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Scientists at Yale School of Medicine design a virus to treat ovarian cancer

Marisa Peryer, Senior Photographer

A new Yale study showed that certain genetically modified viruses can cure ovarian cancer in mice. It may be of use in the treatment of ovarian cancer in humans.

Researchers at the Yale School of Medicine have tested a chimeric virus — containing genes from two different viruses — that can selectively infect and kill ovarian cancer cells in mice. Their findings represent a potential breakthrough in the long-term treatment of ovarian cancer in humans. The study was published in the journal Virology on Nov. 12, two weeks after the death of the paper’s lead author Anthony Van den Pol, former professor of neurosurgery and psychiatry at Yale.

“Every year, around 20,000 women are diagnosed with ovarian cancer, which is a smaller number compared to cancer types such as breast cancer,” said Gil Mor, the scientific director of the C.S. Mott Center for Human Growth and Development at Wayne State University and a co-author of the paper. “However, unfortunately only around 4,000 of those women can survive the disease.”

The main reason behind the lethality of ovarian cancer is the lack of treatments preventing the recurrence of the disease. In 80 percent of cases, patients who respond positively to chemotherapy still experience a return of the disease, according to Mor. He explained that once the cancer comes back and begins to spread, there is little that doctors can do.

The inspiration for the study was born out of a collaboration between Van den Pol and Mor many years ago, when they worked in adjacent labs at the Yale School of Medicine. Van den Pol, a research scientist in the Neurosurgery Department, had concentrated his research on the long-term treatment of brain tumors. Mor, on the other hand, had been working on treatments for ovarian cancer. The two scientists decided to collaborate to find an alternative treatment for ovarian cancer through oncolytic viruses, which selectively infect and kill cancer cells.

In the experiment’s in vitro phase, in which the research takes place in laboratory tubes or petri dishes without a living component, researchers made a virus called Lassa-VSV in the laboratory. Lassa-VSV consists of three parts: the Lassa virus, the vesicular stomatitis virus, or VSV, and a fluorescent label to facilitate tracing, according to Nazli Albayrak, a scientist who was involved in the in vitro phase. During this phase, the team infected different ovarian cancer cell lines, eventually choosing the ones that were infected most frequently to proceed with the research. 

Then, after deciding on the cell line, the team injected tumor cells into the bodies of the mice, the paper explains. As the tumor cells began to replicate, the team then injected the Lassa-VSV virus into the tumor clusters. They observed that the virus infected the tumor cells very effectively yet did not harm the healthy cells

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Scientists identify brain cells that help drive bodily reaction to fear, anxiety — ScienceDaily

Strong emotions such as fear and anxiety tend to be accompanied and reinforced by measurable bodily changes including increased blood pressure, heart rate and respiration, and dilation of the eyes’ pupils. These so-called “physiological arousal responses” are often abnormally high or low in psychiatric illnesses such as anxiety disorders and depression. Now scientists at the UNC School of Medicine have identified a population of brain cells whose activity appears to drive such arousal responses.

The scientists, whose study is published in Cell Reports, found that artificially forcing the activity of these brain cells in mice produced an arousal response in the form of dilated pupils and faster heart rate, and worsened anxiety-like behaviors.

The finding helps illuminate the neural roots of emotions, and point to the possibility that the human-brain counterpart of the newly identified population of arousal-related neurons might be a target of future treatments for anxiety disorders and other illnesses involving abnormal arousal responses.

“Focusing on arousal responses might offer a new way to intervene in psychiatric disorders,” said first author Jose Rodríguez-Romaguera, PhD, assistant professor in the UNC Department of Psychiatry and member of the UNC Neuroscience Center, and co-director of the Carolina Stress Initiative at the UNC School of Medicine.

Rodríguez-Romaguera and co-first author Randall Ung, PhD, an MD-PhD student and adjunct assistant professor in the Department of Psychiatry, led this study when they were members of the UNC laboratory of Garret Stuber, PhD, who is now at the University of Washington.

“This work not only identifies a new population of neurons implicated in arousal and anxiety, but also opens the door for future experiments to systematically examine how molecularly defined cell types contribute to complex emotional and physiological states,” Stuber said. “This will be critical going forward for developing new treatments for neuropsychiatric disorders.”

