Culture

BOSTON - (July 27, 2020) - Type 1 diabetes occurs when a person's own immune system destroys insulin-producing beta cells in the pancreas. In recent years, scientists have learned how to grow large volumes of replacement beta cells, but the researchers are still trying out many options to protect these cells against the immune attack. Joslin Diabetes Center researchers now have found an unusual strategy that eventually may help to guard such transplanted beta cells or to slow the original onset of the disease.

Research in mouse models and in human cells has shown that targeting a protein called renalase may protect beta cells against autoimmune attack by strengthening them against stress, says Stephan Kissler, an investigator in Joslin's Section on Immunobiology, associate professor of medicine at Harvard Medical School, and co-senior author on a paper describing the work in Nature Metabolism.

Kissler, co-senior author Peng Yi, PhD, and their colleagues also demonstrated that an existing FDA-approved drug inhibits renalase and increases the survival of beta cells in those lab models.

The Joslin study joins a growing set of evidence suggesting that functional problems with beta cells themselves may help to trigger the autoimmune attack in type 1 diabetes, say Kissler and Yi, who is an assistant investigator in the Islet Cell and Regenerative Biology Section. "You might have genes that make the beta cell a little bit dysfunctional and more prone to becoming a target of the immune system," Kissler explains.

The research began with a casual hallway conversation between Kissler and Yi about potential ways to protect beta cells from autoimmune attack. The two ended up launching a bold gamble to try inhibiting genes across the genome, one at a time, using a screening technique based on the CRISPR gene-editing method with a beta cell line from a "non-obese diabetic" (NOD) mouse that models type 1 diabetes. "Whole genome CRISPR screening is a powerful tool for new target discovery and we hoped that it would help us find any mutations that protect the beta cell," Yi says.

The CRISPR screen for surviving beta cells produced a dozen genes of interest. The most striking was the gene for renalase, which previous research had shown is associated with type 1 diabetes.

Next, the researchers created NOD mouse beta cells, some with the renalase gene functionally "knocked out" and some not. They transplanted these cells to NOD mice with autoimmune diabetes.

Intact beta cells died off--but the renalase knock-out cells survived. "This was a very black-and-white research model," Kissler comments. "If the cells aren't protected, they're gone."

The investigators then looked to see if the cells that lacked the renalase gene provoked a diminished response from T immune cells (which spearhead the autoimmune assault) in a dish. The scientists found that one type of T cell was less likely to attack these knockout cells than to attack normal beta cells.

But what was slowing this autoimmune assault?

In earlier work to analyze beta cell survival, Yi had analyzed how the cells respond to a condition called endoplasmic reticulum (ER) stress. Now when the team tried three ways of introducing ER stress to mouse beta cells in a dish, the researchers saw that the renalase mutation was protecting against this condition.

In the next step, to see if the same mechanisms were at work in human cells, the team joined up with Douglas Melton of the Harvard department of Stem Cell and Regenerative Biology to create human beta cells for similar tests in a dish. "Again, we saw that the renalase knockout protected cells against ER stress," Kissler says.

The functions of renalase are not well understood, but Yi and Kissler knew that the protein is an enzyme (which often can be targeted by drug compounds) and that other scientists had produced a three-dimensional crystal structural map of the protein.

Wondering if this map would give clues to uncover a compound that could target renalase, the Joslin investigators began working with Celia Schiffer of the University of Massachusetts Medical School. Structural biologists at the university's structure-based drug design core facility soon noticed that renalase is very similar to another enzyme that is inhibited by existing drugs--including one drug known as pargyline that was approved by the Food & Drug Administration almost 60 years ago to treat hypertension.

Testing pargyline in their mouse transplant model, the Joslin researchers found that the drug protected beta cells extremely well, says Kissler. Studying it in the mouse beta cells themselves, the scientists demonstrated that pargyline indeed was protecting against ER stress. In experiments with human cells, pargyline also displayed a protective effect.

Kissler and Yi hope to test pargyline in a pilot clinical trial to see if it slows the progress of new onset type 1 diabetes in a small number of patients. "Since it's FDA-approved and the drug is safe, this would be the best approach to test if the protection we observed in mice and human cells will hold true in people," Kissler remarks. If research results continue to be positive, their next goal will be to find industry backing to develop a small molecule drug that provides even better protection than pargyline.

In a study published in Nature Astronomy, an international team of researchers has presented a new, detailed look inside the "central engine" of a large solar flare accompanied by a powerful eruption first captured on Sept. 10, 2017 by the Owens Valley Solar Array (EOVSA) -- a solar radio telescope facility operated by New Jersey Institute of Technology's (NJIT) Center for Solar-Terrestrial Research (CSTR).

The new findings, based on EOVSA's observations of the event at microwave wavelengths, offer the first measurements characterizing the magnetic fields and particles at the heart of the explosion. The results have revealed an enormous electric current "sheet" stretching more than 40,000 kilometers through the core flaring region where opposing magnetic field lines approach each other, break and reconnect, generating the intense energy powering the flare.

Notably, the team's measurements also indicate a magnetic bottle-like structure located at the top of the flare's loop-shaped base (known as the flare arcade) at a height of nearly 20,000 kilometers above the Sun's surface. The structure, the team suggests, is likely the primary site where the flare's highly energetic electrons are trapped and accelerated to nearly the speed of light.

Researchers say the study's new insight into the central engine that drives such powerful eruptions may aid future space weather predictions for potentially catastrophic energy releases from solar flares -- the solar system's most powerful explosions, capable of severely disrupting technologies on Earth such as satellite operations, GPS navigation and communication systems, among many others.

