Culture

The European General Data Protection Regulation (GDPR) includes specific clauses that put restrictions on the collection and processing of sensitive personal data, defined as any data revealing racial or ethnic origin, political opinions, religious or philosophical beliefs, or trade union membership, also genetic data, biometric data for the purpose of uniquely identifying a natural person, data concerning health or data concerning a natural person's sex life or sexual orientation...

The After two years of hard work, and having crunched more than one billion web-sites (most of the English speaking web), an international team, with Nikolaos Laoutaris (Research Professor at IMDEA Networks Institute, Madrid), as well as researchers from TU Berlin and the Cyprus University of Technology, has developed specialised machine learning classifiers that are able to identify sensitive URLs on the web and used them to search for such URLs on a corpus of some 1 billion URLs in total. As a main (and disturbing) result, some 150 million of them were find to include sensitive content related to Health, Political Beliefs, Sexual Orientation, etc ... and still be tracked nearly as much as the rest of the web.

A real time detection

Existing legislation about sensitive personal data is targeted mostly for use by humans, e.g., to file complaints, conduct investigations, and even pursue cases in courts of law. With the use of the new automated machine learning classifiers, however, additional proactive measures can also be put in place for the first time. For example, the browser of the user, or an add-on program, can warn him before clicking and following URLs pointing to sensitive content. Upon visiting such sites, trackers can be blocked, and complaints can be automatically filed. Being able to do the above hinges on being able to classify automatically whether a URL is a sensitive one or not, in real time.

The latter is easier said than done. The reason has to do with the ambiguity of terms such as "Health", that are used by legal documents to indicate what types of information are considered as sensitive. Indeed, the word Health can be found in both web-sites about healthy eating, sports, and organic food, but also on web-sites about chronic diseases, sexually transmitted diseases, and cancer. Most of the effort on producing the aforementioned classifier went into collecting sufficient "ground-truth" data for training the classifier and allowing it to distinguish truly sensitive uses of words such as health from less sensitive ones.

The results of the work of the team will be presented, as a scientific paper, in ACM IMC'20 (ACM Internet Measurement Conference 2020, 27-29 October, Pittsburgh, USA). Laoutaris also participates in PIMCity (Building the next generation personal data platforms), the EU-funded project to increase transparency and provide users with control over their data. "Privacy law is made for use by humans -Laoutaris comments-, typically after a privacy breach has occurred - e.g., an illegal processing of such data- ... but how can we teach this law to machines and have them protect us before privacy breaches occur?". The research team is working to bring a technological solution to the user in 2021.

"Tracking people -add the researcher- when they visit websites with content that belongs to the GDPR sensitive categories is the true 'Elephant in the Room' of privacy. Most people don´t mind be tracked about things that they consider innocent, but would be very upset to know that their visit to sensitive websites are being logged and released to unknown third parties. Our study is, by far, the biggest study about tracking of sensitive topics on the web. It shows that a good part of the web includes content of sensitive character. Unfortunately, these sensitive pages appear to be as tracked as the rest of the web".

Winter is on its way. And in this year of coronavirus, with it comes the potential for a second wave of COVID-19. Add in flu season and our tendency to head inside and close our windows to the cold, wet weather, and it appears the next several months are going to present us with new health challenges.

UC Santa Barbara researchers Yanying Zhu and Lei Zhao hope to arm people with better knowledge of how SARS-CoV-2 spreads as the seasons change. Their new study investigates the secret of this virus's unusual success: its transmissibility, or how it manages to get from host to host. The dominant mode, it turns out, changes according to environmental conditions.

"Back at the beginning of April a lot of people were wondering if COVID would go away in the summer, in the warmer weather," said Zhu, a professor of mechanical engineering and one of the authors of a paper that appears in the journal Nano Letters. "And so we started to think about it from a heat transfer point of view, because that's what our expertise is."

The virus, of course, did not disappear during the summer as hoped, and in fact COVID cases across the country continued to climb. To understand how the novel coronavirus manages to persist in circumstances in which the flu virus fails, Zhu, Zhao and colleagues modeled different temperatures and relative humidities along a continuum from hot and dry to cold and humid in typical indoor spaces, where the virus is distributed by normal speech and breathing -- and, according to the paper, where people "only sneeze or cough into a tissue or their elbows." To these scenarios they added emerging knowledge about the highly contagious microbe; in particular, how long it remains infectious outside a host.

The results are sobering. For one thing, respiratory droplets -- the most common mode of transmission -- don't obey our social distancing guidelines.

"We found that in most situations, respiratory droplets travel longer distances than the 6-foot social distance recommended by the CDC," Zhu said. This effect is increased in the cooler and more humid environments to distances of up to 6 meters (19.7 feet) before falling to the ground in places such as walk-in refrigerators and coolers, where temperatures are low and humidity is high to keep fresh meat and produce from losing water in storage. In addition to its ability to travel farther, the virus is particularly persistent in cooler temperatures, remaining "infectious from several minutes to longer than a day in various environments," according to several published studies.

"This is maybe an explanation for those super-spreading events that have been reported at multiple meat processing plants," she said.

At the opposite extreme, where it is hot and dry, respiratory droplets more easily evaporate. But what they leave behind are tiny virus fragments that join the other aerosolized virus particles that are shed as part of speaking, coughing, sneezing and breathing.

"These are very tiny particles, usually smaller than 10 microns," said lead author Lei Zhao, who is a postdoctoral researcher in the Zhu Lab. "And they can suspend in the air for hours, so people can take in those particles by simply breathing.

"So in summer, aerosol transmission may be more significant compared to droplet contact, while in winter, droplet contact may be more dangerous," he continued. "This means that depending on the local environment, people may need to adopt different adaptive measures to prevent the transmission of this disease." This could mean, for example, greater social distancing if the room is cool and humid, or finer masks and air filters during hot, dry spells.

Hot and humid environments, and cold and dry ones, did not differ significantly between aerosol and droplet distribution, according to the researchers.

The quantitative descriptions of virus propagation under varying local conditions could serve as useful guidance for decision-makers and the general public alike in our efforts to keep the spread to a minimum.

"Combined with our study, we think we can maybe provide design guidelines for the optimal filtering for facial masks," said Zhao, adding that the research could be used to quantify real exposure to the virus -- how much virus could land on one's body over a certain period of exposure. This knowledge could, in turn, lead to better strategies for airflow and ventilation to prevent virus accumulation. In addition, the insights, according to the study, "may shed light on the course of development of the current pandemic, when combined with systematic epidemiological studies."

A review of 39 randomized clinical trials by scientists from UCLA and their colleagues from other institutions has found that combining the use medication with psychoeducational therapy is more effective at preventing a recurrence of illness in people with bipolar disorder than medication alone.

For the paper, published in JAMA Psychiatry researchers analyzed studies that included adult and adolescent patients currently receiving medication for bipolar disorder who were randomly assigned to either an active family, individual or group therapy, or "usual care," meaning medication with routine monitoring and support from a psychiatrist.

