Researchers advance 3D printing to aid tissue replacement

Professor Arda Gozen looks to a future someday in which doctors can hit a button to print out a scaffold on their 3-D printers and create custom-made replacement skin, cartilage, or other tissue for their patients.
Gozen, George and Joan Berry associate professor in the Washington State University School of Mechanical and Materials Engineering, and a team of researchers have developed a unique scaffolding material for engineered tissues that can be fine-tuned for the tricky business of growing natural tissue. They report on their research in the journal, Bioprinting. The team also includes researchers from WSU’s Gene and Linda Voiland School of Chemical Engineering and Bioengineering as well as from the University of Texas-San Antonio (UTSA), Morehouse College, and University of Rochester. The lead author is Mahmoud Amr, who received his PhD at UTSA.
In recent decades, researchers have been working to use biological material in 3D printing to create tissue or organs for patients recovering from injury or disease. Using 3D printing, or additive manufacturing, makes it possible to print complex, porous, and personalized structures and could allow doctors someday to print out tissue for a patient’s particular body and needs. To create biological structures, biological materials known as “bioinks” are dispensed out of a nozzle and deposited layer-by-layer, creating complex “scaffolds” for real biological material and providing a nice place for cells to grow.
Nature, however, has so far been more complicated than researchers can keep up with. Real biological cells like to grow on a scaffold that approaches their own properties. So, for instance, a skin cell wants to grow on a scaffold that feels like skin while a muscle cell will only develop on a scaffold that feels like muscle.
“The success of this method in manufacturing functional tissues relies heavily on how well the fabricated structures mimic the native tissues,” Gozen said. “If you want to grow cells and turn them into functional tissue, you need to match the mechanical environment of the native tissue.”
The way that researchers have traditionally varied their scaffolds was to simply remove trusses to make them softer or stiffer — a method that is too simple to address all the needed complexity in tissue engineering.

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Scientists find gene mutation linked to exfoliation syndrome, most common cause of glaucoma

A team of researchers from the Agency for Science, Technology and Research’s (A*STAR) Genome Institute of Singapore (GIS) and Bioprocessing Technology Institute (BTI), as well as Singapore Eye Research Institute (SERI), have identified a genetic mutation (functionally defective CYP39A1 gene) associated with exfoliation syndrome, the most common cause of glaucoma. The findings could pave the way for future research on the cause of exfoliation syndrome and potential cures. Their research was published in Journal of the American Medical Association (JAMA) on 24 February 2021.
Exfoliation syndrome is a systemic disorder characterised by abnormal protein material that progressively accumulates in the front of the eye. This disorder is the most common cause of glaucoma, and a major cause of irreversible blindness.
In this study, the scientists sequenced all protein encoding genes of more than 20,000 participants from 14 countries across Asia, Europe, and Africa, including more than 1,200 Singaporeans. They observed that people with exfoliation syndrome are twice as likely to carry damaging mutations in the gene encoding for the CYP39A1 protein, an enzyme which plays an important role in the processing of cholesterol. Further extended analyses suggest that defective CYP39A1 function is strongly associated with increased risk of exfoliation syndrome.
Although exfoliation syndrome is the most common cause of glaucoma, its origin is shrouded in mystery because it is not known where the abnormal protein deposits (exfoliative material) originate, and how the disease comes about. Answers to these questions could provide approaches to design and develop an effective treatment. The current findings point to the important role of cholesterol processing in the exfoliation syndrome disease process. As cholesterol is found abundantly in all cells, disruption to how cholesterol is processed due to defective CYP39A1 activity could adversely impact their normal functions. In particular, this study discovered that epithelial cells in the front of the eye responsible for filtering the blood supply to produce the clear fluid known as aqueous humour that bathes and nourishes other cells in the eye, were most affected by the CYP39A1 gene mutation. Disruption to the gene function can compromise the filtering function of epithelial cells and lead to leakage of exfoliative material from the blood into the eye.
Prof Patrick Tan, Executive Director of GIS, said, “This is a ground-breaking study that could facilitate future research efforts aimed at restoring defective CYP39A1 function and inhibiting the formation of exfoliation material in the eye as treatments for exfoliation syndrome and glaucoma.”
Prof Aung Tin, Director of SERI and Deputy Medical Director of SNEC, said, “This is a major eye disease, affecting over 70 million people worldwide, which causes a lot of visual morbidity and blindness, not only from glaucoma but also due to complications related to cataract surgery. This study was notable for involving many centres from many different countries around the world, but led from Singapore. The study findings are very exciting as we found a new pathway for the disease which opens up possibilities for new treatments.”
Prof David Friedman, the Albert and Diane Kaneb Chair in Ophthalmology at Harvard University and Director of the Glaucoma Service at the Massachusetts Eye and Ear Infirmary, Boston, commented, “Very exciting work. The researchers have identified rare gene variants that results in disrupted cholesterol homeostasis and transport that will open the door to novel therapeutics. Having studied over 20,000 individuals, the study demonstrates the power of studying rare variants to detect disease-causing genes in complex conditions.” Prof Friedman was not involved in the study.
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Materials provided by Agency for Science, Technology and Research (A*STAR), Singapore. Note: Content may be edited for style and length.

