Culture

As interest in the application of plasma medicine -- the use of low-temperature plasma (LTP) created by an electrical discharge to address medical problems -- continues to grow, so does the need for research advancements proving its capabilities and potential impacts on the health care industry. Across the world, many research groups are investigating plasma medicine for applications including cancer treatment and the accelerated healing of chronic wounds, among others.

Researchers from Penn State's College of Engineering, College of Agricultural Sciences and College of Medicine say direct LTP treatment and plasma-activated media are effective treatments against bacteria found in liquid cultures. The researchers also say they have devised a unique way to create plasma directly in liquids.

The team, comprised of engineers, physicists, veterinary and biomedical scientists and medical professionals, is using an atmospheric-pressure plasma jet to use room temperature -- "cold" -- plasma to treat bacteria.

Plasma, the fourth state of matter, is typically very hot -- thousands to millions of degrees. By using plasma generated at atmospheric pressure or in liquids, the researchers can create molecules and atoms with antibacterial effects without burning anything. Sean Knecht, assistant teaching professor of engineering design at Penn State and leader of the Cross-disciplinary Laboratory for Integrated Plasma Science and Engineering, said this process creates many different types of reactive particles, making the likelihood of bacterial mutations to simultaneously combat all the particles almost nonexistent.

Knecht explained that the team's research results, published in Scientific Reports, show that plasma technology generates large amounts of reactive oxygen species or reactive particles created from molecules that contain oxygen atoms, including oxygen molecules in the air and water vapor. The plasma's effect on different bacteria such as E. coli and Staph. aureus is significant, resulting in many bacterial deaths through multiple generations.

"Over the course of four generations of bacteria, these bacteria do not acquire any form of resistance to the plasma treatment," he said.

Girish Kirimanjeswara, associate professor of veterinary and biomedical sciences at Penn State, said this is extremely important due to the typical way bacteria mutate, making them resistant to antibiotics.

Antibiotics target a specific metabolic pathway, essential protein or nucleic acids in bacteria. Because of this, antibiotics have to enter a bacterial cell to find and bind to that specific target. Any bacterial mutation that decreases an antibiotic's entry capabilities or increases its rate of exit makes the antibiotic less effective. Mutations happen naturally at a low rate but can rapidly accumulate by selection pressure when introduced to antibiotics aimed at fighting the bacteria.

According to Kirimanjeswara, the team's research results show that plasma treatment produces various reactive oxygen species at a concentration high enough to kill bacteria, but low enough to not have negative impacts on human cells. He explained that the oxygen species quickly target virtually every part of the bacteria including proteins, lipids and nucleic acids.

"One can call it a sledgehammer approach," Kirimanjeswara said. "It is difficult to develop resistance by any single mutation or even by a bunch of mutations."

The team also applied these findings to design a system that can create plasma directly in liquids. The researchers intend to create plasma in blood to address cardiovascular infections directly at the source. To do so, high electric voltage and large electric currents are typically used. In the plasma system created by the researchers, the electrical current and energy that might reach the patient are minimized by using dielectric, or electrically-insulating, materials. Materials that the team would typically use to create the plasma include glass and ceramic due to their capability to withstand high local temperatures. These materials tend to make blood clot and may not be very flexible, a necessity if they are to be used in the cardiovascular system. The team is investigating insulating coatings that are biocompatible, or acceptable by the human body, and flexible. Knecht said the team has identified a polymer called Parylene-C and reported the initial results in the journal IEEE Transactions on Radiation and Plasma Medical Sciences. The team is further pursuing this avenue, as polymers have low melting points and may not withstand repeated exposure to plasma.

"Biocompatible polymers can be used for plasma generation in biological liquids, but their lifetime is limited," Knecht said. "New unique plasma generation designs must be developed to produce lower intensity plasma discharges that can extend their lifetime. That is what we are continuing to work on."

Kirimanjeswara said scientists typically work to understand how different bacteria cause disease or how host immune responses eliminate bacteria to create new antibiotics and vaccines. Though these more traditional approaches are essential, they are often gradual and time-consuming. The team's innovative research highlights the importance of continuing to investigate new ways to combat bacteria.

"Transformative and cross-disciplinary approaches have the potential to speed up finding solutions to urgent global problems," he said. "It is important for the general public to be aware of and appreciate the fact that the scientific community is engaged in several approaches, some traditional and others nontraditional, to combat the growing problem of antibiotic resistance. We hope our research reinforces the idea of embracing nonantibiotic approaches to treat bacterial infections in the future."

CORVALLIS, Ore. -- In the ongoing struggle to address health care disparities in rural communities across the U.S., a recent Oregon State University study found that the perfect partner may be hiding in plain sight.

The grange, founded in 1867 and officially titled the National Grange of the Order of Patrons of Husbandry, is a community-based organization that is likely familiar to anyone who's spent time in a small town or attended a county fair. In addition to political advocacy on behalf of farmers, the grange's missions around community and family also align closely with the goals of public health.

OSU's study, recently published in the Journal of Community Health, reviewed scientific literature that mentioned the grange, in both medical and agricultural publications. Researchers also pored over the grange's own materials to assess the organization's key messages for the past two decades.

A significant portion of those publications dealt with the study's domains of health and health care, social cohesion and community context, economic stability -- including food instability -- and the neighborhood and the built environment.

"It's this overlooked source that's been there this whole time. They've been in the community for more than a hundred years," said Veronica Irvin, assistant professor in OSU's College of Public Health and Human Sciences and one of the authors of the paper. "They have community support, they have physical space, they have similar missions to public health -- it's this natural partner that we've just not met up with."

Compared with big cities, rural communities have less access to health care services. The populations are generally older than urban populations; the towns have fewer walking paths and other places dedicated to physical activity; and despite being centered around farms, many rural areas are termed "food deserts" because of limited availability of healthy foods.

Those issues are all relevant to grange members, said Susan Noah, master of the Oregon State Grange and co-author of the paper.

"Everyone is becoming more and more conscious of what it means to be a healthy society, especially as it relates to food and agriculture," she said.

While individual granges have different areas of focus, they all have physical buildings equipped with kitchens and classroom space, which has allowed them to partner on several health initiatives, including blood drives, mental health awareness classes and Alzheimer's caretaker education programs. In Philomath, the Marys River Grange has hosted a low-cost medical clinic for farm workers.

Now, researchers and grange leaders hope the new findings will spur greater collaboration with health care providers, including as communities start to reopen from COVID-19 shutdowns.

As with most fraternal organizations, the grange's membership is aging. But it's working to adapt and bring in new people, Noah said. There's no longer a requirement that members be actively involved in agriculture, and many granges are now focusing on sustainable practices, growing your own food and eating local. Some are offering yoga and jazzercise classes.