David Miklowitz, PhD, the study's lead author, and a distinguished professor of psychiatry at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, said the studies reviewed followed patients for at least a year, measured rates of recurrence of bipolar disorder, depression and mania symptoms, and included study attrition or dropout rates.

The findings were:

Psychoeducation with guided practice of illness management skills (for example, how to keep regular sleep and wake cycles) in a family or group format was more effective in reducing recurrences of mania and depressive symptoms than the same strategies in an individual therapy format.

Cognitive behavioral therapy, family therapy and interpersonal therapy were better at stabilizing depressive symptoms than other forms of treatment.

Rates of dropout were lower in patients who received family-oriented therapies.

Of the findings, Miklowitz said they point to the importance of having a support system.

"Not everyone may agree with me, but I think the family environment is very important in terms of whether somebody stays well," he said. "There's nothing like having a person who knows how to recognize when you're getting ill and can say, 'you're starting to look depressed or you're starting to get ramped up.' That person can remind their loved one to take their medications or stay on a regular sleep-wake cycle or contact the psychiatrist for a medication evaluation."

Miklowitz said the same is true for a patient who may not have close relatives but does have support through group therapy.

"If you're in group therapy, other members of that group may be able to help you recognize that you're experiencing symptoms," he said. "People tend to pair off. It's a little bit like the AA model of having a sponsor."

A group of 80 researchers warn that a so-called herd immunity approach to managing COVID-19 by allowing immunity to develop in low-risk populations while protecting the most vulnerable is "a dangerous fallacy unsupported by the scientific evidence".

Faced with a second wave of COVID-19, and more than a million recorded deaths worldwide, the authors present their view of the scientific consensus on our understanding of COVID-19, and the strategies that need to be put in place to protect our societies and economies.

The open letter, referred to by its authors as the John Snow Memorandum, is published today by The Lancet. It is signed by 80 international researchers (as of publication) with expertise spanning public health, epidemiology, medicine, paediatrics, sociology, virology, infectious disease, health systems, psychology, psychiatry, health policy, and mathematical modelling [1]. The letter will also be launched during the 16th World Congress on Public Health programme 2020.

They state: "It is critical to act decisively and urgently. Effective measures that suppress and control transmission need to be implemented widely, and they must be supported by financial and social programmes that encourage community responses and address the inequities that have been amplified by the pandemic."

"Continuing restrictions will probably be required in the short term, to reduce transmission and fix ineffective pandemic response systems, in order to prevent future lockdowns. The purpose of these restrictions is to effectively suppress SARS-CoV-2 infections to low levels that allow rapid detection of localised outbreaks and rapid response through efficient and comprehensive find, test, trace, isolate, and support systems so life can return to near-normal without the need for generalised restrictions. Protecting our economies is inextricably tied to controlling COVID-19. We must protect our workforce and avoid long-term uncertainty."

The authors acknowledge that ongoing restrictions have understandably led to widespread demoralisation and diminishing trust among the public, and that in the face of a second wave of infection there is renewed interest in so-called natural herd immunity approaches (allowing a large uncontrolled outbreak in the low-risk population while protecting the vulnerable, which some argue could lead to the development of infection-acquired population immunity in the low-risk population, which will eventually protect the vulnerable). They say any pandemic management strategy relying upon immunity from natural infections for COVID-19 is flawed.

They explain that uncontrolled transmission in younger people risks significant ill-health and death across the whole population - with real-world evidence from many countries showing that it is not possible to restrict uncontrolled outbreaks to certain sections of society, and it being practically impossible and highly unethical to isolate large swathes of the population. Instead, they say that special efforts to protect the most vulnerable are essential, but must go hand-in-hand with multi-pronged population-level strategies.

They also state that there is no evidence for lasting protective immunity to SARS-CoV-2 after natural infection, and warn that this waning immunity as a result of natural infection would not end the COVID-19 pandemic but instead result in repeated waves of transmission over several years. They say that this could place vulnerable populations at risk for the indefinite future, as natural infection-based herd immunity strategies would result in recurrent epidemics, as seen with many infectious diseases before mass vaccination. Instead, the authors call for suppression of the virus until the population can be vaccinated.

The authors also warn that natural infection-based herd immunity approaches risk impacting the workforce as a whole and overwhelming the ability of healthcare systems to provide acute and routine care. They note that we still do not understand who might suffer from 'long COVID', and that herd immunity approaches place an unacceptable burden on healthcare workers, many of whom have died from COVID-19 or experienced trauma as a result of having to practise disaster medicine.

The letter concludes: "The evidence is very clear: controlling community spread of COVID-19 is the best way to protect our societies and economies until safe and effective vaccines and therapeutics arrive within the coming months. We cannot afford distractions that undermine an effective response; it is essential that we act urgently based on the evidence."

BOSTON - Genetic mutations that promote the growth of the most common type of adult brain tumors can be accurately detected and monitored in blood samples using an enhanced form of liquid biopsy developed by researchers at Massachusetts General Hospital (MGH).

Comparing blood samples from patients with gliomas with tumor biopsy tissues from the same patients, Leonora Balaj, PhD, Bob S. Carter, MD, and other MGH investigators in the Department of Neurosurgery found that a novel digital droplet polymerase chain reaction (ddPCR) blood test they pioneered could accurately detect and monitor over time two mutations of the gene TERT. The mutations, labeled C228T and C250T, are known to promote cancer growth and are present in more than 60 percent of all gliomas, and in 80 percent of all high-grade gliomas, the most aggressive and life-threatening type.

Their discovery, which has the potential to substantially improve the diagnosis and monitoring of gliomas, is reported in the journal Clinical Cancer Research.

Gliomas are tumors of glia, central and peripheral nervous system cells that support and protect neurons, the cells that transmit electrical impulses.

Liquid biopsy is a method for detecting cancer by looking for fragments of tumor DNA that circulate in blood. The technique has been shown to be sensitive at detecting the presence of some forms of cancer, but brain tumors have until now posed a formidable barrier.

"Liquid biopsy is particularly challenging in brain tumors because mutant DNA is shed into the bloodstream at much lower level than any other types of tumors," Balaj says.

"By 'supercharging' our ddPCR assay with novel technical improvements, we showed for the first time that the most prevalent mutation in malignant gliomas can be detected in blood, opening a new landscape for detection and monitoring of the tumors," she says.

The researchers first tested the performance of the ddPCR assay in tumor tissue and found that the results were in perfect agreement with the results from an independently performed clinical laboratory assessment of TERT mutations in the tumor specimens.

They then looked at samples of blood plasma matched to patient tumors and found that the ddPCR assay could detect TERT mutations both in samples from MGH as well as from similarly matched plasma and tumor samples from collaborators at other institutions.

The ddPCR assay has an overall sensitivity (ability to detect the presence of a glioma) of 62.5 percent, which is a tenfold improvement over any prior assay for TERT mutations in the blood for brain tumors, compared to the standard of tissue-based detection of TERT mutations.