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The micro-environment of breast cancer in three dimensions

Cancerous tumors thrive on blood, extending their roots deep into the fabric of the tissue of their host. They alter the genetics of surrounding cells and evolve to avoid the protective attacks of immune cells. Now, Penn State researchers have developed a way to study the relationship between solid, difficult-to-treat tumors and the microenvironment they create to support their growth.
The method has the potential to act as a testbed for drugs and other anticancer treatments, according to Ibrahim T. Ozbolat, associate professor of engineering science and mechanics and biomedical engineering, who led the research. The details of the approach were published in Advanced Biology.
Using metastatic triple-negative breast cancer cells — the most aggressive breast cancer, for which there are few treatments — and specialized modeling techniques, the researchers cultivated tumor microenvironments.
“We brought together the tumor and its microenvironment and studied how the embedded tumor affects its surrounding matrix,” said Madhuri Dey, first author on the paper and a doctoral student in the Department of Chemistry in the Eberly College of Science. “Then we asked if we could get any meaningful genetic information from this composite system.”
Typically, researchers examine the genetic information of single cells in a system to understand which signals are being sent and received to encourage specific behaviors. However, Dey said, the individual actions may not reveal every facet of a composite system.
“We looked at the genome of the entire system,” Dey said. “The result was a far more representative understanding of how cells talk to each other in the native conditions.”
They found that the physiological changes in tumor behavior — such as growth or movement — are a direct result of cellular communication in the tumor’s microenvironment. Cancer cells communicate with the cells lining blood vessels, called endothelial cells, that also control the exchange of materials between blood and the extracellular environment. Cancer also communicates with the cells that secrete collagen to produce the scaffolding of tissues, called fibroblasts.

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Insights from color-blind octopus help fight human sight loss

University of Bristol research into octopus vision has led to a quick and easy test that helps optometrists identify people who are at greater risk of macular degeneration, the leading cause of incurable sight loss.
The basis for this breakthrough was published in the latest issue of the Journal of Experimental Biology and describes new technology developed by lead researcher, Professor Shelby Temple, to measure how well octopus- which are colour-blind — could detect polarized light, an aspect of light that humans can’t readily see. Using this novel technology, the research team showed that octopus have the most sensitive polarization vision system of any animal tested to date. Subsequent research used the same technology in humans and led to the development of a novel medical device that assesses the risk factor for sight loss later in life.
Prof Shelby Temple, who holds honorary positions at the School of Biological Sciences, University of Bristol and the School of Optometry, Aston University, explained the impact of the team’s findings. He said: “We knew that octopus, like many marine species, could see patterns in polarized light much like we see colour, but we had no idea that they could do so when the light was only 2% polarized — that was an exciting surprise, but even more surprising was when we then tested humans and found that they were able to see polarization patterns when the light was only 24% polarized.
“Humans can perceive polarized because macular pigments in our eyes differentially absorb violet-blue light depending on its angle of polarization, an effect known as Haidinger’s brushes. It’s like a super sense most of us don’t even know we have, revealing a faint yellow bow-tie shape on the retina. The more of these pigments a person has, the better protected they are against sight-loss.
“By inventing a method to measure polarization vision in octopuses, we were able to use the core technology to develop a novel ophthalmic device that can quickly and easily screen people for low macular pigments, a strong risk factor for increased susceptibility to macular degeneration.”
Macular pigments are the body’s natural protection against damaging violet-blue light. This new testing approach enables optometrists to provide preventative advice to patients. Empowering patients to make simple lifestyle choices, like wearing sunglasses or eating more dark green and brightly coloured fruits and vegetables that can help them protect their sight through life.
Prof Temple said, “I am so happy this work has been published, as it was the foundation upon which we developed our exciting new technology for measuring macular pigments.”
Macular pigments are the carotenoids lutein, zeaxanthin and meso-zeaxanthin that we can only acquire from our diet. They provide long term protection to the retina and this helps prevent age-related macular degeneration by acting as antioxidants and by strongly absorbing the most damaging high energy visible (violet-blue) wavelengths (380-500 nm) of light that reach our retina. A challenge to the eye care industry is that it is not possible to determine someone’s macular pigment levels without measurement, and until now most techniques have been too time consuming, difficult, or expensive to become part of regular eye exams. The new technology developed by Prof Temple through his start-up company Azul Optics Ltd, enables rapid screening of macular pigment levels and can be used on patients from 5 -95 years of age. Prof Temple added: “We are all living longer and expecting to do more in our older age, so I hope this serendipitous invention will help empower people to do more to look after our eyes, so they don’t suffer from this devastating disease.”
Notes
Age-related macular degeneration (AMD): is the leading cause of incurable blindness globally with over 288M predicted to be affected by 2050. AMD is caused by the long-term accumulation of damage with strong risk factors being age, genetics and smoking, violet-blue light exposure and low macular pigments.
What is polarized light? Light travels as a wave. The length of the waves we perceive as colour, and the orientation of the plane of vibration of the waves is their polarization. If light waves are randomly oriented, the light is unpolarized (0%), but if all of the waves are vibrating in the same plane, then the light is 100% polarized. Humanmade light sources and filters often produce nearly 100% polarized light (e.g. LCD computer screens and polarized lenses in sunglasses and camera filters) but natural light rarely exceeds 70% polarization.
How humans and cephalopods detect polarised light differently: Octopus and cuttlefish use their photoreceptors, which are adapted to detect the orientation of polarized light, and are oriented vertically and horizontally across their retinas, whereas humans use the shadow formed on the retina by the absorption of violet-blue light by macular pigments that differentially absorb polarized light depending on orientation. This shadow forms faint yellow bowtie/hourglass like shape first described by Karl von Haidinger in 1844 and now bears his name (Haidinger’s brushes).
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People with familial longevity show better cognitive aging

