Personalized cancer vaccine deemed safe, shows potential benefit against cancer

A personalized cancer vaccine developed with the help of a Mount Sinai computational platform raised no safety concerns and showed potential benefit in patients with different cancers, including lung and bladder, that have a high risk of recurrence, according to results from an investigator-initiated phase I clinical trial presented during the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.
“While immunotherapy has revolutionized the treatment of cancer, the vast majority of patients do not experience a significant clinical response with such treatments,” said study author Thomas Marron, MD, PhD, Assistant Director for Early Phase and Immunotherapy Trials at The Tisch Cancer Institute and Assistant Professor of Medicine (Hematology and Medical Oncology) at the Icahn School of Medicine at Mount Sinai. “Cancer vaccines, which typically combine tumor-specific targets that the immune system can learn to recognize and attack to prevent recurrence of cancer. The vaccine also contains an adjuvant that primes the immune system to maximize the efficacy.”
To generate the personalized cancer vaccine, Dr. Marron and colleagues sequenced each patient’s tumor and germline DNA and tumor RNA. They also identified the patient’s tumor-specific target to help predict whether the patient’s immune system would recognize the vaccine’s targets.
The Mount Sinai computational pipeline, called OpenVax, allows the researchers to identify and prioritize immunogenic targets to synthesize and incorporate into the vaccine.
Following any standard cancer treatment such as surgery for solid tumors or bone marrow transplant for multiple myeloma, patients received 10 doses of the personalized vaccine over a six-month period. The vaccine was given with the immunostimulant, or adjuvant, poly-ICLC, which is “a synthetic, stabilized, double-stranded RNA capable of activating multiple innate immune receptors, making it the optimal adjuvant for inducing immune responses against tumor neoantigens,” said study author Nina Bhardwaj, MD, PhD, Director of the Immunotherapy Program and the Ward-Coleman Chair in Cancer Research at The Tisch Cancer Institute at Mount Sinai.
“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” said Dr. Bhardwaj. “We have therefore developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in multiple myeloma, when patients have minimal — typically microscopic — residual disease. Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types.”
Before the vaccine, the trial participants statistically had a high chance of disease recurrence. Thirteen patients received the Mount Sinai team’s vaccine: 10 had solid tumor diagnoses and 3 had multiple myeloma.
After a mean follow-up of 880 days, four patients still had no evidence of cancer, four were receiving subsequent lines of therapy, four had died, and one chose not to continue the trial. The vaccine was well tolerated, with roughly one-third of patients developing minor injection-site reactions.
A phase 1 trial’s primary goal is to determine the safety of an experimental treatment, which was achieved in this trial. Researchers also saw early potential benefits of the vaccine after blood tests of one of the patients showed an immune response from the vaccine, and two other patients had robust response to immunotherapy afterward, results that are normal after being exposed to a cancer vaccine.

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New CAR T approach minimizes resistance, helps avoid relapse in non-Hodgkin's B-cell lymphoma

Early results from a new, pioneering chimeric antigen receptor (CAR) T cell immunotherapy trial led by researchers at the UCLA Jonsson Comprehensive Cancer Center found using a bilateral attack instead of the conventional single-target approach helps minimizes treatment resistance, resulting in long-lasting remission for people with non-Hodgkin’s B-cell lymphoma that has come back or has not responded to treatment.
The new approach, which will be presented at the American Association for Cancer Research Annual Meeting during one of the clinical oral plenary sessions, achieves a more robust defense and helps avoid relapse by simultaneously recognizing two targets — CD19 and CD20 — that are expressed on B-cell lymphoma.
In the small trial, four out of the five patients enrolled demonstrated a complete metabolic response, with minimal toxicity. While the median duration of the response, progression-free survival and overall survival endpoints have not yet been reached, the results are very promising.
“These responses are overall very impressive,” said lead author Sanaz Ghafouri, MD, a hematology/oncology fellow at the David Geffen School of Medicine at UCLA. “We are hopeful that dual targeting CD19/CD20 CARs in naïve memory T-cells will provide patients with relapsed or refractory aggressive B-cell lymphomas, that are otherwise chemotherapy-refractory, a chance at a possible cure or at the very least a lasting long-term remission.”
Patients diagnosed with relapsed or refractory B-cell lymphoma tend to have poor outcomes with second-line therapies. While CAR T cell therapy has been a game-changer for many people with this disease, recurrence is still a common phenomenon — approximately 50% of patients relapse by six months.
“One of the reasons CAR T cell therapy can stop working in patients is because the cancer cells escape from therapy by losing the antigen CD19, which is what the CAR T cells are engineered to target,” said Sarah Larson, MD, assistant professor of hematology/oncology at the David Geffen School of Medicine at UCLA and the principal investigator on the trial. “One way to keep the CAR T cells working is to have more than one antigen to target. So by using both CD19 and CD20, the thought is that it will be more effective and prevent the loss of the antigen, which is known as antigen escape, one of the common mechanisms of resistance.”
The patients enrolled in the trial all had measurable disease after either undergoing two or more lines of therapy for primary mediastinal B-cell lymphoma, or three or more lines of therapy for mantle cell lymphoma or follicular lymphoma. All patients had CD19/CD20 positive B-cell malignancy on tissue biopsies prior to the CAR T therapy.

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Immune-stimulating drug before surgery shows promise in early-stage pancreatic cancer

Giving early-stage pancreatic cancer patients a CD40 immune-stimulating drug helped jumpstart a T cell attack to the notoriously stubborn tumor microenvironment before surgery and other treatments, according to a new study from researchers in the Abramson Cancer Center (ACC) at the University of Pennsylvania. Changing the microenvironment from so-called T cell “poor” to T cell “rich” with a CD40 agonist earlier could help slow eventual progression of the disease and prevent cancer from spreading in more patients.
The data — which included 16 patients treated with the CD40 agonist selicrelumab — was presented today by Katelyn T. Byrne, PhD, an instructor of Medicine in the division of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania, during a plenary session at the American Association for Cancer Research annual meeting.
“Many patients with early-stage disease undergo surgery and adjuvant chemotherapy. But it’s often not enough to slow or stop the cancer,” Byrne said. “Our data supports the idea that you can do interventions up front to activate a targeted immune response at the tumor site — which was unheard of five years ago for pancreatic cancer — even before you take it out.”
The purpose of CD40 agonists is to help “push the gas” on the immune system both by activating antigen-presenting cells, such as dendritic cells, to “prime” T cells and by enhancing immune-independent destruction of the tumor site. The therapies have mostly been investigated in patients with metastatic pancreatic cancer patients in combination with other therapies, such as chemotherapy or other immunotherapies. This is the first time the drug has been shown to drive an immune response in early-stage patients both at the tumor site and systemically — which mirrors what researchers found in their mouse studies.
The phase 1b clinical trial was conducted at four sites, including the ACC, Fred Hutchinson Cancer Research Center at the University of Washington, Case Western Reserve University, and Johns Hopkins University.
Sixteen patients were treated with selicrelumab before surgery. Of those patients, 15 underwent surgery and received adjuvant chemotherapy and a CD40 agonist. Data collected from those patients’ tumors and responses were compared to data from controls (patients who did not receive the CD40 agonist before surgery) treated at Oregon Health and Science University and Dana Farber Cancer Institute.
Multiplex imaging of immune responses revealed major differences between the two groups. Eighty-two percent of tumors in patients who received the CD40 agonist before surgery were T-cell enriched, compared to 37 percent of untreated tumors and 23 percent chemotherapy or chemoradiation-treated tumors. Selicrelumab tumors also had less tumor-associated fibrosis (bundles of tissue that prevent T cells and traditional therapies from penetrating tumors), and antigen-presenting cells known as dendritic cells were more mature.
In the treatment group, disease-free survival was 13.8 months and median overall survival was 23.4 months, with eight patients alive at a median of 20 months after surgery.
“This is a first step in building a backbone for immunotherapy interventions in pancreatic cancer,” Byrne said.
Based on these findings, researchers are now investigating how other therapies combined with CD40 could help strengthen the immune response even further in pancreatic cancer patients before surgery.
“We’re starting to turn the tide,” said Robert H. Vonderheide, MD, DPhil, director of the ACC and senior author. “This latest study adds to growing evidence that therapies such as CD40 before surgery can trigger an immune response in patients, which is the biggest hurdle we’ve faced. We’re excited to see how the next-generation of CD40 trials will take us even closer to better treatments.”

