Culture

Less-than-perfect kidneys can be successfully used for transplants, study shows

image: Johns Hopkins Medicine surgeons performing a kidney transplant. A new study provides the strongest evidence to date that hundreds of currently discarded, less-than-perfect kidneys can be transplanted safely and effectively each year.

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Johns Hopkins Medicine

A new Johns Hopkins Medicine-led study provides the strongest evidence to date that hundreds of deceased donor kidneys, discarded each year after being deemed not suitable under current medical criteria, can be transplanted safely and effectively.

Based on its findings reported in the Jan. 8, 2020, issue of JAMA Network Open, the research team strongly recommends that harvested kidneys with acute kidney injury (AKI) no longer be rejected outright, in order to bolster efforts to reduce the drastic shortage of organs available for transplant in the United States. Currently, the national discard or rejection rate for all potential donor kidneys is approximately 18%, but for AKI kidneys, it jumps to about 30%.

According to October 2019 statistics from the U.S. Department of Health and Human Services, some 95,000 Americans with kidney failure -- also known as end-stage renal disease, or ESRD -- are awaiting donor organs. Unfortunately, as reported by the U.S. Centers for Disease Control and Prevention, nearly 9,000 of these patients drop off the waiting list each year because they cannot get a kidney in time, succumbing to death or deteriorating health that makes transplantation no longer possible.

Making matters worse, says the National Institute of Diabetes and Digestive and Kidney Diseases, the need for donor kidneys is rising at 8% per year, yet their availability has not grown to match.

The latest research confirms on a larger scale the results of an earlier study by Johns Hopkins Medicine-led researchers showing that acutely injured deceased-donor kidneys do not fail or get rejected after transplantation at any greater rate than noninjured kidneys from similar deceased donors.

"We estimate there may hundreds of kidneys with AKI each year that are going unused but could be transplanted," says Chirag Parikh, M.D., Ph.D. M.B.B.S., director of the Division of Nephrology at the Johns Hopkins University School of Medicine and senior author of the JAMA Network Open paper. "Therefore, we are urging the transplant community to bring AKI kidneys into the donor pool with more confidence."

AKI, as described by the National Kidney Foundation, is a "sudden episode of kidney failure or kidney damage that happens within a few hours or a few days." This causes waste products to build up in the blood, making it hard for kidneys to maintain the correct balance of fluids in the body.

AKI symptoms differ depending on the cause and may include: too little urine leaving the body; swelling in the legs and ankles, and around the eyes; fatigue; shortness of breath; confusion; nausea; chest pain; and in severe cases, seizures or coma. The disorder is most commonly seen in hospitalized patients whose kidneys are affected by medical and surgical stress and complications.

In 2018, a team led by Parikh reviewed the medical records documenting approximately 2,500 kidneys transplanted from nearly 1,300 deceased donors -- of which 24% (about 600) had AKI at the time of donation. The researchers reported no significant differences in the rates of organ rejection among kidneys from deceased donors with or without AKI.

For the latest study, the researchers greatly expanded the number of transplanted kidneys analyzed to validate or refute the 2018 results. Organs from 13,444 deceased donors were transplanted into 25,323 ESRD patients in the United States between Jan. 1, 2010 and Dec. 31, 2013. Of this number, 12,810 received kidneys with AKI and 12,513 were given kidneys without any signs of acute injury and that had been matched to the AKI kidneys on other criteria.

For this matching, each AKI kidney was paired at the beginning of the study with a non-AKI kidney using a statistical method that mathematically linked as many donor characteristics as possible, including age, sex, ethnicity and medical conditions other than AKI. This allowed the investigators to more accurately measure the impact, if any, of just AKI on transplant success.

The transplant recipients were followed for four to six years after their surgery.

"We found that deceased-donor AKI had no association with either short-term or long-term survival of the organ, strongly supporting our idea that kidneys with AKI should be actively harvested and transplanted," Parikh says.

To determine how many potentially viable kidneys with AKI were lost during the study period (2010 to 2013), the researchers looked at how many deceased donor kidneys with AKI were recovered, then either transplanted or discarded.

"We found that although nearly 17,500, or 85%, of the more than 20,500 available AKI kidneys were harvested over the three years, only slightly more than 12,700 were transplanted," Parikh says. "This means almost 8,000 organs were either rejected after procurement or never obtained at all simply because the donors had acute kidney injury."

Increasing the donor pool to include AKI kidneys, Parikh adds, would help achieve the goal of the Advancing American Kidney Health initiative, a 2019 presidential directive that aims to double the number of kidneys available for transplant by 2030.

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Johns Hopkins Medicine

Egg-based flu vaccines: Not all they're cracked up to be?

Flu season is underway in the Northern Hemisphere, sickening millions of people and in rare cases, causing hospitalization or death. The best prevention is a flu shot, but it's not unusual for these vaccines to be less effective than intended. Some researchers suspect that the common practice of producing vaccines in chicken eggs could be partially to blame, according to an article in Chemical & Engineering News (C&EN), the weekly newsmagazine of the American Chemical Society.

Before each flu season, the World Health Organization (WHO) selects specific influenza viruses to include in that year's shot. Currently, most vaccines are made by growing these viruses in fertilized chicken eggs, purifying the viruses and inactivating them. However, sometimes the WHO guesses wrong on which viruses will be active that year, or viruses mutate in the wild so that they are different from the ones in the flu shot. Viral mutations can also occur during vaccine production: Because avian cells display different proteins on their surfaces than human cells, sometimes the influenza virus mutates so that it can better latch onto and infect bird cells, Associate Editor Leigh Krietsch Boerner writes. As a result, the immune system of a person who got a flu shot might not recognize and attack the influenza virus they become infected with.