Noah sees the grange playing an important role in helping communities recover from the social isolation caused by COVID-19, as well as potentially becoming a source of trusted, evidence-backed information for members with questions about the virus.

Lead author Lilly Anderson, a 2019 OSU master's in public health graduate, says more coordination between the grange and public health organizations could help avoid unnecessary duplication of effort and allow them to work in tandem more often.

"This very well-established and trusted community resource is in a position to be an excellent partner for public health in rural areas where we desperately need it," she said. "I think if we combined resources and gave them some much needed publicity for their good work, we could really increase our outreach in these areas."

The direction of ocean currents can determine the direction of gene flow in rafting species, but this depends on species traits that allow for rafting propensity. This is according to a City College of New York study focusing on seahorse and pipefish species. And it could explain how high genetic diversity can contribute to extinction in small populations.

Published in the British-based journal "Proceedings of the Royal Society B," the paper by City College scientists led by Michael Hickerson and Laura Bertola is entitled: "Asymmetrical gene flow in five co-distributed syngnathids explained by ocean currents and rafting propensity."

It reveals that ocean circulation driving macro-algal rafting is believed to serve as an important mode of dispersal for many marine organisms. This leads to predictions on population-level genetic connectivity and the directionality of effective dispersal.

The CCNY Division of Sciences researchers used genome-wide single nucleotide polymorphism data to investigate whether gene flow directionality in two seahorses (Hippocampus) and three pipefishes (Syngnathus) follows the predominant ocean circulation patterns in the Gulf of Mexico and northwestern Atlantic. They also explored whether gene flow magnitudes are predicted by traits related to active dispersal ability and habitat preference.

"We inferred demographic histories of these co-distributed syngnathid species, and coalescent model-based estimates indicate that gene flow directionality is in agreement with ocean circulation data that predicts eastward and northward macro-algal transport," said Hickerson. "However, the magnitude to which ocean currents influence this pattern appears strongly dependent on the species-specific traits related to rafting propensity and habitat preferences."

The study, he said, highlights how the combination of population genomic inference together with ocean circulation data can help explain patterns of population structure and diversity in marine ecosystems.

Leesburg, VA, May 8, 2020--Although the clinical symptoms of new pediatric lung disorders such as severe acute respiratory syndrome (SARS), swine-origin influenza A (H1N1), Middle East respiratory syndrome (MERS), e-cigarette or vaping product use-associated lung injury (EVALI), and coronavirus disease (COVID-19) pneumonia may be nonspecific, some characteristic imaging findings "have emerged or are currently emerging," according to an open-access article in the American Journal of Roentgenology (AJR).

"Although there are some overlapping imaging features of these disorders," wrote first author Alexandra M. Foust of Boston Children's Hospital and Harvard Medical School, "careful evaluation of the distribution, lung zone preference, and symmetry of the abnormalities with an eye for a few unique differentiating imaging features, such as the halo sign seen in COVID-19 and subpleural sparing and the atoll sign seen in EVALI, can allow the radiologist to offer a narrower differential diagnosis in pediatric patients, leading to optimal patient care."

At most institutions, whereas the first imaging study performed in patients with clinically suspected COVID-19 is chest radiography, Foust and colleagues' review of the clinical literature found that studies on chest radiography findings in patients with COVID-19 were relatively scarce.

Regarding the limited studies of pediatric patients with COVID-19, Foust et al. noted chest radiography "may show normal findings; patchy bilateral ground-glass opacity (GGO), consolidation, or both; peripheral and lower lung zone predominance."

Similarly, while the literature describing chest CT findings in patients with COVID-19 are more robust than those describing chest radiography findings, only a few articles have reported CT findings of COVID-19 in children.

A study of 20 pediatric patients with COVID-19 reported that the most frequently observed abnormalities on CT were subpleural lesions (100% of patients), unilateral (30%) or bilateral (50%) pulmonary lesions, GGO (60%), and consolidation with a rim of GGO surrounding it, also known as the halo sign (50%).

The authors of this AJR article also pointed to a smaller study of five pediatric patients with COVID-19, where investigators reported modest patchy GGO, one with peripheral subpleural involvement, in three patients that resolved on follow-up CT examination.

WASHINGTON (May 7, 2020) "We have seen this before." Global health scholars have issued a clarion call about the needless loss of life expected because of a foreseeable prospect of "slow and inadequate access to supplies" to control COVID-19 in sub-Saharan Africa. They say what is unfolding now is similar to when lifesaving diagnostics and treatments came to the region long after they were available elsewhere.

COVID-19 cases in Africa have doubled in the last two weeks--with Africa Centres for Disease Control and Prevention and the World Health Organization tracking exponential growth in some countries, raising concern Africa might be the next epicenter of the pandemic.

"A governance crisis is unfolding alongside the pandemic as health officials around the world compete for access to scarce medical supplies," writes the global health team including lead author Matthew M. Kavanagh, PhD, assistant professor in the Department of International Health at Georgetown University Medical Center and director of Global Health Policy and Governance at the O'Neill Institute for National and Global Health Law. He and his colleagues published their article today in The Lancet.

They write, "Having navigated Ebola, HIV, and tuberculosis epidemics, and a range of annual, sporadic, and concurrent outbreaks, several African countries have unparalleled disease response capacity."
Despite this level of preparedness, and even where there's enough money, "many African health authorities are unable to obtain the supplies needed as geopolitically powerful countries mobilise economic, political, and strategic power to procure stocks for their populations."

To help avoid being locked out of the market, the authors argue say political leadership and political convening powers are needed to develop short and medium term actions.

On May 4th, the European Union hosted a virtual pledging conference that secured $8 billion for Africa, as heads of state launched a new COVID-19 "accelerator" for vaccines, diagnostics, and treatment. The authors note it has not yet dealt with several "thorny ethical issues in affordability, access, and distribution" of current and future tools to African countries.
"This is an ethical imperative but also a shared interest; the COVID-19 pandemic has taught us that unaddressed outbreaks in one part of the world put people throughout the world at risk," they write. "It is entirely foreseeable that many countries will be locked out of the market. Governments have structured the global trading system and they have the power now to ameliorate its ill effects amidst crisis."

The authors conclude, "In 2020, we have the opportunity to learn from past mistakes by countering market forces, thus ensuring that lives on the African continent count equally. Doing so will take both moral clarity and political courage."

In everyday life, matter behaves in a predictable, expected way. If you throw a ball, you assume it will travel in a certain direction and have a predictable recoil. What's more, forces exerted on one object would not have an impact on another, independent object.