The test is easy to use, quick, and low cost, and could be performed in most laboratories, Balaj says. Importantly, the test can also be used to follow the course of disease. "We envision the future integration of tests like this one into the clinical care of our patients with brain tumors," says Carter, chief of Neurosurgery and co-director of the MGH Brain Tumor Center. "For example, if a patient has a suspected mass on MRI scanning, we can take a blood sample before the surgery and assess the presence of the tumor signature in the blood, and then use this signature as a baseline to monitor as the patient later receives treatment, both to gauge response to the treatment and gain early insight into any potential recurrence."

The team's goal is to expand this blood test to be able to differentiate many types of brain tumors.

To date, a few verified repeat SARS-CoV-2 infections have been documented around the world. "Should reinfection [with SARS-CoV-2] prove commonplace, and barring a highly effective vaccine delivered to most of the world's population, SARS-CoV-2 will likely become endemic," write Jeffrey Shaman and Marta Galanti in this Perspective. For many viruses, a number of processes - particularly insufficient adaptive immune response, waning immunity, and immune escape - can allow subsequent reinfection. In the case of SARS-CoV-2, many questions remain about the nature of these immune responses and trajectories, though, say the authors, insight from other respiratory viruses points to the possibility of reinfection with SARS-CoV-2. If this does happen, the pattern of endemicity that results will depend on the typical time scale at which individuals experience reinfection, seasonal differences in transmissibility, vaccine availability and efficacy, and social, immune, and innate factors that modulate virus transmissibility, say the authors. In addition, the cyclic persistence of SARS-CoV-2 in human populations may be affected by ongoing opportunities for interaction with other respiratory pathogens, say the authors; it is possible infection with a different virus could provide some short-lived protection to SARS-CoV-2. Greater monitoring of the clinical and population-scale interactions of SARS-CoV-2 with other respiratory viruses, particularly influenza viruses, is needed, they write. At the population scale, a possible overlap between influenza and SARS-CoV-2 outbreaks poses a serious threat to public health systems. Conversely, the nonpharmaceutical interventions adopted to mitigate SARS-CoV-2 transmission (personal protective equipment, social distancing, increased hygiene, limited indoor gatherings) may reduce the magnitude of seasonal influenza outbreaks, note Shaman and Galanti. Based on modeling of post-pandemic scenarios for SARS-CoV-2 to date, a duration of immunity similar to that of the other betacoronaviruses (~40 weeks) could lead to yearly outbreaks of SARS-CoV-2, the authors note, whereas a longer immunity profile, coupled with a small degree of protective cross-immunity from other betacoronaviruses, could lead to apparent elimination of the virus followed by resurgence after a few years. "Other scenarios are, of course, possible, because there are many processes at play and much that remains unresolved," say the authors.

Understanding sounds in language is a critical building block for child literacy, yet this skill is often overlooked. Researchers from Michigan State University have developed a new software tool to assess children's phonological awareness -- or, how they process the sound structure of words.

The ATLAS, or Access to Literacy Assessment System, program -- the first test of its kind for children with speech and/or language impairment -- can help parents, early childhood teachers and paraeducators more accurately measure progress for children with a range of skill levels.

Research conducted by the MSU ATLAS team, published in the journal Language, Speech and Hearing Services in Schools, demonstrated that the software was effective when tested with over 1,100 children between the ages of 3 and 7 -- both with and without speech and language impairments.

"Phonological awareness is one of the strongest predictors of literacy skill development later in life," said Lori Skibbe, professor of human development and family studies at MSU and study lead author. "It can include rhyming, recognizing how sounds go together to make words and understanding how words can be broken apart into sounds."

Skibbe explained that the software, available free of charge, is adaptive, which means that test items are unique for each child. Children can take the test without speaking, and the test is shorter than many others in the field. ATLAS is also helpful for many children with disabilities, including those with speech and/or language impairment.

"For children with a primary speech and/or language impairment, meeting educational literacy goals can be difficult," Skibbe said. "However, the ATLAS software allows children to demonstrate what they know, even if they struggle to answer questions verbally. This ensures their skills are accurately assessed, and that they receive the right support to keep them on track to meet literacy milestones."

Researchers at the National Institute of Standards and Technology (NIST) and their colleagues have proposed a novel method for finding dark matter, the cosmos' mystery material that has eluded detection for decades. Dark matter makes up about 27% of the universe; ordinary matter, such as the stuff that builds stars and planets, accounts for just 5% of the cosmos. (A mysterious entity called dark energy accounts for the other 68%.)

According to cosmologists, all the visible material in the universe is merely floating in a vast sea of dark matter -- particles that are invisible but nonetheless have mass and exert a gravitational force. Dark matter's gravity would provide the missing glue that keeps galaxies from falling apart and account for how matter clumped together to form the universe's rich galactic tapestry.

The proposed experiment, in which a billion millimeter-sized pendulums would act as dark matter sensors, would be the first to hunt for dark matter solely through its gravitational interaction with visible matter. The experiment would be one of the few to search for dark matter particles with a mass as great as that of a grain of salt, a scale rarely explored and never studied by sensors capable of recording tiny gravitational forces.

Previous experiments have sought dark matter by looking for nongravitational signs of interactions between the invisible particles and certain kinds of ordinary matter. That's been the case for searches for a hypothetical type of dark matter called the WIMP (weakly interacting massive particles), which was a leading candidate for the unseen material for more than two decades. Physicists looked for evidence that when WIMPs occasionally collide with chemical substances in a detector, they emit light or kick out electric charge.

Researchers hunting for WIMPs in this way have either come up empty-handed or garnered inconclusive results; the particles are too light (theorized to range in mass between that of an electron and a proton) to detect through their gravitational tug.

With the search for WIMPs seemingly on its last legs, researchers at NIST and their colleagues are now considering a more direct method to look for dark matter particles that have a heftier mass and therefore wield a gravitational force large enough to be detected.

"Our proposal relies purely on the gravitational coupling, the only coupling we know for sure that exists between dark matter and ordinary luminous matter," said study co-author Daniel Carney, a theoretical physicist jointly affiliated with NIST, the Joint Quantum Institute (JQI) and the Joint Center for Quantum Information and Computer Science (QuICS) at the University of Maryland in College Park, and the Fermi National Accelerator Laboratory.

The researchers, who also include Jacob Taylor of NIST, JQI and QuICS; Sohitri Ghosh of JQI and QuICS; and Gordan Krnjaic of the Fermi National Accelerator Laboratory, calculate that their method can search for dark matter particles with a minimum mass about half that of a grain of salt, or about a billion billion times the mass of a proton. The scientists report their findings today in Physical Review D.

Because the only unknown in the experiment is the mass of the dark matter particle, not how it couples to ordinary matter, "if someone builds the experiment we suggest, they either find dark matter or rule out all dark matter candidates over a wide range of possible masses," said Carney. The experiment would be sensitive to particles ranging from about 1/5,000 of a milligram to a few milligrams.

That mass scale is particularly interesting because it covers the so-called Planck mass, a quantity of mass determined solely by three fundamental constants of nature and equivalent to about 1/5,000 of a gram.