Partly in response to this concern, some manufacturers have developed egg-free methods. For cell-based vaccines, viruses are grown in canine kidney cells, which are more similar to a human's than bird cells are. To produce recombinant vaccines, researchers transcribe viral antigens - cell-surface proteins that trigger an immune response - into DNA, which they insert into a carrier virus. This virus is then used to infect the cells of fall armyworms, which make large amounts of the flu antigen proteins. However, few studies have been conducted on whether the egg-free preparations are really more effective, and most scientists agree that getting any flu vaccine is better than none.

The article, "Flu shots aren't always effective. Could chicken eggs be a culprit?," is freely available here.

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American Chemical Society

Catalytic protocells get zingy

image: Darkfield microscopy image of a single multi-compartmentalized capsule containing thousands of catalytic protocells that decompose hydrogen peroxide into water and oxygen gas.

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Dr. Pierangelo Gobbo and Dr. B. Pavan Kumar, University of Bristol

Artificial cells capable of oxygen gas production and chemical signalling have been prepared using a combination of synthetic and biological catalysts through an international collaboration between the University of Bristol and the University of Padua in Italy.

From the synthesis of drugs to the generation of plastics, catalysts - substances that speed up chemical reactions without being consumed - are the backbone of many industrial processes.

Catalysts come in many forms such as inorganic nanoparticles, organic liquids and aqueous enzymes, and can be linked to solid surfaces to increase their performance.

In a new study published in the journal Nature Communications, an international research team, led by University of Bristol chemists, used two different types of catalysts to develop a new type of artificial cell capable of decomposing hydrogen peroxide and generating oxygen.

The team used a ruthenium-based inorganic catalyst in the form of a synthetic enzyme (synzyme) as a membrane structuring agent to generate copious amounts of oxygen bubbles that they then exploited to construct synzyme-driven buoyant microcapsules.

In addition, the natural enzyme horseradish peroxidase was captured inside the protocells so that the synthetic and biological catalysts competed for hydrogen peroxide present in the solution.

The team used the antagonistic arrangement of the two catalysts to implement a rudimentary chemical signalling pathway between members of an artificial protocell community that were dispersed in solution or trapped within small droplets.

Professor Marcella Bonchio, from the University of Padua, said: "As the ruthenium-based catalyst has significant potential in bio-inspired catalysis, it seems feasible that communities of synzyme protocells could provide a step towards synthetic metabolic networks based on light-activated stimuli."

Professor Stephen Mann from the University of Bristol's School of Chemistry, added: "Our results highlight a new type of catalytic micro-compartment with multi-functional activity and provide a step towards the development of protocell reaction networks."

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University of Bristol

Directly measuring function in tiny hearts

image: Directly measuring neonatal heart function Image caption The COstatus Monitor uses an extracorporeal loop attached to arterial and venous lines to measure cardiac output using ultrasound dilution. The research team injected 1mL/kg of body temperature saline into the loop and performed up to two measurement sessions daily.

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Children's National Hospital

The amount of blood that the heart pumps in one minute (cardiac output) can be directly measured safely in newborns by monitoring changes in blood velocity after injecting saline, indicates a paper published online Dec. 17, 2019 in the Journal of Pediatrics and Neonatal Medicine. The research, conducted by Children's National Hospital faculty, is believed to be the first clinical study of direct cardiac output measurement in newborns.

Right now, cardiac output is measured indirectly in the nation's neonatal intensive care units (NICU) using newborns' blood pressure, heart rate, urine output and other indirect measures. However, these techniques can produce imprecise readings in children. And the field lacks a feasible "gold standard" to measure cardiac output in newborns.

The COstatus monitor already uses ultrasound dilution - the expected decrease in the velocity of blood when saline is injected, producing a dilution curve. A Children's National research team used ultrasound dilution in their small pilot study to gauge the feasibility of directly measuring cardiac output in newborns.

"Infants who stand to benefit most from directly monitoring cardiac hemodynamics are often so sick they already have central venous access," says Khodayar Rais-Bahrami, M.D., an attending neonatologist at Children's National and the study's senior author. "Using the COstatus monitor in these children would enable the clinical team to personalize care based on the newborn's current hemodynamic status, while introducing minimal fluid during measurements," Dr. Rais-Bahrami adds.

The research team recruited 12 newborns younger than 2 weeks old who already had central venous and arterial access. The venous line of the arteriovenous AV loop is connected to the umbilical venous catheter while the COstatus monitor's arterial line is connected to the umbilical arterial catheter. During measurement sessions, two injections of solution are injected into the venous loop, allowing for two measures of cardiac output, cardiac index, active circulating volume index, central blood volume index and systemic vascular resistance index.

Infants enrolled in the pilot study underwent up to two measurement sessions per day for up to four days, for a total of 54 cardiac hemodynamic measurements. The newborns ranged from 720 to 3,740 grams in weight and 24 to 41.3 weeks in gestational age.

The infants' mean cardiac output was 0.43L/min and increased with gestational age. By contrast, the mean cardiac index was 197mL/kg/min and changed little with infants' increasing maturity - either by gestational age or postnatal age. Two of the study participants were undergoing therapeutic cooling for hypoxic-ischemic encephalopathy and had their measurements taken during cooling and after rewarming.

"Although this study size is small, it demonstrates that this minimally invasive technique can safely be used in newborns to directly measure cardiac hemodynamics," says Simranjeet S. Sran, M.D., a Children's National neonatalogist and the study's lead author. "This technology may allow for more precise and personalized care of critically ill newborns in a range of disease states - real-world utility in NICUs that serve some of the youngest and sickest newborns," Dr. Sran adds.

The research team notes that direct measurement by ultrasound dilution revealed a stark increase in cardiac index as infants undergoing therapeutic hypothermia were rewarmed, raising questions about whether indirect measures using other technology, such as echocardiography, underestimate hypothermia's effect on hemodynamics.