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My Family’s Global Vaccine Journey

In early February, my sister posted a video in our family’s WhatsApp group.It was a seven-minute CNN report on Malawi, a country in East Africa that is one of the world’s poorest. Coronavirus vaccines were nowhere to be found in Malawi, the report said, because richer countries were hogging the supplies. The video focused on Queen Elizabeth Central Hospital in Blantyre, Malawi’s second-largest city, showing the strain the facility was under as it battled the virus. The hospital’s workers were tending to infected patients but had little prospect of getting vaccinated soon.My sister Pui-Ying, a pediatrician, was one of those unprotected workers.“Sorry to see this,” I texted back, lamely.Unwritten was a question: Would Pui-Ying, a frontline doctor who would have been vaccinated against Covid-19 months ago if she worked in the United States, be the last of my family to be inoculated?For more than a year, the pandemic has divided families around the world, with relatives unable to travel to see one another without fearing for their health, waiting out quarantines and navigating red tape. But even as vaccines become available, the hopes for reunions have been tempered by the higgledy-piggledy nature of the rollouts.Many families are at the mercy of a global game of vaccine geopolitics, as wealthier countries struggle to balance immunizing their own citizens against providing supplies to others. Some nations have no doses. Where there are supplies, there are also vaccine misinformation, technological hurdles and personal doubts about the efficacy and safety of vaccines.My family, spread across three continents, has been a microcosm of these forces. Our parents live in Hong Kong; Pui-Ying in Blantyre; and another sister, Pui Ling, and I in the San Francisco Bay Area. We are separated by many time zones and thousands of miles.My parents have worried about the safety of the vaccines, their anxiety fueled by a combination of media reports and their political views and health histories. Pui Ling and I have grumbled about our chaotic local vaccine situations, knowing that we would soon get our chance — even as Pui-Ying, who works in a two-room Covid ward for children, wondered if she would get any shot at all.Dr. Kate O’Brien, director of immunizations and vaccines at the World Health Organization, said that what my family faced was the result of a “very discoordinated and incoherent set of approaches, where every country was making decisions for their own context.” Many families — including her own — were grappling with the same inequities, she said.Once countries procure vaccines, they generally give priority access to the highest-risk groups, including health care workers and seniors. If that were the case with my family, Pui-Ying would be at the front of the line, along with Dad and Mom, who are in their mid-70s. Pui Ling, who works at a foundation, and I, a New York Times editor, would be at the back of the queue.That was not how it turned out.Hong KongAs Britain and the United States began administering vaccines in December, Mom and Dad surprised us. Maybe, they said during a WhatsApp video call, they wouldn’t get vaccinated. What if the shots were unsafe?I was shocked. The coronavirus had made it impossible for us to see one another in person. Hong Kong, a densely packed city of 7.5 million, had instituted strict travel and quarantine rules. In the United States, the pandemic was out of control. Vaccines held the key to freeing us from a year of stifling restrictions.And it wasn’t like my parents to fall for anti-vaccine conspiracy theories. What was I missing?They explained that their concerns were rooted in Mom’s medical history. She had once had a severe allergic reaction to medication (something that they hadn’t deemed important enough to tell us at the time). And they were closely following Chinese and Western media reports about people suffering health problems after getting vaccinated, even if it was unclear whether those were coincidences or actual reactions to the shots.I called Benjamin Cowling, the head of epidemiology and biostatistics at Hong Kong University. Vaccine hesitancy was widespread in Hong Kong, he said. In a January survey, 50 percent of respondents said they intended to get vaccinated, compared with 89 percent in China and 75 percent in the United States.The low numbers in part reflected Hong Kong’s success at containing the virus, Dr. Cowling said. Roughly one-tenth of 1 percent of the city’s population had received a Covid diagnosis. With the risk of infection seemingly small, people were in no hurry to be inoculated.Pui-Wing Tam’s parents in Hong Kong. They initially had concerns about getting vaccinated.Lam Yik Fei for The New York TimesThat didn’t stop us from urging Mom and Dad to get the vaccines. Pui-Ying, who carries the voice of authority as a doctor, told them that she might be able to visit Hong Kong this summer and would prefer them to be alive.Our parents’ thinking evolved. It helped when an 80-year-old uncle in Tallahassee, Fla., was vaccinated in January. He was the first in our extended family to be inoculated, and the news sparked much excitement on a WhatsApp thread among my aunts, uncles and parents.“It would be safer to get it” than not to, Dad concluded.Then came another curveball. Mom and Dad announced that they were willing to get only vaccines made in China. At least four Chinese biopharmaceutical companies, such as Sinovac and Sinopharm, had developed Covid vaccines, joining a field that also included Britain and Sweden’s AstraZeneca, Russia’s Gamaleya Research Institute and America’s Johnson & Johnson, Moderna and Pfizer, the last of which had teamed up with the German company BioNTech.The wrinkle was that Sinovac’s two-shot vaccine had an efficacy rate of about 50 percent, according to clinical trials. That was substantially lower than the European and American vaccines, in particular the shots from Pfizer-BioNTech and Moderna. Those prevented about 90 percent of infections, according to the Centers for Disease Control and Prevention.Yet Dad was firm. Years of a deteriorating relationship between China and the United States, including a trade war, had made him skeptical of American superpower. A proponent of a strong, united China, he was proud of the country’s rise in recent decades. “I’m patriotic,” he said about the vaccine choice.China and other countries have nurtured such vaccine patriotism. Last month, Beijing promised expedited visa processing to foreigners inoculated with Chinese-made vaccines. Britain has also wrapped the Union Jack around the AstraZeneca vaccine, which was developed with researchers at Oxford University, said Claire Wardle, the U.S. director of First Draft, a nonprofit focused on global misinformation.My sisters and I were simply relieved that Dad and Mom would take a vaccine. Get whatever you can, we told them, because any vaccine was better than none.Ultimately, the matter of which one they could get was dictated not by nationalism but by supply. In late February, Hong Kong got its first vaccine shipments: one million doses of Sinovac. (Hong Kong would later receive 585,000 doses of the BioNTech vaccine via a Chinese company, Fosun.)On Feb. 22, Mom texted that she and Dad had booked a March 11 appointment to get their first shots, followed by second doses in April. A day later, she reported that Dad hadn’t pressed the button to confirm the appointment on the online booking system and had lost the slots.The next week, they texted again: They had walked to a private clinic that was dispensing Sinovac shots. After a short wait, they received the vaccine. On April 2, they told us that they had gotten their second dose of Sinovac and were feeling fine. Mom groused that even though they had an appointment, they “still need to wait for half an hour.”Our responses were more enthusiastic.