But in quantum mechanics - the physics of the tiny - the rules are completely different. In one, two, and three-particle systems, actions that happen in one spot can strongly influence atoms far away. Scientists don't yet have a full understanding of this but, by analyzing the behavior of these systems and more complex ones, they are hoping to find insights.

Researchers from the Quantum Systems Unit at the Okinawa Institute of Science and Technology Graduate University (OIST), alongside collaborators at University College Dublin and Durham University, simulated one of these systems, which revealed quantum states - ways that particles arrange themselves in isolated systems - that were unexpected. Their results, published in New Journal of Physics, could have applications for quantum technologies.

"If you throw a stone off a boat, the stone goes one way and the boat goes the other," explained Professor Thomas Busch, who leads the Unit. "In quantum mechanics, we can have much stronger correlations at much greater distances. It's like if you put on one red sock and one green sock, then someone in Antarctica, who you've never met, would have to do the same. And our work has found new states with these very strong correlations, which can be controlled very well."

Experimenting with two atoms

When scientists research macroscopic systems, they tend to look at many particles - say 10 to the 23 atoms. Because there are so many, they can't follow every atom and must make assumptions. To avoid this, the researchers in this study used another option.

"We simulated a system with just two atoms," said first author Ayaka Usui, a Ph.D. student in the Unit. "This provided a building block of the larger system, but we could control everything and see exactly what was happening. And, to further control this system, we considered super-cold atoms."

At room temperature, particles move around very quickly. The warmer it is, the faster they move. By using laser cooling, these atoms can be slowed and cooled down until they reach almost zero velocity and are thus super-cold. This made it much easier for Ayaka and colleagues to describe them in their simulations.

In a system like this, the simplest thing the particles can do is collide with each other. This forces them to move around and change direction, but particles also have something called spin. The spin of a particle is either pointing up or down and further influences how it moves - an effect called spin-orbit coupling. When the researchers simulated a system with two super-cold atoms that were spin-orbit coupled, these new states, with their very strong correlations, were revealed.

"We have the systems with two-particles where you get these states and the ones with 10 to the 23 where you don't," said Dr. Thomas Fogarty, Postdoctoral Scholar in the Unit. "Somewhere along this long chain of adding particles, these new states go away."

Engineering further insights

"Alongside the new states, we've discovered the formulas that describe this system exactly," said Ayaka. "So now, we can engineer it."

By finding these formulas, the researchers have control over the system and they now plan on changing the parameters to look at the system's dynamics.

"We're going to split the system, so we have two of them," said Ayaka. "We can use the strong correlations to help us measure the system. If we find one atom in one of the systems, we know the other one is also in that one, without measuring it, because they are tightly correlated."

Although this research is just concentrating on a small aspect of what quantum mechanics can do, it has numerous applications, said Professor Busch.

"Quantum technologies need these correlations," he explained. "These new states have the strongest non-classical correlations that we know, and we can engineer them. With this research, we could build more powerful computers. We could create measurement devices that measure tiny differences in gravity or electric pulses in the brain. There're so many applications to work towards."

An international team of researchers including the University of Adelaide, has completed the first large-scale study of DNA belonging to ancient humans of the central Andes in South America and found early genetic differences between groups of nearby regions, and surprising genetic continuity over thousands of years.

In the study, published in the journal Cell, researchers analysed the DNA of 89 ancient humans who lived in the central Andes between 500 and 9,000 years ago, and compared it with the genetic diversity of present day occupants, to shed light on the genetic changes over time.

The ancient remains included 65 newly reported humans never before studied.

Associate Professor Bastien Llamas from the University of Adelaide's Australian Centre for Ancient DNA, who was part of the research team, says there are many unanswered questions about the population history of the central Andes and in particular the large-scale societies that lived there including Inca, Tiwanaku, Moche and Wari.

"We know from archeological research that the central Andes region is extremely rich in cultural heritage, however up until now the genomic makeup of the region before arrival of Europeans has never been studied," he said.

"While archaeological records play a role in connecting cultures, studying ancient DNA can provide a finer grain picture.

"For example, archaeological information may tell us about two or three cultures in the region, and eventually who was there first, but ancient DNA can inform about actual biological connections underlying expansion of cultural practices, languages or technologies."

In the study, researchers found that genetic differences between the people of the central Andean Highlands and Coastal regions were in place as early as 9,000 years ago; with a north-south substructure of the Highlands developing by 5,800 before present (BP). These differences are still apparent in people living in those areas today.

After 5,800 BP there was evidence of genetic mingling, indicating movement of the Highlands people between north and south, central and coastal regions. However, the migrations appear to slow down by 2,000 BP, with minimal changes to the genetic structure of the central Andean region between 2,000 and 500 BP.

"This was quite surprising given this period saw the rise and fall of many large-scale Andean cultures such as Moche, Wari and Nasca, and suggests that these empires implemented a cultural domination without moving armies," Associate Professor Llamas said.

There were two exceptions to the slowing of migration, and these were within the Tiwanaku and Inca populations, whose administrative centres were largely cosmopolitan - people of diverse ancestries living side-by-side.

"It was interesting to uncover signs of long-range mobility during the Inca period. Archaeology shows Incans occupied thousands of kilometres from Ecuador through to northern Chile - which is why when Europeans arrived they discovered a massive Inkan empire, but we found close genetic relationships between individuals at the extreme edges of the empire," Associate Professor Llamas said.

Scientists across eight countries and multiple institutions were involved in the study including Harvard University, the Max Planck Institute, and the University of California at Santa Cruz. The key members of the team were from Bolivia, Argentina, Chile and Peru where the ancient remains originated.

"Ancient DNA is fascinating because it literally connects past and present people, but it is only by engaging early on and continually with local communities and governments, and with scholars who work closely with these communities, that we can perform research that respects people's cultural heritage and provide results that are truly meaningful," said Associate Professor Llamas.

Associate Professor Llamas, who has been studying ancient DNA within South America for more than 10 years, says that the study has expanded previous research, which provided an overall picture of the whole continent and how people arrived in migration waves.

"We hope this more detailed genetic picture of populations of the central Andean Highlands will allow archeologists to ask new questions about the history of the region and will lead to further cultural learnings and strengthen collaboration with local communities," he said.

Women have a good chance of having a second child with the help of fertility treatment after the birth of their first child born this way, according to the first study to investigate this, published today (Friday) in Human Reproduction [1], one of the world's leading reproductive medicine journals.

Researchers in Australia calculated that after a woman successfully achieved a live birth using in vitro fertilisation (IVF), also known as assisted reproductive technology (ART), the chances of a second ART baby were between 51% and 88% after six cycles of treatment. These calculations depended on whether or not previously frozen embryos were used or fresh embryos from a new ovarian stimulation cycle, and on assumptions made about the likely success rate for women who discontinued treatment.