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Children's National Hospital

Next generation wound gel treats and prevents infections

Researchers at Lund University in Sweden have developed a new hydrogel based on the body's natural peptide defense. It has been shown to prevent and treat infections in wounds. The formulation kills multi-resistant bacteria, something that is increasing in importance with antibiotic resistance growing globally.

"The ability to effectively heal wounds is key for our survival in evolutionary terms. There are peptides in wounds that defend against bacteria and prevent their toxins from causing inflammation. The gel is based on these natural defense mechanisms and has had a dual effect - by both preventing as well as treating wound infections", says Artur Schmidtchen, professor of dermatology and venereology at Lund University.

There is an increasing need for new treatments that improve wound healing and reduce complications in patients with various types of wounds, such as burns, surgical wounds, or other types of wounds that don't heal easily. Current treatments are primarily directed solely at the bacteria. The patient is treated with antibiotics either preventively or when they get an infection, and various antiseptics are used. The extensive use of antibiotics is adding to the issue of antibiotic resistance. Infections with multi-resistant bacteria are a major global problem today, and they cannot be treated with antibiotics.

"Antibiotics and antiseptics kill the bacteria but do not affect the subsequent harmful inflammatory process. Another problem is that the active substances in today's antiseptic wound treatment often are toxic and harmful to the environment. We have not seen this with our active substance, and it also kills multi-resistant bacteria", says Artur Schmidtchen.

The wound gel is not only antibacterial, it also has an immunosuppressive effect. The researchers have previously shown that the peptides in the gel can inactivate so-called lipopolysaccharides (LPS), that are found in cell walls of bacteria, and that trigger an inflammatory reaction. The reaction is an essential part of our immune system as we quickly respond to and fight bacteria.

"However, severe and uncontrolled inflammation inhibits wound healing, and it is very interesting to see that the gel lowers the inflammatory response within 24 hours of the treatment, and then further reduces the bacterial levels over a period of 3 to 4 days.

We have designed a whole new type of treatment that uses nature's own principles by not only killing bacteria but also acting as an immune-modulatoring", says Manoj Puthia, researcher at Lund University and first author of the study.

The researchers are now planning a collaboratingon with the company in2cure AB in order to get the gel approved for use in clinical studies involving patients with burn injuries.

"We will also look into the possibility of developing new peptide-based drugs for eye infections and infections in other internal organs. It could become a new way of treating both infection and inflammation without using antibiotics", concludes Artur Schmidtchen.

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Lund University

Fish switch: Identity of mystery invader in Florida waters corrected after 20 years

image: The chanchita, Cichlasoma dimerus, is a subtropical species native to southern South America. For at least 20 years, it has also made its home in Central Florida waters, where it was misidentified as a similar-looking invasive fish, the black acara.

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Ryan Crutchfield/FishMap.org

GAINESVILLE, Fla. --- Sometimes scientists make mistakes. Case in point is the chanchita, a South American freshwater fish that has been swimming in Florida's waters for at least two decades, all the while identified by experts as another invader, the black acara.

Although the two species look strikingly similar, the black acara is tropical, a native of equatorial South America, while the subtropical chanchita isn't typically found north of Southern Brazil. Because the chanchita is more cold-tolerant, researchers say it could have a more widespread impact in Florida than the black acara and could threaten native species in North Central Florida ecosystems.

"Even the professionals get it wrong," said Robert Robins, Florida Museum of Natural History ichthyology collection manager. "The chanchita has been right here, right under our noses. It's spread into seven different counties and five different river drainages in Florida, well beyond the Tampa Bay drainage where it appears to have been first introduced."

Introduced by the pet trade, the black acara has been a well-known invader in the Miami area since the 1950s and is now common in South Florida. When a similar cichlid appeared in the waters draining into North Tampa Bay around 2000, scientists assumed the black acara was simply expanding its range or had been introduced a second time.

The misidentification was finally spotted by sharp-eyed amateur fish collectors as well as Mary Brown, a biologist who studies non-native fishes. Brown questioned Robins' assertion that a specimen he brought home from holiday collecting near Tampa in 2017 was a black acara, Cichlasoma bimaculatum. Although the fish had the same general appearance, something wasn't adding up.

"The body color and the pattern on the scales on its head just looked a little different," said Brown, a scientist at the U.S. Geological Survey Wetland and Aquatic Research Center. "It wasn't the same as the black acara I've come across while conducting non-native fish surveys in South Florida."

Meanwhile Ryan Crutchfield, founder of the fish identification database FishMap.org, was getting feedback from amateur collectors that he'd misidentified a fish as a black acara for an article on the history of the species in Florida. Crutchfield, Robins and Brown took a closer look at the specimens in question, eventually identifying them as the chanchita, Cichlasoma dimerus.

"I don't think anyone except for the amateurs who have an interest in fishes of Florida thought twice about whether or not these fish were black acara," Robins said. "They're out there collecting stuff while quite honestly a lot of us are stuck behind our computers typing emails."

Because of their hardiness and bright colors, cichlids are often coveted by aquarists. But with about 1,900 species - 20 of which are invasive in Florida - and constant revision to the family's classification, cichlid identification becomes tricky, Robins said.

Robins said that life color, or how a fish appears in its environment, was likely an essential indicator to amateur collectors the chanchita had found its way to Central Florida. Cichlids can change color according to their surroundings, temperament and time of day. But the colorful variations between species disappear in a laboratory setting, where they're often preserved in alcohol and lose nearly all coloration.

"When we started going out into the field and collecting them and actually finding them in breeding condition or as dominant males, they're stunningly beautiful," Robins said. "I think that's what the amateur community was keying in on. They're the ones detecting life color, and that was really instructive in determining this was a different species."