“Great news,” I wrote.“Yay!” Pui-Ying texted, followed by celebratory emojis.“Congrats!” Pui Ling said.Blantyre, MalawiPui-Ying had moved with her family to Malawi in 2016 to work as a doctor and conduct clinical research on children’s health. Resources at the Queen Elizabeth Central Hospital, where she works, were limited. When Madonna’s charity helped finance the construction of a new children’s wing at the hospital, which opened in 2017, it was big news.Staffing was tight even before the coronavirus, Pui-Ying said. When the pandemic came, the hospital decided on a one-week-on, one-week-off routine to reduce staff exposure to Covid-19 while ensuring that enough medical professionals would be working at all times. Masks, gloves and other protective equipment were scarce.In pediatrics, Pui-Ying and her colleagues set up a “respiratory zone” for children with Covid-19. It was essentially a two-room ward, with about a dozen beds in the main room. The second room, which was an isolation unit, had space for four children.For a while, Malawi kept the coronavirus under control. But in December, the country was crushed by a second wave of Covid-19, which may have been supercharged by a South African variant.Staffing was tight and protective equipment scarce at Pui-Ying’s hospital, she said.Thoko Chikondi for The New York TimesPositivity rates for Covid-19 soared at one point to 40 percent, said Dr. Queen Dube, who was head of pediatrics at Queen Elizabeth Central Hospital and recently was appointed chief of health services at Malawi’s Ministry of Health. (By comparison, the peak positivity rate in the United States was around 22 percent last April, according to Johns Hopkins University.)The number of adult Covid patients at Pui-Ying’s hospital tripled to 106; it had to open two additional wards, Dr. Dube said.“I don’t remember in my career such a ravaging disease,” Dr. Dube said. “We lost colleagues. We lost close friends.”Fortunately, Pui-Ying only glimpsed the worst. The isolation room for children never had more than three patients, she said.Britain, the United States and other wealthy countries began ramping up campaigns to immunize their populations — something that was possible because they had spent billions of dollars last year placing advance orders for hundreds of millions of doses. Malawi did not have a single dose of a vaccine. The CNN report about the country’s lack of vaccines, which aired on Feb. 8, was forwarded throughout the medical community there.“I don’t think we knew what to expect with vaccines,” Pui-Ying said after she posted the video in our family WhatsApp group. “We just knew we wouldn’t be able to afford them.”In early March, after an application from Malawi’s government, the vaccine-sharing initiative Covax sent 360,000 doses of the AstraZeneca vaccine. When the shipment arrived at the airport in Malawi’s capital, Lilongwe, health workers there were photographed flashing celebratory V-signs.The bad news was that the shipment covered less than 2 percent of the population.Dr. Dube said she hoped for 960,000 more doses soon. The goal was to be able to vaccinate 60 percent of the country by the end of next year. By contrast, the United States is inoculating more than three million people a day, and all adults who want a vaccine will be able to get one by this summer.In the meantime, what doses there were had been earmarked for high-risk groups. Pui-Ying, who was eligible, said she was elated. Based on what she had read in the media, she hoped she would get a shot within days.San FranciscoAs Pui-Ying waited to hear about a vaccine, the situation in California brightened.The rollouts of the Moderna and Pfizer-BioNTech vaccines, which the U.S. Food and Drug Administration authorized for emergency use in December, were rocky. Federal, state and local officials had underestimated the challenges of a mass-vaccination campaign. Supplies were tight, yet thawed vaccines sometimes had to be discarded.Slowly, though, the situation improved. In February, as segments of the general population became eligible for vaccines, ballparks and conference centers — such as the Coliseum stadium in Oakland and the giant Moscone Center in San Francisco — were transformed into efficient vaccination hubs. Most important, supplies were becoming abundant.Pui-Wing, right, and Pui Ling Tam in Emeryville, Calif. By April, more than 18.4 million doses had been given in the state.Cayce Clifford for The New York TimesAs of April 1, more than 18.4 million vaccine doses had been administered in California, up from 3.5 million two months earlier. Gov. Gavin Newsom declared that everyone 16 and older would be eligible for the vaccines on April 15.Even with the occasional hiccup, California’s situation mirrored the country’s, said Dr. Bob Wachter, chairman of the department of medicine at the University of California, San Francisco. He called it a “true triumph of science and policy.” The United States has commitments from manufacturers for enough doses to cover 400 million people, about 70 million more than its total population.Even so, Covid-19 continues to spread. In early March, my husband’s aunt and uncle, both in their 70s and living in Queens, N.Y., died from Covid-19. The disease has killed more than 550,000 Americans.As more vaccines became available in California, colleagues and friends urged one another to make appointments or seek leftovers, sending spreadsheets of various inoculation sites. I signed up for a slot.On the evening of March 10, I got one of the last Pfizer-BioNTech shots of the day at a Walgreens. A bored pharmacist injected me with the vaccine in a screened-off area of the dimly lit drugstore. It was strangely anticlimactic. But after a year of lockdowns, it was also a great relief.I texted the good news to Mom and Dad, using many exclamation marks. They were pleased and immediately quizzed me on whether I felt any side effects. (I didn’t, apart from a slightly sore shoulder.) I called Pui Ling and prodded her to try to get a shot. She said she would wait, knowing her turn would come before long.Pui-Ying receiving the first shot of the AstraZeneca vaccine last month in Malawi.via Pui-Ying TamA few days later, Mom forwarded a photo to our family WhatsApp group. It was of Pui-Ying, mask on and with a sleeve of her T-shirt pushed up. She was getting an AstraZeneca shot outside Queen Elizabeth Central Hospital. Malawi had started vaccinating people on March 11, when a live broadcast showed top officials being immunized. Pui-Ying got hers five days later.I had gotten the vaccine six days before my sister, the frontline doctor.In a phone call, I mentioned to Pui-Ying that it looked like she was smiling underneath her mask when she got the vaccine. “I was!” she said.I asked when her second dose was.“May,” she said.I got mine on Wednesday.