If you come from a family where people routinely live well into old age, you will likely have better cognitive function (the ability to clearly think, learn and remember) than peers from families where people die younger. Researchers affiliated with the Long Life Family Study (LLFS) recently broadened that finding in a paper published in Gerontology, suggesting that people who belong to long-lived families also show slower cognitive decline over time.
The Long Life Family Study has enrolled over 5,000 participants from almost 600 families and has been following them for the past 15 years. The study is unique in that it enrolls individuals belonging to families with clusters of long-lived relatives. Since 2006, the LLFS has recruited participants belonging to two groups: the long-lived siblings (also called the proband generation) and their children. Since they share lifestyle and environmental factors, the spouses of these two groups have also been enrolled in the LLFS as a referent group.
To assess cognitive performance, the researchers administered a series of assessments to the study participants meant to test different domains of thinking, such as attention, executive function and memory, over two visits approximately eight years apart. This allowed researchers to ask whether individuals from families with longevity have better baseline cognitive performance than their spouses do and whether their cognition declines more slowly than does that of their spouses.
To study this question, LLFS researchers used a model to determine the change in score on several neuropsychological tests from one visit to the next. “This model allows us to assess both the cross-sectional effect of familial longevity at baseline visit and the longitudinal effect over follow-up time,” says co-lead author Mengtian Du, a doctoral student in biostatistics at Boston University School of Public Health.
They showed that individuals from long-lived families performed better than their spouses on two tests: a symbol coding test, which has participants match symbols to their corresponding numbers and provides insight into psychomotor processing speed, attention, and working memory, and a paragraph recall test, which asks participants to remember a short story and assesses episodic memory. The researchers from the LLFS also found that individuals in the younger generation (participants born after 1935) exhibited a slower rate of cognitive decline on the symbol coding test than did their spouses.
“This finding of a slower decline in processing speed is particularly remarkable because the younger generation is relatively young at an average age of 60 years and therefore these differences are unlikely to be due to neurodegenerative disease,” explains corresponding author Stacy Andersen, PhD, assistant professor of medicine at Boston University School of Medicine. “Rather we are detecting differences in normal cognitive aging.”
According to Andersen this suggests that people with familial longevity demonstrate resilience to cognitive aging. “By studying the LLFS families we can learn about the genetics, environmental factors, and lifestyle habits that are essential in optimizing cognitive health throughout the lifespan.”
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With Covid Vaccines for Teens and Kids, Timing Matters