Once the researchers determined the Tampa invader wasn't a black acara, it came down to microscopic differences in physiology to identify the species as the chanchita. They relied on CT scanning to zoom in on the number of teeth in the specimen's outer lower jaw and tiny fingerlike structures along the fish's fourth gill arch.

The Florida Museum's ichthyology collection was instrumental in providing insight into the chanchita's invasion timeline, with specimens dating back 20 years. These specimens had been incorrectly cataloged as black acara, but were key indicators of when the chanchita colonized Central Florida, where the species formed reproducing populations as early as 2000.

Brown said non-native fish species like the chanchita have the potential to impact Florida's aquatic ecosystems by outcompeting native fishes for habitat and food resources.

"Locating and identifying non-native fishes requires an interdisciplinary approach and coordination with partners from across the state," she said. "This finding is leading us to look at other non-native fish species - it's possible that there may be other fish out there that are misidentified, and properly identifying the species is critical for proper management."

Florida is a welcoming arena for invaders to compete with native species and one another due to the state's intersection of tropical and temperate climates. Constant invasions pose a challenge to conservationists and can often threaten already-endangered native species. Robins said Florida waters could be the chanchita's first chance at meeting the black acara - and what happens afterward is anyone's guess.

"Will they hybridize? Would it matter other than just making things more confusing? Are there other species of acara that have been let loose and established populations? What's actually happening in the environment?" Robins said. "Florida's aquatic ecosystems are, in a nutshell, one big experiment."

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Florida Museum of Natural History

People view rationality and reasonableness as distinct principles of judgment

When it comes to making sound judgements, most people understand and distinguish that being rational is self-serving and being reasonable is fair and balanced, finds new research from the University of Waterloo.

The study is the first systematic attempt to explore what people consider to be sound judgment and whether they understand rationality and reasonableness along the lines advocated by experts in economics, law, and other social scientists.

"Our results show that laypeople grasp economists' view of rationality, yet they favour socially pragmatic reasonableness as a separate standard of judgment," said Igor Grossmann, professor of psychology at Waterloo and lead author on the study.

To understand how the general public views rationality and reasonableness, Grossmann collaborated with colleagues in Canada and Pakistan to examine impressions of rational and reasonable persons and actions.

"The concept of rationality that we found lay people have corresponds to economists' definition, which emphasizes abstract logic and pursuit of self-interest," said Grossmann. "We also found people tend to uphold a distinct standard of reasonableness that corresponds to philosophical traditions encouraging context-specific balance of self-interest with fairness."

The researchers analyzed the use of the terms "rational" and "reasonable" in web-based news, US Supreme Court Opinions, scripts of popular soap operas, and Google books covering languages spoken in 1/6 of the world today. They quantified common characteristics attributed to rational and reasonable persons.

Researchers also surveyed laypeople's common stereotypes of rational and reasonable agents, and performed 13 experiments contrasting cooperative and self-serving behavior in economic games. Experiments involved participants in North America as well as urban and rural Pakistan.

"Rationality and reasonableness lead people to different conclusions about what constitutes sound judgment in dilemmas that pit self-interest against fairness," said Richard Eibach, professor of psychology at Waterloo and a co-author of the study. "People view rationality as absolute and preference-maximizing, whereas they view reasonableness as paying attention to particulars and fairness."

Researchers also found that people use rational and reasonable standards of judgment strategically, favouring a rational person to represent their side in economic and social disputes, but choosing a reasonable person to represent the other side.

"These findings cast prior demonstrations of people's irrationality in a new light," says Grossmann. "People may choose to be irrational when it violates their preferred standard of reasonable, socially-conscious behavior."

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University of Waterloo

Better science through peer review

The BioScience Talks podcast features discussions of topical issues related to the biological sciences.

Peer review lies at the heart of the grant selection process and, by extension, the scientific enterprise itself. For scientific curiosity to be shaped into concrete research, grant-making bodies must decide which research questions are in the most urgent need of answers--and which researchers are best able to answer them. To inform those decisions, funders rely on grant reviewers--most of whom volunteer their time--to evaluate numerous proposals and recommend the most promising among them. However, despite its massive importance to science and society, peer review itself remains inadequately studied and often poorly understood.

To shed light on this critical institution, American Institute of Biological Sciences chief scientist Stephen Gallo and his colleagues recently published the results of a major survey. It is joined by a grant review report from Publons, a company housed within Clarivate Analytics that helps researchers track their research and review outputs and works to encourage greater recognition of scientists' work.

The publications bear striking similarities. In particular, both highlight the value embedded in the present system, with 78% of participants in the Publons survey reporting that peer review is the best way to allocate research funding and 87% of the respondents to the AIBS survey stating that peer review has had a positive effect on their careers. Troublingly, however, the surveys unearthed potential sustainability problems, with a small number of reviewers carrying out a disproportionately large share of the reviews. Publons, for instance, found that 4% of reviewers were responsible for 25% of the work; the AIBS survey had similar results. To improve reviewer participation and increase the sustainability of the system, the reports encouraged greater professional recognition for reviewer efforts, which are infrequently considered in hiring and promotion decisions.

In this episode of BioScience Talks, we are joined by Stephen Gallo and Matthew Hayes, director of Publons, who discuss the survey results and shed light on the future of peer review.

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American Institute of Biological Sciences

How universities may help bridge social divide between international, domestic students

BUFFALO, N.Y. - Self-esteem is a valuable resource for undergraduate international students trying to socialize with their domestic counterparts at American universities, but new research by a University at Buffalo psychologist suggests that while self-esteem predicts better socialization with domestic students, it is curiously unrelated to how international students socialize with other internationals.

"Self-esteem affords confidence," says Wendy Quinton, a clinical associate professor of psychology in UB's College of Arts and Sciences. "So people higher in self-esteem have more belief in themselves and their abilities, and that is particularly helpful when trying to initiate contact with people from the host culture."