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Daydreaming Can Be Good for You

Far from a waste of time, daydreaming might be one of the best things you can do with your free time.Like many people, Namita Kulkarni has felt trapped during the pandemic. When this travel blogger’s typically intrepid life suddenly became stuck in place, she sought her next adventure in her imagination.“As a child, I fancied being lost in a forest,” Ms. Kulkarni said. “Wilderness expands one’s sense of possibilities, so things tend to get pretty fantastical in the forests I imagine.” While her head is in the clouds, her imaginary feet enjoy magical waterfalls, fields of yellow flowers or cozy bathtubs that overlook lush valleys.She’s not alone. Adults spend as much as 47 percent of their waking lives letting their minds wander, according to one Harvard study that tracked participants with an app. Other studies say that percentage varies wildly, depending how you classify it.However, none of these studies paint staring off into space in a positive light. For decades, psychologists have equated daydreaming with a failure of cognitive control, focusing on how it stunts abilities like task processing, reading comprehension and memory. Yet, Jerome Singer, a former professor at Pennsylvania State University and the father of daydreaming research, hypothesized that daydreaming can have a positive effect. If not, why would our minds be so prone to wander?Unlike the psychologists who have portrayed daydreaming as wholly wasteful, Dr. Singer said some daydreaming was advantageous and some counterproductive. To him, negative daydreams came in two forms: painful, obsessive fantasies, and an undisciplined inability to concentrate.But he also proposed some playful, creative reveries, called positive constructive daydreaming, could be beneficial. Whereas the negative daydreams indicate a loss of control, people purposefully jump into the playful kind.This idea was revolutionary when Dr. Singer proposed it 70 years ago. A few psychologists continued his research in positive daydreaming, but most viewed it as a harmful distraction from typical thought patterns. Even the Harvard app study found daydreamers were less happy. So most psychologists have used daydreaming over the years as a barometer for a patient’s mental state rather than as a productive tool to change it. Now, a growing body of research and evidence from clinical therapy suggest we can use purposeful, playful daydreaming to improve our overall well-being.Harder Than It LooksNew research shows that daydreaming can inspire happiness if you purposefully engage with meaningful topics, such as pleasant memories of loved ones or imagined scenes of triumph in the face of all odds.In a recent study published in the journal Emotion, researchers tested how much pleasure people derived from thinking. Participants left to their own devices were more likely to gravitate toward worrying or neutral topics like work or school, and they were left with negative or neutral feelings after the session.When given a framework that guided them to imagine something positive, like a fantasy of having superpowers or the memory of their first kiss, they were 50 percent more likely to feel positive after the session.Why couldn’t they do that on their own? Erin Westgate, a psychology professor at the University of Florida and the study’s lead author, said that positive daydreaming is a heavier cognitive lift. So, our brains move toward effortless mind wandering, even when the results are negative.Using your imagination “seems like it should be easy,” Dr. Westgate said. When you daydream, you’re acting as the “screenwriter, director, audience and performer in a whole mental drama going on in your head. That’s incredibly cognitively demanding.”And it’s not always good. Some studies suggest too much daydreaming can be bad for your mental health. Maladaptive daydreaming, when people flee into daydreams to escape events or feelings of distress, can be a symptom of post-traumatic stress disorder and other psychiatric conditions. The more trauma survivors delve into their waking dream worlds, the worse their condition can become.But learning how to control your imagination correctly is worth the hassle.The Healing ImaginationAs a trauma therapist, Abigail Nathanson guides her patients in visualization and a storytelling technique called imagery rescripting that can help them understand and cope with traumatic memories.Dr. Nathanson starts by telling patients that imagining themselves in more tranquil settings, especially ones of nature, can be an effective anxiety intervention.Dr. Nathanson often prompts patients to take this technique further by engaging with metaphors and visual symbolism. If her patients feel stuck, they might create a scene where they’re standing behind a brick wall that represents their impasse. She helps them interpret the symbol and can also use it as a tool. “I will say: ‘What are you wearing in front of the brick wall? What is underneath your feet? What is around you? What do you see? What do you smell?’” she said.When purposefully engaging with your daydreams, the more senses you can call into action, the more real you can make the scene feel in your mind.Dr. Nathanson then prods them to take action, “actively engaging in their spontaneous metaphor,” as she puts it. They could climb over the wall, knock it down or do whatever suits their imagination.Although overcoming past trauma isn’t as easy as knocking down an imaginary wall, that action can have real, tangible effects. While reveling in the moment of success might actually de-motivate us from reaching future goals, visualizing the actions you take along the way can be powerful. Screening this movie in your head will make you more likely to follow through, and because you’ve imagined these scenarios before, you’ll be calm as they play out in real life.How to DaydreamAthletes like rugby players, golfers and martial artists who deliberately daydream about their techniques, using imagery and narrative, have found it can improve their performance. Studies of surgeons and musicians have found similar results. Yet, some have trouble engaging with their imaginative creative sides.As Dr. Westgate’s study showed, volitional daydreaming is especially hard without inspiration. Cognitive flexibility and creativity peak in childhood and decline with age. That creativity is still there, but it might need prompting. So, when T.M. Robinson-Mosley, a consulting psychologist for the National Basketball Association, counsels players on how to harness the power of their daydreams, she first helps them break down their mental blocks and brainstorms ideas to focus on.To help players lose their inhibitions, Dr. Robinson-Mosley starts them off by free writing, drawing or using whatever medium suits them. This “allows them to reconnect to some of the kind of creativity that we really enjoy as children,” she said.To do this yourself, set aside a few minutes every day for daydreaming. Start each session with brainstorming exercises. Pick the medium that feels most effortless and enjoyable, whether it’s writing, drawing, playing an instrument or something else, and use the task as inspiration to plumb your subconscious for ideas.Pick one idea to focus on as you daydream. You should also record a goal for the session. Your goal might be to enjoy your thoughts for a few minutes. You could use the time to process something that’s making you anxious, or to envision the steps you’ll take toward achieving a goal. The more details you can use, the better.Dr. Robinson-Mosley likens meaningful daydreaming to the practice of shadowboxing: “Before you even get in the ring to face an actual opponent, you will spend thousands of hours shadowboxing, a form of visualization that’s designed for you to simulate a boxing match in your mind before you ever glove up.”Using daydreaming as mental rehearsal can do more than just hone job performance. Research has shown that imagining scenarios as visual scenes can provide a boost in mood to people suffering from major depression. Dwelling on personally meaningful but imaginary scenes, like the ones in Dr. Westgate’s study, can increase creativity and spur inspiration.Your high school English teacher might have called you a space cadet, but in reality, even the briefest mental vacations can restore a sense of well-being. Sometimes it pays off to have your head in the clouds.

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Social Media Etiquette Review