"One of the major goals of this research is to better understand the fundamental physics of solar eruptions," said Bin Chen, the paper's lead author and professor of physics at NJIT. "It has been long suggested that the sudden release of magnetic energy through the reconnection current sheet is responsible for these major eruptions, yet there has been no measurement of its magnetic properties. With this study we've finally measured the details of the magnetic field of a current sheet for the first time, giving us a new understanding of the central engine of the Sun's major flares."

"The place where all the energy is stored and released in solar flares has been invisible until now. ... To play on a term from cosmology, it is the Sun's 'dark energy problem,' and previously we've had to infer indirectly that the flare's magnetic reconnection sheet existed," said Dale Gary, EOVSA director at NJIT and co-author of the paper. "EOVSA's images made at many microwave frequencies showed we can capture radio emissions to illuminate this important region. Once we had that data, and the analysis tools created by co-authors Gregory Fleishman and Gelu Nita, we were able to start analyzing the radiation to enable these measurements."

Earlier this year in the journal Science, the team reported it could finally provide quantitative measurements of the evolving magnetic field strength directly following the flare's ignition.

Continuing their investigation, the team's latest analysis combined numerical simulations performed at Center for Astrophysics | Harvard & Smithsonian (CfA) with EOVSA's spectral imaging observations and multiwavelength data -- spanning radio waves to X-rays -- collected from the X8.2-sized solar flare. The flare is the second largest to have occurred from the past 11-year solar cycle, occurring with a fast coronal mass ejection (CME) that drove a large-scale shock in the upper solar corona.

Among the study's surprises, the researchers found that the measured profile of the magnetic field along the flare's current sheet feature closely matched predictions from the team's numerical simulations, which were based on a well-known theoretical model for explaining solar flare physics, first proposed in the 1990s with an analytical form.

"It surprised us that the measured magnetic field profile of the current sheet beautifully matched the theoretical prediction made decades ago," said Chen.

"The force of the Sun's magnetic field plays a key role in accelerating plasma during an eruption. Our model was used for computing the physics of the magnetic forces during this eruption, which manifests as a highly twisted 'rope' of magnetic field lines, or magnetic flux rope," explained Kathy Reeves, astrophysicist at CfA and co-author of the study. "It is remarkable that this complicated process can be captured by a straightforward analytical model, and that the predicted and measured magnetic fields match so well."

The simulations, performed by Chengcai Shen at CfA, were developed to numerically solve governing equations for quantifying the behavior of electrically conducting plasma throughout the flare's magnetic field. By applying an advanced computational technique known as "adaptive mesh refinement," the team was able to resolve the thin reconnection current sheet and capture its detailed physics at superfine spatial scales to below 100 kilometers.

"Our simulation results match both the theoretical prediction on magnetic field configuration during a solar eruption and reproduce a set of observable features from this particular flare, including magnetic strength and plasma inflow/outflows around the reconnecting current sheet," Shen noted.

Shocking Measurements

The team's measurements and matching simulation results revealed that the flare's current sheet features an electric field that produces a shocking 4,000 volts per meter. Such a strong electric field is present over a 40,000-kilometer region, greater than the length of three Earths placed together side by side.

The analysis also showed a huge amount of magnetic energy being pumped into the current sheet at an estimated rate of 10-100 billion trillion (1022-1023) joules per second -- that is, the amount of energy being processed at the flare's engine, within each second, is equivalent to the total energy released by the explosion of about a hundred thousand of the most powerful hydrogen bombs (50-megaton-class) at the same time.

"Such an enormous energy release at the current sheet is mind-blowing. The strong electric field generated there can easily accelerate the electrons to relativistic energies, but the unexpected fact we found was that the electric field profile in the current sheet region did not coincide with the spatial distribution of relativistic electrons that we measured," said Chen. "In other words, something else had to be at play to accelerate or redirect these electrons. What our data showed was a special location at the bottom of the current sheet -- the magnetic bottle -- appears to be crucial in producing or confining the relativistic electrons."

"While the current sheet seems to be the place where the energy is released to get the ball rolling, most of the electron acceleration appears to be occurring in this other location, the magnetic bottle. ... Similar magnetic bottles are under development for confining and accelerating particles in some laboratory fusion reactors." added Gary. "Others have proposed such a structure in solar flares before, but we can truly see it now in the numbers."

Approximately 99% of the flare's relativistic electrons were observed congregating at the magnetic bottle throughout the duration of the five-minute-long emission.

For now, Chen says the group will be able to apply these new measurements as a comparative baseline to study other solar flare events, as well as explore the exact mechanism that accelerates particles by combining the new observations, numerical simulations and advanced theories. Because of the breakthrough capabilities of EOVSA, NJIT was recently selected to participate in a joint NASA/NSF DRIVE Science Center Collaboration on Solar Flare Energy Release (SolFER).

"Our goal is to develop a full understanding of solar flares, from their initiation until they finally spray out highly energized particles into the solar wind, and eventually, into the space environment of Earth," said Jim Drake, professor of physics at the University of Maryland and principal investigator of SolFER who was not involved in this study.
"These first observations are already suggesting that relativistic electrons might be trapped in a large magnetic bottle produced as the magnetic fields of the corona 'reconnect' to release their energy. ... The EOVSA observations will continue helping us unravel how the magnetic field drives these energetic electrons."

"Further investigating the role of the magnetic bottle in particle acceleration and transport will require more advanced modeling to compare with EOVSA's observations," said Chen. "There are certainly huge prospects out there for us to study that address these fundamental questions."