Carney, Taylor and their colleagues propose two schemes for their gravitational dark matter experiment. Both involve tiny, millimeter-size mechanical devices acting as exquisitely sensitive gravitational detectors. The sensors would be cooled to temperatures just above absolute zero to minimize heat-related electrical noise and shielded from cosmic rays and other sources of radioactivity. In one scenario, a myriad of highly sensitive pendulums would each deflect slightly in response to the tug of a passing dark matter particle.

Similar devices (with much larger dimensions) have already been employed in the recent Nobel-prize-winning detection of gravitational waves, ripples in the fabric of space-time predicted by Einstein's theory of gravity. Carefully suspended mirrors, which act like pendulums, move less than the length of an atom in response to a passing gravitational wave.

In another strategy, the researchers propose using spheres levitated by a magnetic field or beads levitated by laser light. In this scheme, the levitation is switched off as the experiment begins, so that the spheres or beads are in free fall. The gravity of a passing dark matter particle would ever so slightly disturb the path of the free-falling objects.

"We are using the motion of objects as our signal," said Taylor. "This is different from essentially every particle physics detector out there."

The researchers calculate that an array of about a billion tiny mechanical sensors distributed over a cubic meter is required to differentiate a true dark matter particle from an ordinary particle or spurious random electrical signals or "noise" triggering a false alarm in the sensors. Ordinary subatomic particles such as neutrons (interacting through a nongravitational force) would stop dead in a single detector. In contrast, scientists expect a dark matter particle, whizzing past the array like a miniature asteroid, would gravitationally jiggle every detector in its path, one after the other.

Noise would cause individual detectors to move randomly and independently rather than sequentially, as a dark matter particle would. As a bonus, the coordinated motion of the billion detectors would reveal the direction the dark matter particle was headed as it zoomed through the array.

To fabricate so many tiny sensors, the team suggests that researchers may want to borrow techniques that the smartphone and automotive industries already use to produce large numbers of mechanical detectors.

Thanks to the sensitivity of the individual detectors, researchers employing the technology needn't confine themselves to the dark side. A smaller-scale version of the same experiment could detect the weak forces from distant seismic waves as well as that from the passage of ordinary subatomic particles, such as neutrinos and single, low-energy photons (particles of light).

The smaller-scale experiment could even hunt for dark matter particles -- if they impart a large enough kick to the detectors through a nongravitational force, as some models predict, Carney said.

"We are setting the ambitious target of building a gravitational dark matter detector, but the R&D needed to achieve that would open the door for many other detection and metrology measurements," said Carney.

New research by a University of Georgia scientist reveals that girls who are maltreated show higher levels of inflammation at an early age than boys who are maltreated or children who have not experienced abuse. This finding may forecast chronic mental and physical health problems in midlife.

Led by psychologist Katherine Ehrlich, the study is the first to examine the link between abuse and low-grade inflammation during childhood.

Inflammation plays a role in many chronic diseases of aging--diabetes, cardiovascular disease, stroke, obesity--as well as mental health outcomes, and the findings suggest that maltreatment's association with inflammation does not lie dormant before emerging in adulthood. Instead, the study shows that traumatic experiences have a much more immediate impact.

"We and others have speculated that there's something about the immune system that's getting calibrated, particularly during childhood, that might be setting people up on long-term trajectories toward accelerated health problems," said Ehrlich, assistant professor in the Franklin College of Arts and Sciences. "What I'm struck by is just how early in development we can see these effects. What our study highlights is that, even as early as childhood, we can see that a substantial portion of the children have levels of inflammation that the American Heart Association considers 'moderate risk' for heart disease. This is concerning from a public health perspective and suggests that these children may be at risk for significant health problems at an earlier age than their nonmaltreated peers."

Participants in the study included 155 children aged 8-12 from low-income backgrounds who attended a weeklong day camp. The sample was racially diverse and included maltreated and nonmaltreated children.

Researchers captured detailed information on children's exposure to abuse by utilizing Department of Human Services records about maltreatment experiences in families. The children-documented experiences included neglect (55%), emotional maltreatment (67%), physical abuse (35%) and sexual abuse (8%). Many children experienced more than one type of abuse, and 35% of children experienced abuse across multiple developmental periods.

The team measured five biomarkers of low-grade inflammation using non-fasting blood samples from the children.

Results revealed that childhood maltreatment--for girls--was associated with higher levels of low-grade inflammation in late childhood. Girls who had been abused over multiple periods or had multiple kinds of exposures had the highest levels of inflammation. Girls' greatest risk for elevated inflammation emerged when they were abused early in life, before the age of 5.

For boys in the study, exposure to maltreatment was not reflected in higher levels of inflammation, but Ehrlich cautioned against drawing conclusions without additional research targeted to boys.

"One question is, are these variations due to developmental timing differences?" she said. "We know that girls mature faster than boys in terms of their biological and physical development. If we tested these same boys two years later, would we find the same patterns of inflammation that we found for the girls?"

English has become the de facto language of science: International conferences are held in English, the world's top scientific journals are in English and academics in non-English speaking countries get promoted based on their publications in English language journals. Even scientific jargon is in English -- most non-English speakers use English terms and don't bother inventing equivalent words in their native languages.

Yet, for much of the world -- in particular, the global south, where English is not a common second language -- English limits entry into the the world of science and limits public access to scientific results, even when they pertain to a person's own country.

Valeria Ramírez-Castañeda, a graduate student in the Department of Integrative Biology at the University of California, Berkeley, encountered this firsthand when she began writing her master's thesis at the University of Los Andes in Bogota, Colombia, her native country. While she was one of the lucky ones -- growing up in Bogota, her mother had the foresight to insist she take Saturday English classes -- she found it impossible to write in English. To her, Spanish felt natural, not English.

"When I was writing the thesis, a lot of people told me, 'Just write it in English.' And I couldn't. It was too difficult to write it in English," she said. "I was like, 'No, I have already enough pressure to finish this on time, and it is already difficult to write science -- so, I am going to write it in Spanish.'"

But she also wanted to submit it to a scientific journal, which requires that she translate her thesis -- about how snakes adapt to eating poisonous frogs -- into English.

"Since then, I haven't published that paper. I am still working on that," she admitted. "I felt that English was kind of a handicap for me just to advance, to progress in research."

Her introduction to the "language hegemony in scientific publishing," as she calls it, led her to ask other Colombian doctoral students about the impact this has had on their careers. The results of her survey, published last month in the journal PLOS ONE, document the negative consequences of English dominance in science.

She found that more than 90% of articles published by Colombian researchers are in English, and that this has created financial burdens. More than 40% of those she surveyed reported that one of their papers had been rejected because of English grammar, forcing them to pay for a native English speaker to review the manuscript or ask a favor of an English-speaking friend. Translation and editing services charge between one-quarter and one-half of a typical doctoral student's monthly salary in Colombia, she found.

Fully one-third of the 49 respondents, recruited through Twitter with the hashtag #CienciaCriolla, used between Colombian researchers, reported that they had elected to not attend a scientific conference or meeting because of the requirement that oral presentations be in English.

"When I published this on bioRxiv and tweeted, a lot of people started writing to me with very emotional things like, 'I left science because of English,' 'I cannot graduate with a master's thesis because of English,' 'I thought about studying abroad, but then I had the interview and I froze because of English,' (and) 'I couldn't do it.' Super difficult things," said Ramírez-Castañeda. "People are leaving science because of English. It is not something that is isolated."