Despite your best efforts, you may cause someone pain with that Tweet or Facebook post. Here’s a refresher on social media best practices, along with advice for some pandemic-only dilemmas.In an ideal world, your followers would think every photo, video or thought you post on social media is like a little gift to them. In reality, it’s hard to predict how posts on Instagram, Facebook and other social media will land, especially during the pandemic. After so much loss and isolation over the past year, people are on edge. That vaccine selfie may feel joyous and hopeful to you, but it could be a digital slap in the face to someone who hasn’t received a vaccine shot or who has suffered a grave loss.“Someone could be experiencing loss in such a way that there’s no way someone else won’t post something that compounds their grief,” said Catherine Newman, who has written the Modern Manners etiquette column for Real Simple magazine for 10 years. “That’s how grief is.”Still, it’s hard not to overthink things — and to worry that despite your best efforts, you may cause someone pain. Some social media experts say you should review your sharing practices periodically, so here’s a refresher on social media etiquette, along with advice for some pandemic-only situations. Ask why are you posting.First, identify your motivations. Are you sharing that picture of the exquisite cake you baked because you want praise, or do you want people to feel bad that what they made themselves wasn’t as good? If it is to receive affirmation, that’s OK. But if you find yourself trying to get all your needs met by social media likes, it might be time to think about what else is missing in your life.Second, focus on your friends. If you tried to consider every possible person who might be hurt by a post — your seemingly unobjectionable photo of tulips could very well remind a follower of someone they have lost — you might never post anything on social media. But absolutely think about your inner circle carefully.Ms. Newman, for one, hasn’t posted about her own post-vaccination visits with family because so many in her immediate friend group have lost a parent in the past year. If you’re in a similar situation and you still want to post your vaccine selfie or the first time you’ve hugged your father in a year, consider acknowledging your own good fortune.“I still appreciate it when people say, ‘We’re so lucky and there’s been so much loss and I’m sorry if you’re experiencing loss,’” said Ms. Newman, whose best friend died of cancer five years ago.Before you hit “share,” read your words in multiple tones of voice, as different people can interpret the text differently, suggested Diane Gottsman, an etiquette expert and the founder of the Protocol School of Texas, a San Antonio company specializing in corporate etiquette training. If there’s any doubt, add a cue, such as an emoticon, about your tone.Don’t go low, go high.If you want to post something negative, keep in mind that what you say or share often says more about you. Disagree (respectfully), but avoid sweeping generalizations about entire groups of people — or about one business based on your interaction with a single employee.Additionally, remember that any message you share, even with close family members, will be amplified to your entire online community. (The tension may also be amplified around vaccines, health measures and the stress of a not-normal year.) If you are replying to your sister online about something, that doesn’t mean you can speak to her as harshly as you might privately. Ms. Gottsman advises taking a heated family debate offline.“Don’t start a family feud on social media,” Ms. Gottsman said. “It can affect the next family holiday.”If you are soliciting donations for a particular cause or charity, or asking for money to pay someone’s rent or medical bills with a GoFundMe campaign, recognize that the financial situations of many people have changed this past year and there may be many other appeals compared to times past. Skip shaming phrases, like “How can you not help this person?” Instead, Ms. Gottsman said, use ones like “If your heart moves you, I’m sharing this.”Consider your audience.Think less vigilance is needed, because your text group is small or your settings have been changed to private? Think again. When Heidi Cruz, the wife of Senator Ted Cruz of Texas, shared her family’s plans to flee a devastating winter storm in Texas for a vacation in Mexico, she texted only a small group of neighbors and friends. Screenshots of the messages ended up with journalists. Elaine Swann, an etiquette expert and founder of the School of Protocol in Carlsbad, Calif., points out that it wasn’t just one person who shared the chat with The New York Times; there were others who confirmed it.“Even if you think it’s just your inner circle, there’s always somebody there who isn’t 100 percent on your team,” she said. “That’s the person who takes the screenshot before you delete whatever it is.”Ban body-size talk.Posting about food and fitness may be even more tempting than usual, given that a lot of people have changed what they eat and how much they exercise during the pandemic. But confine your commentary to how these lifestyle changes make you feel, not how they make you look. Among other things, not all people have had the luxury of more time to exercise during the pandemic — or if they did, they might not have had the energy to do so.Dr. Lindsay Kite is a founder of Beauty Redefined, a nonprofit that promotes body image resilience, and an author of “More Than a Body.” She noted that your “before” photo — talking about how fat you look — may be someone else’s “after.”If you really want affirmation and accountability for your fitness goals, avoid the sports-bra selfie and posts about body measurements. Instead, Dr. Kite suggested posting a picture of yourself in a blood pressure cuff, or a less body-focused snapshot of you jogging to your favorite coffee shop.“Loving your body and improving your health doesn’t always lead to a more ideal-looking body,” she said.Acknowledge your mistakes.There may be situations in which a post doesn’t land as you had intended. Maybe you shared a photo of a masked-up pandemic wedding, but followers pointed out that attending still involved travel. Or you posted a video of your family’s Easter egg hunt, because all the adults participating had been lucky enough to be vaccinated.Ask yourself how many people reacted negatively. If only one follower is unhappy, it may just be that one person is raw.“We have a genre in my family we call ‘hurting your own feelings,’” Ms. Newman said. “Where you’re looking for something to hang some pain on and you find it.”You don’t have to own the person’s grief, but you do have to take responsibility for yourself and apologize. You can keep it simple, Ms. Newman said: I see your pain. I’m so sorry.If you post something that is hurtful to a wider audience — you inadvertently said something offensive or you didn’t consider all the issues — it should absolutely be deleted if it’s causing people pain.If it’s not, consider keeping the post up, Ms. Newman said, because deleting it erases the post from public view but does not address the hurt it caused. On Facebook, she suggested an “edited to add” with your heartfelt apology. This should not include the words “but” or “if,” as in, “I apologize if you were offended.” These words don’t acknowledge the hurt person’s truth and their situation, or your role in hurting them.“If you accidentally step on someone’s foot, you don’t say, ‘I’m sorry if I stepped on your foot,’” Ms. Swann said. “You did it. It’s not a question.”Your apology should also include a thoughtful plan about how you’ll do things differently in the future, which can be calibrated based on how grievous the offense. For lesser instances, Ms. Gottsman said, a sentence like “I’ll think twice before I post,” may be enough.These are words all of us could live by.

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AstraZeneca Vaccine and Blood Clots: What Is Known So Far

