Culture

Drug linked to 45% lower risk of dying among COVID-19 patients on ventilators

image: This graph shows the outcomes over time for the COVID-19 patients on ventilators treated with and without tocilizumab at Michigan Medicine, the University of Michigan's academic medical center. The data are from an observational study that looked back at patient data from March and April, after the hospital's pharmacy guidelines early in the pandemic gave physicians information about the potential benefits and risks of prescribing the drug.

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University of Michigan/Clinical Infectious Diseases

Critically ill COVID-19 patients who received a single dose of a drug that calms an overreacting immune system were 45% less likely to die overall, and more likely to be out of the hospital or off a ventilator one month after treatment, compared with those who didn't receive the drug, according to a new study by a team from the University of Michigan.

The lower risk of death in patients who received intravenous tocilizumab happened despite the fact that they were also twice as likely to develop an additional infection, on top of the novel coronavirus.

The study is published in the peer-reviewed journal Clinical Infectious Diseases after being available as a preprint last month.

It suggests a benefit from timely and targeted efforts to calm the "cytokine storm" caused by the immune system's overreaction to the coronavirus. Tocilizumab, originally designed for rheumatoid arthritis, has already been used to calm such storms in patients receiving advanced immunotherapy treatment for cancer.

The researchers base their conclusions on a thorough look back at data from 154 critically ill patients treated at Michigan Medicine, U-M's academic medical center, during the first six weeks of the pandemic's arrival in Michigan from early March to late April. The analysis looked at patients' records through late May.

During that time, when little was known about what would help COVID-19 patients on ventilators, about half of the studied patients received tocilizumab and half did not. Most received it within the 24-hour period surrounding their intubation.

This created a natural opportunity for comparing the two groups' outcomes in an observational study, though clinical trials are still needed to truly see if the drug provides a benefit, the authors say.

Promising result

Lead author Emily Somers, Ph.D., Sc.M., an epidemiologist who has studied both rheumatologic and immunologic diseases, says the research team went into their analysis uncertain whether they would find a benefit, a risk, or no clear effect associated with tocilizumab in the patients with life-threatening COVID-19. But they knew it was a critically important question that they were uniquely positioned to answer at that point in the pandemic.

"One role of epidemiology is to rigorously evaluate real-world data on treatment effects, especially when evidence from clinical trials is not available. We kept trying to prove ourselves wrong as signals of benefit emerged in the data, both because of the immediate implications of these data, and in part because of concern about the supply of the medication for other patients," she says. "But the difference in mortality despite the increase in secondary infection is quite pronounced, even after accounting for many other factors."

Somers is an associate professor in the U-M Medical School's Department of Internal Medicine and member of the U-M Institute for Healthcare Policy and Innovation. She co-leads the COVID-19 Rapid Response Registry, which is supported by the Michigan Institute for Clinical and Health Research.

The paper's co-first author is Gregory Eschenauer, Pharm.D., a clinical pharmacist at Michigan Medicine and clinical associate professor at the U-M College of Pharmacy. He and senior author Jason Pogue, Pharm.D., are members of the Michigan Medicine Antimicrobial Stewardship Program.

The ASP group developed treatment guidelines provided to Michigan Medicine physicians in mid-March that identified tocilizumab as a potentially beneficial therapy for the most severely ill COVID-19 patients. Those guidelines also pointed out its risks and the lack of evidence for its use in COVID-19, and recommended a dose of 8 milligrams per kilogram.

This led some physicians to choose to use it, while others did not - setting the stage inadvertently for a natural comparison.

More research needed

Pogue, clinical professor at the U-M College of Pharmacy and an infectious disease pharmacist at Michigan Medicine, notes that more robust data released in June from a large randomized controlled trial in the United Kingdom has led him to recommend the steroid dexamethasone as the first choice to treat critically ill COVID-19 patients.

"For a retrospective, single-center study, our data are robust. But at this time, due to the lack of randomized controlled trial data and the much higher cost, we recommend reserving tocilizumab for the treatment of select patients who decompensate while on or after receiving dexamethasone or in patients where the risks of adverse events from steroid therapy outweigh the potential benefits" says Pogue.

"Further studies of tocilizumab, which is more targeted than dexamethasone in addressing the hyperinflammatory process, could include combining these agents or comparing them head-to-head," he adds.

Pogue notes that a single dose of tocilizumab is roughly 100 times more expensive than a course of dexamethasone. He also notes that another drug that aims to treat cytokine storm by targeting the interleukin-6 (IL-6) receptor - one called sarilumab - appears to have failed to improve outcomes in a clinical trial in COVID-19 patients including those on ventilators.

Michigan Medicine had been participating in the sarilumab study at the time the patients in the current study were treated, but not all patients qualified because of the timing of their admission or issues around testing for COVID-19. The current study does not include any patients who received sarilumab.

If the evidence around IL-6 targeting bears out in further studies, the authors note that it will be important to select the dose and timing carefully, to address the cytokine storm without interfering with IL-6's other roles in activating the body's response to infections and its processes for repairing tissue.

More about the study

The majority of the patients were transferred to U-M from Detroit-area hospitals after diagnosis with COVID-19, and those who received tocilizumab were less likely overall to have been transferred while already on a ventilator.

By the end of the 28-day period after patients went on a ventilator, 18% of those who received tocilizumab had died, compared with 36% of those who had not. When adjusted for health characteristics, this represents a 45% reduction in mortality. Of those still in the hospital at the end of the study period, 82% of the tocilizumab patients had come off the ventilator, compared with 53% of those who didn't receive the drug.

In all, 54% of the tocilizumab patients developed a secondary infection, mostly ventilator associated pneumonia; 26% of those who didn't receive tocilizumab developed such infections. Such "superinfections" usually reduce the chance of survival for COVID-19 patients.

Hydroxychloroquine was included in the treatment guidelines for COVID-19 inpatients at Michigan Medicine for the first two and a half weeks of the study period, before being removed as evidence of its lack of benefit and risks emerged. In all, it was used in one-quarter of the patients who received tocilizumab and one-fifth of those who didn't. Similar percentages of the two patient groups received steroids, though none received dexamethasone.

The patients in the two groups were similar in most ways except for a slightly higher average age in the non-tocilizumab group, and lower rates of chronic obstructive pulmonary disease and chronic kidney disease among the tocilizumab patients.

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Michigan Medicine - University of Michigan

COVID-19 and Brexit can help with the recovery of UK fish stocks

The United Kingdom has a unique opportunity to start rebuilding its fish stocks by taking advantage of the slowdown in commercial fishing caused by the COVID-19 pandemic and ongoing Brexit negotiations, new research has shown.

A study by the University of Southampton, the GEOMAR Helmholtz Centre for Ocean Research and the Sea Around Us initiative at the University of British Columbia sets out how the UK Government can take a new approach to managing its fishing waters.

After Brexit the UK will no longer be bound by the Common Fisheries Policy and therefore has the chance to develop a new policy focused on sustainability and preserving the livelihoods of fishing communities. Furthermore, the reduction in fishing activity caused by the COVID-19 pandemic has seen pressure on some threatened species fall to levels not seen since World War II, giving opportunities to help fish populations recover and increase the potential economic returns for fishers.