Understanding that self-esteem -- someone's feelings of self-worth and personal value -- contributes to socialization with one group and not the other is among the factors distinguishing Quinton's study, recently published in the International Journal of Intercultural Relations.

"These results underscore the importance of examining individual differences to better understand how international students adapt to their new learning environment," says Quinton, PhD, an expert in the international student experience. "The findings also indicate that self-esteem may be viewed as a coping resource for international students when they interact with domestic students."

In addition to self-esteem, Quinton also examined university identity and perceived discrimination in the current study.

University identity, the degree to which students feel connected with their university community, was associated with greater socialization with both groups, although not as strongly as self-esteem. Perceived discrimination, the feeling that you or a group you belong to is the target of prejudice, was unrelated to socialization.

Previous research in this area hasn't looked at these predictors of socialization together, nor has it explored the interesting divergence between the two student groups, a method that enabled Quinton to statistically control for socialization with one group in order to investigate the other.

"This approach allowed for a specific test of what predicts socialization with each student group, above and beyond an individual's general level of sociability," she says.

International students often prioritize interacting with host nationals as an important part of their experience while studying in the U.S. But for the vast majority of international students, that aspiration is a challenging and often unfulfilled goal, hampered by structural barriers that range from cultural adaptation to navigating the trials of higher education.

But socialization has benefits beyond human interaction. It's associated with less depression, lower levels of homesickness, better stress management, and greater life satisfaction. It is not friendship, but rather an entry-level interaction between people with the potential to become friendship, which Quinton measured as time spent doing joint recreational activities, with whom people are studying and with whom they choose to spend their free time.

Quinton's study focused on East and Southeast Asian students, the largest international demographic attending American universities.

"This group also has some of the largest cultural divides to bridge when coming to the U.S.," says Quinton. "The independence emphasized in Western culture is often at odds with the emphasis on cooperation and interdependence in collectivistic cultures like China, South Korea and many Southeast Asian countries. That's a very different orientation to what these students are accustomed to in their home culture."

But it's something universities can address, according to Quinton. Anything that fosters a connection and sense of a shared experience between international and domestic students, both the stress and anxieties, as well as the joys and pleasures, is going to be a "win-win." Quinton also highlighted low self-esteem as "a potential risk factor for international students, one that universities might look for in terms of identifying students who are potentially vulnerable for missing out."

"International students who fall short of the expected connection with U.S. students are clearly disappointed, but there's also a loss for the domestic student population, entering a global community, who are deprived of the benefits associated with interacting with people from varied and different backgrounds.

"Domestic students, in this case, are undoubtedly losing out, by not getting to know international students," says Quinton.

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University at Buffalo

APS Tip Sheet: Trudging until take-off

image: How noodles' mechanical properties control the way they soften.

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APS Journals

December 27, 2019 - With packed flights during the holiday season, getting from jet bridge to plane seat seems to take forever. Some airlines have tried to speed up the process by boarding passengers from back-to-front or boarding those without overhead luggage first. However, these practices have been challenging to implement. Now, scientists from universities in Norway, Latvia, and Israel suggest letting slow passengers board first may actually decrease time before take off. Researcher Erland et al. wanted to know whether there was in fact an optimal boarding process, so used physics to they created a model to simulate passengers trying to reach their seats. They predicted the passengers' speed based on their line position, row designation, and aisle-clearing time. The model calculated the average boarding time for passenger groups by gauging how long it would take each group to clear the plane's aisles. Results showed that boarding slow passengers first is up to 28% faster. Boarding time remained faster regardless of the percentage of slow passengers and how fast they cleared the aisles. The findings could inform airline boarding policies.

Credit: 
American Physical Society

An often-made claim that e-cigarettes are '95% safer' is not valid

video: Thomas Eissenberg, Ph.D., co-director of the Center for the Study of Tobacco Products at Virginia Commonwealth University, on the claim that e-cigarettes are 95% safer.

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Virginia Commonwealth University

The frequently cited claim that e-cigarettes are "95% less risky" or "95% less harmful" than combustible cigarettes is outdated, misleading and invalid -- and should no longer be made in discussions on the dangers of vaping, according to an editorial published today in the American Journal of Public Health by six leading experts on e-cigarettes and public health.

"The '95% safer' estimate is a 'factoid': unreliable information repeated so often that it becomes accepted as fact," wrote the authors, including Thomas Eissenberg, Ph.D., co-director of the Center for the Study of Tobacco Products at Virginia Commonwealth University.

"Public health practitioners, scientists, and physicians should expose the fragile status of the factoid emphatically by highlighting its unreliable provenance and its lack of validity today, noting the many changes in e-cigarette devices and liquids, the accumulation of evidence of potential harm, the increased prevalence of use, and the growing evidence that e-cigarette use is associated with subsequent cigarette smoking," they wrote.

The editorial, "Invalidity of an Oft-Cited Estimate of the Relative Harms of Electronic Cigarettes," re-examines the "95% safer" claim that originated in July 2013 when a group of experts in decision science, medicine, pharmacology, psychology, public health policy and toxicology rated the relative harm of 12 nicotine-containing products by using 14 criteria addressing harms to self and others. They concluded that combustible cigarettes were the most harmful and that electronic nicotine delivery systems were substantially less harmful.

However, the experts acknowledged that their study lacked hard evidence for the harms of most products it was evaluating. Despite that lack of evidence, the claim that e-cigarettes are "95% less risky" or "95% less harmful" was widely publicized, notably by Public Health England and the Royal College of Physicians.

Since then, Eissenberg and his co-authors wrote, a considerable amount of evidence of the potential harms of e-cigarettes has accumulated.

E-cigarette devices have changed significantly since the original study, they wrote, so much so that even if the original estimate was valid in 2013, it can no longer apply.