In rare cases, an immune reaction has led to antibodies that caused a serious clotting disorder. But public health experts maintain the vaccine’s benefits far outweigh the risks for most people.The AstraZeneca-Oxford vaccine has been deployed against Covid-19 in at least 115 countries, some of them for several months now. But it wasn’t until a few cases of a rare blood-clotting disorder — some fatal — emerged within the past month or so that many European nations began to rethink its use across all age groups.Several of those countries, well stocked with alternate vaccines, have now limited use of the AstraZeneca-Oxford shot to older people, and a few have stopped using it altogether. While the incidence of these clotting disorders is extremely low, regulators and researchers are trying to raise public awareness of certain symptoms — including headaches, leg swelling and abdominal pain — especially in younger people who have been vaccinated.Public health experts, however, have expressed concern that publicity surrounding the rare vaccine-related reactions will fuel hesitancy, a particular problem in Europe. They continue to emphasize that the AstraZeneca-Oxford vaccine’s benefits far outweigh the risks. In many nations, it is the only vaccine available.Below are some frequently asked questions.What is a blood clot and what causes them generally?A blood clot is a thickened, gelatinous blob of blood that can block circulation. Clots form in response to injuries and can also be caused by many illnesses, including cancer and genetic disorders, certain drugs and prolonged sitting or bed rest. Covid itself can trigger serious clotting problems. Clots that form in the legs sometimes break off and travel to the lungs or, rarely, to the brain, where they can be deadly.The clots in recipients of the AstraZeneca-Oxford vaccine have drawn heightened concern because of their unusual constellation of symptoms: blockages in major veins, often those that drain blood from the brain, combined with low platelet counts. Platelets are a blood component involved in clotting.Researchers in Germany and Norway found that vaccine recipients who developed the clotting disorder had produced antibodies that activated their platelets and led to the clots. The scientists suggested naming the unusual reaction “vaccine-induced immune thrombotic thrombocytopenia,” or VITT.So far, researchers in Europe have not identified any underlying medical condition among the vaccine recipients who developed severe clotting issues that would help explain their susceptibility.Some health officials have said that younger people appear to be at slightly higher risk from the clots. Because those people are also less likely to develop severe Covid, regulators said, any vaccine being given in that age group has to clear a higher safety bar.What is the frequency of unusual cases in Europe?As of April 4, European regulators had received reports of 222 cases of the rare blood-clotting problem in Britain and the 30-nation European Economic Area (the European Union plus Iceland, Norway and Liechtenstein). They said that about 34 million people had received the AstraZeneca vaccine in those countries, and that the clotting problems were appearing at a rate of about one in 100,000 recipients.European regulators said that as of March 22, they had carried out detailed reviews of 86 cases, 18 of which had been fatal.British health officials have described a somewhat lower incidence of cases, perhaps as a result of having begun their rollout of the vaccine in older people, who they say appear to be less susceptible.But they offered evidence this week that the risk of being admitted to intensive care with Covid exceeded the dangers of the blood clots in almost every scenario. The only group for whom they said the risk of the clotting problems outstripped that of coronavirus-related intensive care admissions was people under 30 living in a place with low rates of Covid cases.People of all ages with a medium or high risk of exposure to Covid were more likely to suffer serious health problems from catching the virus than from being given the vaccine, they said.How the Oxford-AstraZeneca Vaccine WorksAn adenovirus helps prime the immune system to fight the coronavirus.What actions are Britain, European countries and other nations taking as a safety precaution?Germany, the Netherlands, the Philippines, Portugal and Spain have recommended that the AstraZeneca vaccine be given only to people over 60. Canada and France have limited it to those over 55; Australia, over 50; and Belgium, over 56. Britain, where the AstraZeneca vaccine was developed, has been its staunchest defender, but announced on Wednesday that it would begin offering alternative shots to people under 30.Denmark and Norway have stopped using the vaccine, and the Democratic Republic of Congo delayed the start of its inoculation program.Full vaccination with the AstraZeneca vaccine requires two doses, but regulators in France have recommended that people under 55 who have had one dose get a different vaccine for their second shot. German health officials have recommended the same for people under 60.The AstraZeneca vaccine is not authorized for use in the United States, but the company has said it would seek Food and Drug Administration review.On Wednesday, the European Medicines Agency said that the vaccine’s labeling should be revised to include the clotting disorder as a “very rare” side effect of the vaccine.How common are blood clots?In the United States, 300,000 to 600,000 people a year develop blood clots in their lungs or in veins in the legs or other parts of the body, according to the Centers for Disease Control and Prevention.Based on that data, about 1,000 to 2,000 blood clots occur in the U.S. population every day. With several million people a day now being vaccinated, some of those clots will occur in those receiving the shots just as part of the normal background rates, unrelated to the vaccine.In Britain, regulators have said, roughly one in 1,000 people are affected by a blood clot in a vein every year.But medical experts said it was harder to discern the typical background rate of the more unusual clotting cases being observed in small numbers of recipients of the AstraZeneca-Oxford vaccine. Cerebral venous thrombosis, or clotting in the brain, has not always been well diagnosed, researchers have said.Still, German researchers have said those clots were appearing more frequently in recipients of the AstraZeneca-Oxford vaccine than would be expected in people who had never received the shot.What symptoms should doctors and vaccine recipients look for in case of an adverse reaction like blood clots?European regulators had recommended that recipients of the vaccine seek medical assistance for a number of possible symptoms, including swelling in the leg, persistent abdominal pain, severe and persistent headaches or blurred vision, and tiny blood spots under the skin beyond the area where the injection was given.But that set of symptoms was so vague that almost immediately, British emergency rooms experienced a surge in patients who were worried that they fit the description. As a result, some emergency room doctors have asked for more central guidance about how to handle what they described as largely unnecessary hospital visits.German researchers have described specialized blood tests that can be used to diagnose the disorder, and suggested treatment with a blood product called intravenous immune globulin, which is used to treat various immune disorders.Drugs called anti-coagulants, or blood thinners, can also be administered, but not a commonly used one — heparin — because the vaccine-related condition is very similar to one that occurs, rarely, in people given heparin.Do vaccines cause other bleeding disorders?Other vaccines, particularly the one given to children for measles, mumps and rubella, have been linked to temporarily lowered levels of platelets, a blood component essential for clotting.Lowered platelet levels have been reported in small numbers of patients receiving the Moderna, Pfizer-BioNTech and AstraZeneca vaccines. One recipient, a physician in Florida, died from a brain hemorrhage when his platelet levels could not be restored, and others have been hospitalized. U.S. health officials have said that the cases are being investigated, but they have not reported the findings of those reviews and have yet to indicate that there is any link to the vaccines.What has been the impact in Europe?Shortly after the safety concerns emerged last month, surveys began to show that in Germany, France and Spain, a majority of people doubted the safety of the AstraZeneca-Oxford vaccine.Use of the shot has suffered: Across Europe, 64 percent of delivered doses of AstraZeneca’s vaccine have been injected into people’s arms, markedly lower than the rates for other shots.But European countries have been able to withstand restricting use of the vaccine because they have purchased shots from other makers, too. The European Union is expecting the arrival of 360 million doses of coronavirus vaccines in the second quarter of this year, much of that the Pfizer-BioNTech vaccine, which is becoming a bigger part of the continent’s rollout.And in many cases, people on the continent still eligible to receive the AstraZeneca-Oxford vaccine were eager to get it. Germany, for instance, where the vaccine is recommended only for people over 60, has administered shots at a fast clip since the new restrictions were put in place.

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At Last, Aid for Senior Nutrition That Offers More Than Crumbs