She found, too, that colleagues with high English proficiency were more likely to have backgrounds higher on the socioeconomic ladder. In Colombia, as in the U.S., socioeconomic status is correlated with race.

"Now that we (in the U.S.) are speaking about the Black community, in many places, including Colombia, race means socioeconomic differences, poverty," she said. "We don't see a lot of Black scientists from Colombia, not only because being from a political minority and being a scientist is difficult, but also because of English. At the end, it is another layer to the difficulty, and we are not talking about it. That is the thing that worries me the most, that it is something that is super-quiet and silent, as if if didn't exist."

Even for U.S. citizens, English can be a barrier

Poor English skills are even an issue for those raised in the U.S., said José Pablo Vázquez-Medina, an assistant professor of integrative biology who came to UC Berkeley three years ago.

"I have friends who are Latinos, but born and raised in the U.S. They send in a paper, and they are asked to run it by a native speaker," he said. "With students who have come from disadvantaged backgrounds, you can see that in how they write. I see it as another hurdle."

He ascribes this to poor schools that fail to teach English to students from non-English speaking families.

"That comes back to segregation. Where you live is where you go to school, and if you live in a rich neighborhood, you go to a school with resources; if you live in a poor neighborhood, you go to a school with less resources," he said. "Without fixing that problem, I don't see us making a lot of impact."

Growing up in San Luis Potosi in Mexico, Vázquez-Medina had access to some English education. His parents were teachers. But he still has flashbacks about the writing suggestions of mentors and friends, most of them offered graciously, he said.

"I remember my very first paper. I wrote it in Spanish, and I translated it (into English). It was horrible," said Vázquez-Medina, who obtained his undergraduate degree from the Autonomous University of Baja California Sur in La Paz. Luckily, a coauthor on the paper made helpful comments. "It is definitely a barrier when you want to move up and go to grad school. Even if you go to grad school in Mexico, you have to publish papers in English."

Vázquez-Medina benefitted from working with a mentor who had studied in Canada and the U.S. and provided English tips. This mentor also sparked his interest in the physiology of marine mammals, which led him to a Ph.D. program at UC Merced, where he studied the diving and fasting physiology of elephant seals and was supported by the UC MEXUS program.

"I always thought, 'Why don't more people apply to this program? This is a great opportunity,'" he said. "But I felt that English was probably one of the main reasons why people didn't feel comfortable applying for scholarships to study abroad."

Betsabé Castro Escobar, a doctoral candidate in integrative biology, saw how the hurdle of English fluency affected the lives of her friends, family and even her future husband. She grew up in Puerto Rico, which, as an unincorporated U.S. territory, mandates 12 years of English in K-12 education. All other instruction is in Spanish, and it's the language of preference for more than 85% of Puerto Ricans, both at home and in their daily activities.

While some people have the privilege and access to a good education and exposure to English, she said, as a society, many Puerto Ricans still struggle with poor class curriculums in many public schools, as well as lack of exposure to opportunities to speak English, lack of interest in learning it and even resistance to learning and becoming fluent in English. Spanish, though a colonial language like English, is preferred in Puerto Rico and is, in fact, a majority language worldwide: one of the top 5 languages spoken.

"I see people leave their academic fields because they don't feel like they belong, many struggling with very clear language exclusion barriers. One thing about belonging is not just being part of a community, but also, how do we communicate? And one of those factors is language. There are clear language hurdles, and some people just don't make it through because they have been excluded from the start," said Castro Escobar, who is studying the ethnobotany of the calabash tree in the Caribbean. "Sadly, this is a funnel, and not everyone is going to make it through, due to language and communication obstacles. Unfortunately, this is how the system has been set up in order to participate in the globalized world; against others that don't speak the 'majority' language, basically."

Language hegemony

"It is very much an issue," agreed UC Berkeley professor of linguistics Lev Michael, who studies and seeks to revitalize indigenous languages in Perú.

"If you are Dutch, the fact that the language of science is English really is not a big hurdle, since, in my experience, many Dutch people speak better English than many English speakers," he said, jokingly. "But in Perú, for example, many people where I work -- even in some universities -- don't have great access to English education. It even plays out to the level where some people at that level have a hard time reading important works in English."

Michael admits to encountering a language hurdle when translating his English works -- recently, a dictionary of the Iquito language -- into Spanish and Portuguese.

In his field, multilingualism is common, and academic meetings about South American indigenous languages are typically trilingual, he said. Speakers can deliver talks in Spanish, Portuguese or English, and most people in the audience understand. A small journal he edits, Cadernos de Etnolingüística, also is trilingual.

But that is not typical in other areas of science. Few journals even publish abstracts in other languages, let alone full papers in translation.

English hasn't always been the language of science and scholarship, of course. Latin was the gatekeeper until 200 years ago, Michael pointed out, while German, French and Russian -- and, recently, Chinese -- have given English a run for the money.

Aside from the issue of fairness, forcing people to communicate in a language other than their native tongue affects how clearly and effectively they interact with others. For Augusto Berrocal, who is from Mexico City and recently earned his Ph.D. from UC Berkeley in molecular and cell biology, English is a barrier to networking with colleagues at conferences, because his mind slows down when speaking English and, frankly, it can be exhausting.

"It is my opinion that language is the main burden," said Berrocal, who investigates the genetics of development in fruit flies. "I feel that my mind runs faster in my native tongue, which is Spanish. In a debate, for example, my conversations are more fluent in my native language. I think that has an impact at meetings or when discussing and getting ideas."

Castro Escobar says she gets more out of meetings where she can converse with colleagues in Spanish, and her field of ethnobotany has been gaining a critical mass of Spanish speakers. Spanish-speaking students and postdocs at UC Berkeley also are a growing community, a network where students and faculty members can discuss their work more naturally, or just let down their hair.

"Throughout the years, there has been a growing number of us Latinx people on campus," Castro Escobar said. "In my home department now, there are both grad students and professors I can talk to in Spanish. I find it refreshing to escape and speak my own language. I am more expressive, my ideas and connections are much faster, and my energy comes through more. I have more expressions I can use in Spanish. Sorry, I am biased, but Spanish is a beautiful language."

One of those professors is her adviser, Paul Fine, who actively recruits Latin American students to join his lab and converses with them in both Spanish and Portuguese. He studies tree diversity in the Amazon rainforest and has had students from Brazil, Ecuador, Colombia, Perú, Mexico and Costa Rica, not to mention Puerto Rico.

Castro Escobar said that when she finishes her dissertation, she hopes -- if her committee approves -- to present her thesis in Spanglish: that is, both in English and Spanish.

"It will certainly be an interesting exercise for our department," she said. "My slides would be in English -- the idea is not to lose everyone in this language code-switching, but to actually show other people that their voice matters, too."

Solutions

As Michael noted, scholarship in the past was conducted in Latin, a language that no one spoke natively. That put everyone in the same boat, assuming you were among the elite who could learn Latin. English is different, he said, having achieved ascendency because the rise of science after World War II coincided with the hegemony of two English-speaking world powers, Britain and the U.S..