There can be a seven- or eight-week window around Covid vaccines when other shots can’t be given, so those who need them for camp, school or sports have to plan ahead.Greg Gold, a high school senior from Westchester County, N.Y., went to the doctor for a checkup last week. His pediatrician, Dr. Jane Guttenberg, had planned to give him his meningococcal B shot, which she wanted him to get before he goes to college this fall. But when Dr. Guttenberg heard that he had an appointment for his first Covid-19 vaccination the next day, she told him they would hold off on the meningococcal vaccine until after he was fully vaccinated against Covid-19.According to current recommendations from the Centers for Disease Control and Prevention, you aren’t supposed to get any other vaccine for two weeks before or after a Covid vaccine. That means that Mr. Gold, 17, will wait until mid-June to start the meningococcal B sequence — two shots, a month apart. He’ll still have time to get it done before he heads to Vanderbilt University in the fall, but the scheduling and juggling came as something of a surprise to him and his mother.Dr. Guttenberg, who practices in New York City and in Scarsdale, N.Y. (and at Bellevue Hospital where she is one of my colleagues), said, “I’m prioritizing the Covid vaccine for all these kids going to college.”Anyone with a teenager who is up against a deadline to be vaccinated for fall — or for camp this summer — should remember that vaccines have to be spaced, which can mean a seven- or eight-week window around Covid vaccines when other shots can’t be given.Dr. Lee Beers, a professor of pediatrics at Children’s National Hospital who is the president of the American Academy of Pediatrics, said, “We’re really trying to push the message, get in and see your pediatrician and get caught up on your routine vaccines now or you’re going to end up in this really tricky place and have to delay Covid vaccine or other vaccines.”With the news Monday that the Food and Drug Administration is preparing to authorize use of the Pfizer-BioNTech Covid-19 vaccine in children 12 to 15 years old by early next week, parents will need to plan with their pediatricians how to coordinate those along with catching up on their other shots. And younger children who have other shots due might want to consider catching up right now, so that they’re fully up-to-date for sports, camp or school. That way, as soon as they are eligible for Covid vaccines, there won’t be so much juggling to be done.And a lot of kids have catching up to do, said Dr. Bonnie Maldonado, a professor of global health and infectious diseases at Stanford who is the chair of the A.A.P. committee on infectious diseases. When it comes to immunization, she said, “We lost a lot of ground in the pandemic, and the biggest gaps are in the adolescent age group.”The regular vaccination schedule is determined primarily by burden of disease, said Dr. James Campbell, a professor of pediatric infectious diseases at the University of Maryland School of Medicine who is the chairman of the American Academy of Pediatrics subcommittee on vaccinations. You want peak protection at the age of peak risk, he said.Dr. Campbell pointed out that for all the stories about vaccine hesitancy, only 1 percent of the parents in the United States actually choose not to vaccinate their children at all — and that he believes the publicity drumbeat of the Covid vaccination campaign will ultimately leave parents more comfortable, not less.“In the end, this will be very good for vaccines that so much emphasis has been put on the process and the safety and the review,” Dr. Campbell said.“In the past, I think people didn’t realize just how much scrutiny there is,” of serious reactions to any vaccine, Dr. Campbell said, or how much attention is paid to schedule, dose, and immune response when a new vaccine is tested.When it comes to the Covid vaccines, Dr. Maldonado said, “We’re not overly specifically concerned about anything with this vaccine, we’re just following the normal processes.”Still, it’s possible that younger children, who typically have more robust immune systems than adults, may react more strongly to the Covid vaccines. That is why vaccine studies in children look carefully at dosage and immunologic reactivity, Dr. Beers said: “They often start with a smaller group, give a lower dose of vaccine, test the response, work their way up to the dose needed for adequate immunity.”Dr. Campbell and his colleagues at Maryland are just starting their first study of Covid vaccine in children under 12. And no one, he said, should be trying to convince parents that the vaccines are safe and effective in this age group until the data are available: “I have no reason to believe they won’t be safe and effective, but the proof is in the pudding — I want to see the pudding.”Getting children caught up on their regular vaccines makes sense because it will keep them well protected if other diseases flare up now that the pandemic has driven down the rates of the usual childhood immunizations. Doctors are worried about a whole list of vaccine-preventable diseases, including measles, whooping cough, meningitis, HPV and flu.Will Covid vaccines eventually fit into the schedule of routine childhood immunizations, and if so, at what age? Because the new vaccines are still in an emergency use authorization phase, “Nobody has answers; we’ll have to see over time,” Dr. Maldonado said.For some diseases, it’s possible to vaccinate children for lifelong protection. Sometimes you wait to vaccinate until you reach the age when risk is higher. For example, we give HPV vaccine to children sometime between 9 and 12, so they will be immune before they become sexually active. We time the meningococcal vaccine for that age because the disease is more common in teenagers and young adults than in elementary school children.Other diseases are most dangerous to infants or young children, so you need to vaccinate in infancy — such as rotavirus, which can cause severe dehydrating diarrhea in infants and small children, or whooping cough. Covid-19 is a disease that tends to be less severe in children, but which has still caused a great deal of serious illness. “We appreciate the fact that children are less at risk, but take seriously that they can get quite ill, that they can have long-haul symptoms or MIS-C,” Dr. Beers said, referring to the rare but serious Covid-related inflammatory condition in children.And in addition to protecting children, immunizing them against Covid-19 may protect the adults around them; Dr. Campbell said that having pneumococcal vaccine in the infant schedule had meant not only a major reduction in disease for children, but also a drop disease in older adults who have contact with kids who are immunized.Many families are waiting eagerly for vaccines to be available for their under-16 children. And many 16- to 18-year-olds are as eager to be vaccinated as their pediatricians are to see them get their shots. Mr. Gold, who, along with his whole family, had Covid-19 in March, was happy to be able to keep his vaccine appointment, and to come back in June for his first meningococcal B shot, and happy that there was time to get it all done before the fall.