The chances of a second ART baby decreased with increased maternal age. Compared to women younger than 30 years, the likelihood of women aged 35-39 having a second ART-conceived baby reduced by 22% if they recommenced treatment with a frozen embryo from a previous cycle and by 50% if they recommenced treatment with a new cycle and a fresh embryo. Factors that improved their chances of a successful second pregnancy included requiring only one cycle and a single embryo transfer to achieve a first live birth, and where infertility was caused by factors affecting the male partner.

Although many parents would like more than one child, there has been no published report on the chances of achieving a second ART-conceived baby after a first ART child until now. The researchers hope that this information can be used to counsel patients.

Professor Georgina Chambers, director of the National Perinatal Epidemiology and Statistics Unit at the University of New South Wales (Sydney, Australia), looked at data from 35,290 women who received ART treatment between 2009 and 2013 in Australia and New Zealand and had a live baby during this time. These women were followed for a further two years to 2015, providing between two and seven years of follow-up data, and live births up to October 2016 were included.

"We calculated two measures: what is a woman's chance of achieving a second live birth in a particular cycle of treatment if previous cycles have failed, for instance in cycle three if the first two cycles have failed; and what is the overall, or cumulative, chance of a woman achieving a live birth after a particular number of cycles, including all the previous cycles. For example, what is the overall chance of a woman having a baby after up to three cycles," said Prof Chambers.

A cycle includes the stimulation of the ovaries to mature multiple eggs, the collection of eggs for fertilisation in the laboratory to create embryos, and then all embryo transfer procedures that use the embryos from the egg retrieval procedure. This can include fresh embryo transfers and frozen embryo transfers.

Prof Chambers and her colleagues calculated estimates of cumulative live birth rates (CLBR) for women who were trying for a second ART baby that took account not only of the women who continued treatment, but also those who discontinued treatment. The conservative CLBR assumed that women who dropped out would have no chance of achieving a second live birth if they had continued treatment. The optimal CLBR assumed these women would have the same chance of a live birth in a particular cycle as women who had continued treatment. The range between the conservative and optimal estimates gives a realistic idea of success rates.

Just over 43% (15,325) of the 35,290 women, with an average (median) age of 36, returned for treatment to conceive a second child by December 2015.

Among these women, 73% used a frozen embryo from the egg retrieval cycle that had resulted in their first child, and for them the CLBR ranged from 61% (conservative estimate) to 88% (optimal estimate) after six cycles. Among the women who had a new stimulation cycle and used a fresh embryo, the CLBR ranged from 51% to 70%.

"Overall, 43% of women who recommence treatment with one of the frozen embryos from a previous stimulation cycle will have a baby after their first embryo transfer procedure. Between 61% and 88% of these women will have a baby after six cycles," said Prof Chambers. "Among those who recommence treatment with a new stimulation cycle and a fresh embryo transfer, 31% will have a baby after their first cycle and between 51% and 70% after six cycles."

Although success rates declined with female age, the researchers found that after three cycles of treatment, the conservative and optimal CLBRs in women aged 40 to 44 years were 38% and 55% respectively in those that started with a frozen embryo, and 20% and 25% in those recommencing with a new stimulated cycle and fresh embryos. [2]

Prof Chambers said: "Couples can be reassured by these figures. Our findings also underline the fact that ART treatment should be considered as a course of treatment, rather than just one single cycle of treatment: if couples don't achieve a pregnancy in the first cycle, it could very well happen in the next. However, it would be best not to wait too long, especially if a new stimulation cycle is needed."

Co-author, Dr Devora Leiberman, a fertility clinician at City Fertility, Sydney, added: "These results can be used to counsel patients, but it is important to note that these are population estimates and every couple is different. Our analysis does not take account of all individual factors that affect a woman's chance of ART success, including duration of infertility, and body mass index. Whether ART treatment should be commenced or continued should ultimately be a decision for the fertility clinician and patient, taking into account all medical and non-medical factors. But this study provides the range of results that could be expected."

Another limitation is that in Australia and New Zealand, couples are funded to have treatment for infertility with no restrictions on the number of cycles or on the mothers' age, numbers of previous children and factors such as body max index and smoking. Therefore, the findings may not be generalisable to other countries with less supportive funding provision for ART.

Dr Christos Venetis, a fertility clinician and clinical academic from the research team at the University of New South Wales, concluded: "As the restrictions imposed due to the COVID-19 pandemic on the provision of non-urgent ART services are gradually being lifted in many countries, including Australia and New Zealand, many people are considering expanding their family through ART. This study can provide reassurance that, in most cases, the chance of them having a second baby through ART is quite favourable."

Over 80% of people surveyed in a study do not plan to conceive during the COVID-19 crisis, perhaps putting to rest suggestions that the lockdown could lead to rise in birth numbers.

Looking at parenthood desires during the ongoing pandemic crisis in Italy, a team of experts, led by the University of Florence, carried out 1,482 online interviews. Their results, published in the peer-reviewed Journal of Psychosomatic Obstetrics and Gynecology, show that some 1,214 (81.9%) did not intend to conceive during the pandemic crisis.

Moreover, of the 268 participants who were planning to have a child before the pandemic, over one-third (37.3%) then abandoned the intention. The main reasons that led people to this decision included worries related to future economic difficulties (58%) and any potential consequences on pregnancy (58%) due to the disease.

The questionnaire, carried out in the third week of the lockdown in Italy, surveyed 944 women (63.7%) and 538 men (36.3%) aged between 18-46 years, and in a stable heterosexual relationship for at least twelve months. Study author, Dr Elisabetta Micelli from the Assisted Reproduction Technologies Center, suggested that mental wellbeing during lockdown had an impact on the desire to have a baby.

"The impact of the quarantine on general population's perception of their stability and peacefulness is alarming. In our study sample, the majority of participants gave significantly higher total scores to their mental wellbeing before the pandemic, while lowest scores were reported in the answers referred to the COVID-19 period.

"We aimed to evaluate if pandemic-related concerns and worries are affecting the desire for parenthood in couples who were already planning to have a child or if quarantine is encouraging reproductive desire.

"What we found the main reasons that led people to not wanting to conceive included worries related to future economic difficulties and consequences on pregnancy.

"Interestingly, although almost half of the people referred no interruption in their job activity and no variations of salaries, probably due to the 'smart working' adapting strategy, over 40% of participants reported a worrying reduction of monthly profits. Remarkably, the fear of imminent and future economic instabilities led those who were searching for a pregnancy to stop their intention in 58% of cases."