Anxiety disorders, depression, and other disorders featuring abnormally high or low arousal responses affect a large fraction of the human population, including tens of millions of adults in the United States alone. Treatments may alleviate symptoms, but many have adverse side effects, and the root causes of these disorders generally remain obscure.

Untangling these roots amid the complexity of the brain has been an enormous challenge, one that laboratory technology has only recently begun to surmount.

Rodríguez-Romaguera, Ung, Stuber and colleagues examined a brain region within the amygdala called the BNST (bed nucleus of the stria terminalis), which has been linked in prior research to fear and anxiety-like behaviors in mice.

Increasingly, scientists view this region as a promising target for future psychiatric drugs. In this case, the researchers zeroed in on a set of BNST neurons that express a neurotransmitter gene, Pnoc, known to be linked to pain sensitivity and more recently to motivation.

The team used a relatively new technique called two-photon microscopy to directly image BNST Pnoc neurons in the brains of mice while the mice were presented with noxious or appealing odors — stimuli that reliably induce fear/anxiety and reward behaviors, respectively, along with the appropriate

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medicine

Commentary: Why scientists and public health officials need to address vaccine mistrust instead of dismissing it

Recent polls indicate that more than a third of the country has concerns about a vaccine that in all likelihood will be the only reliable way to end to the COVID-19 pandemic.
These results reflect a similar public sentiment in the U.S. in the 1950s when a polio vaccine was introduced. There are likely multiple reasons for this suspicion, including safety concerns, lack of transparency from the scientific community, lack of trust in the government and the desire to wait until a longer track record of safety can be established.
We are experts in media literacy, health and political communication and biostatistics and biomedical research for future health care providers, from Washington State University’s Edward R. Murrow Center for Media & Health Promotion Research and the Elson S. Floyd College of Medicine. We also live in the communities we hope to serve with our science.
Based on our research, we believe that officials need to use this testing period to build trust, not to create reasons for diminishing it. Respect and forthrightness can turn the tone from adversarial to collaborative, and from a provider-directed practice to a shared decision-making process. Scientists and public health officials must anticipate and address people’s concerns and not brush aside concerns, a process that has become commonplace across other areas of the provider-patient relationship, but vaccine decisions remain a notable exception.
Vaccines and complications
Vaccines are among the safest, most transformative drugs on Earth, with adverse events so low that very nearly universal vaccination is a reasonable expectation. With such a safety record, and with so much at risk with diseases like COVID-19, measles and influenza, vaccine advocates have good reason to stress the overwhelmingly positive safety record.
History has included some vaccines of questionable quality as well as vaccination tactics of even more concern. Certain minority groups have been targeted with egregious coercion. This included cases of forced vaccination for smallpox of African Americans at gunpoint in the southern United States in the early 1900s. At a tenement house in Manhattan’s Little Italy, over 200 men in 1901 in essence performed a smallpox vaccination raid in the middle of the night, trying to vaccinate as many people as they could.
When the miracle vaccine for polio was widely distributed in 1955, speed took precedent over safety, and many doses were distributed that contained live polio virus. As a result, 70,000 children developed muscle weakness, 164 were paralyzed permanently and 10 children died. This led to direct government intervention that has led to thousands of required tests in order to ensure safety and effectiveness.
Instances like these undoubtedly fuel people’s concerns. Such occurrences should give us all pause, scientist or not, to do better next time and strive to never repeat such notable grievances.
Why can’t vaccines bounce back from mistakes?
As medical and public health researchers, we have found it interesting that corporations that have been lax and dishonest have bounced back without lasting damage to their reputations. For example, Volkswagen was caught in

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health

Scientists Can Detect COVID Outbreaks in Communities by Testing Sewage Samples

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Scientists have found another way to identify clusters of COVID-19 outbreaks in communities across the country.

According to a new report from CNN, researchers now test sewage for the coronavirus, checking the samples for signs of COVID-19 infections that often show up in human waste before people present symptoms. “It’s a leading indicator,” researcher Rosa Inchausti told the outlet. “The proof is in the poop.”

Mariana Matus, the CEO of Biobot Analytics, told CNN that testing sewage can often indicate a COVID outbreak before hospitals begin to crowd. Plus, the method can identify more infections since it doesn’t rely on individuals to submit to a COVID test — although the sewage method doesn’t flag sick people individually.