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A Real-World Look at COVID-19 Vaccines Versus New Variants

Credit: Getty Images/Andrey Popov

Clinical trials have shown the COVID-19 vaccines now being administered around the country are highly effective in protecting fully vaccinated individuals from the coronavirus SARS-CoV-2. But will they continue to offer sufficient protection as the frequency of more transmissible and, in some cases, deadly emerging variants rise?

More study and time is needed to fully answer this question. But new data from Israel offers an early look at how the Pfizer/BioNTech vaccine is holding up in the real world against coronavirus “variants of concern,” including the B.1.1.7 “U.K. variant” and the B.1.351 “South African variant.” And, while there is some evidence of breakthrough infections, the findings overall are encouraging.

Israel was an obvious place to look for answers to breakthrough infections. By last March, more than 80 percent of the country’s vaccine-eligible population had received at least one dose of the Pfizer/BioNTech vaccine. An earlier study in Israel showed that the vaccine offered 94 percent to 96 percent protection against infection across age groups, comparable to the results of clinical trials. But it didn’t dig into any important differences in infection rates with newly emerging variants, post-vaccination.

To dig a little deeper into this possibility, a team led by Adi Stern, Tel Aviv University, and Shay Ben-Shachar, Clalit Research Institute, Tel Aviv, looked for evidence of breakthrough infections in several hundred people who’d had at least one dose of the Pfizer/BioNTech vaccine [1]. The idea was, if this vaccine were less effective in protecting against new variants of concern, the proportion of infections caused by them should be higher in vaccinated compared to unvaccinated individuals.

During the study, reported as a pre-print in MedRxiv, it became clear that B.1.1.7 was the predominant SARS-CoV-2 variant in Israel, with its frequency increasing over time. By comparison, the B.1.351 “South African” variant was rare, accounting for less than 1 percent of cases sampled in the study. No other variants of concern, as defined by the World Health Organization, were detected.

Caption: Changing variant frequencies during the study. Credit: Adapted from Kustin T, medRxiv, 2021

In total, the researchers sequenced SARS-CoV-2 from more than 800 samples, including vaccinated individuals and matched unvaccinated individuals with similar characteristics including age, sex, and geographic location. They identified nearly 250 instances in which an individual became infected with SARS-CoV-2 after receiving their first vaccine dose, meaning that they were only partially protected. Almost 150 got infected sometime after receiving the second dose.

Interestingly, the evidence showed that these breakthrough infections with the B.1.1.7 variant occurred slightly more often in people after the first vaccine dose compared to unvaccinated people. No evidence was found for increased breakthrough rates of B.1.1.7 a week or more after the second dose. In contrast, after the second vaccine dose, infection with the B.1.351 became slightly more frequent. The findings show that people remain susceptible to B.1.1.7 following a single dose of vaccine. They also suggest that the two-dose vaccine may be slightly less effective against B.1.351 compared to the original or B.1.1.7 variants.

It’s important to note, however, that the researchers only observed 11 infections with the B.1.351 variant—eight of them in individuals vaccinated with two doses. Interestingly, all eight tested positive seven to 13 days after receiving their second dose. No one in the study tested positive for this variant two weeks or more after the second dose.

Many questions remain, including whether the vaccines reduced the duration and/or severity of infections. Nevertheless, the findings are a reminder that—while these vaccines offer remarkable protection—they are not foolproof. Breakthrough infections can and do occur.

In fact, in a recent report in the New England Journal of Medicine, NIH-supported researchers detailed the experiences of two fully vaccinated individuals in New York who tested positive for COVID-19 [2]. Though both recovered quickly at home, genomic data in those cases revealed multiple mutations in both viral samples, including a variant first identified in South Africa and Brazil, and another, which has been spreading in New York since November.