"Several stocks targeted by UK fishers are in a degraded and precarious state, with around 40 per cent that will continue to be overfished when normal activity resumes," said Professor Paul Kemp, lead author of the study and a researcher at the University of Southampton. "One of the reasons for this is that fishing quotas - or how much of each species can be caught in a certain area by each country - are set by the EU at levels higher than those that would enable the recovery of the populations."

To regulate the ongoing harvest beyond sustainable limits, the researchers propose fishing targets be set to levels in which fishers leave more fish in the water than the minimum required to generate maximum sustainable yields.

"Maximum Sustainable Yield or MSY is defined as the highest catch that can be continuously taken from a stock under existing environmental conditions," said Rainer Froese, co-author of the study and senior scientist at GEOMAR. "Smart fisheries management, such as applied in Australia, aims for a little less than MSY. That reduces the risk of unintentional overfishing and ensures close to maximum catches, year after year."

"This will allow fish populations to recover to levels that are higher than those that can produce MSY to ensure large and diverse populations that will be better prepared for climate change, stabilize ecosystems, and at the same time maximize fishers' profits," said Daniel Pauly, co-author of the study and principal investigator of the Sea Around Us initiative at the University of British Columbia. "The opportunity to do this is now because of the slowdown caused by COVID-19 and because after Brexit, the UK will be in a position to insist in its negotiations with the EU that fishing quotas advised by scientists not be exceeded."

As an additional safeguard for sustainable and highly profitable fishing in the post-Brexit and post-COVID-19 world, the researchers propose further creation of a "blue belt" of Marine Protected Areas around the UK coast, and enforcement of their protected status, something that up until now has been seriously lacking.

"The establishment of MPAs is one of the most cost-effective ways to restore overexploited stocks and habitats on which fish depend, to the mutual benefit of the fishing industry who experience increased catches in grounds immediately outside of MPAs," Pauly said.

The researchers warn that strong conviction will be required to ensure these areas are suitably protected as there are likely to be disputes with EU members who may regard this as a challenge to their perceived historic fishing rights.

"Brexit divided the UK and the whole world has been challenged by the global health pandemic" added Professor Kemp. "However, regardless of how people voted, UK politicians have the chance to bring people together over a common goal that supports fishing communities, wider society and environmental sustainability. The opportunity is there but it will require political vision; with the necessary strength of character the negotiators can deliver a positive outcome from the combined systemic shocks of Brexit and COVID19."

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University of Southampton

Simultaneous, reinforcing policy failures led to Flint water crisis, providing lessons during pandemic

Concurrent failures of federal drinking water standards and Michigan's emergency manager law reinforced and magnified each other, leading to the Flint water crisis, according to a University of Michigan environmental policy expert.

Flint's experience offers lessons during the COVID-19 pandemic, which has exacerbated local financial challenges while highlighting the importance of access to clean, safe drinking water, said U-M's Sara Hughes, an assistant professor at the School for Environment and Sustainability.

"As we wrestle to combat the coronavirus, we should keep in mind that building healthy communities starts with a renewed commitment to investing in 21st-century drinking water systems and supporting cities as they navigate systemic financial challenges," Hughes said. "Learning from the Flint water crisis requires counteracting and confronting the marginalizing effects of infrastructure underinvestment and urban austerity measures."

The Flint water crisis resulted from simultaneous failures of the federal Safe Drinking Water Act and Michigan's Local Financial Stability and Choice Act, Hughes writes in an article published July 13 in the journal Perspectives on Politics. Also known as Public Act 436, the Michigan law places cities deemed by the state to be experiencing fiscal distress under the control of a state-appointed emergency manager.

Both policies rationalize complex problems--safe drinking water and municipal financial distress--by providing purely technical solutions, and the weaknesses of each reinforced and magnified the harmful consequences of the other for the residents of Flint, according to Hughes.

For nearly 18 months, from April 2014 to October 2015, the city of Flint delivered inadequately treated Flint River water to residents, exposing thousands to elevated lead levels and other contaminants. Poor children and families were particularly affected.

At both the state and federal levels, the primary response to the Flint water crisis has been to strengthen drinking water safety standards and monitoring practices, Hughes said. But providing safe drinking water to city residents is only partly a technical problem.

Much less attention has been paid to funding and supporting local governments in ways that ensure their capacity to build and maintain infrastructure, provide reliable services, and sustain meaningful dialogue and engagement with their residents, according to Hughes.

Failure to address these longstanding problems will complicate efforts to recover from the coronavirus pandemic, especially in hard-hit places like Southeast Michigan, which has the state's highest concentration of COVID-19 cases.

"If addressed, these policy failures would mitigate against the disproportionate and unequal patterns emerging in the coronavirus outbreak," Hughes said. "But absent change, poor and minority cities remain vulnerable to the marginalizing effects of these multiple and reinforcing rationalized policy domains."

By a rationalized policy Hughes means one that is presented as purely technical in nature and politically neutral. Techno-rational approaches to policy hold out the promise of more effective, unbiased decision-making, but they often cloak decisions and priorities in the language of rationality and science while failing to consider the public's preferences, according to Hughes.

Rationalized policy approaches were at the heart of the Flint water crisis, involving both the federal drinking water act and the state emergency manager law.

Flint first came under emergency management in 2011 through the law that preceded Public Act 436, then in 2012 through the provisions of PA 436, which was developed and championed by former Michigan Gov. Rick Snyder. Flint's state-appointed emergency managers made or forced decisions about the city's water supplies and treatment protocols that were ostensibly made with the goal of cutting costs.

The second policy failure implicated in the Flint water crisis involves the federal Safe Drinking Water Act's Lead and Copper Rule. The LCR provides two important sets of criteria: water quality standards and treatment/testing protocols for lead and copper in drinking water systems.

The law requires that local water utilities monitor and test their water supplies and report their results to the state government, which in turn reports all data to the U.S. Environmental Protection Agency. The EPA is ultimately responsible for ensuring compliance.

When Flint switched its drinking water source to the Flint River in April 2014, the state environmental quality department failed to require the city to treat the water for corrosion, as would be necessary to meet federal Safe Drinking Water Act (SDWA) standards.

Federal standards for lead in drinking water are 15 parts per billion. Lead levels of up to 1,000 ppb were detected in Flint homes during the water crisis, yet enforcement actions were not triggered.

"The fact that such systemic and prolonged noncompliance, and clear evidence of a threat to public health, failed to trigger regulatory action by EPA calls into question the adequacy of public protections embedded in the SDWA and LCR," Hughes said.

In much the same way that Michigan's emergency manager law represents a rationalized approach to municipal financial distress, the federal Lead and Copper Rule is a rationalized approach to protecting human health, according to Hughes.

"The provisions and standards in the LCR create a policy environment that facilitates decision-making that is reactionary, prioritizes cost-effectiveness, excludes the public and tolerates risk," she said. The LCR has no enforceable health-based standard "and does not protect any individual or household from exposure to elevated lead levels."

In 2018, the state of Michigan passed its own set of stricter standards for lead, shifting to a lower 12 ppb standard and requiring that communities replace 5% of lead service lines annually. At the national level, the EPA has submitted proposed revisions to the LCR to the Office of Management and Budget, but they have yet to take effect.

Critically, the policy changes resulting from the Flint water crisis have not extended to a reevaluation of how municipal financial distress is addressed and prevented, according to Hughes. Michigan's emergency manager law remains unchanged. Poor, minority U.S. communities consistently receive lower-quality drinking water, and lead contamination cases fit a pattern of low-income, unequal and largely black cities, according to Hughes.