Nevertheless, despite most people not wanting to conceive during the pandemic, 60% of the 268 correspondents already planning to conceive have carried on in their quest - with the experts suggesting that the fear of infertility potentially occurring in the future, outweighs the worries of the consequences of COVID-19 infection.

Additionally, some 140 (11.5%) people in fact revealed a new desire for parenthood during quarantine.

Specifically, the wish was mainly expressed by women. In most cases, the respondents referred "the will for change" (50%) and "the need for positivity" (40%) to be the main reasons of this intention. Only six out of the 140 (4.3%), however effectively tried to get pregnant in this period.

Co-author Dr Gianmartin Cito, in specialist training in Urology at the University of Florence, added: "Again, fear of consequences on pregnancy in addition to the economic impact on families are probably the reasons why almost the whole group of couples who unexpectedly started to express a desire for parenthood during quarantine did not translate this dream into a concrete attempt."

The study also measured people's reported levels of sexual activity. 712 respondents (66.3%) who did not experience the desire for parenting before the pandemic, nor during, reported no reduction in sexual intercourses - with no significant differences among genders. 60% of the couples who were already involved in childbearing attempts, continued in this project and did not report a reduction in the number of sexual intercourses.

Commenting on the limitations of the study, the authors add that "it is unknown whether these findings will result in a substantial modification of birth rate in the near future".

Results from 29 Italian patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation indicate that high-dose intravenous anakinra may show promise

Results are from an observational study, so randomised controlled trials are needed to fully understand the drug's effectiveness

The first study to report use of the rheumatoid arthritis drug anakinra to treat COVID-19 patients found that high-dose anakinra was safe and was associated with respiratory improvements and reduced signs of cytokine storm [1] in 72% (21/29) of patients, according to results from patients studied for 21 days (enrolled from 17 to 27 March 2020) in a Milan hospital, published in The Lancet Rheumatology journal.

All 29 patients received standard care (of non-invasive ventilation (CPAP), hydroxychloroquine, and lopinavir/ritonavir) as well as the drug treatment (daily high-dose intravenous infusions of anakinra at 10 mg/kg bodyweight). They were compared to 16 patients who received standard care only. However, the study was not a randomised controlled trial, which is the gold standard for establishing the effectiveness of a treatment.

Prof Lorenzo Dagna, head of the Unit of Immunology, Rheumatology, Allergy and Rare Diseases at San Raffaele Hospital and Vita-Salute San Raffaele University, Italy, says: "Until a vaccine is available, we urgently need to find a way to help people survive the most severe symptoms of COVID-19, and to do that without overwhelming the intensive care capacity of hospitals. A treatment that has already met strict safety tests and that is available in sufficient quantities to meet the needs of the current pandemic is ideal." [2]

Dr Giulio Cavalli, from the Unit of Immunology, Rheumatology, Allergy and Rare Diseases at San Raffaele Hospital and Vita-Salute San Raffaele University, Italy, says: "Our study is the first to suggest that a high dose of the arthritis drug anakinra may be able to block the overreaction of the immune system caused by COVID-19. The results are interesting and the drug deserves controlled testing in large randomised trials." [2]

Most people with COVID-19 experience only mild symptoms, but in severely affected patients the immune system overreacts, triggering a storm of immune proteins called cytokines. The cytokines contribute to hyperinflammation, leading to acute respiratory distress syndrome (ARDS) and reducing oxygen levels in the blood. ARDS is the main cause of death from coronavirus disease. Of patients admitted to intensive care units with COVID-19 and ARDS, the estimated death rate ranges from 28% to 78% [3]. Patients' breathing is supported until inflammation recedes, but the number of patients needing ventilation can exceed the number intensive care units with mechanical ventilators. Treatments are urgently needed to improve the prognosis of critically ill patients treated outside of ICUs.

The drug anakinra is already approved by the US Food and Drug Administration and the European Medicines Agency to treat rheumatoid arthritis, Still's disease, and recurrent fever. It works by blocking the proinflammatory cytokine IL-1. A Viewpoint piece, also published in The Lancet Rheumatology earlier this week, explains why intravenous anakinra might be effective and safe in treating cytokine storm syndromes generally [4]. The authors of the current study note that compared with other cytokine-blocking agents, anakinra has a strong safety record and a short half-life, making it suitable for critically ill patients.

In the study, at 21 days, treatment with high-dose anakinra was associated with reductions in serum C-reactive protein [1] and with progressive improvements in respiratory function in 21 (72%) of 29 patients. Survival was 90% (26 out of 29). Five of 29 patients (17%) needed mechanical ventilation.

The authors compare these observations with what they saw in a group of 16 patients who received standard treatment before the start of the current study (between 10 and 17 March). Most of the 16 patients experienced persistent or recurrent increases in C-reactive protein. Respiratory function improved for half of the patients (8 patients, 50%), and 56% (nine of 16) survived. One patient received mechanical ventilation (6%).

The authors report that high-dose anakinra was generally safe. Among adverse effects, four patients (14%) in the high-dose anakinra group had bacteraemia (bacteria in the blood), compared to two patients (13%) in the standard treatment group. Discontinuation of anakinra was not followed by inflammatory relapses. Causes of death in patients receiving high-dose intravenous anakinra were pulmonary thromboembolism, respiratory insufficiency, and multiorgan failure (1 patient per cause of death). Causes of death in the comparison group were respiratory insufficiency (3 patients), multiorgan failure (3 patients), and pulmonary thromboembolism (1 patient).

The authors caution that the retrospective nature of the study and the small number of patients in group make it impossible to draw definitive conclusions. The findings need to be validated with a controlled trial, conducted over a longer period to check for long-term outcomes. A randomised controlled trial of intravenous anakinra to treat COVID-19 is underway, but is assessing lower doses and does not include patients with ARDS.

"The patients in our study were severely ill, had an average age of 62, and underlying health conditions, giving them a high risk of dying from COVID-19. Administration of high-dose intravenous anakinra in these patients, who were managed outside of the ICU in a setting overwhelmed by the COVID-19 pandemic and with a shortage of ICU resources, appeared to dampen systemic inflammation and was associated with progressive improvement in respiratory function. While great attention has been focused so far on viral control, inflammation control might also be as crucial for the treatment of COVID-19. This seems to have allowed us to postpone or avoid intubation in most patients. Based on our promising results, this approach may be considered irrespective of resource availability. Again, results will need to be confirmed in controlled trials." says Chiara Tassan Din, co-author of this study from the Department of Infectious Diseases at San Raffaele Hospital, Italy. [2]

Writing in a linked Comment, lead author Dr Scott Canna (who was not involved in the study) from the University of Pittsburgh Medical Center, USA, says: "In view of the biological plausibility of anakinra, the pharmacokinetic and safety profile of the drug, and a growing body of positive experience in autoinflammation and cytokine storm, these data are promising and support prioritising this approach in the planning and enrolment of randomised controlled trials."