"When you are engaged in some type of project, like science, where you have participants from all sorts of different groups speaking all sorts of different languages, there is a tension between adopting a lingua franca which facilitates intergroup communication and the fact that that very same move creates inequities, because that language is the native language of some people and not of others," he said.

Ramírez-Castañeda noted that most of those whom she surveyed preferred English as the common language of science for its ease of communicating internationally. But she argues that scientists, universities and journals should acknowledge and address the costs to non-English speakers, in terms of time, finances, productivity and anxiety.

Science could, for example, encourage more multilingualism, she said, including publishing abstracts or entire articles in multiple languages. She chose to publish her survey in PLOS ONE because the journal allowed her to co-publish the complete article in Spanish.

"We need to encourage diversity, and that needs to take into account language and taking more effort to do multilingual science," she said. "All the actors have to be involved: journals, universities, governments, institutions. We need to stress more affordable or free translating and editing services at journals. Scientists can volunteer to edit papers, not just for English, but both ways. Simultaneous translation at conferences and meetings. Editing and translating services at universities and journals. Promoting annual editions in other languages."

She and many others look with hope to Google Translate or other platforms, which in the future could make Star Trek's sci-fi "universal translator" a reality, obviating the language problem. At the moment, however, Google Translate is still "awful" for translating the technical terms and prose that permeate science, Michael said.

"We, as scientists, have to do the work," Ramírez-Castañeda said. "(That means) translating papers with the tools that we have, so that students (in these countries) and local communities can read them. We don't need to put more effort on these communities, they already have to deal with a lot of things to be a scientist. We just have to make them feel it is easy to be a scientist, not more difficult."

Lockdowns initiated to curb the spread of the coronavirus in China and Europe at the beginning of the pandemic improved air quality, averting tens of thousands of deaths in regions where air pollution has a significant impact on mortality, a new study shows.

According to research published in The Lancet Planetary Health, scientists at the University of Notre Dame found that particulate matter concentrations in China dropped by an unprecedented 29.7 percent, and by 17.1 percent in parts of Europe, during lockdowns that took place between Feb. 1 and March 31 in China and Feb. 21 to May 17 in Europe. Particulate matter (PM2.5) -- tiny airborne particles smaller than 1/10,000 of an inch in diameter -- comes from various combustion-related sources including industrial emissions, transportation, wildfires and chemical reactions of pollutants in the atmosphere.

"We look on these lockdowns as the first global experiment of forced low-emission scenarios," said Paola Crippa, assistant professor in the Department of Civil and Environmental Engineering and Earth Sciences at Notre Dame and corresponding author of the study. "This unique, real-world experiment shows us that strong improvements in severely polluted areas are achievable even in the short term, if strong measures are implemented."

Air pollution is considered the leading environmental cause of death. In 2016, the World Health Organization attributed air pollution to 4.2 million premature deaths worldwide, with Western Pacific and Southeast Asian regions being the most affected. Long-term exposure can be hazardous to human health, with premature death associated to lung cancer, ischemic heart disease, stroke and chronic obstructive pulmonary diseases.

Crippa and her team integrated advanced computer simulations with measured particulate matter concentrations from more than 2,500 sites in Europe and China in total between Jan. 1, 2016, and June 30, 2020 -- during which both regions initiated lockdowns as COVID-19 began spreading rapidly.

The team estimated rates of premature death against four different economic recovery scenarios: an immediate resumption to normal activity and subsequent emissions, a gradual resumption with a three-month proportional increase of emissions, the potential of a second outbreak of COVID-19 between October and December in each region, and a permanent lockdown for the remainder of 2020 in the case of ineffective control strategies.

"The most surprising part of this work is related to the impact on human health of the air quality improvements," Crippa said. "It was somewhat unexpected to see that the number of averted fatalities in the long term due to air quality improvements is similar to the COVID-19 related fatalities, at least in China where a small number of COVID-19 casualties were reported. These results underline the severity of air quality issues in some areas of the world and the need for immediate action."

From February to March, the study found an estimated 24,200 premature deaths associated with particulate matter were averted throughout China compared to 3,309 reported COVID-19 fatalities, and "improvements in air quality were widespread across China because of extended lockdown measures." The study found the situation in Europe to be quite different. While COVID-19 related deaths were far higher in Europe compared to what was reported in China, an estimated 2,190 deaths were still avoided during the lockdown period when compared to averages between 2016 and 2019. The averted fatalities figures become much larger (up to 287,000 in China and 29,500 in Europe) when considering long-term effects, which will depend on the future pathway of economic recovery.

The study serves as an example of the need for ad hoc control policies to be developed to achieve effective air quality improvements, said Crippa, and highlights the issue of risk perception between the current immediate crisis of the coronavirus pandemic versus the ongoing crisis of hazardous pollutants in the atmosphere.

"In China, we saw that lockdowns implied very significant reductions in PM2.5 concentrations, which means that policies targeting industrial and traffic emissions might be very effective in the future," Crippa said. "In Europe those reductions were somewhat smaller but there was still a significant effect, suggesting that other factors might be considered to shape an effective mitigation strategy."

Those strategies could include subsidies to electric vehicles, prioritizing public transport in heavily trafficked cities and adoption of more stringent emission limitations for industries. Heating emissions and agriculture are also contributors to total particulate matter concentrations. In the study, researchers stressed that aggressive mitigation strategies to reduce air pollution could achieve significant improvements to health, stating, "If interventions of a similar scale to those adopted to address the COVID-19 pandemic were widely and systematically adopted, substantial progress towards solving the most pressing environmental and health crisis of our time could be achieved."

Scientists have engineered tissue grafts that, in pigs, regenerated both bone and cartilage in the temporomandibular joint (TMJ), a part of the jaw that can cause debilitating pain and disability when damaged. The results represent a stride toward a safer and more effective intervention for patients with TMJ disorders, which affect approximately 10 million people in the U.S. alone. The TMJ routinely experiences high loads due to its complexity and involvement in various jaw movements, and can develop damage from congenital defects, traumatic injuries, and arthritis. TMJ disorders can be a huge burden on quality of life - causing symptoms such as jaw pain and difficulty chewing - and in the worst cases can only be repaired with surgeries. However, surgical interventions are imprecise and involve multiple operations; other treatments, including medical implants and steroid injections, can cause side effects such as allergies or cannot provide permanent relief. David Chen and colleagues took a different approach where they engineered tissue grafts that, unlike previous bone-focused designs, can repair both cartilage and bone within the ramus-condyle unit of the TMJ. The researchers grew their cartilage-bone grafts using several bioreactor designs over 5 weeks and then implanted the grafts into the TMJs of pigs. The grafts remained intact 6 months after transplantation, and boosted the regeneration of TMJ tissue more effectively than other graft designs that could only repair bone. "Overall, this study resulted in a promising approach to large-scale joint reconstruction using viable tissues and opens several avenues of investigation," Chen et al. write.