The study is based on interviews with local activists, decision-makers, scientists, journalists and scholars working in or with the city of Flint, as well as a review of reports, testimony, newspaper articles and secondary demographic and financial data.

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University of Michigan

Study calls for action to protect BAME and migrant groups from economic impact of COVID-19

The COVID-19 lockdown has had a disproportionate economic impact on Black, Asian and Minority Ethnic (BAME) migrants in the UK, new research, which also calls for racial justice, reveals today (13 July 2020).

BAME migrants are 3.1 times more likely than white British to lose their jobs during the pandemic, while BAME British are 40% less likely to benefit from employee protection such as furloughing.

As a result, white British in work before the pandemic were 5.7 times more likely to experience furlough than job loss (18.9% vs. 3.3%), the rate was as low as 1.4 times for BAME migrants (16.3% vs. 11.4%).

'Intersecting ethnic and native-migrant inequalities in the economic impact of the COVID-19 pandemic in the UK' by Dr Yang Hu, of Lancaster University, is published open access in 'Research on Social Stratification and Mobility' - an official journal of the International Sociological Association.

The report also highlights:

While BAME migrants are 35% less likely to reduce their work hours than white British, they are 1.3 times more likely to experience income loss due to COVID-19.

Compared with white British, BAME migrants are 2.2 times more likely to experience an increase in financial strain, such as keeping up to date with bills (e.g. utility, credit card, etc.), during the COVID-19 lockdown.

White British (28.8%) are 1.4 times more likely than BAME migrants (20.9%) to report leading a financially comfortable life during the pandemic. In contrast, BAME migrants (11.1%) are 1.5 times more likely than white British (7.2%) to report experiencing financial difficulty during the pandemic.

BAME migrants (26.6%) are 1.3 times more likely than white British (20.2%) to experience an increase in their perceived level of financial hardship during the lockdown.

Dr Hu, a Senior Lecturer in Sociology and Data Science, presents nationwide evidence based on the analysis of data from the Understanding Society COVID-19 survey--an initiative funded by the UK Research and Innovation.

The initiative collected data from a national sample of more than 10,000 people from both before the pandemic and in April, the 'prime time' of the COVID lockdown in the UK.

"As the information was collected from the same people, it provides a very clear and effective comparison of the impact of COVID-19," said Dr Hu, an expert in the study of how socio-economic, political and institutional developments and cultural changes impact on everyday family and intimate lives.

"The findings show that as the pandemic hits BAME migrants particularly hard, it widens entrenched racial disparities in people's labour market participation and economic well-being. They urge policy makers to place racial justice at the centre of the government's immediate and long-term response to the pandemic.

"As we enter the third decade of the 21st century, the COVID-19 pandemic and the global rise of racism and anti-racism movements are two of the most prominent developments to define people's lives in many countries."

As many countries start to ease and lift lockdown measures, Dr Hu said it would also be crucial to examine and tackle inequalities in people's long-term economic recovery from the pandemic.

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Lancaster University

About nine family members to suffer grief from every COVID-19 fatality

UNIVERSITY PARK, Pa. -- Deaths from COVID-19 will have a ripple effect causing impacts on the mental health and health of surviving family members. But the extent of that impact has been hard to assess until now. Every death from COVID-19 will impact approximately nine surviving family members, according to a study.

In a study of kinship networks in the United States, the researchers said that approximately nine surviving close family members will be affected by each death from the virus in the country. For example, if the virus kills 190,000 people, 1.7 million will experience the loss of a close relative, said Ashton Verdery, associate professor of sociology, demography and social data analytics, and an affiliate of the Population Research Institute and Institute for Computational and Data Sciences, Penn State.

A kinship network includes grandparents, parents, siblings, spouses and children.

According to Verdery, the multiplier could serve as an indicator to help raise awareness about the scale of the disease and the ripple effects that the disease may have on a community, as well as prepare officials and business leaders to manage those effects.

"It's very helpful to have a sense of the potential impacts that the pandemic could have," said Verdery. "And, for employers, it calls attention to policies around family leave and paid leave. At the federal level, it might inform officials about possible extensions for FMLA (Family and Medical Leave Act). There could also be some implications for caretaking. For example, a lot of children grow up in grandparent-led houses and they would be impacted."

The researchers, who released their findings in the current issue of the Proceedings of the National Academy of Sciences, said some slight differences in the bereavement multiplier exist between white and black Americans. For white Americans, the median multiplier is estimated at 8.86, while it is 9.18 for black Americans, said Verdery.

The researchers also suggest that people may be facing the loss of a close loved one at a younger age because of the virus, according to Verdery, who worked with Emily Smith-Greenaway, associate professor of sociology, USC; Rachel Margolis, associate professor of sociology, the University of Western Ontario and Jonathan K. Daw, associate professor of sociology and demography, Penn State.

"There are a substantial number of people who may be losing parents that we would consider younger adults and a substantial number of people may be losing spouses who are in their 50s or 60s," he said.

While there are some limitations, the indicator could help local officials understand the waves of grief that may affect specific areas and regions of the country.

"Our statistics are based on national averages, so it might not translate perfectly, but you could imagine that this could serve as a baseline level to go forward to understand the differences between areas where the outbreaks are severe and places where the outbreaks may not be so severe," said Verdery. "There are regional differences in some of these kinship statistics that would make it less than perfect, but it would be a reasonable first approximation."

For this study, the team built on previous investigations that happened soon after the virus began to spread worldwide.

"The big challenge with the former work was that we used a certain percentage of infections and a certain percentage of deaths," said Verdery. "In that model, there is an inherent prediction that if so many people are infected, there would be a certain number of people who would die and, then, the model estimated how many people will be affected by those deaths. But, thinking through this, we wanted to create a statistic that is easy to understand and one that doesn't rely on specific predictions about death counts."

The researchers undertook a computational analysis of COVID-19 mortality in kinship networks of white and black Americans. The demographic data was drawn from the historical record or recent Census Bureau national projections to create a complete kinship network, from which the researchers analyzed grandparents, parents, siblings, spouses and children.

In the future, the researchers plan to investigate how the bereavement factor during other mortality spikes, such as the opioid epidemic, changes over time and how to better understand when that factor becomes broadly felt across the community.

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Penn State

The colorful history of plastids

image: Members of the Archaeplastida have primary plastids stemming directly from cyanobacteria. The primary plastids of red and green algae have spread from the Archaeplastida to other branches of the tree, including Rhizaria, Discoba, and Stramenopila. The colored taxon names in these lineages reflect the green or red algal secondary or tertiary endosymbiotic origin of their plastids. Taxon names highlighted in gray indicate the presence of one or more secondarily non-photosynthetic members.

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S Sibbald and J Archibald

A billion years ago, a single-celled eukaryote engulfed a cyanobacterium--an organism capable of converting the sun's energy into food in the form of carbohydrates. In one of the single most pivotal events in the history of life, instead of the bacterium being digested, an endosymbiosis was formed, with the bacterial cell persisting inside the host eukaryote for millennia and giving rise to the first photosynthetic eukaryotes. The descendants of this merger include plants, as well as a large number of single-celled eukaryotes that are collectively referred to as algae (i.e. kelp, nori). The remnants of the cyanobacterium eventually evolved into an organelle known as a plastid or chloroplast, which allows photosynthetic eukaryotes to produce their own food--and thus to provide food to animals like us. Despite the importance of this event, a variety of aspects of plastid evolution have long remained shrouded in mystery. In a review in Genome Biology and Evolution, Shannon Sibbald and John Archibald highlight emerging genome data in this field and provide new insight into plastid evolution.