According to a new Position Paper published in the American Journal of Infection Control (AJIC) online, improved everyday hygiene practices, such as hand-washing, reduces the risk of common infections by up to 50%, reducing the need for antibiotics, by up to 30%. Global public health experts responsible for the Position Paper, are now calling for home and community hygiene to become part of strategic plans to reduce hundreds of thousands of deaths from AMR globally each year.

As witnessed during the recent global efforts to delay the spread of COVID-19, hygiene practices, including hand-washing, have become an essential part of everyone's daily routine and are considered to be the first line of defence in reducing the spread of common infections. However, national and international AMR strategies, while focussing on the important role of hygiene in the healthcare setting, fail to recognise the key role that home and community hygiene plays.

This Position Paper, developed on behalf of the Global Hygiene Council (GHC), and published online in AJIC, explores the role of targeted hygiene in the home and everyday life settings to reduce antibiotic prescribing and its likely impact on antibiotic resistance. It provides evidence that practising hand hygiene in homes and community settings can prevent infections and therefore reduce the need for antibiotics. One intervention study demonstrated a 30% reduction of antibiotic prescriptions for common respiratory infections in a group who used hand sanitisers compared with a control group.

The Position Paper, also demonstrates the increasing prevalence of multidrug-resistant bacteria in the home and community. It is considered that 35% of common infections occurring in healthcare and the community are already resistant to antibiotics, and that in some low-and middle-income countries, resistance to antibiotics is as high as 90%,4 causing 2,000 people to die every day globally.

According to the lead author, Jean-Yves Maillard, Professor of Pharmaceutical Microbiology at the School of Pharmacy and Pharmaceutical Sciences, at Cardiff University; "In light of the current COVID-19 pandemic and evidence presented in this Paper, it is more urgent than ever for policy makers to recognise the role of community hygiene to minimise the spread of infections, which in turn will help in reducing the consumption of antibiotics and help the fight against AMR.

To coincide with the publication of the Paper, the GHC has launched a Manifesto calling upon national and international policy makers, health agencies and healthcare professionals to further recognise the importance of hygiene in the home and everyday life settings and acknowledge the following:

1/ IPC committees, responsible for implementing national AMR plans, should recognise that improved hand and surface hygiene in the home and community are key to minimise the spread of infections and as a consequence the consumption of antibiotics, which will then help in the fight against AMR. To achieve this, recommendations for improved hygiene in the wider community should be included in global AMR action plans by 2022 and in all national plans by 2025.

2/ IPC advice, guidance and education for HCPs on hand and surface hygiene and its relation to AMR should not be limited to healthcare settings, but also include recommendations to influence the wider community with immediate effect.

3/ Relevant medical associations should ensure messaging around home and community hygiene is cascaded to members through amending on-going and existing AMR training and education.

With evidence to show that home and community hygiene urgently needs to be taken more seriously, it is time for the global community to collaborate and recognise that reducing the need for antibiotic prescribing and the circulation of AMR strains in healthcare settings cannot be achieved without also reducing the circulation of infections and AMR strains in the community.

People with the mental health condition known as body integrity dysphoria (BID) often feel as though one of their healthy limbs isn't meant to be a part of their bodies. They may act as though the limb is missing or even seek its amputation "to feel complete." Now, researchers reporting in the journal Current Biology on May 7 have found that these feelings that a limb doesn't belong are mirrored in the brains of people with this condition.

"The feeling that a limb belongs to us relies on the extent to which the sensorimotor limb area is functionally connected to all the other brain regions," says first author Gianluca Saetta, a doctoral student at the University of Zurich. "Crucially involved in this feeling are also the functional connectivity and the density of gray matter in the most crucial area for the representation of how our bodies should look--the right parietal region of the brain."

"Interestingly, we found that the less gray matter in the right parietal region of the brain, the stronger the desire for amputation, and the more BID individuals acted as if they were amputees," Saetta adds. "This simulation behavior helps them to cope with the distressing mismatch between how they want their body to look and how they see it."

To explore the brain mechanisms associated with BID in the new study, Saetta and senior author Peter Brugger of the Psychiatric University Clinic (PUK), Zurich, enrolled 16 men who wanted to remove their healthy left legs and sixteen healthy controls. The question was whether the men with BID would show changes in the brain's functional connectivity or structure--and the researchers found that they did.

Their studies revealed alterations in two key regions associated with BID. The right paracentral lobule (rPCL), which houses the primary somatosensory representation of the affected left leg, showed reduced intrinsic functional connectivity to other parts of the brain, they report. The right superior parietal (rSPL) also showed reduced intrinsic functional connectivity and a reduced concentration of gray matter. That's especially notable because this brain region has been previously identified as a critical hub for body image.

Interestingly, the researchers report, there were no structural alterations evident in the rPCL. In other words, there was no evidence that the men lack the ability to feel or move their left legs.

"We show clear associations between a mental state and changes in brain structure and functionality," Brugger said. "Whether the neural signature of BID comes first and hampers the development of normal limb ownership or whether decades of concern about the lack of such ownership modulate cerebral circuits mediating bodily awareness cannot be answered."

In other words, it's hard to say whether BID leads to a lack of functional connectivity in the brain or vice versa. Nevertheless, the new findings suggest that the desire for amputation in BID individuals may be related to specific anomalies in brain architecture.

The findings show that there's more to BID than has sometimes been suggested. The researchers note that BID is expected to be included in the forthcoming 11th revision of the International Classification of Diseases (ICD-11) as a "disorder of bodily distress or bodily experience." While the condition is considered rare, it's unclear how many people may be affected. After all, Brugger says, it's likely many people with BID don't share this with anyone.

Based on the new findings, the researchers suggest that brain stimulation techniques might hold promise in helping people with BID, a possibility that now warrants further study. Brugger also notes that there are many other variants of BID still to explore and understand better, including people who feel they should be paraplegic or blind.

At a glance:

Analysis yields first comprehensive genomic profile of ancient populations in central Andes

Findings emerge from DNA of 89 individuals who lived as long as 9,000 years ago, including some of the legendary ancient civilizations such as Inca and Nasca

Study reveals surprising genetic structure, mixing and continuity despite cultural upheaval

An international research team has conducted the first in-depth, wide-scale study of the genomic history of ancient civilizations in the central Andes mountains and coast before European contact.