The differing immune system responses of patients with COVID-19 can help predict who will experience moderate and severe consequences of disease, according to a new study by Yale researchers published July 27 in the journal Nature.

The findings may help identify individuals at high risk of severe illness early in their hospitalization and suggest drugs to treat COVID-19.

Researchers examined 113 patients admitted to Yale New Haven Hospital, and analyzed the varying immune system responses they exhibited during their hospital stay, from admittance to discharge or death. They found that all patients shared a common COVID-19 "signature" in immune system activity early in the course of disease. But those who experienced only moderate symptoms exhibited diminishing immune system responses and viral load over time. Patients who went on to develop severe cases of the disease showed no decrease in viral load or immune system reaction, and many of the immune signals in these patients accelerated.

But even in the early course of treatment, researchers found indicators that predicted which patients were at greatest risk of developing severe forms of the illness.

"We were able to pull out signatures of disease risk," said senior author Akiko Iwasaki, the Waldemar Von Zedtwitz Professor of Immunobiology and Molecular, Cellular and Developmental Biology and investigator for the Howard Hughes Medical Institute.

Researchers had known that the immune system unleashed a massive and damaging "cytokine storm" in severe cases of COVID-19. But the specific elements of the immune system response most responsible for the damage were unknown.

The Yale analysis found some intriguing links to poor outcomes. Curiously, said researchers, one risk factor was the presence of alpha interferon, a cytokine mobilized to combat viral pathogens such as the flu virus. However, COVID-19 patients with high levels of alpha interferon fared worse than those with low levels.

"This virus just doesn't seem to care about alpha interferon," Iwasaki said. "The cytokine appears to be hurting, not helping."

Another early prognosticator of poor outcomes is activation of the inflammasome, a complex of proteins that detects pathogens and triggers an inflammatory response to infection. Inflammasome activation was linked to poor outcomes and death in several patients.

Researchers found that people who respond better to the infection tend to express high levels of growth factors, a type of cytokine that repairs tissue damage to the linings of blood vessels and lungs.

Taken together, the data can help predict patients at high risk of poor outcomes, the authors said.

They also said drugs that target specific causes of inflammation identified in the study could help treat patients at risk of developing severe cases of COVID-19.

COLUMBUS, Ohio - Concrete sewer pipes around the world are most likely to fail either because their concrete is not strong enough or because they can't handle the weight of trucks that drive over them, a new study indicates.

The study used a statistical analysis to show that those two factors were the most likely to trigger a problem among 16 common causes of sewer pipe failure they examined.

The study was published online earlier this year in the journal Structure and Infrastructure Engineering.

"There is a vast array of pipes underground that is working every day and if there is disruption - leakage or collapsing in a pipe, for example - not only will there be discomfort for the residents, but also economic, health and environmental consequences," said Abdollah Shafieezadeh, senior author on the study and an associate professor of civil, environmental and geodetic engineering at The Ohio State University. "The losses can be significant."

And so can the cost of repairs and maintenance: In 2017, the American Society of Civil Engineers estimated the cost to fix and maintain the U.S. sewer system at $150 billion.

For this study, researchers gathered data and analyzed buried sewer pipes, which, in the United States, are commonly made of concrete. Then, they identified the most likely causes of sewer pipe failure. Those causes included things like the density of soil surrounding sewer pipes, the elasticity and strength of the concrete materials and the weight of trucks that regularly drive over them.

They then built a statistical model that could evaluate the stress caused to the pipes by each variable individually and in combinations, and conducted several statistical analyses using the Ohio Supercomputer Center.

The analyses showed that, statistically, cracks that will eventually influence the structural integrity of sewer pipes are most likely to form when the concrete is made from weak components and not maintained properly, or when heavy trucks regularly drive on roads above the pipes. Cracks that influence structural integrity, the researchers say, are the first signs that a sewer pipe is on its way to collapse.

"It's a worldwide problem, and part of the issue is that, for many cities around the world, these sewer systems have been installed long ago, and the challenge now is to maintain these old systems," Shafieezadeh said.

Systems can be complex and expensive to maintain. Cities often have tens of thousands of miles of sewer pipes running beneath them. And, because they are underground, spotting issues is not as simple as finding issues with above-ground infrastructure like roads or power lines, said Soroush Zamanian, a graduate research associate in civil, environmental and geodetic engineering at Ohio State and lead author of the paper.

"In 2017, the American Society of Civil Engineers gave the United States' overall sewer system a D+ rating," Zamanian said. "And that's part of why we are looking at this question and seeing if we could help predict where lines might fail."

The researchers said future studies should examine the way aging and corrosion of pipes affects the way in which system operators can repair them. And, they said, future studies could analyze other pipe configurations, or analyze more details about the types of soil that surround those pipes.

"The big picture is if we want to design sewer pipes for the future, or if we want to assess the current condition and predict future conditions of these pipes, one key element is to know the important factors contributing to their failures - and how do those factors play out in the real world," Zamanian said.

CONTACTS: Abdollah Shafieezadeh, shafieezadeh.1@osu.edu

Soroush Zamanian, zamanian.2@osu.edu

Written by: Laura Arenschield, arenschield.2@osu.edu

Journal

Structure and Infrastructure Engineering

DOI

10.1080/15732479.2020.1762674

In mid-April, as the COVID-19 epidemic roared through the nation, 2,017,105 jobholders were absent from work because they were ill. The April figure was the highest number since at least 1976, and more than double the rate from mid-April 2019, according to a new study from researchers at Harvard Medical School and CUNY's Hunter College. The findings suggest that the official counts of COVID-19 cases greatly understate the number of people sickened by the virus.