"For example, in addition to using different materials and more numerous heating coils, many e-cigarettes today can attain power output that exceeds that of most over-the-counter 2013 models by 10 to 20 times (i.e., up to and sometimes exceeding 200 watts)," they wrote. "Greater power increases the potential harms of e-cigarette use because more aerosol is produced that exposes users to increased levels of nicotine and other toxicants."

E-liquids also have changed since 2013, with widespread availability of thousands of flavors that use chemicals "generally recognized as safe" to eat but with unknown pulmonary toxicity, they wrote.

One particularly notable change has been the pervasive marketing of liquids with protonated nicotine, also known as "nicotine salt," which is made by adding an acid to free-base nicotine. Aerosolized protonated liquid is less aversive to inhale than free-base nicotine, thereby allowing users to increase the nicotine concentration of the liquid and likely increase their own nicotine dependence.

"Protonated nicotine e-cigarette liquids are available today in concentrations greater than 60 milligrams per milliliter, and these liquids have become very popular, sparking a 'nicotine arms race,'" they wrote.

Recent evidence also suggests that vaping harms users. One recent study cited in the article found that "[e-cigarette] aerosol constituents could injure the respiratory system or worsen preexisting lung disease through a variety of mechanisms." It also points to research associating wheezing, a symptom of potential respiratory disease, with e-cigarette use. And it notes that e-cigarette use has been shown to increase heart rate, blood pressure and platelet activation, and decrease flow-mediated dilation and heart rate variability, effects that suggest long-term cardiovascular risk.

The editorial also highlights research conducted since 2013 that found e-cigarette use is linked with a greater risk of the user starting to smoke combustible cigarettes.

Studies in the past six years also have shown that e-cigarette aerosol is not harmless, they wrote.

"For example, propylene glycol (PG) is one of the primary constituents of e-cigarette aerosol and is generally recognized as safe when eaten but, when injected intravenously over a period of days, is toxic," they wrote. "E-cigarette aerosols containing propylene glycol and vegetable glycerin, another common constituent, cause inflammation in human lungs, suggesting differing safety profiles for inhaled versus ingested propylene glycol and vegetable glycerin."

Along with Eissenberg, a professor in the VCU Department of Psychology in the College of Humanities and Science, the editorial was co-written by Aruni Bhatnagar, Ph.D., of the American Heart Association Tobacco Regulation Center, University of Louisville; Simon Chapman, Ph.D., of the School of Public Health, University of Sydney, Australia; Sven Eric Jordt, Ph.D., of the Department of Anesthesiology, Duke University School of Medicine; Alan Shihadeh, Sc.D., of the Maroun Semaan Faculty of Engineering and Architecture, American University of Beirut in Lebanon; and Eric K. Soule, Ph.D., of the Department of Health Education and Promotion, East Carolina University.

Eissenberg and his colleagues were inspired to write the editorial after hearing report after report at the annual meeting of the Society for Research on Nicotine and Tobacco on the risks associated with e-cigarette use.

"It just occurred to me that with all these pieces of evidence, that we needed perhaps to revisit this '95% safer' claim to see whether it still had any validity today," Eissenberg said. "We all agreed that this was something that we really needed to do. We wanted people to take a look at the number and decide for themselves."

It's important to understand the "95% safer" claim is bogus, he said, because it continues to be cited as a reason to start or continue vaping.

"People are using that claim as a reason to either keep using e-cigarettes if they started some time ago, or if they're nicotine-naive -- if they've never used nicotine before -- they hear 95% safer than combustible cigarettes and they say, 'Well, that's safe enough for me.' And so then they started using," he said.

The editorial's biggest takeaway, Eissenberg said, is that we simply do not know the long-term risks of e-cigarette use.

"It doesn't make any sense for us to claim that we know that it's 95% safer than combustible cigarettes," he said. "The fact is: we don't know whether e-cigarette use is as lethal as combustible cigarette use, less lethal than combustible cigarette use, or more lethal than combustible cigarette use.

"You have to understand: We've been studying combustible cigarettes for the last 60 to 70 years. And so we have a huge database with which we can look at how many people die from that behavior," he continued. "We don't have anything near that kind of history with electronic cigarettes. What we do know is that they are delivering toxicants to the human lung and that over repeated use, in some cases, we see health effects from those toxicants that e-cigarette users are inhaling."

Credit: 
Virginia Commonwealth University

How do corals make the most of their symbiotic algae?

image: A fluorescence image of the sea anemone Exaiptasia pallida, which was used in this study. The red dots each represent fluorescence from a single symbiotic algae, Breviolum minutum.

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Photograph is courtesy of Tingting Xiang

Stanford, CA-- Corals depend on their symbiotic relationships with the algae that they host. But how do they keep algal population growth in check? The answer to this fundamental question could help reefs survive in a changing climate.

New work published in Nature Communications by a team including Carnegie's Tingting Xiang, Sophie Clowez, Rick Kim, and Arthur Grossman indicates how sea anemones, which are closely related to coral, control the size of their algal populations that reside within their tissue.

Like corals, anemones host photosynthetic algae, which can convert the Sun's energy into chemical energy. An alga shares some of the sugars that it produces with its anemone or coral hosts, which in turn provide the alga with other necessary nutrients such as carbon dioxide, phosphorus, sulfur, and nitrogen.

The molecular mechanisms underlying this relationship have remained mysterious.

"We are eager to understand the precise interactions between the alga and its host because if algal populations within the host disappear--as happens during bleaching events caused by ocean warming or pollution--the corals and anemones lose access to vital sustenance and may not be able to survive. On the flip side, rampant population growth of symbiotic algae could overtax the hosts' metabolism and make them susceptible to disease." Grossman explained. "We want to understand how corals and anemones maintain a balance, which may enable us to assist threatened reef communities."