“People start shedding virus pretty quickly after they are infected and before they start showing symptoms,” said Matus, who added: “We are seeing an upturn in the wastewater data, which I think broadly matches what we are seeing across the country. It’s been interesting seeing this almost second wave.”

New U.S. infections have increased 41 percent in the last two weeks and hospitals in several states — primarily in the Midwest — are running out of ICU beds.

RELATED: More Than 40 States Have Spiking COVID Cases and Midwestern Hospitals Are ‘Struggling’ to Keep Up

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On Wednesday, the U.S. recorded the second-highest number of new infections in one day with 81,457, just below the all-time record of 85,085, set last Friday.

As of Thursday morning, more than 8.9 million Americans have tested positive for COVID-19, and at least 227,697 have died from the virus, according to The New York Times.

The White House’s head of coronavirus testing said that the record-breaking numbers of new infections in the U.S. are “real,” and not because of an increase in testing. Testing czar Admiral Brett Giroir confirmed that U.S. COVID-19 cases are rising.

RELATED: More Than 62,000 Used Masks and Gloves Found in Oceans and on Beach Shorelines: ‘A Significant Threat’

“Testing may be identifying some more cases, I think that’s clearly true, but what we’re seeing is a real increase in the numbers,” he told the Washington Post.

“Compared to the post-Memorial Day surge, even though testing is up, this is a real increase in cases,” he said. “We know that not only because the case numbers are up and we can calculate that, but we know that hospitalizations are going up.”

Giroir urged Americans to keep up hygiene practices, wear masks and social distance as the crisis could get worse. “We really have to reengage the public health measures that we know work or those hospitalizations can go up substantially,” he said.

As information about the coronavirus pandemic rapidly changes, PEOPLE is committed to providing the most recent data in our coverage. Some of the information

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health

Trump said that he is “cured” of COVID-19. Scientists say that’s not how it works

Donald Trump
Donald Trump

U.S. President Donald Trump debates Democratic presidential nominee Joe Biden at Belmont University on October 22, 2020 in Nashville, Tennessee. This is the last debate between the two candidates before the November 3 election. Jim Bourg-Pool/Getty Images

This article originally appeared here on Salon.com

In a night full of many bold claims made by President Trump, one stood out to immunologists: Trump’s statement, during the Thursday night debate with Joe Biden, that he had been “cured” of COVID-19. 

“I can tell you from personal experience that I was in the hospital, I had it,” Trump claimed. “And I got better and I will tell you that I had something that they gave me — a therapeutic, I guess they would call it. Some people could say it was a cure. But I was in for a short period of time and I got better very fast or I wouldn’t be here tonight. And now they say I’m immune. Whether it’s four months or a lifetime, nobody’s been able to say that, but I’m immune.”

The only problem? Immunity doesn’t work that way, experts say. And there are other reasons to take Trump’s comments with a grain of salt, too.

“There is no cure for this disease,” Dr. Georges Benjamin, executive director of the American Public Health Association (APHA) and former secretary of health in Maryland, wrote to Salon. “The treatments are very limited and reduce the severity of the disease in a subset of patients. So this is inaccurate.”

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He added, “He may be immune but we don’t know for sure. More importantly, if he is, we don’t know for how long he will have protections. [The] current thinking is a few months, but studies are ongoing to find out how long. Reinfections are very rare so far which argues for immunity. Remember the disease is less than a year old so we don’t yet know it’s long term course.”

Benjamin was referring to a host of new research that indicates that immunity is only temporary for the virus — in scientific speak, immunity is not “durable.” A Nature Medicine article suggested that those who contract the novel coronavirus and recover may be immune to it for about twelve months. There are reported cases around the world of some becoming re-infected after three months. 

Dr. Russell Medford, Chairman of the Center for Global Health Innovation and Global Health Crisis Coordination Center, reacted to Trump’s claim of having been cured by writing to Salon that “the President’s clinical course with COVID-19 is a single case study.  None of the therapies the President received have been demonstrated to be ‘cures’ in clinical trials that test hundreds or thousands of patients infected with the SARS-CoV-2 virus. Indeed, only a handful of patients outside of clinical trials have received Regeneron’s monoclonal antibody.”