The immune response to infections is a delicate balance. We need just enough action to clear away the offending bacteria or viruses, but not so much that our own bodies suffer collateral damage.

Macrophages are immune cells at the front line, detecting pathogens and kicking off an inflammatory response when needed. Understanding how macrophages determine when to go all-out and when to keep calm is key to finding new ways to strike the right balance -- particularly in cases where inflammation goes too far, such as in sepsis, colitis and other autoimmune disorders.

In a study published October 14, 2020 in the Proceedings of the National Academy of Sciences, researchers at University of California San Diego School of Medicine discovered that a molecule called Girdin, or GIV, acts as a brake on macrophages.

When the team deleted the GIV gene from mouse macrophages, the immune cells rapidly overacted to even small amounts of live bacteria or a bacterial toxin. Mice with colitis and sepsis fared worse when lacking the GIV gene in their macrophages.

The researchers also created peptides that mimic GIV, allowing them to shut down mouse macrophages on command. When treated with the GIV-mimic peptide, the mice's inflammatory response was tempered.

"When a patient dies of sepsis, he or she does not die due to the invading bacteria themselves, but from an overreaction of their immune system to the bacteria," said senior author Pradipta Ghosh, MD, professor at UC San Diego School of Medicine and Moores Cancer Center. "It's similar to what we're seeing now with dangerous 'cytokine storms' that can result from infection with the novel coronavirus SARS-CoV-2. Macrophages, and the cytokines they produce, are the body's own immune-stimulating agents and when produced in excessive amounts, they do more harm than good."

Digging deeper into the mechanism at play, Ghosh and team discovered that the GIV protein normally cozies up to a molecule called Toll-like receptor 4 (TLR4). TLR4 is stuck right through the cell membrane, with bits poking inside and outside the cell. Outside of the cell, TLR4 is like an antenna, searching for signs of invading pathogens. Inside the cell, GIV is nestled between the receptor's two "feet." When in place, GIV keeps the feet apart, and nothing happens. When GIV is removed, the TLR4 feet touch and kick off a cascade of immune-stimulating signals.

Ghosh's GIV-mimicking peptides can take the place of the protein when it's missing, keeping the feet apart and calming macrophages down.

"We were surprised at just how fluid the immune system is when it encounters a pathogen," said Ghosh, who is also director of the Institute for Network Medicine and executive director of the HUMANOID Center of Research Excellence at UC San Diego School of Medicine. "Macrophages don't need to waste time and energy producing more or less GIV protein, they can rapidly dial their response up or down simply by moving it around, and it appears that such regulation happens at the level of gene transcription."

Ghosh and team plan to investigate the factors that determine how the GIV brake remains in place when macrophages are resting or is removed to mount a response to a credible threat. To enable these studies, the Institute for Network Medicine at UC San Diego School of Medicine recently received a new $5 million grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Ghosh shares this award with her colleagues Debashis Sahoo, PhD, assistant professor at UC San Diego School of Medicine and Jacobs School of Engineering, and Soumita Das, PhD, associate professor of pathology at UC San Diego School of Medicine.

A new species of small pterosaur - similar in size to a turkey - has been discovered, which is unlike any other pterosaur seen before due to its long slender toothless beak.

The fossilised piece of beak was a surprising find and was initially assumed to be part of the fin spine of a fish, but a team of palaeontologists from the universities of Portsmouth and Bath spotted the unusual texture of the bone - seen only in pterosaurs - and realised it was a piece of beak.

Professor David Martill of the University of Portsmouth, who co-authored the study, said: "We've never seen anything like this little pterosaur before. The bizarre shape of the beak was so unique, at first the fossils weren't recognised as a pterosaur."

Careful searching of the late Cretaceous Kem Kem strata of Morocco, where this particular bone was found, revealed additional fossils of the animal, which led to the team concluding it was a new species with a long, skinny beak, like that of a Kiwi.

Lead author of the project, University of Portsmouth PhD student Roy Smith, said: "Just imagine how delighted I was, while on field work in Morocco, to discover the lower jaw to match the upper jaw found by Dr Longrich of this utterly unique fossil animal."

The new species, Leptostomia begaaensis, used its beak to probe dirt and mud for hidden prey, hunting like present-day sandpipers or kiwis to find worms, crustaceans, and perhaps even small hard-shelled clams.

Pterosaurs are the less well-known cousins of dinosaurs. Over 100 species of these winged-reptiles are known, some as large as a fighter jet and others as small as a sparrow.

Professor Martill said: "The diets and hunting strategies of pterosaurs were diverse - they likely ate meat, fish and insects. The giant 500-pound pterosaurs probably ate whatever they wanted.

"Some species hunted food on the wing, others stalked their prey on the ground. Now, the fragments of this remarkable little pterosaur show a lifestyle previously unknown for pterosaurs."

The scientists used a computerised tomography (CT) scan to reveal an incredible network of internal canals for nerves that helped detect the prey underground.

Dr Nick Longrich, from the Milner Centre for Evolution at the University of Bath, said: "Leptostomia may actually have been a fairly common pterosaur, but it's so strange - people have probably been finding bits of this beast for years, but we didn't know what they were until now."

Long, slender beaks evolved in many modern birds. Those most similar to Leptostomia are probing birds - like sandpipers, kiwis, curlews, ibises and hoopoes. Some of these birds forage in earth for earthworms while others forage along beaches and tidal flats, feeding on bristle worms, fiddler crabs, and small clams.

Leptostomia could probably have done either, but its presence in the Cretaceous age Kem Kem strata of Africa - representing a rich ecosystem of rivers and estuaries - suggests it was drawn there to feed on aquatic prey.

"You might think of the pterosaur as imitating the strategy used successfully by modern birds, but it was the pterosaur that got there first," said Dr Longrich. "Birds just reinvented what pterosaurs had already done tens of millions of years earlier."

Dr Longrich suggests the new species shows how, more than a century after pterosaurs were first discovered, there's still so much to learn about them. He said: "We're underestimating pterosaur diversity because the fossil record gives us a biased picture.

"Pterosaur fossils typically preserve in watery settings - seas, lakes, and lagoons - because water carries sediments to bury bones. Pterosaurs flying over water to hunt for fish tend to fall in and die, so they're common as fossils. Pterosaurs hunting along the margins of the water will preserve more rarely, and many from inland habitats may never preserve as fossils at all.

"There's a similar pattern in birds. If all we had of birds was their fossils, we'd probably think that birds were mostly aquatic things like penguins, puffins, ducks and albatrosses. Even though they're a minority of the species, their fossil record is a lot better than for land birds like hummingbirds, hawks, and ostriches."

Over time, more and more species of pterosaurs with diverse lifestyles have been discovered. That trend, the new pterosaur suggests, is likely to continue.

COVID-19 continues to wreak havoc globally, with over one million deaths to date. Yet what if an existing vaccine could make COVID-19 less deadly? A study just published put the theory to test, with promising results.