The findings, published online May 7 in Cell, reveal early genetic distinctions between groups in nearby regions, population mixing within and beyond the Andes, surprising genetic continuity amid cultural upheaval, and ancestral cosmopolitanism among some of the region's most well-known ancient civilizations.

Led by researchers at Harvard Medical School and the University of California, Santa Cruz, the team analyzed genome-wide data from 89 individuals who lived between 500 and 9,000 years ago. Of these, 64 genomes, ranging from 500 to 4,500 years old, were newly sequenced--more than doubling the number of ancient individuals with genome-wide data from South America.

The analysis included representatives of iconic civilizations in the Andes from whom no genome-wide data had been reported before, including the Moche, Nasca, Wari, Tiwanaku and Inca.

"This was a fascinating and unique project," said Nathan Nakatsuka, first author of the paper and an MD/PhD student in the lab of David Reich in the Blavatnik Institute at HMS.

"It represents the first detailed study of Andean population history informed by pre-Colonial genomes with wide-ranging temporal and geographic coverage," said Lars Fehren-Schmitz, associate professor at UC Santa Cruz and co-senior author of the paper with Reich.

"This study also takes a major step toward redressing the global imbalance in ancient DNA data," said Reich, professor of genetics at HMS and associate member of the Broad Institute of MIT and Harvard.

"The great majority of published ancient DNA studies to date have focused on western Eurasia," he said. "This study in South America allows us to begin to discern at high resolution the detailed history of human movements in this extraordinarily important part of the world."

Attention on the Andes

The central Andes, surrounding present-day Peru, is one of the few places in the world where farming was invented rather than being adopted from elsewhere and where the earliest presence of complex civilizations in South America has been documented so far. While the region has been a major focus of archaeological research, there had been no systematic characterization with genome-wide ancient DNA until now, the authors said.

Geneticists, including several of the current team members, previously studied the deep genetic history of South America as a whole, including analysis of several individuals from the Andean highlands from many thousands of years ago. There have also been analyses of present-day residents of the Andes and a limited number of mitochondrial or Y-chromosome DNA analyses from individual ancient Andean sites.

The new study, however, expands on these findings to provide a far more comprehensive portrait. Now, Nakatsuka said, researchers are "finally able to see how the genetic structure of the Andes evolved over time."

By focusing on what is often called pre-Columbian history, the study demonstrates how large ancient DNA studies can reveal more about ancient cultures than studying present-day groups alone, said Reich.

"In the Andes, reconstruction of population history based on DNA analysis of present-day people has been challenging because there has so been much demographic change since contact with Europeans," Reich explained. "With ancient DNA data, we can carry out a detailed reconstruction of movements of people and how those relate to changes known from the archaeological record."

'Extraordinary' ancient population structure

The analyses revealed that by 9,000 years ago, groups living in the Andean highlands became genetically distinct from those that eventually came to live along the Pacific coast. The effects of this early differentiation are still seen today.

The genetic fingerprints distinguishing people living in the highlands from those in nearby regions are "remarkably ancient," said Nakatsuka, who will receive his PhD in systems, synthetic and quantitative biology in May.

"It is extraordinary, given the small geographic distance," added Reich.

By 5,800 years ago, the population of the north also developed distinct genetic signatures from populations that became prevalent in the south, the team found. Again, these differences can be observed today.

After that time, gene flow occurred among all regions in the Andes, although it dramatically slowed after 2,000 years ago, the team found.

"It is exciting that we were actually able to determine relatively fine-grained population structure in the Andes, allowing us to differentiate between coastal, northern, southern and highland groups as well as individuals living in the Titicaca Basin," said Fehren-Schmitz.

"This is significant for the archaeology of the Andes and will now allow us to ask more specific questions with regards to local demographies and cultural networks," said study co-author Jose Capriles of Pennsylvania State University.

Genetic intermingling

The team discovered genetic exchanges both within the Andes and between Andean and non-Andean populations.

Ancient people moved between south Peru and the Argentine plains and between the north Peru coast and the Amazon, largely bypassing the highlands, the researchers found.

Fehren-Schmitz was especially interested to uncover signs of long-range mobility in the Inca period. Specifically, he was surprised to detect ancient North Coast ancestry not only around Cusco, Peru, but also in a child sacrifice from the Argentinian southern Andes.

"This could be seen as genetic evidence for relocations of individuals under Inca rule, a practice we know of from ethnohistorical, historical and archaeological sources," he said.

Although the findings of genetic intermingling throughout the Andes correlate with known archaeological connections, they will likely prompt additional archaeological research to understand the cultural contexts underlying the migrations, said Nakatsuka.

"Now we have more evidence demonstrating important migrations and some constraints on when they happened, but further work needs to be done to know why exactly these migrations occurred," he said.

Long-term continuity

The analyses revealed that multiple regions maintained genetic continuity over the past 2,000 years despite clear cultural transformations.

The finding contrasts with many other world regions, where ancient DNA studies often document substantial genetic turnover during this period, said Reich.

The population structures that arose early on persisted through major social changes and on into modern societies, the authors said. The discoveries offer new evidence that can be incorporated alongside archaeological and other records to inform theories on the ancient history of different groups in the region.

"To our surprise, we observed strong genetic continuity during the rise and fall of many of the large-scale Andean cultures, such as the Moche, Wari and Nasca," said Nakatsuka. "Our results suggest that the fall of these cultures was not due to massive migration into the region, e.g., from an invading military force, a scenario which had been documented in some other regions of the world."

Two exceptions to the continuity trend were the vast urban centers that the Tiwanaku and Inca cultures called home. Rather than being fairly genetically homogeneous, the capital regions of these civilizations were cosmopolitan, hosting people from many genetic backgrounds, the team found.

"It was interesting to start to see these glimpses of ancestral heterogeneity," said Nakatsuka. "These regions have some similarity to what we see now in places like New York City and other major cities where people of very different ancestries are living side by side."

Cooperative authorship

The study included authors from many disciplines and many countries, including Argentina, Australia, Bolivia, Chile, Germany, Peru, the United Kingdom and the United States.

"This is an impressive interdisciplinary but, just as importantly, international collaboration," said study co-author Bastien Llamas of the University of Adelaide. "All worked very closely to draft this manuscript under the leadership of Fehren-Schmitz and Reich."

It was important to team up with local scientists who belong to communities that descend from the individuals analyzed in the study, Fehren-Schmitz said, and to obtain permission from and continually engage with indigenous and other local groups as well as local governments.

The analysis of DNA from ancient individuals can have significant implications for present-day communities. One concerns the physical handling of the skeletal materials, which might be sensitive to the groups involved.