Plastids can be found patchily distributed across a number of eukaryotic lineages, often nested within groups that are otherwise non-photosynthetic. This irregular distribution has historically made it difficult for scientists to uncover the evolutionary origin and history of plastids and to trace their transfer from branch to branch on the eukaryotic tree. Both biochemical and molecular data point to a single origin of plastids from the engulfment of a member of the β-cyanobacteria by the single-celled ancestor of the Archaeplastida, a group consisting of all green algae (including land plants), red algae, and glaucophyte algae.

Secondary, tertiary, and higher order acquisitions of plastids are thought to have occurred when a eukaryotic cell containing a plastid was then engulfed by another eukaryote, which was then engulfed by yet another eukaryote, and so on. This type of plastid acquisition appears to have involved green algal endosymbionts on at least two occasions and perhaps even more often with red algae, giving rise to so-called "complex" plastids. According to Archibald, "Multigene phylogenies have gradually improved our understanding of the structure of the eukaryotic tree, and, consequently, the field has started to shift--the emerging consensus is that secondary/tertiary endosymbiosis is more common than previously assumed." However, co-author Sibbald points out that this does not mean that the puzzle has been solved. "We still don't know how many secondary, tertiary, and higher endosymbiotic events gave rise to the plastid diversity we see today or, in many cases, who the host and endosymbiont partners were."

Even more confusing, recent data show that the majority of eukaryotes with plastids acquired from red or green algae (i.e. complex red or green plastids) actually harbor a mosaic of genetic material from both red and green algae in their nuclear genomes. This has led to the "shopping bag" model of plastid evolution, which suggests that multiple red and green algae may have been transiently housed by various eukaryotic lineages over time before the establishment of the permanent (or at least current) resident plastid. Indeed, a number of lineages participate in a practice known as "kleptoplasty", in which they consume plastid-containing algae and steal their plastids, harboring them for several weeks to months and benefiting from the carbohydrates they produce before replenishing them with new ones. Thus, while it seems at least plausible that some lineages may have harbored a mix of both red and green algae before one eventually became more permanently established, Archibald notes that "understanding the evolutionary significance of this 'red-green' mosaicism in modern-day algae remains a particularly challenging task."

Additional difficulties in tracing plastid evolution arise from the loss of photosynthesis in some lineages, which can be accompanied by the further loss of the plastid genome and, in a few cases, complete loss of the plastid itself. For example, most apicomplexans like the malaria parasite Plasmodium contain a relict plastid-like organelle known as the apicoplast, which still carries out a number of biosynthetic processes. In the closely related human parasite Cryptosporidium parvum, however, the plastid has been completely lost (or was never present), and key metabolites are instead scavenged from the host. There are also a number of plants that have lost the ability to photosynthesize and instead parasitize other plants or rely on fungi to provide nutrients, such as the parasitic flowering plant Rafflesia.

Perhaps most interestingly, the tenet that all plastids stem from a single eukaryotic-cyanobacterial endosymbiosis has even been called into question by recent data showing that the freshwater shell-building amoeba Paulinella chromatophora possesses photosynthetic organelles derived from an independent acquisition of an α-cyanobacterium, which is thought to have occurred only a hundred million years ago. This suggests that more widespread sampling may reveal other lineages with independently derived plastid-like organelles. These more recent events may provide new insight into the mechanisms by which a cyanobacterium evolves into a plastid within the host cell.

Rather than answering the decades-old questions in the field of plastid evolution, it appears that recent genomic data have for now revealed even more unknowns. As Archibald notes, "It is sobering to consider that as we have collected more sequence data, the picture of plastid evolution has become less and less clear." Answering these questions will require addressing what Archibald describes as "a longstanding challenge in the field": integrating data from independent lines of inquiry, including phylogenetics, biochemistry, and membrane biology.

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SMBE Journals (Molecular Biology and Evolution and Genome Biology and Evolution)

Researcher develops method for mapping brain cell change, development in mice

Hershey, Pa. -- Penn State researchers have developed a new method for studying key moments in brain development. Yongsoo Kim, assistant professor of neural and behavioral sciences at Penn State College of Medicine, is using the method to understand how oxytocin receptor expression changes in normally developing mice and mouse models of autism spectrum disorder.

The technique allows scientists to create maps of developing mouse brains that can display how much of certain cell types are present in different regions -- and it is a critical first step in being able to study neurodevelopmental disorders in the brain.

"Key neural connections form during early development," said Kim. "We can apply this mapping method to study changes of different brain cell types in developing mouse brains to understand neurodevelopmental disorders at a cellular level."

Kim and his colleagues created maps to help them understand how oxytocin, a neurotransmitter produced by the brain, is utilized by the brain during the course of early development. Previous research revealed that oxytocin plays a role in regulating social behavior, but there is little information on how the receptors that mediate oxytocin's effect across the brain's neural networks are present in different parts of the brain across time during development.

The research team hypothesized that different brain regions would have different expression levels of oxytocin receptor (OTR) as individual brain areas mature. Previous studies investigating oxytocin receptor expression used methods where only select regions of the brain could be analyzed in portions.

Kim's new technique is able to image whole mouse brains at a cellular resolution using serial two-photon tomography and machine learning-based algorithms to detect fluorescently-labeled neurons that express oxytocin receptors.

The team created template brains from different early postnatal development periods -- 7, 14, 21 and 28 days after birth. The templates were created by generating averages of brain images and labelling key anatomy. They served as a reference point for imaging, detecting and quantifying the oxytocin receptors during different phases of development.
The results of the study were recently published in Nature Communications.

Kim and colleagues found that OTR expression reached its peak in mouse brains 21 days after birth, which is equivalent to early childhood in humans. OTR expression in the hypothalamus continued to increase until adulthood, indicating that oxytocin signaling may play a role in generating sex-specific behavior. They also studied mice who were unable to produce oxytocin receptors and noted that there was significantly reduced synaptic density -- indicating that oxytocin plays a key role in wiring the brain.

Kim says the same method used to study OTR in this study could be applied to other brain cell types in order to understand their spatial arrangement across time. The research team built a web-based platform to host and display the new images for other researchers to access.

"These images will serve as an essential baseline to compare OTR expression in various mouse models of brain disorders," Kim said. "We were able to study OTR expression in a mouse model of autism and will build on these findings by further studying functional and anatomical changes of different brain cell types and how genetic and environmental factors may affect brain development in early childhood."

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Penn State

Invisible defence against adenoviruses

image: Dr. Sabrina Schreiner in her laboratory at the Institute of Virology at Helmholtz Zentrum Muenchen.

Image: 
Andreas Heddergott / TUM

An adenovirus infection can be potentially life-threatening, especially for children after a stem cell transplant. Virologists at the Technical University of Munich (TUM) and the German Research Center for Environmental Health Helmholtz Zentrum München have successfully shown that a previously approved medication used in cancer treatment could help inhibit this virus infection. Due to the special mechanism of action, the virus cannot develop defence strategies.