The researchers--including Stanford University's Erik Lehnert, Jan DeNofrio, and John Pringle, as well as UC Riverside's Robert Jinkerson--revealed that limiting the supply of shared nitrogen is key to an anemone's ability to control the size of its symbiotic algal population.

The team demonstrated that as the populations of the symbiotic alga Breviolum minutum, hosted by the anemone Exaiptasia pallida, reached high densities, they expressed elevated levels of cellular products specifically associated with nitrogen limitation. This is the same behavior that is observed in free-living algae that are growing outside of the host when available nitrogen in their environment becomes scarce.

Crucially, as the population of algae within the host tissue increases, they deliver more and more photosynthetically produced sugars to the anemone. The anemones can then use the carbon backbones of these molecules to retain and recycle its nitrogen-containing ammonium waste. This arrangement both results in more robust anemone growth and limits the amount of nitrogen available to the algae. So, the team demonstrated that the dynamics of nutrient exchange between the algae and the anemone change as the algal population increases, which is the key to understanding algal population control within the host.

"Our work elucidates how the association between anemones and algae, or coral and algae, ensures that this symbiotic relationship remains stable and beneficial to both partner organisms," said lead author Xiang, who is now an assistant professor at UNC Charlotte. "With ongoing research, we hope to even better understand the various mechanisms and specific regulators that are crucial for integrating the metabolisms of these two organisms, which could eventually allow for the transplantation of hardier algae into bleached coral and also for manipulating both corals and algae to have greater tolerance to adverse conditions."

Credit: 
Carnegie Institution for Science

New research shows live chats can increase sales by nearly 16%

CATONSVILLE, MD, January 8, 2020 - Live chat tools allow for communication between sellers and buyers. They are popular instruments for e-commerce sites that don't have the advantage of face-to-face communication that brick-and-mortar stores do. New research in the INFORMS journal Information Systems Research says these live chats can actually increase sales and boost profits.

The study, "Impact of Live Chat on Purchase in Electronic Markets: The Moderating Role of Information Cures," looked at data from Alibaba on consumers' purchase decisions of Apple and Samsung tablets from March through June 2013.

"We found live chat can increase purchase probability of tablets by 15.9%," said Xue (Jane) Tan of Indiana University. "We see that human interaction results in better sales performance."

Tan, Youwei Wang of Fudan University and Yong Tan of the University of Washington say the fact that sellers and buyers cannot speak in person, like brick-and-mortar stores, leads to uncertainty about product quality and seller credibility. Live chat tools allow e-vendors to communicate with customers in real time.

The data source, Alibaba, has a reputation of being similar to eBay, where feedback is collected after each transaction. The data consisted of consumer browsing, live chat and purchase histories. The live chat tool is moderated by existing information cues: product sales volume and seller feedback score.

"Sellers with limited feedback benefit more from live chat conversations than sellers with a lot of feedback. And products with high past sales volume sell better after live chat, indicating a reinforcement effect," continued Tan. "It is interesting that a seller can sell multiple products with varying levels of sales performance, and the seller feedback is measured based on all products."

Credit: 
Institute for Operations Research and the Management Sciences

Pretrial publicity hinders prosecutors' ability to prove guilt

Media coverage is more likely to influence jurors to vote for acquittal than for conviction. This new finding challenges arguments that pretrial publicity is of greater concern to defendants due to their Sixth Amendment right to a fair trial.

Researchers at the University of South Florida studied the verdicts of juries exposed to news articles perceived to weaken the prosecution's case (anti-prosecution), such as those that question whether the right person is on trial, and compared them to stories that strengthen the likelihood of a defendant's guilt (anti-defendant). They found juries purely exposed to anti-prosecution stories ahead of deliberation delivered 'not guilty' verdicts 100 percent of the time. However, those whom solely read anti-defendant articles delivered 'guilty' verdicts just 38 percent of the time. This research also discovered that pretrial publicity has a strong impact on how jurors interpret evidence and their impressions of key trial players, such as witnesses and defendants.

The study published in Psychology, Public Policy, and Law is based on CA v. Debra Cummings. The then-babysitter was charged in the 1990 murder of a nine-month-old boy placed in her care. Researchers formed 96 mock juries comprised of 500 people between ages 18 and 58 whom were unfamiliar with the case. Prior to the trial, the authors provided 67 percent of participants six news articles. Half were edited to appear anti-prosecution and included information about the victim's parents' prior criminality and lack of concern for the baby's injuries. The others mentioned how the babysitter had another child die in her care, alluding to the defendant's guilt. The remaining 33 percent of jurors were not exposed to any pretrial publicity.

The jurors were broken into six groups of 16 juries, each group with a specific composition based on familiarity with the case. They watched recordings of the actual trial, which included opening and closing arguments, testimony from four doctors, direct and cross-examination of the victim's mother and the defendant, direct examination of the victim's father and testimony from the defendant's sister.

Study participants issued jury verdicts and provided their personal verdicts before and after the trial to determine the influential power of deliberation. Researchers discovered that deliberating on juries consisting of only anti-prosecution jurors resulted in an increase in anti-prosecution bias, with jurors being more likely to render a 'not guilty' verdict after deliberations than prior to them. In addition, jurors exposed to anti-prosecution publicity swayed their fellow jurors without background on the case to vote 'not guilty' 81 percent of the time, while those whom read anti-defense-slanted stories influenced the others to vote 'guilty' 38 percent of the time.

"These findings suggest that the courts, in high-profile cases, should not rely on jury deliberation to correct the bias associated with pretrial publicity exposure - doing so may result in an increase or spread of bias," said Christine Ruva, PhD, psychology professor at the University of South Florida Sarasota-Manatee. "In addition, juror exposure to pretrial publicity should not only be the concern of the defense's efforts to be granted a fair trial but should also be the concern of prosecutors as it can challenge their ability to prove guilt."