A research team led by Dr. Larenas-Linnemann working at Medica Sur, Mexico City, reported on their clinical observations in 255 subjects vaccinated with the measles-mumps-rubella (MMR) vaccine since the start of the Coronavirus disease-2019 (COVID-19) pandemic. Many vaccinated patients were family members or caregivers of patients who already had contracted COVID-19, and thus at extremely high risk. Thirty-six of the patients have now contracted COVID-19, but all with a remarkably mild course, with less severe symptoms than would be expected given their health status and age. The paper, published in the September issue of Allergy, the European Journal of Allergy and Immunology, is now available for free download.

MMR vaccination in the context of COVID-19, taking advantage of a measles outbreak

At the start of the COVID-19 pandemic, observing the highly contagious and virulent nature of the virus and the lack of available preventive measures, the investigators searched for methods to enhance innate immunity -- in effect, give the immune system a boost to prepare it for a variety of assaults. Since COVID-19 was new to humans, there was no existing treatment or vaccine to specifically fight it. But Dr. Larenas-Linnemann, being Dutch and having done her basic training in the Netherlands, had followed with admiration the work of a fellow countryman on a little-known concept called "trained immunity." In technical terms, trained immunity refers to the enhanced immune response to a certain pathogen, after being exposed (by vaccination or natural illness) to another non-related pathogen; the immune reaction after a subsequent exposure to a non-related pathogen is faster in onset and accompanied by an increased production of certain cytokines. This means that, surprisingly, some vaccinations could not only prevent the target disease (such as measles), but also help people fight other diseases.

Trained immunity is a form of non-specific immunity. It was controversial at first, but after decades of pioneering fieldwork from a Danish team studying the tuberculosis vaccine and the live polio vaccine in both Northern Europe and Africa, followed by years of authoritative laboratory work from Dr. Larenas-Linnemann's countryman Mihai Netea and others, it is now accepted that certain live-attenuated vaccines can make the body better prepared to fight off a range of pathogens.

Dr. Larenas-Linnemann's team wondered: Could a live-attenuated vaccine be protective against this entirely new disease, COVID-19, for their patients? Taking advantage of the fact that the pandemic in Mexico coincided with a rise in measles cases, which had motivated the Ministry of Health to recommend measles re-vaccination, the team decided to put the concept of trained immunity to the test. As such, from March 2020 onward, the researchers recommended MMR vaccination to their patients, especially among family members of COVID-19 cases.

Observational trial of MMR for COVID-19 prevention

In a prospective observational trial in Hospital Médica Sur, ranked since 2011 as the best hospital of Mexico City, the team gave their patients boosters of a standard childhood vaccine, measles-mumps-rubella (MMR), which is considered safe worldwide (a booster is even required in many places to start college or military service). The patients were followed closely to watch for COVID-19 infection. The patients were considered high risk for COVID infection because many were caring for ill family members and were vulnerable due to their age or other risk factors.

COVID-19 infection was considered confirmed with a positive result of a SARS-CoV-2 antigen test, the detection of specific antibodies, or the combined presence of a direct contact with a confirmed case plus anosmia/ageusia and at least two classic COVID-19 symptoms. Direct contact with a confirmed case, accompanied by classic symptoms, but without smell or taste changes were considered highly probable cases. The clinical severity of COVID-19 was graded on a simplified scale from zero for asymptomatic cases, through 1 for mild, 2 for moderate, 3 for lower respiratory symptoms without the need for oxygen, up to 6 for fatality. Also, home measurements of pulse oximetry and peak-expiratory-flow rate (PEFR) were used to determine severity.

Outcomes: none of the 36 cases needed supplementary oxygen

Among the 255 vaccinated subjects, there were 24 confirmed and 12 (highly) probable COVID-19 cases, thirteen with risk factors that can often make COVID-19 more serious (hypertension, diabetes, obesity, smoking, or uncontrolled asthma). In their publication, the authors detail the risk factors for each patient. All received general supportive measures; some received off-label high-dose ivermectin the first two days. In general, the cases were less severe than would be expected. All had minor respiratory symptoms at most. Only one patient, with uncontrolled asthma, had one day of mild low blood oxygen. No patients had respiratory insufficiency to the degree of needing oxygen.

"We were relieved that MMR, which is commonly thought of as a childhood vaccination, seemed to help our older adult patients weather the storm too," said Dr. Larenas-Linnemann.

Reaction

"We would not be surprised if MMR could provide some protection against severe COVID-19," said researcher Peter Aaby, of Bandim Health Project in Guinea-Bissau and Research Centre for Vitamins and Vaccines (CVIVA), Statens Serum Institut, a governmental public health and research institution under the Danish Ministry of Health in Copenhagen, Denmark and a pioneer in the field. "Together with my partner Dr. Christine Stabell Benn, we've been reporting on mortality reductions from live-attenuated vaccines such as polio, BCG and measles vaccine/MMR for multiple decades now, and arguing for optimized vaccine schedules. With the COVID-19 crisis adding urgency, it's good to see the potential of non-specific immune effects being taken seriously."

Global research applying trained immunity to COVID-19 prevention

Researchers around the world are studying the ability of existing live-attenuated vaccines to prevent severe complications of COVID-19.

Several clinical trials are now ongoing with tuberculosis (BCG) vaccination of SARS-CoV-2 exposed health-care workers to reduce the severity of an eventual infection. However, one of the effects described in experiments with BCG-trained-immunity was a rise in interleukin 6 cytokine (IL-6), which made the Médica Sur team reluctant to use this method due to immune over-activation linked to high IL-6 levels described in severe COVID-19 cases. In addition, BCG vaccine and live polio vaccine are not used in the United States of America or Canada, making work with the BCG and polio vaccines harder to apply widely across North America. Existing supplies of BCG are also critically needed to save infant lives around the globe. Dr. Larenas-Linnemann's team instead chose the MMR vaccine for its safety profile, as well as for previous research describing trained immunity from MMR in newborns of hepatitis-infected mothers and retrospective studies showing 26-49% decreases in all-cause mortality rates after measles vaccination programs.

What's next

These first observational data gathered by Dr. Larenas-Linnemann and her group in Mexico City, demonstrating a milder course of COVID-19 in recently MMR-vaccinated individuals, are promising. The investigators are continuing their strategy to recommend MMR vaccination to household contacts of COVID-19 patients and plan to keep collecting data on further clinical cases. They are also searching for cooperation with basic immunologists to study the immunologic background of their observations. Said Dr. Larenas-Linnemann, "We are grateful to be able to have been able to offer this to our patients and hope these first real-life data will spark interest in the approach."

Conclusive evidence of the value of MMR vaccine to reduce COVID-19 complications requires a prospective, randomized trial. This is exactly what microbiologist Dr. Paul Fidel of Louisiana State University has recently launched. He has hypothesized that live attenuated vaccines induce myeloid-derived suppressor cells (MDSCs), another form of trained innate immunity, to suppress the fatal sepsis often seen in severe COVID-19 cases, as outlined in an opinion/hypothesis piece in mBio. With funding from the Parsemus Foundation and Fast Grants, the MMR randomized controlled trial is enrolling first responders and healthcare workers in the hard-hit New Orleans region. Dr. Fidel's team is still seeking funding to test whether MMR can provide protection to nursing home residents, who are particularly vulnerable to this disease.