Human adenoviruses cause conjunctivitis, gastrointestinal illnesses and pneumonia, among other things. In most cases however an infection exhibits no symptoms or only mild symptoms in healthy adults. "Generally speaking, every adult has probably had several adenovirus infections already," says Dr. Sabrina Schreiner. She works at the TUM Institute of Virology and the German Research Center for Environmental Health Helmholtz Zentrum. In the past human viruses, of which more than 85 different variants are currently known, were not considered to be particularly dangerous.

No medication or vaccine available as yet

However, for individuals with immune system deficiencies the course of the infection can have serious effects or even be fatal. An infection is particularly dangerous for children following a stem cell transplant. In this case the mortality rate for infected patients can be as high as 80 percent.

"We've known that adenovirus infections in healthy patients can also cause severe pneumonia ending in death since 2006," says Schreiner. However, as yet there is still no medication that is specifically effective against adenoviruses, and there is also no vaccine for the general population.

Protein complexes with antiviral effects

Schreiner and her team are investigating how the virus reproduces in the cell. They observed marked changes in what are called PML nuclear, complexes made up of several proteins within the cell, in cases of adenovirus infection.

These structures, which are otherwise round, dissolve and form elongated fibrils. "We assume that the PML bodies have an antiviral effect," says Schreiner. "The viruses destroy the round structures of the protein complexes and then make use of this cellular manipulation for their own reproduction."

Body's own defenses strengthened

The scientists noticed in cancer patients that the structures of the PML bodies were also dissolved. But when the patients were treated with arsenic trioxide (ATO) the round structures reformed. "ATO is a known active ingredient which has already been approved and is currently in clinical use for leukemia patients," Schreiner explains.

The researchers tested the efficacy of ATO in cell cultures infected with adenoviruses. Here too the PML bodies once again reformed into round structures and the virus concentration dropped. "So we can actually restore the endogenous antiviral factories which then fight the virus," says Schreiner.

No direct attack

Following laboratory testing, in the next step the medication will be used on patients with adenovirus infections. The virologists are in close contact with pediatricians in Munich hospitals. Since the medication has already been approved, it can be used in treatment immediately. "This compound contains arsenic, but there are no cytotoxic side-effects in the concentrations in which it is used and for which it has already been approved," says Schreiner.

The special thing about this medication is that it affects the cell's own structures instead of directly attacking the virus. "Viruses often become resistant to medications which attack them directly," explains Schreiner. "For example they can mutate in such a way that they are no longer recognized by the medication. But in this case, since the virus has no direct interaction with the active ingredient, it can't develop any defense mechanisms."

Credit: 
Technical University of Munich (TUM)

Researchers present concept for a new technique to study superheavy elements

image: Laser resonance chromatography is based on optical excitations of ions and subsequent detection of their arrival at the detector.

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Ill./©: Mustapha Laatiaoui

Superheavy elements are intriguing nuclear and atomic quantum systems that challenge experimental probing as they do not occur in nature and, when synthesized, vanish within seconds. Pushing the forefront atomic physics research to these elements requires breakthrough developments towards fast atomic spectroscopy techniques with extreme sensitivity. A joint effort within the European Union's Horizon 2020 Research and Innovation program and led by Dr. Mustapha Laatiaoui from Johannes Gutenberg University Mainz (JGU) culminated in an optical spectroscopy proposal: The so-called Laser Resonance Chromatography (LRC) should enable such investigations even at minute production quantities. The proposal has recently been published in two articles in Physical Review Letters and Physical Review A.

Superheavy elements (SHEs) are found at the bottom part of the periodic table of elements. They represent a fertile ground for the development of understanding on how such exotic atoms can exist and work when an overwhelming number of electrons in atomic shells and protons and neutrons in the nucleus come together. Insights into their electronic structure can be obtained from optical spectroscopy experiments unveiling element-specific emission spectra. These spectra are powerful benchmarks for modern atomic-model calculations and could be useful, for example, when it comes to searching for traces of even heavier elements, which might be created in neutron-star merger events.

LRC approach combines different methods

Although SHEs have been discovered decades ago, their investigation by optical spectroscopy tools lack far behind the synthesis. This is because they are produced at extremely low rates at which traditional methods simply do not work. So far, optical spectroscopy ends at nobelium, element 102 in the periodic table. "Current techniques are at the limit of what is feasible," explained Laatiaoui. From the next heavier element on, the physicochemical properties change abruptly and impede providing samples in suitable atomic states."

Together with research colleagues, the physicist has therefore developed the new LRC approach in optical spectroscopy. This combines element selectivity and spectral precision of laser spectroscopy with ion-mobility mass spectrometry and merges the benefits of a high sensitivity with the "simplicity" of optical probing as in laser-induced fluorescence spectroscopy. Its key idea is to detect the products of resonant optical excitations not on the basis of fluorescent light as usual, but based on their characteristic drift time to a particle detector.

In their theoretical work, the researchers focused on singly charged lawrencium, element 103, and on its lighter chemical homolog. But the concept offers unparalleled access to laser spectroscopy of many other monoatomic ions across the periodic table, in particular of the transition metals including the high-temperature refractory metals and elements beyond lawrencium. Other ionic species like triply-charged thorium shall be within reach of the LRC approach as well. Moreover, the method enables to optimize signal-to-noise ratios and thus to ease ion mobility spectrometry, state-selected ion chemistry, and other applications.

Dr. Mustapha Laatiaoui came to Johannes Gutenberg University Mainz and the Helmholtz Institute Mainz (HIM) in February 2018. In late 2018, he received an ERC Consolidator Grant from the European Research Council (ERC), one of the European Union's most valuable funding grants, for his research into the heaviest elements using laser spectroscopy and ion mobility spectroscopy. The current publications also included work that Laatiaoui had previously carried out at GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt and at KU Leuven in Belgium.

This work was conducted in cooperation with Alexei A. Buchachenko from the Skolkovo Institute of Science and Technology and the Institute of Problems of Chemical Physics, both in Moscow, Russia, and Larry A. Viehland from Chatham University, Pittsburgh, USA.

Credit: 
Johannes Gutenberg Universitaet Mainz

COVID-19: Pandemic behavior change, financial support and better data collection needed

image: Percent of respondents reporting each protective behavior by perceived COVID-19 infection risk (in quartiles). Quartiles reflect (1) 0-1.00% (N=1730); (2) 1.01-10.00% (N=1620); (3) 10.01-39.10 (N=1665).

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American Journal of Preventive Medicine

Ann Arbor, July 13, 2020 -- New research and guidance in the American Journal of Preventive Medicine, published by Elsevier, focus on critical topics pertaining to community and individual health during the COVID-19 epidemic.

Researchers issue a transdisciplinary "Call to Action" to strengthen pandemic behavioral science to overcome COVID-19
The only evidence-based strategy currently available to halt the transmission of COVID-19 is population-wide behavior change. Although information about COVID-19 protective behaviors such as hand washing, mask wearing, and social distancing has been widely disseminated in the United States by federal and local governments, research has shown significant gaps in the public's understanding and behavior, maybe because of inconsistency and lack of optimal tailoring. Researchers say the narrative is missing the behavioral science expertise that is central to achieving protective behaviors. "Fighting this pandemic will require new 'weapons' and a new resolve on the part of the government and the public," says lead author John Allegrante, PhD, Columbia University's Teachers College and the Mailman School of Public Health, New York, NY, USA. "A national historic commitment is needed in which behavior change methodology is a dominant weapon in the nation's public health arsenal." The researchers say there is an urgent need for accurate data about the public understanding of COVID-19 risk and preferred sources for obtaining information about how to stay safe. Better utilization of digital technology would enable more efficient targeting of at-risk individuals and tailoring of behavioral interventions. And, to drive these changes now and for the future, pandemic behavioral science, methodology, and evidence need to be updated and expanded.