The surge in sickness-related work absences was largest for immigrant workers, a group that includes many essential workers at high risk of coronavirus exposure; immigrant jobholders' absence rate rose almost five-fold from 12 months earlier, when their absenteeism rate had been 37% lower than that of native-born jobholders. Workers 55 and older, and those with less education also had larger than average year-over-year increases in sickness-related absences. The research appears Monday, June 27 in the Journal of the American Medical Association (JAMA): Internal Medicine.

Researchers analyzed the Census Bureau's monthly Current Population Survey which tracks U.S. employment. Because the survey asked only about work absence during a single week in mid-April, the figures likely understate the number of jobholders who were out sick during the course of the month.

The share of workers who were out sick was virtually identical in the first two months of 2019 and 2020. As in most years, work absences began dropping in the early spring of 2019, falling to 0.58% of the workforce by April. In contrast, in 2020 the number who were out sick began rising in March as COVID-19 illnesses began spreading, and soared in April, when 1.51% of all job holders were out sick, nearly triple the percentage from a year earlier.

"I've seen firsthand COVID-19's impact on the critically ill patients in our ICU, and we've known that many more were also ill at home," noted lead author Dr. Adam Gaffney, a pulmonary and critical care specialist at Harvard Medical School and the Cambridge Health Alliance, a safety-net hospital system at an epicenter of the pandemic in eastern Massachusetts. "But our study indicates that the pandemic has sickened many more people than we had realized, especially vulnerable employees like immigrants."

"Millions of immigrants and people of color have put themselves in harm's way to keep vital services running during the COVID-19 crisis," said Dr. Steffie Woolhandler, a primary care doctor, Distinguished Professor of Public Health at CUNY's Hunter College, and Lecturer in Medicine at Harvard. Many are uninsured and have no income if they miss work. The least we can do to protect them is to assure paid sick leave and universal health care, benefits that workers in every other wealthy nation already enjoy."

Some smokers might rationalize continuing to smoke because of lower body weight often associated with the habit. However, Vanderbilt University Medical Center investigators have determined that even with a lower body mass index (BMI), smokers have a higher risk of depositing fat in and around organs and tissues compared to those who never smoked.

This is concerning because excess fat, also known as adipose tissue, deposited in the abdomen and around organs such as the liver and non-adipose tissues including muscles, may disrupt their normal functions and cause health problems. This disruption is associated with a higher risk for health complications such as cardiovascular disease and type 2 diabetes.

Investigators used computed tomography (CT) body scans to measure abdominal fat deposited just below the skin's surface (subcutaneous fat), around organs including the intestines (visceral fat) and abdominal muscles (intermuscular fat), and inside the muscles (intramuscular fat) in 3,020 middle-aged participants in the federally funded Coronary Artery Risk Development in Young Adults (CARDIA) study.

"We found that current smokers had abdominal muscles that were significantly higher in fat," said lead author James "Greg" Terry, research programs manager in Radiology and member of Vanderbilt Translational and Clinical Cardiovascular Research Center (VTRACC). "Smokers also had a higher proportion of visceral fat, the fat around their internal organs, compared to never smokers, whereas those who had quit smoking had intermediate levels of visceral and intramuscular fat. This might contribute to the higher prevalence of cardiovascular disease and age-related physical deconditioning and disability that is well-documented among those who smoke."

Co-author David Jacobs, PhD, professor of Public Health at the University of Minnesota and one of the founding CARDIA investigators, said he considers "cigarette smoking as a weight-loss tool to be a risky strategy. Our data show that the fat deposition pattern apparent in smokers is associated with metabolic damage."

The longitudinal CARDIA study was begun in 1985 with the recruitment of young adult participants (aged 18-30), equally balanced by male and female sex and black and white race, at four locations in the United States. The CT measurements were taken at the 25-year mark. The investigation is published in the online, open access journal PLOS Medicine.

If given the chance, a Kenyan herder is likely to keep a mix of goats and camels. It seems like an irrational economic choice because goats reproduce faster and thus offer higher near-term herd growth. But by keeping both goats and camels, the herder lowers the variability in growth from year to year. All of this helps increase the odds of household survival, which is essentially a gamble that depends on a multiplicative process with no room for catastrophic failure. It turns out, the choice to keep camels also makes evolutionary sense: families that keep camels have a much higher probability of long-term persistence. Unlike businesses or governments, organisms can't go into evolutionary debt -- there is no borrowing one's way back from extinction.

How biological survival relates to economic choice is the crux of a new paper published in Evolutionary Human Sciences, co-authored by Michael Price, an anthropologist and Applied Complexity Fellow at the Santa Fe Institute, and James Holland Jones, a biological anthropologist and associate professor at Stanford's Earth System Science department.

"People have wanted to make this association between evolutionary ideas and economic ideas for a long time," Price says, and "they've gone about it quite a lot of different ways." One is to equate the economic idea of maximizing utility -- the satisfaction received from consuming a good -- with the evolutionary idea of maximizing fitness, which is long-term reproductive success. "That utility equals fitness was simply assumed in a lot of previous work," Price says, but it's "a bad assumption." The human brain evolved to solve proximate problems in ways that avoid an outcome of zero. In the Kenyan example, mixed herding diversifies risk. But more importantly, the authors note, the growth of these herds, like any biological growth process, is multiplicative and the rate of increase is stochastic.