Other remedies to prevent bias include judges granting a change of venue, yet that rarely happens. The jury selection process is also designed to eliminate potential jurors influenced by pretrial publicity. However, it's difficult for the defense to prove their client won't receive a fair trial. The Fourteenth Amendment's Due Process Clause does not require potential jurors to be questioned about their knowledge on specific case information and the Sixth Amendment's impartial jury requirement is satisfied when prospective jurors refrain from stating they've been prejudiced by pretrial publicity.

CA v. Cummings resulted in a retrial, in which Cummings was acquitted of all charges in 1994.

Credit: 
University of South Florida

Could pancreatitis be a stress hormone deficiency?

image: UTSW researchers (from left) Genaro Hernandez, Dr. David Mangelsdorf, and Dr. Steven Kliewer examine pancreatic section slides related to their study that found a stress hormone deficiency may lead to pancreatitis.

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UTSW

DALLAS - Jan. 8, 2020 - In work that could have clinical implications, UT Southwestern researchers find that humans and mice with pancreatitis are deficient in a stress hormone called FGF21. Normally, FGF21 is more abundant in the pancreas than in any other organ in the body. They also show that replacement therapy reverses the condition in mouse models in about 24 hours and may even prevent it.

The study published today in Science Translational Medicine also reports success with a second treatment strategy. A potential drug called a PERK inhibitor targets a different step in the integrated stress response, the cellular pathway affecting the amount of fibroblast growth factor 21 (FGF21) available in the pancreas.

"Given that several FGF21 drug candidates are or soon will be in clinical trials for conditions related to metabolic disease, it may be possible to test fibroblast growth factor 21 for treating human pancreatitis in the near future," says David Mangelsdorf, Ph.D. In addition to being chair of pharmacology, Mangelsdorf is an investigator in the Howard Hughes Medical Institute (HHMI). He adds that he knows of no current investigations of PERK inhibitors for clinical use.

Pancreatitis, a debilitating and sometimes deadly inflammation of the pancreas, can be acute or chronic. It accounts for about 275,000 U.S. hospitalizations each year, with its incidence on the rise for reasons that are unclear. The many causes of pancreatitis include long-term alcohol abuse, gallstones, and certain inherited conditions, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health (NIH). Pancreatitis also can occur as a complication of endoscopic retrograde cholangio-pancreatography, or ERCP, a procedure in which a camera, contrast dye, and X-rays are used to view the bile duct, gall bladder, and pancreatic ducts.

Treatment for acute pancreatitis is generally supportive. Most patients recover after a few days in the hospital, where they are given intravenous fluids and pain relief. Chronic pancreatitis, which is more common in those with alcohol use disorder, worsens over time. The progressive damage to the pancreatic tissue can affect the ability to digest food and sometimes requires prescription enzymes to avoid malnutrition.

The pancreas, an organ near the small intestine, creates the hormone insulin that helps keep blood sugar in balance. The organ also creates enzymes that normally get released into the small intestine to aid digestion, says Mangelsdorf, who runs a joint laboratory with Steven Kliewer, Ph.D., professor of molecular biology and pharmacology. For nearly two decades the researchers have studied FGF21, learning valuable information about this important metabolic hormone.

In 2017, the researchers reported the hormone's role in keeping digestive enzymes from damaging the pancreas. "We found that FGF21 stimulates the pancreas to secrete digestive enzymes into the small intestine," Mangelsdorf says. "If this mechanism fails, the enzymes remain in the pancreas, where they damage the tissue and cause inflammation."

Mangelsdorf says his and other labs have shown that loss of FGF21 magnifies damage and slows recovery in animal models of pancreatitis. That led him and collaborators at the University of Pittsburgh, Stanford University in California, and Shanghai Jiao Tong University in China to wonder whether the stress hormone might hold promise as a pancreatitis therapy.

To answer that question, the researchers studied the effect of pancreatitis on the FGF21 pathway by analyzing samples from the pancreata of mice and humans with acute and chronic forms of the disease. They found in mice that pancreatic levels of FGF21 rose during the first four hours of pancreatitis and, unexpectedly, dropped at the 12-hour mark, becoming nearly undetectable after 18 hours. FGF21 was also reduced in human pancreatitis.

They were able to verify FGF21 behaves similarly in three different mouse models of the disease: pancreatitis induced by the drug cerulein, which causes excessive secretion of pancreatic enzymes; alcohol-induced pancreatitis; and ERCP-induced pancreatitis. The experiments confirmed that loss of FGF21 is a hallmark of the illness. Next, they wanted to know if FGF21 replacement therapy would work, using these same three mouse models of pancreatitis.

The researchers conducted several experiments using each of the three mouse models, repeating each investigation three to four times with three to eight mice per test group. They also ran experiments on 66 human tissue samples: 14 from healthy people and 52 from people with pancreatitis.

Injecting 1 milligram per kilogram of mouse body weight of FGF21 four times over a 12- to 16-hour period after inducing pancreatitis increased the amount of FGF21 in the bloodstream and caused inflammation, necrosis, and swelling to mostly disappear within 24 hours in the mice with drug- or alcohol-induced pancreatitis.

To see if they could somehow prevent ERCP-induced pancreatitis, the researchers mixed FGF21 with the contrast dye normally used in the procedure and found that by doing so, they were able to maintain normal FGF21 levels and prevent them from dropping, thereby preventing procedure-induced inflammation.

Mangelsdorf cautions that the study's limitations include that the models mimicked but fell short of completely reproducing human disease, and that a definitive conclusion about pancreatitis in humans will require an analysis of a greater number of test subjects.

"Nevertheless, we show that pancreatitis is broadly characterized as an FGF21-deficient state and restoring FGF21 pharmacologically reverses or prevents it," he says.

Credit: 
UT Southwestern Medical Center