"Preventing COVID-19 and Its Sequela: "There is No Magic Bullet . . . It's Just Behaviors," by John P. Allegrante, PhD, M. Elaine Auld, MPH, and Sundar Natarajan, MD, MSc (https://doi.org/10.1016/j.amepre.2020.05.004). Journalists wishing to speak with the authors should contact John Allegrante at jpa1@tc.columbia.edu.

Perception of the risk of contracting or dying from COVID-19 strongly influences people's decision to take protective actions, a national survey finds

As coronavirus began to spread across the United States, researchers conducted a cross-sectional national online survey between March 10 and March 31, 2020 asking participants to assess their risk of COVID-19 infection and fatality. They were also asked about behaviors they had taken to protect themselves from infection such as washing hands or avoiding public spaces and crowds. Individuals disagreed about the risks, and those perceiving higher risk were significantly more likely to engage in protective actions. Risk perceptions for getting COVID-19 and people's willingness to act upon them grew stronger in responses provided after March 13, 2020, when many states declared school closures and bans on large gatherings, and the US declared a state of emergency and implemented travel bans. "Our findings suggest that to motivate protective actions, clear and consistent risk messages are needed. This was the case when states were closing down in March 2020. It will likely also be important when states open up again," observes lead investigator Wändi Bruine de Bruin, PhD, Sol Price School of Public Policy, Dornsife Department of Psychology, Schaeffer Center for Health Policy and Economics; and Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA.

"Relationships Between Initial COVID-19 Risk Perceptions and Protective Health Behaviors: A National Survey," by Wändi Bruine de Bruin, PhD, and Daniel Bennett, PhD (https://doi.org/10.1016/j.amepre.2020.05.001). Journalists wishing to speak to the authors should contact Stephanie Hedt at hedt@healthpolicy.usc.edu.

Financial strain associated with COVID-19 hospitalization may be felt most by younger patients with lower premium, higher deductible health plans

Out-of-pocket spending associated with hospitalizations for respiratory conditions similar to those caused by COVID-19 from January 2016 through August 2019 were significantly higher for patients who have a consumer-directed health plan (CDHP) that features lower premiums but higher deductibles compared with patients who had a traditional, low deductible plan. The difference was largest for those under 21 years old, and decreased as age increased. The largest increase was in the first half of the year when, the researchers note, younger people have likely not exceeded their deductibles. Although some insurers are waiving cost-sharing payments for a hospitalization related to COVID-19, self-insured employers are exempt. "Congress is now debating whether or not to require all plans to waive cost sharing related to COVID-19 treatment. Our findings suggest they might want to take action on cost-sharing waivers, because those out-of-pockets costs are otherwise going to be high for many people," says lead investigator Matthew Eisenberg, PhD, Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

"Financial Risk for COVID-19 Respiratory Hospitalizations in Consumer-Directed Health Plans," by Matthew D. Eisenberg, PhD, Colleen L. Barry, PhD, MPP, Cameron Schilling, MPH, and Alene Kennedy-Hendricks, PhD (https://doi.org/10.1016/j.amepre.2020.05.008). Journalists wishing to speak with the authors should contact Caitlin Hoffman choffman@jhu.edu.

Researchers warn that a lack of a racial/ethnic identifier in health records and medical data may lead to worse health outcomes for Arab Americans during the COVID-19 crisis and beyond

There are increasing calls to better understand the inequities populations of color face in the United States with regard to COVID-19, including increased infection rates, more severe disease, and greater risk of death. Potential health disparities for Arab Americans may never be recognized, however, because most medical data and surveys do not include an option to identify as Arab American. Author Nadia N. Abuelezam, ScD, Boston College William F. Connell School of Nursing, Chestnut Hill, MA, USA, observes that Arab Americans are asked to identify as non-Hispanic white, despite the fact that their health outcomes are significantly different. Arab Americans may be at increased risk for COVID-19 due to xenophobia and stigma, pre-existing conditions, crowded living conditions, lack of social support for new immigrants, and poor adoption of prevention behavior. "Arab Americans have long been 'invisible' in the medical and public health literature due to a lack of an ethnic identifier," explains Dr. Abuelezam. "The COVID-19 crisis has forced the medical and public health community to reimagine the ways that healthcare can be provided and data can be collected in real time. In this moment of reimagination and creativity, we can embrace and enhance our racial and ethnic reporting measures to ensure we are collecting data on all ethnic and racial subgroups in the US."

"Health Equity During COVID-19: The Case of Arab Americans," by Nadia Abuelezam (https://doi.org/10.1016/j.amepre.2020.06.004). Journalists wishing to speak to Dr. Abuelezam may contact her at nadia.abuelezam@bc.edu.

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Elsevier

Cost prevents one in five US women from using their preferred contraception

AUSTIN, Texas-- More than one in five women at risk of an unplanned pregnancy in the U.S. would use a different method of contraception if cost were not a factor, says a new study from the Texas Policy Evaluation Project (TxPEP) published in Contraception X. Uninsured women (one in three) and publicly insured women (one in four) were more likely to prefer a different method than privately insured women (one in five), indicating the importance of insurance coverage in ensuring access to the contraceptive methods women desire. The U.S. Supreme Court recently ruled in Little Sisters of the Poor v. Pennsylvania that employers can refuse to cover birth control for religious or moral reasons. Out-of-pocket costs for contraception will rise for many U.S. women, and they will be less likely to get the birth control they want.

"Whether people are able to afford the type of birth control they want to use is a strong indicator of the quality of reproductive healthcare in the U.S.," says Dr. Kari White, principal investigator of TxPEP and Associate Professor of Social Work and Sociology at The University of Texas at Austin. "The Supreme Court's ruling, along with other recent policies that have limited publicly funded services for low-income women, will likely reverse some of the gains in access and affordability we have seen in recent years."

Affordable access to contraception in the U.S. improved over the last 7 years as a result of the Affordable Care Act (ACA) contraceptive coverage mandate, which made all Food and Drug Administration-approved contraceptive methods available for no charge to women enrolled in most private insurance plans. The Court's ruling will impact an estimated 70,500 - 126,400 women of childbearing age who will now need to pay out-of-pocket for their birth control, and some of the most effective methods, such as female sterilization, IUDs and implants, are very expensive in the U.S. Some women who lose coverage may look for a new provider at a publicly funded health center that offers low-cost contraception. These facilities, which receive federal Title X family planning funds or other federal and state funding to serve low-income women, will likely not be able to meet the demand of new patients, leaving more women with cost barriers to using the birth control method they desire.

The new TxPEP study, based on data collected after the implementation of the ACA, also showed that Black and Hispanic women and those of other races/ethnicities were less likely to be using the birth control they wanted compared with white women, reflecting the structural disadvantage women of color face in the U.S. healthcare system. "Black women can face additional barriers accessing affordable contraceptive care that is free of bias, and affording contraception may be especially challenging for recent and undocumented immigrants, many of whom are Hispanic, due to limited insurance coverage options," says Kristen Burke, a doctoral student in sociology and graduate research associate at TxPEP. "The COVID-19 pandemic has highlighted incredible racial disparities in health outcomes, including access to reproductive health services, and the Court's decision will likely exacerbate these gaps in care."