As Jones explains, most economics is additive -- adding value, adding utility. But evolutionary fitness is multiplicative, so it can't tolerate zero. The size of the Kenyan's herd next year is essentially the size of the herd this year times the net birth rate. If there is ever a zero in that equation - a drought kills the whole herd of goats - it becomes a catastrophic loss that the herder can't overcome.

"These multiplicative factors influence variables that matter for evolutionary fitness," Price says. In the herder scenario, the decision to diversify ultimately benefits fertility and the long-term survival of the family. The two liken major life decisions -- diversifying the herd, buying a house, having more kids -- to lotteries with inherent risks and uncertain payoffs. They theorize that evolution strongly favors "pessimistic probability weighting" - choosing lower-profit camels despite the immediate potential payoff of goats. In the long run, Jones says, this may "leave money on the table" but it keeps people in the evolutionary game.

Price gives another example: climate change. From a purely economic standpoint, he says, one could argue it would be cheaper to do nothing now and wait until geoengineering offers a solution however many years down the road. But we don't know all the risks and potential consequences of multiplicative factors like Arctic permafrost thaws and oceanic circulation changes coming together at once. "We should probably deal with climate change," Price says, because "the success of our species is probably way more important than eking out a little bit more efficiency over the next five years of economic growth."

Price also hopes to apply these ideas to archaeology. "I am interested in pushing this perspective into the past." He aims to study the problems and decision-making patterns that preceded the Maya collapse.

The element phosphorus (P) is central to life, agriculture, and food security. Approximately 90% of global phosphate rock demand is for food production. Access to P is put under pressure by population growth, limited P recycling and reuse, and finite P mining resources. In addition to access, the network resilience of P cycling (that is, a system attribute that ensures continuous access of P within the network and is critical for sustainable P management) is vulnerable to socio-environmental shocks and disturbances. To eradicate hunger and achieve food security, it is essential to better understand the metabolic network of P flows.

A study recently published on Nature food evaluates the evolution of the resilience of the P cycling network in China over four centuries (1600-2012), as well as its underlying determinants. "Our results reveal that, in the most recent decades, the network resilience of the P cycling in China has declined", commented Ali Kharrazi, CMCC researcher at ECIP - Economic analysis of Climate Impacts and Policy Division. Dr. Kharrazi is a Marie Curie Research Fellow at Ca' Foscari University and CMCC Foundation Euro-Mediterranean Center on Climate Change in Venice, Italy; his research focuses on examining the resilience of food trade networks under climate change.

"The key factors underlying this trend include the growth of food demand and the changes of the food structure from a modest, mostly vegetarian-based diet to a more complex diet (that is, more animal-based foods with higher P content). This is because, after the year 2000, urbanization accelerated in China and higher living standards were adopted.

Should this trend persist, China's food security shall be increasingly vulnerable to P availability under socio-environmental shocks and disturbances to its P cycling network. Moreover, the P declining trend observed in China it's definitely a global trend", he adds.

The resilience of the P cycling network is influenced by human food demand/fertilizer P proportion: to meet this demand, the animal husbandry and aquaculture sectors expanded their production, subsequently increasing the demand for agricultural products such as grains and beans and P fertilizer use in the cultivation sector.

So, how we can satisfy the increasing food demand and guarantee sustainable development?

The authors tried to give some suggestions to increase the resilience of the P cycling network while guaranteeing food security.

The first suggestion is to reduce food loss and food waste. The second one, to improve the 'farm to fork efficiency' (that is, P productivity) in food supply chains. Possible measures in this avenue include setting guidance limits and standards for P fertilizer use, promoting advanced technologies to reduce food loss during food processing, and reducing food wastage during food consumption through education and public awareness campaigns.

The third suggestion is to reduce fertilizer use. A potential measure to achieve this is developing technologies to enhance fertilizer use efficiency.

Approaches to increase fertilizer use efficiency range from high-tech solutions (for example, precision agriculture, e.g. hydroponics) to organic farming techniques aimed at optimizing soil conditions to increase the P availability of soil. Other approaches focus on the addition of microbial inoculants to increase the P availability of soil. An obstacle in spreading these approaches is the fact that poorest countries in the world may be not able to adopt these options because they don't have the necessary know-how.

An alternative for decreasing the proportion of mineral P fertilizer use is to increase the P recycling rate: there are lots of other measures to recover and reuse P, such as ploughing crop residues back into the soil; composting food waste; and P recovery from sewage sludge, steelmaking slags and wastewater.

"P geographical distribution and availability is very limited", Kharrazi explains; "it is in fact located in few countries, such as Morocco, Australia and China; other countries, and especially European countries, don't have great stocks of P and import this key chemical element from other countries. Another problem is that P is not adequately recycled: we use an increasing amount of fertilizers in the agricultural sector but all the data indicate that the current P cycling network is actually a 'one-way journey', where the majority of the P is directly deposited in the soil or discharged in solid wastes and water bodies causing critical environmental problems, such as algae blooms and eutrophication. We should not only rely on P rocks to maintain the high efficiency of P cycling, but also improve the network resilience through P recycling and P productivity improvement in food supply chains. In our study, we proposed some ideas to solve this well-know, critical issue."

Children, and especially boys, show stronger stereotyping about masculine and feminine jobs than previously suspected, an innovative study by the University of Sussex reveals.

New research reveals the extent to which girls exaggerated their gendered voices to imitate workers in different professions dropped off at around seven but continues to increase beyond that age with boys.

Boys also used an overtly masculine voice even when imitating workers in gender-neutral roles, the study found.