Regarding Trump’s claim of being immune, he was skeptical that he could even know that. “As a new disease, our understanding of the body’s immune response

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Rush for results could lead to inferior Covid vaccine, say scientists

Scientists have warned that early adoption of a Covid vaccine with only moderate effectiveness could disrupt efforts to test and create improved versions. Immunising against the disease is not going to be a simple business of turning off the virus once the first vaccine appears, they say. In fact, there could be considerable confusion as researchers struggle to pinpoint the best versions for different vulnerable groups, such as the elderly.



Photograph: David Cheskin/PA


© Provided by The Guardian
Photograph: David Cheskin/PA

“The vaccines coming through fastest are the most experimental. It is possible they won’t be all that great and that others – created using more tried-and-tested but slower methods – might be better,” said Professor Adam Finn of Bristol University. “But to prove that point will become very difficult if lots of individuals have already been given the first vaccine. It will need vast numbers of people to demonstrate which is best or if a different vaccine is more suitable for particular groups, like the elderly.”



Some of the vaccines that are coming through fastest are also the most experimental.


© Photograph: David Cheskin/PA
Some of the vaccines that are coming through fastest are also the most experimental.

Finn said such confusion could cause setbacks in dealing with Covid, adding: “We should be preparing to meet this challenge and work out ways to compare the effectiveness of early vaccines – but at present we are not doing that well enough.”

A total of 198 Covid vaccines are now under development across the globe with four key versions undergoing final phase 3 trials. These include Pfizer’s BNT162b2 and the Oxford AstraZeneca vaccine.

Results of those trials – in which each is compared with a placebo – are expected in weeks or months. Once the first vaccine that shows efficacy in countering Covid-19 is revealed, there will be enormous pressure to use it immediately. Key candidates would be healthcare workers who deal with Covid cases and others at high risk of becoming infected.

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But for groups such as the elderly, who tend to have weaker immune systems, caution will be required.

“The problem is that early vaccine trials are not likely to show how well these products work in these populations,” said Kanta Subbarao, a World Health Organization director, in an editorial in Nature last week. “We know vaccines often work better in young, healthy adults, which is why they are enhanced with a higher dose or an adjuvant to boost immunity for diseases such as flu and shingles. It is also unclear how well clinical trials will assess effectiveness in those in minority ethnic communities.”

In other words, by spring, several vaccines may have passed their trials without any mechanism being in place to select which is the most effective for different groups. Nor is the problem confined to the UK.

“The complexity and chaos and confusion that will happen in a few short months has hardly

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Wastewater coronavirus testing helps scientists around the world track outbreaks

Elsewhere in the world, countries have been expanding their use of sewage sampling. Here are some of their key findings.

Canada

Every morning at 5, a group of scientists in Ottawa receives samples of the previous day’s sewage to test for traces of the coronavirus in wastewater pooled from “over a million souls,” said Alex MacKenzie, a senior scientist at the CHEO Research Institute.

MacKenzie is part of a team at CHEO and the University of Ottawa that piloted the program, which Ottawa’s public health department uses to provide daily reports on the coronavirus’s spread. In early October, MacKenzie’s team reported that concentrations of the virus in the area’s wastewater had doubled in the past month and increased tenfold since June.

Other cities and provinces across Canada, as well as several universities, are watching sewage systems for signs of the virus.

Such testing provides crucial information at little cost, MacKenzie said. Each sample costs only several hundred dollars and gives a reliable snapshot of the big picture, and there are few privacy concerns because the tests do not detect individual infections.

“There’s a general realization that we should be doing this as much as possible,” he said.

The model could have applications for vulnerable populations, he said, such as those living in homeless shelters, prisons and elder-care homes, if plumbing systems in buildings or apartment blocks were frequently tested.

While many countries and cities test wastewater for virus RNA, MacKenzie said his team is also looking for the protein that surrounds the genetic matter. The virus’s RNA, he said, “is a fragile beast,” while the protein is sturdier and could provide an even more accurate picture of the virus’s spread.