The study used data from the 2015-2017 National Survey of Family Growth, focusing on sexually active women of reproductive age in the United States who were neither pregnant nor trying to become pregnant. Previous studies by TxPEP have shown that women often prefer to use more effective methods such as the IUD, implant, and sterilization, which may not be readily available at publicly funded or private health care providers.

Credit: 
University of Texas at Austin

Bird droppings carry risk of antibiotic resistance

image: Urban crows, ducks and gulls are a potentially important reservoir of antimicrobial resistance genes, according to Rice University engineers who studied their droppings.

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Rice University

HOUSTON - (July 13, 2020) - Bird poop may pose more health risks than people realize, according to Rice University environmental engineers who study antibiotic resistance.

Their study found high levels of genes that encode antibiotic resistance harbored by opportunistic pathogens in the droppings of common urban ducks, crows and gulls.

The study led by postdoctoral research associate Pingfeng Yu of Rice's Brown School of Engineering appears in the Elsevier journal Environmental Pollution. Yu is a member of the lab of civil and environmental engineer and co-author Pedro Alvarez.

Previous studies determined bird-carried antibiotic resistant genes (ARGs) and bacteria (ARBs) can be transferred to humans through swimming, contact with feces or impacted soil or inhalation of aerosolized fecal particles. Studies have also analyzed bird feces found near ARG hotspots like wastewater treatment plants and drainage from poultry farms.

But the Rice study digs deeper to quantify the abundance, diversity and seasonal persistence of ARGs.

"We still do not fully understand what factors exert selective pressure for the occurrence of ARGs in the gastrointestinal system of wild urban birds," Alvarez said. "Residual antibiotics that are incidentally assimilated during foraging is likely one of these factors, but further research is needed to discern the importance of other potential etiological factors, such as bird diet, age, gut microbiome structure and other stressors."

The team that included lead authors Huiru Zhao, a student at Nankai University in China, and Rice graduate student Ruonan Sun compared "freshly deposited" samples from each species found around Houston during the winter and summer months to samples from poultry and livestock known to carry some of the same mutations.

They found that ARGs in all of the species, regardless of season, encoded significant resistance to tetracycline, beta-lactam and sulfonamide antibiotics. The researchers were surprised to see the relatively high abundance of ARGs were comparable to those found in the fresh feces of poultry occasionally fed with antibiotics.

They also found intI1, an integron that facilitates rapid bacterial acquisition of antibiotic resistance, was five times more abundant in the birds than in farm animals.

"Our results indicate that urban wild birds are an overlooked but potentially important reservoir of antimicrobial resistance genes, although their significance as vectors for direct transmission of resistant infections is possible but improbable due to low frequency of human contact," Alvarez said.

The team also looked for ARGs in soil up to 1 inch deep around bird deposits and discovered they are "moderately persistent" in the environment, with half-lives of up to 11.1 days.

Of the three species, crows showed a significantly lower level of ARGs during the summer compared to ducks and gulls, they reported.

"That's probably due to differences in their ecological niches, foraging patterns and gut microbiome," Sun said. "Crows are omnivores and feed on abundant natural food with less anthropogenic contaminations in the summer. In addition, the composition of their gut microbiome impacts ARG dissemination and enrichment in vivo, and therefore influences ARG levels in the excreted bird feces."

The researchers found that opportunistic pathogens including bacteria that cause urinary tract infections, sepsis and respiratory infections were common in the feces of all of the birds, and another associated with food poisoning was detected in samples collected during the winter.

Winter feces, they wrote, contained more of the bad bacteria that may also harbor ARGs, possibly due to lower sunlight inactivation and differences in moisture levels and temperature.

"Our study raises awareness to avoid direct contact with bird droppings in urban public areas, especially for vulnerable or sensitive populations," Yu said. "Meanwhile, regular cleaning should also help to mitigate associated health risks."

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Rice University

Airplane noise appears to negatively impact fetal health

Prolonged exposure to loud noise is more than annoying?it is bad for human health. Beyond the obvious potential damage to hearing, chronic noise exposure has also been linked to adverse cardiovascular effects, such as increased risks of heart attacks and strokes.

Now, for the first time, researchers have provided a causal estimate linking high-level noise exposure to another key health challenge: low birth weight (

Health economists from Lehigh University, Lafayette College and the University of Colorado, Denver were able to pinpoint a causal link by studying residential neighborhoods impacted by recent changes in airplane flight patterns going in and out of Newark Liberty International Airport, one of the largest airports in the United States.

Muzhe Yang, who holds the Francis J. Ingrassia ?75 and Elizabeth McCaul Endowed Professorship in Lehigh's Department of Economics, along with Laura Argys from University of Colorado, Denver and Susan Averett from Lafayette College, used unique birth records from 2004 to 2016 containing information on mothers' home addresses and National Transportation Noise data providing measured noise levels at exact locations. Their analysis revealed an increase of 1.6 percentage points--or 22 percent--in the risk of having a low birth weight baby among mothers living close to the airport, in the direction of the runway, exposed to noise levels over the 55 dB threshold (the threshold used by the EPA and the WHO for the protection of public health), and during the period when the new flight pattern changes were more actively implemented at the airport.

Their paper describing these results, "Residential Noise Exposure and Health: Evidence from Aviation Noise and Birth Outcomes," was published online Friday in the Journal of Environmental Economics and Management.

"Our findings have important policy implications regarding the trade-off between flight pattern optimization and human health," says Yang. "This is especially important given the long-term negative impact of low birth weight on a range of later-life outcomes such as lifetime earnings, educational achievement and long-term health."

Unintended Consequences

The changes in flight patterns around the Newark airport, as well as many airports in the United States, were triggered by a Federal Aviation Administration (FAA) air traffic control initiative called the Next Generation Air Transportation System, known as NextGen. Designed to reduce flight time and save fuel, one component of NextGen employs precision satellite monitoring instead of old-fashioned radar to guide airplanes. These satellite-designed optimum routes are made to be more direct. The use of satellite monitoring allows for more planes in the air, safely spaced and flying closer together, so more planes can use the same route.

Usage of these new routes by more and more aircraft and the adoption of a gradual descent approach?resulting in planes coming in to land at lower altitudes-have exposed residents living in areas under the satellite-designed routes to, as one resident impacted by changes in Arizona told CBS News, "a constant barrage of airplanes flying over their homes."

NextGen provided the researchers with a rare circumstance to study the causal effect of noise pollution on birth weight, in which noise exposure is close to being randomly assigned because residents were caught off-guard. The implementation of NextGen by the FAA was exempted by the U.S. Congress from normal environmental impact reviews and public hearings. The randomness and the sharp change in noise exposure are important to ensure that the estimated effect of noise pollution on birth weight is not confounded by other factors that are related to both noise pollution and fetal health, such as air pollution. This study focuses on mothers living close to the airport, where air pollution is likely to be evenly distributed while sharp changes in noise pollution exist.

"The National Transportation Noise data provided a map that revealed sharp changes in noise exposure in areas near the airport," says Yang. "We find that NextGen indeed created a narrow band around the runways, which is a noise pollution corridor. We argue that conditional on those who already live close to the airport, the redistribution of aviation noise, due to NextGen, occurred in a way that is outside of the residents' control--since the NextGen's implementation was exempted from public hearings."