These findings in Israel and the United States also highlight the importance of tracking coronavirus variants and making sure that all eligible individuals get fully vaccinated as soon as they have the opportunity. They show that COVID-19 testing will continue to play an important role, even in those who’ve already been vaccinated. This is even more important now as new variants continue to rise in frequency.

Just over 100 million Americans aged 18 and older—about 40 percent of adults—are now fully vaccinated [3]. However, we need to get that number much higher. If you or a loved one haven’t yet been vaccinated, please consider doing so. It will help to save lives and bring this pandemic to an end.

References:

[1] Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals. Kustin T et al. medRxiv. April 16, 2021.

[2] Vaccine breakthrough infections with SARS-CoV-2 variants. Hacisuleyman E, Hale C, Saito Y, Blachere NE, Bergh M, Conlon EG, Schaefer-Babajew DJ, DaSilva J, Muecksch F, Gaebler C, Lifton R, Nussenzweig MC, Hatziioannou T, Bieniasz PD, Darnell RB. N Engl J Med. 2021 Apr 21.

[3] COVID-19 vaccinations in the United States. Centers for Disease Control and Prevention.

Links:

COVID-19 Research (NIH)

Stern Lab (Tel Aviv University, Israel)

Ben-Shachar Lab (Clalit Research Institute, Tel Aviv, Israel)

NIH Support: National Institute of Allergy and Infectious Diseases

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$100 as a Vaccine Incentive? Experiment Suggests It Can Pay Off.

A cash reward works best with Democrats, and relaxing safety guidelines seems to motivate Republicans, a survey study shows.What’s the best way to persuade the millions of Americans who are still unvaccinated against Covid-19 to get their shots?Reassuring public service announcements about the vaccine’s safety and effectiveness have proliferated. But increasingly, people are realizing that it will take more than just information to sway the hesitant.In recent randomized survey experiments by the U.C.L.A. Covid-19 Health and Politics Project, two seemingly strong incentives have emerged.Roughly a third of the unvaccinated population said a cash payment would make them more likely to get a shot. This suggests that some governors may be on the right track; West Virginia’s governor, Jim Justice, for example, recently announced the state would give young people $100 bonds if they got an inoculation.

Similarly large increases in willingness to take vaccines emerged for those who were asked about getting a vaccine if doing so meant they wouldn’t need to wear a mask or social-distance in public, compared with a group that was told it would still have to do those things.

The U.C.L.A. project, which is still going on, has interviewed more than 75,000 people over the last 10 months. This collaboration between doctors and social scientists at U.C.L.A. and Harvard measures people’s pandemic experiences and attitudes along political and economic dimensions, while also charting their physical and mental health and well-being.To assess the effectiveness of different messages on vaccine uptake, the project randomly assigns unvaccinated respondents to groups that see different information about the benefits of vaccination. Random assignment makes the composition of each group similar. This is important because it allows the researchers to conclude that any differences that emerge across the groups in people’s intentions to get vaccinated are a result of the messages each group saw and not of other underlying attributes.Last October, one group saw messages that framed the benefits of vaccination in a self-interested way — “it will protect you” — while others saw messages that framed benefits in a more social manner: “It will protect you and those around you.” The subtle change did little; roughly two-thirds of people in both groups said they intended to get the shots.Another experiment investigated the persuasive power of certain endorsements. Endorsers included prominent figures, like then-president Donald J. Trump and Dr. Anthony Fauci, but also included more personal medical sources like “your doctor.”Most of the effects were small. Telling people their doctor, pharmacist or insurer believed the vaccine to be safe and effective had no discernible effect on intentions to vaccinate, though an endorsement by Dr. Fauci increased uptake likelihood by about six percentage points.Endorsements by political figures evoked strong partisan reactions, with Mr. Trump’s endorsement decreasing uptake among Democrats in 2020 and increasing uptake for Republicans to a smaller degree. President Biden’s endorsement decreased uptake among Republicans in 2021. There were hints in 2021 that a Trump endorsement might still increase uptake among Republicans, but the effects were much smaller than when he was in office.Last month, researchers randomly assigned unvaccinated respondents to see messages about financial incentives. Some people were asked about the chances they would get a vaccine if it came with a $25 cash payment; other people were asked about receiving $50 or $100.Roughly a third of the unvaccinated population said a cash payment would make them more likely to get a shot. The benefits were largest for those in the group getting $100, which increased willingness (34 percent said they would get vaccinated) by six points over the $25 group.The effect was greatest for unvaccinated Democrats, 48 percent of whom said they would be more likely to get vaccinated if it came with a $100 payment.Some past research shows that payment for vaccines can backfire, and in the U.C.L.A. study about 15 percent of unvaccinated people report a decrease in willingness to vaccinate because of payments. But at this later stage of a vaccine campaign — when attention has now turned to the hesitant — the net benefit seems to be tilting toward payment.The incentive to stop wearing a mask and social-distancing in public also had a strong result. On average, relaxing the mask and social distancing guidelines increased vaccine uptake likelihood by 13 points. The largest gains came from Republicans, who reported an 18-point increase in willingness to get vaccinated.These results show both the difficulty of getting the remaining unvaccinated people to clinics and the promise of efforts aimed at doing so. While most messaging effects were small, monetary payments seem to motivate Democrats, and relaxing cautionary guidelines seems to work for Republicans. (The C.D.C. recently relaxed guidelines on mask wearing outdoors for vaccinated people.)The movement toward vaccinations among the hesitant may pick up as time passes, and as people observe the consequences of vaccination among those who were first inoculated. When we asked unvaccinated people why they hadn’t tried to get a shot, 38 percent said they were worried about the side effects, and 34 percent said they didn’t think the vaccine was safe. Efforts at persuasion that demonstrate the continued and consistent absence of side effects for most people and the safety of inoculation may allay these fears. Still, a quarter of the unvaccinated say they just don’t trust the government’s motives, and 14 percent say Covid-19 is not a threat to them. These people will be harder to convince.Data from the project shows how eager Americans are to return to normal activities. Among people who work outside their home, 76 percent of the survey’s respondents said they wanted to go back to doing their job the way they were doing it before the pandemic, and 66 percent said they thought it was safe to do so as of April. These numbers are similar regardless of vaccination status.The April survey also asked people what kinds of social activities they had done in the last two weeks. Roughly 30 percent reported eating at a restaurant; 17 percent reported attending an in-person religious gathering; and 11 percent met up with a group of more than 10 nonfamily members. Nearly all took place indoors.