Netherlands

In early February, over a month before the global pandemic was declared, scientists from the Dutch KWR Water Research Institute in Nieuwegein began periodically testing sewage samples from seven cities and one airport, according to a paper they published in July. Initial tests came back negative. But on March 5, Dutch scientists detected the coronavirus in wastewater at a treatment plant in the city of Amersfoort, about 32 miles southeast of Amsterdam. Weeks later, Amersfoort’s first case of the virus was confirmed.

Since March, the Dutch National Institute for Public Health and the Environment has been taking weekly samples from sewage systems across the country. As in the first study, researchers were able to detect small traces of the virus before cases or outbreaks were confirmed. While the program began with a few dozen sites, since Sept. 7 the institute has been testing systematically each of the country’s more than 300 sewage treatment centers, according to its website.

Hong Kong

During the 2003 SARS outbreak, researchers in Hong Kong were puzzled by the question of how the virus had infected hundreds of people in a 33-story apartment building. Their conclusion: SARS, a coronavirus related to the one causing covid-19, had probably aerosolized and spread through the plumbing system. Scientists narrowed in on a patient zero, who had diarrhea in

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EPA refuses to reduce particulate pollution, linked by scientists to coronavirus deaths | Environment

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In April, as coronavirus cases multiplied across the country, the head of the U.S. Environmental Protection Agency rejected scientists’ advice to tighten air pollution standards for particulate matter, or soot.

In the next few weeks, EPA Administrator Andrew Wheeler likely will reaffirm that decision with a final ruling, despite emerging evidence that links particulate pollution to COVID-19 deaths.

There was enough evidence to support a stricter standard before the pandemic, said Christopher Frey, an environmental engineering professor at North Carolina State University who studies air pollution. The added threat from the coronavirus is like “icing on the cake.”

Particulate matter kills people. “It is responsible for more deaths and sickness than any other air pollutant in the world,” said Gretchen Goldman, a research director at the Union of Concerned Scientists.

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Wheeler’s decision was specifically about fine particulate matter, or PM2.5, microscopic solid and liquid droplets less than one-thirtieth the width of a human hair. The pollution comes from cars, power plants, wildfires and anything that burns fossil fuels. It causes health complications that can lead people to die earlier than they would have, and it is linked to conditions such as COPD, asthma and diabetes.

Frey was part of a 26-member scientific panel that advised the EPA on particulate pollution until Wheeler disbanded the group in 2018. Twenty of the former members continued to review the science and provided unofficial advice to Wheeler as part of the public comment process. Their letter told Wheeler— a former coal lobbyist — that tightening the standard would avoid tens of thousands of premature deaths per year.

Firing the advisory panel and opting not to pursue a more stringent particulate standard were in keeping with the administration of President Donald Trump’s dim view of environmental regulation. By one tally compiled by The New York Times, 72 regulations on air, water and soil pollution, climate change and ecosystems have been canceled or weakened, with an additional 27 in progress. EPA leadership has sidelined or ignored research by agency scientists, and career staff are censoring their reports to avoid terms like “climate change” out of fear of repercussions from political staff.

The EPA has an “apparatus of particulate matter science denial” that rivals its attacks on climate science, Frey said. “If I wanted to get rid of [regulations on] particulate matter, I would do all the things Wheeler is doing.”

Wheeler made his decision “after carefully reviewing [the] scientific evidence and consulting with the agency’s independent science advisors,” an EPA spokesperson said in a statement. “The U.S. now has some of the lowest fine particulate matter levels in the world, five times below the global average, seven times below Chinese levels, and 20 percent lower than France, Germany and Great Britain.”

These

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Scientists Failed to Use Common Sense Early in the Pandemic

As a scientist and historian of science, I get asked a lot by friends and family to comment on scientific questions. Are vaccines safe? Is red meat bad for you? How much time do we have left to fix climate change? Many of these matters are not nearly as complicated as they have sometimes been made out to be. Vaccination is broadly safe for most people; eating large amounts of red meat is associated with higher rates of death from a number of cancers; and scientists think we have about a decade left to get greenhouse gas emissions under control and avoid the worst consequences.