Meal programs for older adults have long been underfunded. The new economic recovery plan will help.Long before the coronavirus hit, nutrition programs that served the nation’s older adults struggled to keep up with a growing demand. Often, they could not.In Charlotte, N.C., and nine surrounding counties, for example, the waiting list for Meals on Wheels averaged about 1,200 people. But Linda Miller, director of the Centralina Area Agency on Aging, which coordinates the program, always assumed the actual need was higher.She knew some clients skipped meals because they couldn’t travel to a senior center for a hot lunch every weekday; some divided a single home-delivered meal to serve as both lunch and dinner.Some never applied for help. “Just like with food stamps, which are underused,” Ms. Miller said, “people are embarrassed: ‘I worked hard all my life; I don’t want charity.’”In Northern Arizona, state budget cuts coupled with only modest increases in federal dollars through the Older Americans Act also produced waiting lists.“We get flat funding and say: ‘Thank you! We didn’t get cut!’” said Mary Beals-Luedtka, director of the Area Agency on Aging that serves four largely rural counties there. “But flat funding is like a decrease. It’s not adequate.”Covid-19 made the task immeasurably harder. Across the country, it shut down the senior centers and church halls that served meals to healthier, more mobile seniors. Then those closures, plus shelter-in-place policies and fears of exposure, drastically boosted the number of older people who needed meals delivered.Many volunteers, also at risk because of age, stayed away. Sometimes, so did family members who had pitched in with shopping and cooking, now worried about infecting their elders.The Arizona team scrambled to distribute 150 percent more meals at home last year than the year before. “My staff was reeling,” Ms. Beals-Luedtka said. “It was crazy.” She still has about 70 people on a waiting list.Help has come, however. To the relief of administrators and advocates, the first three federal Covid recovery packages included substantial increases in funding for the Older Americans Act, which supports both congregant, or group, meals (which serve the majority of participants) and Meals on Wheels.Nicole Carey, left, and Tameika Drye, center, prepared meals for delivery to seniors and others at Cabarrus Meals on Wheels in Concord, N.C.Travis Dove for The New York TimesThe fourth infusion and the largest by far, $750 million, will come from the American Rescue Plan that President Biden signed last month. It brings the total increase for senior nutrition services to $1.6 billion. In fiscal 2019, they received $907 million.“It’s a victory and a validation of the value of this program,” said Bob Blancato, executive director of the National Association of Nutrition and Aging Services Programs. “Older adult malnutrition is an ongoing problem.”Separately, a 15 percent increase for everyone who qualifies for food stamps, more formally the Supplemental Nutrition Assistance Program, will benefit an estimated 5.4 million older recipients.For years, advocates for older adults have lobbied Congress for more significant federal help. Although the Older Americans Act has enjoyed bipartisan support, small annual upticks in appropriations left 5,000 local organizations constantly lagging in their ability to feed seniors.From 2001 to 2019, funding for the Older Americans Act rose an average of 1.1 percent annually — a 22 percent increase over almost two decades, according to an analysis by the AARP Public Policy Institute. But adjusted for inflation, the funding for nutrition services actually fell 8 percent. State and local matching funds, foundation grants and private donations helped keep kitchens open and drivers delivering, but many programs still could not bridge their budget gaps.At the same time, the number of Americans over 60 — the age of eligibility for O.A.A. nutrition and other services — grew by 63 percent. About one-quarter of low-income seniors were “food insecure,” meaning they had limited or uncertain access to adequate food.And that shortfall was before the pandemic. Once programs hastily closed congregant settings last spring, a Meals on Wheels America survey found that nearly 80 percent of the programs reported that new requests for home-delivered meals had at least doubled; waiting lists grew by 26 percent.Along with money, the Covid relief legislation gave these local programs needed flexibility. Normally, to qualify for Meals on Wheels, homebound clients must require assistance with activities of daily living. The emergency appropriations allowed administrators to serve less frail seniors who were following stay-at-home orders, and to transfer money freely from congregant centers to home delivery.Even so, the increased caseloads, with people who had never applied before seeking meals, left some administrators facing dire decisions.In Northern Arizona, about 800 clients were receiving home-delivered meals in February 2020. By June, that number had ballooned to 1,265, including new applicants as well as those who had previously eaten at the program’s 18 now-shuttered senior centers. Clients were receiving 14 meals each week.By summer, despite federal relief funds, “I was out of money,” Ms. Beals-Luedtka said. She faced the grim task of telling 342 seniors, who had been added to the rolls for three emergency months, that she had to remove them. “People were crying on the phone,” she recalled. “I literally had a man say he was going to commit suicide.” (She reinstated him.) Even those who remained started receiving five meals a week instead of 14.Now, Ms. Beals-Luedtka awaits an estimated $1.34 million from the rescue plan, which will largely eliminate the waiting list, increase the number of meals for each recipient and help local providers acquire and repair kitchen equipment as senior centers reopen.Amanda Buck, right, a volunteer with Cabarrus Meals on Wheels, delivered a meal to Gloria Grooms, a former caregiver in Kannapolis, N.C.Travis Dove for The New York TimesIn North Carolina last month, the Centralina agency, working with a food bank, started delivering grocery boxes — containing produce, canned food and other staples — to low-income seniors, using federal money from last year’s CARES Act. “They’re a huge hit,” Ms. Miller said. “I could never do that before.”It may seem unnecessary for senior nutrition programs to accomplish anything beyond feeding hungry older people, but research has demonstrated their broader impact.“Addressing nutritional needs isn’t good only for people’s quality of life,” said Kali Thomas, a researcher at Brown University whose studies have demonstrated multiple benefits to Meals on Wheels. “It improves their health.” These programs diminish loneliness and help keep seniors out of expensive nursing homes. They also may help reduce falls, although those findings were based on a small sample and did not achieve statistical significance.Interestingly, Dr. Thomas’s research found daily meal deliveries had greater effects than weekly or twice-monthly drop-offs of frozen meals, a practice many local organizations have adopted to save money.Frail or forgetful clients may have trouble storing, preparing and remembering to eat frozen meals. But the primary reason daily deliveries pay off, her study shows, is the regular chats with drivers.“They build relationships with their clients,” Dr. Thomas said. “They might come back later to fix a rickety handrail. If they’re worried about a client’s health, they let the program know. The drivers are often the only people they see all day, so these relationships are very important.”Congregant meals contribute to participants’ well-being, too, staving off food insecurity and providing socialization and healthier diets, a prepandemic evaluation found.So while program administrators relish a rare opportunity to expand their reach, they worry that if Congress doesn’t sustain this higher level of appropriations, the relief money will be spent and waiting lists will reappear.“There’s going to be a cliff,” Ms. Beals-Luedtka said. “What’s going to happen next time? I don’t want to have to call people and say, ‘We’re done with you now.’ These are our grandparents.”

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Yehuda Ben-Yishay, Pioneer in Treating Brain Injuries, Dies at 88