The rates of vaccination among people doing these activities largely reflect the rates in the population, which means not everyone who is out and about has gotten the vaccine.Among those dining out, 32 percent reported being fully vaccinated (53 percent reported not being vaccinated at all). The balance among people attending in-person religious gatherings was about equal — 41 percent said they were fully vaccinated and 41 percent reported not being vaccinated at all.Most of the people at social functions with more than 10 nonfamily members were not fully vaccinated, though the share of vaccinated people was higher for indoor gatherings (40 percent) compared with outdoor functions (27 percent).People are venturing out into social spaces, but around them, unvaccinated people still outnumber the inoculated — and rates of vaccination are slowing. Reversing this trend will take more than impassioned pleas from politicians, friends or medical professionals. Delivering real rewards beyond the vaccine’s health benefits may be required.Lynn Vavreck, the Marvin Hoffenberg Professor of American Politics and Public Policy at U.C.L.A., is a co-author of “Identity Crisis: The 2016 Presidential Campaign and the Battle for the Meaning of America.” Follow her on Twitter at @vavreck. She is also a principal investigator of the U.C.L.A. Covid-19 Health and Politics Project, along with Arash Naeim, Neil Wenger and Annette Stanton at the David Geffen School of Medicine at U.C.L.A. as well as Karen Sepucha of Massachusetts General Hospital and Harvard Medical School.

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How to Forget Something

With effort, it’s possible to forget certain memories. Start by identifying what triggers them.“We are what we remember of ourselves,” says Michael Anderson, a professor of cognitive neuroscience at the University of Cambridge who studies memory. How you will remember your life as an 80-year-old will depend on the ways you hold on to, or let go of, memories. Your brain is always in the process of forgetting, but Anderson believes you can forget with more intentionality — what he calls motivated forgetting — and that you can get better at it with practice. “You sculpt your memories,” he says.Memory relies on what cognitive scientists call retrieval cues. Say you’re trying not to think about a painful breakup, but then the same type of blue Prius your ex drove pulls up next to you at a red light. Memories flood in. If you’re trying to forget something, become attuned to that memory’s retrieval cues so you can reshape the way your brain responds to them. You can try to avoid such triggers, but that strategy rarely works. A Vietnam War veteran might take care to shun anything reminiscent of warfare and still get yanked back into combat imagery while trying to order dinner at a restaurant. “How could you anticipate that a bamboo place mat would remind you of war?” Anderson says. Rather than total retrieval-cue avoidance, try a technique called thought substitution. If you had a bitter argument with your sister and think of it every time you see her, work to focus on other, more positive associations. Practice until your brain sees her face and surfaces those better memories first and not the fight. You can also work on what cognitive scientists call direct suppression. “You just kind of put up the mental hand and say, ‘Nope, I don’t want to think about that,’” Anderson says. While these two mechanisms for forgetting often work together, they’re neurologically distinct. Thought substitution relies on the left prefrontal cortex; direct suppression on the right.Your ability to forget is determined, in part, by your specific neural architecture. Studies also show that extreme stress and lack of sleep will make you worse at motivated forgetting. People who have experienced more adversity in their lives are better at it than people who haven’t known such hardships. If you’ve lived through something traumatic, it’s unlikely that you’ll be able to wipe the experience from your brain entirely. What you can do is limit the extent to which those memories will intrude, unwanted.