Furthermore, by focusing on those living close to the airport, the research team argues that "people probably do not have the knowledge about the exact landing and takeoff paths of aircraft, or they may think they will be exposed to similar levels aviation noise since landing and takeoff paths, prior to NextGen, were less concentrated." Thus, there is a plausibly exogenous variation in noise exposure among those living near the airport--whether or not the mother lives inside the noise pollution corridor can be random. In their study they focus on mothers living within 5 miles of the airport.

"We hope our study helps people recognize the adverse effect of noise exposure on fetal health," says Yang, "as well as the urgency of finding solutions to the problem of excessive noise endured by communities overflown by aircraft using satellite-designed optimum routes."

Credit: 
Lehigh University

University research and the private sector

image: An experiment demonstrating the safety of food additive pectin in specialty infant formulas exemplifies how public-private partnerships can benefit both university scientists and industry. Pictured are University of Illinois professor Ryan Dilger (left) and Stephen Fleming, Dilger's former student and co-founder of contract research startup Traverse Science.

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Lauren D. Quinn, University of Illinois

URBANA, Ill. - Food additives get a bad rap, but a natural ingredient from orange peels and apple skins, pectin, is a thickener safely added to many food products, most notably jellies. The additive is also the subject of a University of Illinois experiment highlighting both the power and the challenges of public-private partnerships in university research.

The experiment, recently published in Regulatory Toxicology and Pharmacology, was pretty simple. It showed neonatal pigs tolerated milk replacer with pectin included at 0.2%. The research was done at the request of and with funding from formula manufacturer Mead Johnson Nutrition (now a division of RB), who hoped to prove the safety of the natural food additive for infants against a backdrop of new European standards.

Translating basic science into actionable industry and practitioner insights is part of the DNA of the College of Agricultural, Consumer and Environmental Sciences (ACES) at Illinois. From the college's perspective, public-private partnerships help industry and the public by providing unbiased, transparent science to back up or refute industry claims and practices. These partnerships also give ACES students opportunities to work within the industry landscape before entering the workforce.

"What's beautiful about these public-private partnerships is their ability to more quickly create what's needed on the front lines of agriculture and other industries," says ACES Dean Kim Kidwell. "When industry is talking directly to our talented scientists and students, innovation is inevitable."

Ryan Dilger, study co-author and associate professor in the Department of Animal Sciences at Illinois acknowledges there can be a negative public perception about university scientists working with private companies. "It's tricky, but for us, it's always science first."

In 2015, Mead Johnson approached Dilger with a proposal that would fund construction of a new research center to study infant brain and gut development using the neonatal pig as a preclinical model. Within the scientific community, piglets are accepted as a more informative proxy for human infants than mice and rats. That's because, to a much greater degree than rodents, piglet digestive systems, behavioral responses, and brain development mirror those of human babies.

Dilger worked with neonatal piglets prior to 2015, but he knew having a dedicated building to conduct the research was a major boon with benefits that would go far beyond Mead Johnson's investment.

"We work with other partners using that same infrastructure. Every company we work with makes investments in the tools we need to do cutting-edge research, which then everybody gets access to," Dilger says. "We don't like exclusivity. Public-private investments build up our capacity as university scientists to be steadfast in an ever-changing world."

The partnership with Mead Johnson also led Stephen Fleming, a former doctoral student working with Dilger and co-author on the pectin study, to identify hurdles facing private companies who want to work with university scientists. To address the issue, Fleming and Dilger launched a startup company to help companies traverse the intricacies of the university research landscape. They call it Traverse Science.

"There was no service we knew of, especially in the biological sciences, connecting students and faculty with commercial presences who need help or expertise to perform and publish basic research. Traverse Science does that in the context of food and nutrition," Fleming says.

He points to a growing industry trend to downsize in-house research and development capacity, relying instead on university researchers or contract research organizations. Traverse Science, part of the EnterpriseWorks Incubator at the University of Illinois Research Park, connects companies with Illinois experts and offers project administration, data analysis, and publication services.

"We exist so scientists can focus on the science and business can keep moving forward," Fleming notes. "We think science should enable business, not slow it down."

Many university scientists working with industry are motivated to infuse more transparent, high-quality, peer-reviewed science into product claims, industry practice, and policy.

"Conducting practical research studies is something we want to continue to promote through ACES and Traverse. We want to hold industry to the high standards of our scientific training for the benefit of the public," Dilger says. "We'll always be scientists first."

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University of Illinois College of Agricultural, Consumer and Environmental Sciences

Listeria protein provides a CRISPR 'kill switch'

ITHACA, N.Y. - A single protein derived from a common strain of bacteria found in the soil will offer scientists a more precise way to edit RNA.

The protein, called AcrVIA1, can halt the CRISPR-Cas13 editing process, according to new research from Cornell, Rockefeller University and the Memorial Sloan Kettering Cancer Center published in the journal Science July 3.

"We're expanding our scientific toolbox to effectively use a CRISPR without causing side effects," said co-author Martin Wiedmann, Ph.D. '97, the Gellert Family Professor in Food Safety and director of Cornell's Food Safety Laboratory and Milk Quality Improvement Program. "Thanks to this bacterium, we're getting a chance to turn off and on our ability to make changes to RNA."

CRISPR, or the clustered regularly interspaced short palindromic repeats, is a laboratory mechanism that can act like microscopic scissors and precisely edit the genes contained in DNA. Among the half-dozen types of CRISPRs in use today, CRISPR-Cas13 can edit RNA, which until now had lacked a brake in the editing process.

Since SARS-CoV-2, the coronavirus that causes the COVID-19 disease, is an RNA virus, this new editing accessory may be useful to coronavirus researchers, the scientists said.

Lead author Alex Meeske, postdoctoral researcher in the lab of senior author Luciano Marraffini, professor at Rockefeller University, had suspected that a protein (bacteriophage) housed in Listeria could be useful for RNA editing.

At the start of this study, Meeske reached out to Wiedmann, a food safety expert, to obtain genetic bacterial samples from his food pathogen collection. Doctoral candidate in the Wiedmann laboratory Jingqiu Liao narrowed down the prospects from about 1,500 bacterial candidates to 62 strains.

The Wiedmann lab transferred those samples to Rockefeller, where intern Alice Cassel sequenced the 62 strains and isolated 20 candidate proteins.

One strain stood out: Listeria seeligeri, a harmless bacteria found everywhere in the soil. Unlike its fierce cousin - the foodborne pathogen L. monocytogenes - it does not cause human disease.

The Rockefeller scientists found that the protein AcrVIA1 - derived from L. seeligeri - instantly stopped the CRISPR editing process. "AcrVIA1 can be very useful in controlling application of Cas13. Anything that the Cas13 edits, this anti-CRISPR protein can shut off," Meeske said. "It's a 'kill switch' you can use during the CRISPR editing process, and it has become an additional tool we have at our disposal."

Wiedmann explained that scientists can now work on RNA problems with more exacting means. "This tool gives us more precision," he said.

The paper, "A Phage-Encoded Anti-CRISPR Enables Complete Evasion of Type VI-A CRISPR- 2 Cas Immunity," was co-written by senior author Dinshaw J. Patel and Ning Jia, both of Memorial Sloan Kettering, and Albina Kozlova of Rockefeller.

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Cornell University