Lately nearly all the questions involve COVID-19—particularly the matter of masks. The argument for wearing them is pretty straightforward: viruses are spread in droplets, which are expelled when an infected person talks, shouts, sings or just breathes. A properly constructed and fitted mask can prevent the spread of those droplets and therefore the spread of the virus. That is why surgeons have been routinely wearing medical-grade masks since the 1960s (and many doctors and nurses wore cloth masks long before then). It is also why in many parts of Asia, people routinely wear masks in public. A flimsy or poorly fitting face covering may not be much use, but—barring the risk of generating a false sense of security—it is unlikely to do harm. So it stands to reason that, when in public, most people should wear masks. The U.S. Centers for Disease Control and Prevention summarizes: “Masks are recommended as a simple barrier to help prevent respiratory droplets from traveling into the air…. This is called source control.”

So why are people confused? One reason is that we have been getting conflicting messages. In April the World Health Organization told the general public not to mask, while the CDC told us we should. In June the WHO adjusted its guidance to say that the general public should wear nonmedical masks where there was widespread community transmission and physical distancing was difficult. Meanwhile CDC director Robert R. Redfield declared that “cloth face coverings are one of the most powerful weapons we have to slow and stop the spread of the virus—particularly when used universally.” Today government guidance around the globe varies from masks only for sick people to masks mandatory for all.

Why the contradictory messaging? In particular, why did the WHO say in April not to wear masks? At the time, there was a severe shortage of personal protective equipment; the WHO evidently feared that ordinary people would rush out to buy masks, denying them to medical personnel. According to one report, officials were also concerned that widespread masking would lead to a false sense of security, leading people to ignore other safety measures, such as handwashing and self-isolation.

If the WHO had simply said this, there would have been a lot less confusion. But apparently there was another problem. At the time, no direct evidence existed regarding community spread of this particular virus, and

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Scientists raise alarm over signs of vaccine ‘hesitancy’

Scientists called for urgent action to improve public trust in immunisation as research suggested sizeable minorities in some nations may be reluctant to be vaccinated against Covid-19. 

With few effective treatments and no cure for the coronavirus, companies and governments are racing to develop vaccines in a bid to arrest the pandemic. 

But there is increasing concern that “vaccine hesitancy” is also on the rise, with misinformation and mistrust colouring people’s acceptance of scientific advances. 

In a new study published Tuesday in Nature Medicine, researchers in Spain, the United States and Britain surveyed 13,400 in 19 countries hit hard by Covid-19 and found that while 72 percent said they would be immunised, 14 percent would refuse and another 14 percent would hesitate. 

When extrapolated across whole populations this could amount to tens of millions of people who may avoid vaccination, the authors said. 

“These findings should be a call to action for the international health community,” said co-author Heidi Larson, who runs the Vaccine Confidence Project at London School of Hygiene and Tropical Medicine. 

“If we do not start building vaccine literacy and restoring public trust in science today, we cannot hope to contain this pandemic.”

Researchers found that people who had least faith in their governments were less likely to accept a vaccine — and even those who had been ill with the virus were not more likely to respond positively. 

While in China 88 percent of respondents said they would take “a proven, safe and effective vaccine”, the highest of all the countries surveyed, the proportion dipped to 75 percent in the US and was as low as 55 percent in Russia.  

“We found that the problem of vaccine hesitancy is strongly related with a lack of trust in government,” said study coordinator Jeffrey Lazarus, of the Barcelona Institute for Global Health.

When asked if they would accept an approved, safe vaccine recommended by their employer, only 32 percent of respondents completely agreed. 

Acceptance rates again varied widely by country, with China again having the most clearly positive responses (84 percent either completely or somewhat agreed) and Russia with the least (27 percent).

People were less likely to accept a vaccine if it was mandated by their employer, the authors said. 

The study, released at the Union World Conference on Lung Health, found greater acceptance of vaccines among people earning more than $32 a day. 

They also found older people were more likely to accept a vaccine than those under 22.  

– Trust building –

In a new initiative launched Tuesday and supported by the Vaccine Alliance Gavi, scientists involved in vaccine development will appear in a series of videos on social media to help raise public confidence in their work.  

The researchers and clinicians in the UK, United States, South Africa, India and Brazil will be posting under the hashtag #TeamHalo — a reference to the circle of global scientific endeavour — on TikTok, Twitter and Instagram. 

“I’m used to spending time pipetting samples and analysing data,”

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