The work provided opportunities to heal past wounds. In one case, a sample from Cusco, previously housed in the U.S., was repatriated to Peru. Other remains that had long ago been taken improperly from burial sites were able to be carbon-dated and reburied.

In the absence of pre-Columbian written histories, archaeology has been the main source of information available to reconstruct the complex history of the continent, said study co-author Chiara Barbieri of the University of Zurich.

"With the study of ancient DNA, we can read the demographic history of ancient groups and understand how ancient and present-day groups are related," she said. "The link with the genetic study of living populations opens a direct dialogue with the past and an occasion to involve local communities."

The researchers sought to deeply involve communities with the help of archaeologists from each area, said Nakatsuka. Their efforts included giving public talks about the study and translating materials into Spanish.

"We were really happy to have the summary and key findings of our paper translated and included as part of the Cell paper itself, to increase accessibility of our work," said Nakatsuka. "We hope future studies will do similar translations, including versions suitable for lay audiences for schools, museum exhibits and cultural organizations, which we are in the process of doing as well."

Highlights

Among adults with kidney failure who were referred for transplantation, 60% of black and 66% of white patients were waitlisted within the first year. Differences in socioeconomic status and comorbidities between black and white patients could explain up to 58% of the disparity in listing.

Fewer black patients on transplant wait lists received transplants compared with white patients, but differences in socioeconomic status and comorbidities did not explain this disparity.

Washington, DC (May 7, 2020) -- Among adults with kidney failure in need of a transplant, socioeconomic status and medical illnesses likely contribute to racial disparities in being put on transplant wait lists. The findings come from a study that will appear in an upcoming issue of CJASN.

Black adults are more likely than white adults to develop kidney failure, and yet their odds of being listed for and receiving a kidney transplant are lower. To assess whether socioeconomic status and illnesses besides kidney disease (comorbidities) affect these disparities, Mara McAdams-DeMarco, PhD, Karly Murphy, MD, MHS (Johns Hopkins Medical Institutions), and their colleagues examined information on 3,013 patients with kidney failure who were referred for and who started the transplant process between 2009 and 2018.

"We examined socioeconomic status--using income, education level, and employment status--and 17 medical comorbidities as potential mediators, both individually and combined, to explain racial disparities in listing for kidney transplant or for receiving a kidney transplant," said Dr. McAdams-DeMarco.

The team found that within the first year, 60% of black and 66% of white patients were waitlisted. Differences in socioeconomic status explained 36% of the disparity in listing, while differences in comorbidities explained 44% of the disparity in listing. Together, differences in socioeconomic status and comorbidities between black and white patients could explain up to 58% of the disparity in listing.

Among 2,109 listed candidates, transplants occurred at rates of 19 and 24 per 100 persons per year for black and white candidates, respectively. Differences in socioeconomic status and comorbidities did not explain the disparities in receipt of transplants between black and white transplant candidates.

"We found that socioeconomic status and medical history most likely influence the likelihood that a person would be listed for transplant but did not change the likelihood of receiving a kidney transplant," said Dr. McAdams-DeMarco.

With so many COVID-19 models being developed, how do policymakers know which ones to use? A new process to harness multiple disease models for outbreak management has been developed by an international team of researchers. The team describes the process in a paper appearing May 8 in the journal Science and was awarded a Grant for Rapid Response Research (RAPID) from the National Science Foundation to immediately implement the process to help inform policy decisions for the COVID-19 outbreak.

During a disease outbreak, many research groups independently generate models, for example projecting how the disease will spread, which groups will be impacted most severely, or how implementing a particular management action might affect these dynamics. These models help inform public health policy for managing the outbreak.

"While most models have strong scientific underpinnings, they often differ greatly in their projections and policy recommendation," said Katriona Shea, professor of biology and Alumni Professor in the Biological Sciences, Penn State. "This means that policymakers are forced to rely on consensus when it appears, or on a single trusted source of advice, without confidence that their decisions will be the best possible."

At the onset of an outbreak, particularly for a new disease, a large amount of information is often unavailable or unknown, and researchers must make decisions about how to incorporate this uncertainty into their models, leading to differing projections. For the COVID-19 outbreak, for example, uncertainty is present in a wide range of areas, from infection rate to details of transmission to the capacity of health care systems. The designers of each model bring their own perspective and approach to address these uncertainties.

"In order to improve modeling and analysis of epidemic disease, it is essential to develop protocols that deliberately generate and evaluate valuable individual ideas from across the modeling community," said Michael Runge, a research ecologist at the U.S. Geological Survey's Patuxent Wildlife Research Center who specializes in decision analysis for wildlife management. "We have identified best practices that allow the synthesis and evaluation of input from multiple modeling groups in an efficient and timely manner."

In the three-part process, multiple research groups first create models for specified management scenarios, for example, addressing how caseload would be affected if social isolation measures were lifted this summer, or how the duration of the outbreak would change if students return to school in the fall. The research groups work independently during this step to encourage a wide range of ideas without prematurely conforming to a certain way of thinking. Then, the modeling groups formally discuss their models with each other--an important addition to previous multiple model methods--which allows them to examine why their models might disagree. Finally, the groups work independently again to refine their models, based on the insights from the discussion and comparison stage.

After group discussion and individual model refinement, the models are combined into an overall projection for each management strategy, which can be used to help guide risk analysis and policy deliberation. At this stage, methods from the field of decision analysis can allow the decision maker, for example a public health agency, to understand the merits of different management options in the face of the existing uncertainty.

Additionally, the combined results can help identify which uncertainty--what pieces of missing information--are most critical to learn about in order to improve models and thus improve decision making, providing a way to prioritize research directions.

"This process allows us to embrace uncertainty, rather than hastening to a premature consensus that could derail or deflect management efforts," said Shea. "The process encourages a healthy conversation between scientists and decision makers, enabling policy agencies to more effectively achieve their management goals."

Even after initial decisions are made, the process can continue as new information about the outbreak and management becomes available. This "adaptive management" strategy can allow researchers to refine their models and make new predictions as the outbreak progresses. For COVID-19, this process might inform how and when isolation and travel bans are lifted, and if these or other measures might be necessary again in the future.

The research team plans to implement this process immediately for COVID-19. By taking advantage of the many research groups already producing models for the current outbreak, the strategy should be easy to implement while producing more robust results from the existing process. The team will share results with the U.S. Centers for Disease Control and Prevention as they are generated.

"We hope this process actively feeds into policy for the COVID-19 response in the United States," said Shea. "It also provides a framework for future outbreak settings, including emerging diseases and agricultural pest species, and management of endemic infectious diseases, including vaccination strategies and disease surveillance."