After working with wounded Israeli soldiers in the 1970s, he developed a holistic approach to helping patients regain some semblance of the life they had before.Yehuda Ben-Yishay, a psychologist whose experience working with wounded Israeli soldiers led him to make pioneering advances in treating traumatic brain injuries, helping countless patients return to some semblance of the life they had before, died on March 24 at the NYU Langone Health hospital in Manhattan. He was 88.His death was confirmed by his wife, Myrna Ben-Yishay, a genetic counselor.Before Dr. Ben-Yishay developed what he called holistic cognitive therapy in the 1970s, most scientists thought that the adult brain was immutable, and that serious injuries — and the behavioral changes that resulted — were permanent.Working with Leonard Diller, his colleague at Rusk Rehabilitation at NYU Langone Health, Dr. Ben-Yishay proved otherwise, setting aside the biology of the brain to show that things like attention, memory and behavior could still be strengthened, or compensated for, in recovering patients.The two first demonstrated their ideas in Israel, where hundreds of soldiers, many of them tank drivers, had suffered traumatic brain injuries in the sprawling tank battles across the Sinai Desert and in the Golan Heights during the Yom Kippur War in 1973.They engaged about a dozen patients in what Dr. Ben-Yishai described as a therapeutic milieu. It wasn’t enough for a doctor to work one-on-one with a patient; everyone from nurses to families to other patients had to be involved in creating a safe environment in which a patient could address a brain injury and its consequences and start to regain or compensate for damaged cognitive skills.The two doctors returned to New York and in 1978 Dr. Ben-Yishay put their experience into practice with the NYU Rusk Holistic Day Program. A talented storyteller with a flair for drama, he was renowned for his ability to engage with patients, and he personally treated hundreds over the next four decades.“The scientific community’s work is irrelevant to what goes on here,” he told The New York Times Magazine in 2000. “The rehabilitation of head-injured individuals is a clinical, creative endeavor. Can you really say how this blob of Jell-O creates all this wonderful feeling and thinking? No. The question really is, Can you reconstruct Humpty Dumpty after he has been shattered to pieces?”The process isn’t easy, or cheap. Dr. Ben-Yishay’s 20-week program involves daylong sessions, often in small groups, and costs about $60,000. Yet it has become the gold standard for treating brain injuries, inspiring similar programs worldwide.“I was giving a talk about my program in Amsterdam,” said Keith Cicerone, the retired director of cognitive rehabilitation at the JFK Medical Center in New Jersey. “Afterward, several people from around the world came up to me and said how similar their programs were. Pretty soon we realized that we had copied from Yehuda.”Yehuda Ben-Yishay was born on Feb. 11, 1933, in Cluj, a city in the Transylvania region of western Romania. His father, Chaim Ben-Yishay, was a businessman; his mother, Leah (Finkelstein) Ben-Yishay, was a seamstress.His family went through World War II largely unscathed. Though hundreds of thousands of fellow Romanian Jews died during the Holocaust, hundreds of thousands survived, especially those in the southern reaches of Transylvania, where the family had moved shortly before the war.The Ben-Yishays were eager Zionists, and in 1946 they boarded a converted cattle ship with about 2,000 other Jews bound for Palestine. The British authorities had banned such mass migration, and on arrival Yehuda he and his two brothers and sister were separated from their parents as they were placed in refugee camps.After Israel’s independence in 1948, Dr. Ben-Yishay served in the Nahal, a part of the Israel Defense Force that built agricultural settlements. He later attended Hebrew University in Jerusalem, hoping to study psychology, but there was no one to teach it: Arab guerrillas had murdered the head of the department and several colleagues in 1948.Dr. Ben-Yishay studied sociology instead, graduating in 1957. He won a scholarship to the New School for Social Research in Manhattan and arrived at the end of that year.To cover his living expenses, he taught Hebrew and worked with retirees, including at a summer camp in Brewster, N.Y. There he met Myrna Pitterman; they married in 1960 and had three sons, Ari, Ron and Seth. All survive him along with his brothers, Yisrael and Meir; his sister, Pnina; and eight grandchildren.At the New School, Dr. Ben-Yishay fell under the guidance of a German émigré psychologist named Kurt Goldstein. Dr. Goldstein insisted that patients with traumatic injuries could recover only in a “holistic” environment, which would take into account not only their physical well-being but also their emotional and spiritual health.Dr. Ben-Yishay joined the Rusk Institute in 1964 and received his Ph.D. in psychology from N.Y.U. three years later. The institute’s founder, Howard A. Rusk, was himself a pioneer in physical rehabilitation, and like Dr. Goldstein he believed in a “whole patient” approach. (He was also a medical columnist for The New York Times.)Dr. Rusk encouraged Dr. Ben-Yishay and Dr. Diller, who ran the psychology department at Rusk, to apply that same approach to brain injuries, an increasingly urgent field. Thanks to improvements in automobile safety and battlefield medicine, more people were surviving accidents and combat incidents but with significant, if not always obvious, damage to their brains.Dr. Ben-Yishay confronted what was then considered a philosophical question: What is the nature of recovery? Is it strictly neurological, a result of biological changes in the brain? Or is it also behavioral, psychological, a result of learning and outside intervention by doctors, friends and family?Most researchers assumed it was the former, and that little could be done, aside from isolated efforts to make life easier for patients whom they thought were destined to live a life of mental anguish. Dr. Ben-Yishay thought otherwise, that cognition — things like memory, attention, reasoning — could be relearned or strengthened after a brain injury, and he spent the better part of the 1970s developing his approach.Though he faced significant skepticism at first, his program showed results. Before he began, only about 20 percent of patients with traumatic brain injuries were able to go back to work in some capacity; about two-thirds of patients who worked with Dr. Ben-Yishay and his team could do so, he estimated.Dr. Ben-Yishay was always quick to note the limits to his program. He was not there to cure a patient; no one could.“Once brain-injured, you are always brain-injured, for the rest of your life,” he told The Times in 2006.What he could do, though, was help patients develop ways to compensate, which began with recognizing what had happened to them and committing to the hard work of building a new life. He used words like persistence and courage to describe the key to success in his program, and he helped his patients unlock those qualities within themselves.“If you are a sourpuss,” he liked to say, “you are not rehabilitated.”

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Brain disease transmitted by tick bites may be treatable

Tick-borne encephalitis is a disease just as nasty as it sounds. Once bitten by an infected tick, some people develop flu-like symptoms that resolve quietly but leave behind rampant neurological disease — brain swelling, memory loss, and cognitive decline. Cases are on the rise in Central Europe and Russia with some 10,000 incidents reported each year. Vaccines can provide protection, but only for a limited time. There is no cure.
Now a new study describes antibodies capable of neutralizing the virus transmitted by tick bites. These so-called broadly neutralizing antibodies have shown promise in preventing TBE in mice and could inform the development of better vaccines for humans. Further, preliminary results suggest that the antibodies may not only prevent tick-borne encephalitis but even treat the condition, as well as the related Powassan virus emerging in the United States.
Lead author Marianna Agudelo and colleagues in the laboratory of Rockefeller’s Michel C. Nussenzweig examined nearly 800 antibodies obtained from individuals who had recovered from TBE or had been vaccinated to prevent infection. The most potent antibodies, designated VH3-48, turned out to be best suited to fend off future infections. They found that VH3-48 neutralized lab-grown varieties of the TBE virus, as well other tick-borne illnesses including the Langat, Louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses.
The researchers also showed that these powerful antibodies are not common; in fact, most of the antibodies produced by humans exposed to TBE virus are of inferior quality, with the coveted VH3-48 antibodies making only occasional appearances. Moreover, vaccinated patients in the study did not manage to develop any VH3-48 antibodies at all. “You’d expect the most prevalent antibodies to be the absolute best, but that is not what we found in TBE,” Agudelo says. “This may explain how the virus tricks the immune system, misdirecting it into producing inferior antibodies.”
The discovery of VH3-48 provides hope for a more effective TBE vaccine. Current vaccines require three doses spaced over two years and only provide about five years of protection before a booster shot is required. Next-generation vaccines built around coaxing the body into producing the rare VH3-48 antibody could be more potent, require fewer booster shots, and also prove protective against a number of tick-borne viruses.
“A vaccine like this would not just be more elegant, but also better focused,” says Michel C. Nussenzweig, the Zanvil A. Cohn and Ralph M. Steinman Professor and head of the Laboratory of Molecular Immunology at Rockefeller. “Now that we have the structures of these antibodies, we know what to target in order to design more effective vaccines.”
Broadly neutralizing antibodies may also provide the first specific treatment for TBE. Nussenzweig, Agudelo, and colleagues found that mice infected with TBE recover after receiving antibody therapy, although it remains to be seen if this finding will translate to humans.
“The next step is a clinical trial with the antibodies,” Nussenzweig says, “perhaps in Europe where there are many cases, to see whether we can ameliorate the symptoms of those suffering from encephalitis.”
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Materials provided by Rockefeller University. Note: Content may be edited for style and length.

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