Research in the field of gender stereotypes usually involves asking study participants what they think about men and women doing different jobs, but there are concerns this can mask people's true beliefs because their answers may be biased by their desire to conform.

So instead, University of Sussex psychologists tapped into children's unconscious stereotypes by asking them to speak in the voices of people with different occupations.

The research found that for stereotypically male jobs, both sexes spontaneously masculinised their voices, by lowering pitch and resonance, and they also feminised their voices for stereotypically female occupations, by raising their pitch and resonance.

The academics are advising authors and children's TV writers to be extra vigilant about associating job roles too strongly with a specific gender, to avoid children associating certain jobs exclusively with a given gender. They also call attention to the voice as an untapped resource to monitor and potentially challenge implicit stereotypes in children.

Dr Valentina Cartei, research fellow at the University of Sussex's School of Psychology, said: "Our study found that boys were especially likely to accentuate the vocal masculinity or femininity of people doing different jobs. This pattern suggests that children have differential evaluations of males and females engaging in stereotypical and counter-stereotypical occupations."

In the study, children between the ages of five and ten took part in a voice production task where they were provided with descriptions of traditionally male, female and gender neutral professions and asked to give voices to people in each of those jobs.

In order to measure children's beliefs about gender stereotypes using the more conventional approach, the researchers also asked them to complete a questionnaire which asked them directly about men and women carrying out particular job roles.

The researchers created a simple Index of Stereotypicality which they believe could be used to quantify implicit occupational stereotyping in children.

Used alongside software that can extract pitch from the recording of children's voices, the academics believe the index could be a useful tool for teachers and practitioners interested in challenging stereotypes.

Professor Jane Oakhill said: "The strength of stereotypicality based on vocal pitch revealed stereotypes that were not found in children's direct responses to the conventional questions about men and women doing different jobs. This suggests that children continue to entertain gender stereotypes even if they are not prepared to say so explicitly.

"If we are to successfully challenge these occupational stereotypes, then as well as having depictions of both male and female nurses, we need occupational role models who vary in vocal masculinity and femininity, such as male nurses with both low and high vocal pitch, Unconscious bias training should also include voice cues to help teachers and parents become aware of and challenge biases about gender stereotypes in relation to particular jobs."

A new study, which analyzed 40 years of Framingham Heart Study data, found an association between lowered rates of hip fractures and decreases in smoking and heavy drinking.The rates of hip fractures in the United States have been declining over the past few decades. Although some experts attribute this change primarily to improved treatments for bone health, a new National Institutes of Health-supported study suggests other factors. These results indicate that modifiable lifestyle factors, along with treatments, may be beneficial to bone health. The findings appear July 27, 2020 in JAMA Internal Medicine.

Timothy Bhattacharyya, M.D., a researcher with the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), part of NIH, led the analysis to determine what may be causing the drop in hip fracture rates. The research team included scientists from NIH's National Cancer Institute, the Hinda and Arthur Marcus Institute for Aging Research, part of the Hebrew SeniorLife, Beth Israel Deaconess Medical Center, Boston, and Harvard Medical School, Boston.

The analysis included information from 4,918 men and 5,634 women who participated in the Framingham Study. These individuals were followed for a first hip fracture between Jan. 1, 1970, and Dec. 31, 2010. The rates for hip fractures, which were adjusted for age, dropped by 4.4% each year across the 40-year study period. The decrease was seen in both men and women.

In this group, the rate of smoking decreased from 38% in the 1970s to 15% in the period from 2006 to 2010. During the same period, heavy drinking (defined as three or more drinks per day) fell from 7% to 4.5%. The rates of other risk factors for hip fracture, such as underweight and early menopause, did not change over the study period.

"This study points to the continued need for public health interventions to target modifiable lifestyle factors such as smoking and drinking, in addition to considering osteoporosis treatments in individuals at risk of hip fractures," said Bhattacharyya.

"As we learn more about lifestyle factors that impact bone health, we continue to conduct research aimed at understanding all the factors that contribute to reducing fractures, including both lifestyle and medications, so that we can all live longer lives without disability," Robert H. Carter, M.D., acting director of NIAMS, added.

The Framingham Heart Study launched in 1948 to determine factors that contribute to cardiovascular disease. The National Heart, Lung, and Blood Institute, assumed responsibility for the project in 1949. Though many of the original participants have passed away, the study continues to examine another two generations of residents in and near Framingham, Massachusetts.

The study authors note that because the data was exclusively from white individuals, it is unclear whether other populations might show a similar correlation based on lifestyle factors. Another limiting factor was that Framingham participants had lower rates of obesity than the national average. Additionally, the study did not include measurements of bone mineral density, because such testing was not available until the 1990s.

Medical and non-medical prescription stimulant use is higher in states without medical cannabis laws (MCLs) than in states with MCLs among heterosexuals and among certain lesbian, gay and bisexual (LGB) subpopulations. The study led by Columbia University Mailman School of Public Health researchers is published in the International Journal of Drug Policy.

Based on an analysis of data from the National Survey on Drug Use and Health between 2015 and 2017, the researchers found that bisexual men self-reported higher medical and non-medical prescription stimulant use than heterosexual men. Bisexual women self-reported higher non-medical prescription stimulant use than heterosexual women. Female and male heterosexuals in MCL states had lower odds of medical stimulant use than their female and male counterparts in non-MCL states; bisexual men in MCL states also reported a lower odds of medical stimulant use than their counterparts in non-MCL states. Female and male heterosexuals living in MCL states also reported lower odds of non-medical prescription stimulant use than their counterparts living in non-MCL states; similar patterns emerged for bisexual men and women. These associations were not significant among lesbian/gay adults.