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India passes 20 million cases amid oxygen shortage

SharecloseShare pageCopy linkAbout sharingimage copyrightGetty ImagesIndia has recorded more than 20 million Covid infections, but the government says that cases are “slowing down”. The country added more than 355,000 cases on Tuesday, down from more than 400,000 daily cases on 30 April. But testing numbers have have dipped as well, sparking fears that India’s true caseload is far higher. Case numbers, however, been consistently falling in Maharashtra state, which had driven the second wave since early April. Meanwhile an oxygen shortage has shown no signs of abating and people in several hotspot cities, including the capital Delhi, are struggling for treatment.India’s second wave, fuelled by lax safety protocols and massive public festivals and election rallies, has also overwhelmed its hospitals. Delays in testing, diagnosis and treatment, as well as a shortage of critical care beds and crucial drugs, has resulted in a spike in deaths too.The country has so far reported more than 222,000 deaths due to the virus. But experts say India’s Covid death toll is vastly under-reported as official tallies don’t appear to match what people are witnessing on the ground – long lines at crematoriums, mass funeral pyres and cities running out of space to bury or cremate the dead. Many states have introduced restrictions, from full lockdowns to night curfews. The northern state of Bihar, which has been adding about 13,000 daily cases in recent days, is the latest to announce a full lockdown -only essential services, such as government offices, groceries and hospitals, will be open. Are infections actually slowing down?While India’s daily caseload does appear to have fallen, it’s too early to say if infections are slowing down. Given delays in testing and official record-keeping, experts typically look at weekly averages rather than daily cases for a more accurate picture. And on average, India’s cases were rising this past week – but at a slower rate than the previous week. But it’s also true that daily cases have fallen, on average, in Delhi, Uttar Pradesh and Maharashtra, all hotspot states.Erratic testing, however, makes it hard to gauge the significance of these numbers. While Maharashtra’s testing numbers have been consistent, Delhi’s have dropped in recent weeks. The other issue, experts say, is insufficient testing. While Uttar Pradesh, one of the worst-affected states, has recorded no drop in testing figures, it’s testing far less than other states. It’s India’s most populated state, with more than 220 million people and is doing about 184,000 tests per million people. Compare that to Tamil Nadu, which has about 75 million people and is doing more than 300,000 tests per million of its population. Health officials said there was “cautious hope” of some respite from the second wave. But Lav Agarwal, joint secretary of the health ministry, said that the “gains” were very early and needed to be sustained by “containment measures at district and state level”.Experts also say that other hotspots are likely to emerge in the coming weeks as the pandemic moves through the country. A struggle for oxygenDelhi’s government has said it wants the army to run Covid care facilities and intensive care units.Delhi Chief Minister Arvind Kejriwal has repeatedly said that the city is not getting enough oxygen from the federal government, which allocates oxygen quotas to states.But federal officials deny there are shortages, saying the challenge has come from transportation.India produces thousands of tonnes of oxygen a day, but some experts say the supply crunch comes from a lack of investment in distribution networks.Anger rises as Covid rages in Modi’s constituencyDelhi running out of space to cremate Covid deadDelhi oxygen crisis deepens as more patients dieDelhi hospitals have resorted to sending SOS messages on social media to secure supplies. For residents, hours spent in queues to top up portable canisters have become part of daily life.Officials have also been urged to find more sites for cremations as the city’s morgues and crematoriums are overwhelmed by masses of Covid deaths.image copyrightGetty ImagesIs India’s vaccination drive helping?A sluggish vaccination campaign has compounded the crisis.Since January, India has administered more than 157 million vaccine doses so far – it ranks third in the world, after China and the United States. But just over 10% of India’s 1.4 billion people have had one dose and only about 2% have got both doses.Despite being the world’s biggest producer of vaccines, India is facing a shortage of supplies. And vaccination rates are down, from 3.7 million doses a day about a month ago to just 1.7 million a day. The chief executive of India’s Serum Institute, the world’s biggest vaccine manufacturer, has warned shortages will last for months. It’s set to deliver 220 million doses over the next few months, which would still only cover 8 per cent of India’s population. The Indian government is reported to be in discussions with Pfizer, which is seeking an “expedited approval pathway” for its Covid-19 vaccine.

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