generous financial incentives offered through the most recent stimulus package have not been enough to persuade any of the 12 states to expand Medicaid, but top Biden administration officials say they remain hopeful that some will come on board.
“We hope we can encourage them,” Xavier Becerra, the Health and Human Services secretary, said in a call with reporters last week. “We want to make sure they’re expanding care and it’s affordable.”
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C.D.C Studies Say Young Adults Are Less Likely to Get Vaccinated

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Younger Americans are less likely to be vaccinated than their elders, and factors like income and education may affect vaccine hesitancy, according to two new studies by the Centers for Disease Control and Prevention.
By May 22, 57 percent of adults had received at least one vaccine dose, the authors of one of the new papers found, but the rate varied considerably by age: Among those who were 65 or older, 80 percent had been at least partially vaccinated, compared with 38 percent of those between 18 and 29.
Some of the gap in rates could be attributed to the fact that many young adults did not become eligible for vaccination until March or April. But uptake has also been slower among younger Americans, and a substantial proportion of them remain hesitant.
If vaccine initiation rates remain stable, by late August, just 58 percent of 18 to 29-year-olds will have been vaccinated, compared with 95 percent of those 65 and up, the researchers found.
Vaccination rates lagged for young men, people living in rural counties and people living in counties where a high share of the population was low-income, uninsured or lacked access to a computer or the internet.
In a second study, 24.9 percent of 18- to 39-year-olds surveyed said that they would probably or definitely not get vaccinated. Those who were young, Black, low-income, lacked health insurance, lived outside of metropolitan areas or had lower levels of education were less likely to report being vaccinated or to say that they definitely planned to be vaccinated.
The studies highlight the hurdles that remain in improving vaccine coverage, with two weeks to go until President Biden’s self-imposed July 4 deadline for getting 70 percent of adults at least partially vaccinated. In recent weeks, his administration has shifted its approach, moving away from mass vaccination sites and adopting more targeted strategies, including the creation of mobile or pop-up vaccination clinics and on-site vaccination events at Black-owned barbershops.
The U.S. vaccination campaign began on Dec. 14. Health care workers, adults who were 75 and older and members of other high risk groups were generally the first to become eligible, though vaccine policies varied from state to state. By April 19, all adults were eligible for the shots. Using vaccination data submitted by the states, a team of C.D.C. researchers analyzed vaccination patterns in various demographic groups.
They also calculated the percentage of people in each age bracket who received their first dose during a given week. This vaccine “initiation rate” was highest for adults 65 and older, peaking during the week of Feb. 7, when 8 percent of adults in that group received their first dose.
Between April 19 and May 22, the share of 18- to 29-year-olds who received their first dose fell to 1.9 percent from 3.6 percent.
“If the current rate of vaccination continues through August, coverage among young adults will remain substantially lower than among older adults,” the researchers wrote.
In the second study, researchers surveyed a nationally representative sample of adults, including 2,726 18- to 39-year olds, between March 5 and May 2. Among those who said they would probably or definitely not get the vaccine, 57 percent said that they did not trust the vaccine, while 56 percent expressed concern about possible side effects and 36 percent said they did not think they needed the shot.
The study also pointed to potential strategies for increasing vaccination coverage. Among those who said they were unsure about or would probably get the vaccine, 20 to 40 percent said they would be more likely to get it if they had more information about its safety and effectiveness, if it would prevent them from spreading the virus to family and friends, or if it would allow them to return to normal social activities.

See where doses have gone, and who is eligible for a shot in each state.
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Morning People May Be at Lower Risk of Depression Than Night Owls

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Going to bed early and waking up early may help to provide some protection against depression, a new study suggests.

If you are a morning person, you may be at reduced risk for major depression, a new study suggests.
Several studies of the body’s circadian sleep-wake cycle have shown that being an early bird is associated with a lower risk for depression. But those studies were observational so could not prove cause and effect.
For example, people who are early birds may have other health or lifestyle behaviors that reduce their risk for depression — they may have a healthier diet, for example, exercise more, or have fewer health conditions, such as chronic pain, that are associated with depression. All these factors, and many others, could explain the decreased risk for depression, and not the fact of being an early bird. Moreover, depression itself causes sleep disturbances, so it could be that depression is a cause of being a night owl, rather than the other way around.
The new study, however, offers more compelling evidence that going to bed early and waking early may, in itself, provide protection against depression, independent of other factors. The study, published in JAMA Psychiatry, uses a research method called Mendelian randomization that helps pinpoint the cause of what may be a cause-and-effect relationship.
With Mendelian randomization, researchers can compare large groups of people based on genetic variants that are independent of other health or behavioral characteristics — in this case, the tendency to being a night owl or a morning person, inherited traits that are randomly allocated during our development in the womb. More than 340 genetic variants associated with circadian sleep rhythm have been identified, and the researchers can compare large groups of people with the genetic variants for being a morning person with groups that lack them. Nature has, in essence, set up the randomized experiment for them.
For the study, the scientists used two genetic databases of more than 800,000 adults to do a Mendelian randomization study of circadian rhythm and the risk for depression. They not only had genetic data, but also data on diagnoses of major depression and information on when people went to bed and woke up, collected with both self-reports and sleep laboratory records, which the researchers used to track the midpoint of sleep, a helpful scientific measure of someone’s sleep tendencies. A morning person who tended to go to bed at 10 and wake up at 6, for example, would have a sleep midpoint of 2 a.m.
They found that in people with the genetic variants for being an early bird, for every hour earlier the sleep midpoint, there was a 23 percent lower risk of major depression.
Dr. Till Roenneberg, an expert in chronobiology who was not involved in the research, said a shortcoming of the study was that the scientists had no data on when these people had to rise for work or other obligations. Even with Mendelian randomization, he said, they can’t account for the fact that late types often need to go to work too early, which in itself may contribute to depression.
“They’ve drawn the right conclusions from their data,” he said, “but life is more complicated than that.”
If you are a night owl, will changing your habits alleviate depression or decrease the risk for developing it? Not necessarily, said the lead author, Dr. Iyas Daghlas, a resident physician at the University of California, San Francisco. The study, he said, looks at large groups of people, not individuals.
“This data tells us that certain trends in society” — such as using smartphones and other blue light devices at night, which make us go to sleep later — “may be having an effect on the level of depression in the population,” he said. “These results do not say that if you go to sleep earlier, you’ll get rid of depression. Discovering which intervention in which populations will be effective — that has to be left to clinical trials.”
Still, he said, “While our data doesn’t tell us where the sweet spot is, I would say that if you’re an evening person, especially one who has to wake up early, advancing your bedtime about an hour or so is a safe intervention that might be helpful for your mental health.”
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Trump supporters aren't crying and looting. Yeah, we are angry, but we are level-minded and strong. We are resilient and we will fight on, not whine and complain. See you in court, Dems!

We love you, President Trump. Hope you and your family recover quickly. Take care and best wishes. https://twitter.com/realDonaldTrump/status/1312158400352972800

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