This study is cross-sectional and thus only shows associations, not causality. Several factors may explain the link between medical and non-medical stimulant use and state MCL status. First, MCL states may have other common characteristics that existed prior to MCL enactment compared to non-MCL states, including lower rates of medical and non-medical prescription stimulant use. Second, MCL states might have different stimulant prescribing regulations that may drive prescribing patterns and thus the amount of prescription stimulants in circulation. In 2016, half of the states above the median in per capita (mg/person) of amphetamine prescriptions were non-MCL states, while only one-third of states that were below the median in prescriptions were non-MCL states. "This suggests that the volume of prescription stimulants may be higher in non-MCL as compared to MCL states, which previous research suggests can lead to diversion, whereby stimulants that were medically prescribed are used non-medically," the authors write.

The study findings are in keeping with research finding elevated rates of stimulant use among LGB individuals--a pattern that may be linked to minority stress, meaning the discrimination, rejection, identity concealment, harassment, and maltreatment these individuals experience.

"Our findings support the need for multi-level approaches to address higher levels of prescription stimulant among LGB adults compared to their heterosexual counterparts," the study authors write. "At a structural level, states should ensure that public health campaigns incorporate information about stimulant use and target LGB individuals, reduce unnecessary stimulant prescriptions to help limit [non-medical-use of these drugs], and offer non-stigmatizing and affordable treatment when clinically indicated. At a community level, harm reduction and medication disposal should be readily accessible."

Researchers from North Carolina State University have identified a microRNA (miRNA) that could promote hair regeneration. This miRNA – miR-218-5p – plays an important role in regulating the pathway involved in follicle regeneration, and could be a candidate for future drug development.

Hair growth depends on the health of dermal papillae (DP) cells, which regulate the hair follicle growth cycle. Current treatments for hair loss can be costly and ineffective, ranging from invasive surgery to chemical treatments that don’t produce the desired result. Recent hair loss research indicates that hair follicles don’t disappear where balding occurs, they just shrink. If DP cells could be replenished at those sites, the thinking goes, then the follicles might recover.A research team led by Ke Cheng, Randall B. Terry, Jr. Distinguished Professor in Regenerative Medicine at NC State’s College of Veterinary Medicine and professor in the NC State/UNC Joint Department of Biomedical Engineering, cultured DP cells both alone (2D) and in a 3D spheroid environment. A spheroid is a three-dimensional cellular structure that effectively recreates a cell’s natural microenvironment.In a mouse model of hair regeneration, Cheng looked at how quickly hair regrew on mice treated with 2D cultured DP cells, 3D spheroid-cultured DP cells in a keratin scaffolding, and the commercial hair loss treatment Minoxidil. In a 20-day trial, mice treated with the 3D DP cells had regained 90% of hair coverage at 15 days.

“The 3D cells in a keratin scaffold performed best, as the spheroid mimics the hair microenvironment and the keratin scaffold acts as an anchor to keep them at the site where they are needed,” Cheng says. “But we were also interested in how DP cells regulate the follicle growth process, so we looked at the exosomes, specifically, exosomal miRNAs from that microenvironment.” Exosomes are tiny sacs secreted by cells that play an important role in cell to cell communication. Those sacs contain miRNAs.

MiRNAs are small molecules that regulate gene expression. Cheng and his team measured miRNAs in exosomes derived from both 3D and 2D DP cells. In the 3D DP cell-derived exosomes, they pinpointed miR-218-5p, a miRNA that enhances the molecular pathway responsible for promoting hair follicle growth. They found that increasing miR-218-5p promoted hair follicle growth, while inhibiting it caused the follicles to lose function.

“Cell therapy with the 3D cells could be an effective treatment for baldness, but you have to grow, expand, preserve and inject those cells into the area,” Cheng says. “MiRNAs, on the other hand, can be utilized in small molecule-based drugs. So potentially you could create a cream or lotion that has a similar effect with many fewer problems. Future studies will focus on using just this miRNA to promote hair growth.”

LOS ANGELES -- For many with end-stage lung disease, lung transplantation has become a viable option to extend lives and improve the quality of life.

However, once lung transplant recipients leave the hospital, they may experience complications, such as an infection or organ rejection, that can result in unplanned hospital readmissions and other poor outcomes.

One of the many challenges patients face is managing their health from home and adhering to medication schedules.

To provide another layer of support for lung transplant recipients, the Keck Medicine of USC lung transplant team launched a two-year observational pilot study to monitor patients post-discharge using Bluetooth-enabled devices and computer tablets. The devices measured blood pressure, heart rate, weight, blood glucose, oxygen saturation and pulmonary function.

The researchers discovered that monitored patients had 44% fewer hospital readmissions and spent 54% fewer days in the hospital when they were readmitted.

"This study is significant because it is the first to use Bluetooth technology to comprehensively monitor transplant patients," says Felicia Schenkel, MSN, lung transplant manager and lead author of the study. "Lung transplant recipients are a high-risk patient population, and we're happy to see that this program worked so well to improve patients' lives."

The study appeared in the American Journal of Transplantation.

Twenty-eight lung transplant patients received the two-year remote tracking and 28 matched control patients did not. With the exception of remote monitoring, all patients received the same level of post-surgical care, which included regular in-person visits and lung function check-ups. The two groups of patients were also similar in respect to demographics, diagnosis and pre-transplant clinical characteristics.

Monitored patients used computer tablets to report symptoms, track appointments and medication compliance, conduct videoconferences with staff and access educational videos along with other materials.

Patients were asked to measure their vital signs and report symptoms daily for the first three months and after that time, three times a week. The results were sent in real time to the transplant team and triggered alerts if out of normal range.

Patients with high compliance rates on reporting vital signs and symptoms received incentives such as badges and humorous memes. Patients with marginal compliance received encouraging reminders and periodic calls from the transplant team.

At the end of the two years, the tracked patients were readmitted to the hospital 66 times versus 112 for the control group. They were less likely to be admitted for infections and non-organ rejection/non-infection causes such as shortness of breath or hypertension. They also had a lower but not statistically significant readmission for organ rejection and for death.

In addition, when monitored patients were readmitted to the hospital, they spent an average of 12 fewer days per patient per year compared to the control group (approximately 10 days versus 22). Hospital costs were also dramatically cut by 48%, translating to a $132,000 reduction in hospital charges per patient per year.

The at-home tracking worked for two reasons, according to Schenkel. "With constant monitoring, we were able to react to data sooner and take intervening steps before a patient's condition worsened," she says. "In addition, because we incentivized data reporting, patients were more likely to check in with us about their health and report symptoms."

Post-surgical remote monitoring is now standard protocol for all lung transplant recipients at Keck Medicine. The department averages between 30 - 40 lung transplants per year.

In the future, study authors hope other medical teams will follow their lead.

"Real-time remote monitoring of patients is not only beneficial to lung transplant patients but can easily be transferred to other types of transplant or critical care patients," Schenkel says. "This program should be a model for how telemedicine can be used in the future, especially as the need for remote monitoring technology has increased due to the COVID-19 pandemic."

An alternative amplification technique to detect SARS-CoV-2 RNA could offer a way to rapidly test large numbers of people for COVID-19, although the technique is not as sensitive as quantitative RT-PCR, the current standard method for COVID-19 testing. Faster and less complicated testing could aid in the rapid isolation of infected people and could help to identify and prevent new outbreaks of the disease until a vaccine becomes available. Quantitative RT-PCR can successfully detect viral RNA but requires expensive machinery and chemical reagents that can sometimes be in short supply. The standard method also depends on time-consuming temperature cycling steps to amplify enough RNA from a patient sample for detection, resulting in a processing time between 3 and 24 hours in most clinical laboratories. Viet Loan Dao Thi and colleagues instead propose using a technique called reverse transcription loop-mediated isothermal amplification (RT-LAMP), which can be carried out at a constant temperature using simple equipment and a different set of reagents. In their tests of RNA isolated from 768 nasopharyngeal swabs from individuals tested for COVID-19, Dao Thi et al. determined that RT-LAMP was less sensitive than quantitative RT-PCR but could be used to evaluate large groups of people, with an average test processing times of 30 minutes. The researchers concluded that RT-LAMP works best for identifying people with moderate to high amounts of SARS-CoV-2 virus in their bodies, but is not sensitive enough to identify infection in people with a low viral load - such as those at the beginning or end of the illness. The researchers also tested the possibility of using RT-LAMP directly on nasopharyngeal swabs - without the need for RNA isolation - but concluded this technique was less sensitive than using isolated RNA.

INFORMS Journal Management Science Study Key Takeaways:

Organizations that provide a safe workplace have significantly lower odds of survival.

Organizations that would typically have better survival odds, benefit most from not providing a safe workplace.

CATONSVILLE, MD, July 27, 2020 - There are conflicting predictions on the relationship between worker safety and organization survival. New research in the INFORMS journal Management Science finds organizations that provide a safe workplace have a significantly lower chance of survival because it costs to be safe.

The study, "The Tension Between Worker Safety and Organization Survival," conducted by Mark Pagell, Mary Parkinson, Michalis Louis and Brian Fynes of University College Dublin, Ireland, Anthony Veltri of Oregon State University, John Gray of The Ohio State University and Frank Wiengarten of Universitat Ramon Llull in Spain, looked at 100,000 organizations across 25 years in the state of Oregon.

"A safe workforce is burdensome and costly for employers," said Veltri, a professor in the College of Public Health and Human Sciences at Oregon State. "As the amount of work increases and buffers or slack decreases, productivity increases, but so does the likelihood of accidents and other harm to workers. Organizations that do not provide a safe workplace gain an economic advantage by avoiding burdensome costs and being more productive."

Classical economics suggests that safety regulations exists because organizations would not provide a safe workplace on their own volition. Organizations that do get inspected could conclude that the fines for noncompliance are miniscule compared to what it costs to have a safe environment. Safety regulations and policies are intended to prevent harm at work. But the implications are whether it is profitable to provide a safe workplace.

"Workers in unsafe environments engage in self-protection and are not motivated to improve the organization's operations," said Veltri. "While workers in safe environments do not have to dedicate resources to self-protection and can be motivated to engage in improving the organization's operations."

This shows that safety provides a necessary condition to leverage human capital into the development of unique capabilities and long-term competitive advantage. This research linking regulation to proven safety indicates that the impact of an inspection is short-term and that inspections do not improve safety in the long term.

Short-term survival or survival in the immediate future may be enhanced by not taking on the costs of providing a safe workplace. For instance, decreasing costs by eliminating safety training. However, over the long-term, the same organizational conduct could increase the severity and frequency of claims, and destroy rather than build human capital.

"The results predict that for most organizations, enhanced survival will conflict with the goal of protecting the workforce," concluded Veltri.