Category: Science

There were fewer cases of multi-system inflammatory syndrome in children during the Omicron wave of the pandemic than the Delta wave, according to a new study.

Multi-system inflammatory syndrome in children (MIS-C) is a rare but severe complication that occurs in children who’ve previously had COVID-19, and has near 1% mortality. Published in the journal Viruses, the findings show that those cases that did occur during Omicron were also milder than during Delta.

As shown in numerous other studies, during both waves, Black children were disproportionately affected by MIS-C, and were more likely to be admitted to the hospital with COVID-19. The authors attribute this to systemic and structural racial health inequities and note that limited analysis beyond this observation was possible as the study was not directed at contributions to racial health disparities.

“…during the change to Omicron, MIS-C has become milder and increasingly rare.”

The study demonstrates how the landscape of MIS-C keeps changing as new COVID-19 variants evolve. At the same time, the authors note that it is difficult to say what it means for the future.

“That’s the hard question,” says senior author Mark D. Hicar, associate professor in the pediatrics department in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo and a pediatrics infectious disease specialist. “Since we don’t know why the early strains of the virus caused more MIS-C and why Omicron causes less, it is hard to say if future strains will be worse or better.”

Likewise, he says, it is difficult to predict what the current strain XBB.1.5 will do, as this variant is beginning to flourish in the national data and it takes weeks before MIS-C cases emerge.

“Some recently published studies have suggested that MIS-C cases are becoming more severe, but those were based on 2021 data, before the Omicron wave really took off,” Hicar notes.

“Our study is one of the first to show that during the change to Omicron, MIS-C has become milder and increasingly rare,” he says. “This trend has continued and MIS-C is currently quite rare per anecdotal reports from colleagues across the country.”

He adds, however, that it is important to remain vigilant, as new strains of the SARS-CoV2 virus could cause an increase in incidence or severity of MIS-C.

MIS-C is changing over time

The retrospective study included 271 patients admitted to Oishei Children’s Hospital in Buffalo from August 2021 to February 2022, which included the majority of the Delta wave and when the Omicron wave (BA.1) was strongest.

A key strength of the study is that a panel of three infectious disease specialists made determinations on each case as to whether a child was admitted to the hospital due to COVID-19 or due to some other reason and then happened to test positive for the virus. To avoid potential false positives, the study relied only on cases proven to be positive through PCR testing.

The panel was established after first author Patrick O. Kenney, a medical fellow in infectious diseases, found that a number of children who were reported to be admitted to the hospital with only an incidental diagnosis of SARS-CoV2 on PCR actually were experiencing symptoms that were not as common during previous waves.

These included croup, which was first described by other groups, but also increased rates of seizures, bleeding events, and intra-abdominal inflammation including pancreatitis and hepatitis.

“Reports at the time supported that there was an increase in pediatric Omicron hospitalizations, but those reports focused on global admission data,” explains Hicar. “We wanted to take a deep dive and have thorough clinical chart review by three infectious disease physicians to decide if a case was admitted due to COVID-19 or for some other reason and happened to have COVID-19.”

“Even during major changes in the virus, from the Delta to Omicron variants, vaccines can be highly protective in preventing hospitalizations among children.”

This detailed approach helps to clarify how MIS-C is changing over time, especially in light of the decrease in severe cases during Omicron, Hicar explains. The study found that during Delta, MIS-C comprised up to 12% of hospital admissions at Oishei while during Omicron it comprised just 6% of hospital admissions. Based on their data, the researchers estimate the risk of MIS-C from Omicron in Western New York is 32% lower than it was during Delta.

The study notes that while there was an increase in pediatric hospitalizations in Buffalo during the Omicron wave, which was also the case nationwide, cases of both COVID-19 and MIS-C were generally less severe than they had been during previous waves of the pandemic. In addition, the length of hospital stays at Oishei Children’s Hospital as a result of either MIS-C or COVID-19 was relatively short during this period.

The researchers report that children testing positive for COVID-19 who didn’t have MIS-C during the Omicron wave exhibited a broad range of symptoms, especially among younger children, including seizures due to high fevers, as well as croup and related conditions.

By contrast, children who had MIS-C during Omicron exhibited a narrower spectrum of symptoms: they always had fever along with abdominal or upper respiratory symptoms. The authors note that none of the patients in the study met even incomplete criteria for Kawasaki disease; early in the pandemic, MIS-C was believed to be similar to Kawasaki disease.

Unvaccinated kids

The authors point out that the majority of children admitted to Oishei Children’s Hospital during Omicron with either COVID-19 or MIS-C had not been vaccinated.

Vaccines for children 12 and older became available before the study began and were available for ages 5-11 during the study. Among the 107 children admitted with acute COVID-19 during Omicron, vaccine status was recorded for 88 of them; of these, five were fully vaccinated and one had received a single dose. The others were unvaccinated.

Based on local county data that showed that 33% of children under 18 had been vaccinated as the Omicron wave began, rising to 42.1% by the end of the study period, the researchers calculated that the vaccines were between 87.8-91.7% effective in preventing hospitalizations for either COVID-19 or MIS-C among children.

“Our data show that even during major changes in the virus, from the Delta to Omicron variants, vaccines can be highly protective in preventing hospitalizations among children,” says Hicar.

Lorna Krabill, a fourth-year medical student in the Jacobs School, and Arthur J. Chang of Children’s Hospital and Medical Center in Omaha are coauthors of the study.

Source: University at Buffalo

New research finds that the worst thing you can do when you’re canceling plans is lie about your reason.

The findings indicate that how cancellations are made may be more important than whether cancellations are made.

William Chopik, associate professor in Michigan State University’s psychology department and lead author of the study in Collabra: Psychology, says he and colleagues talked about how most everyone struggles with canceling plans with a friend.

“Maintaining relationships with others is important to humans, but the reality is that social anxiety exists. Living out in the world—or getting prepared to do so—is exhausting, but staying home provides comfort,” Chopik says. “The pandemic taught us to stay home in our safe haven, but now that the worst parts of the pandemic are hopefully over­, expectations to socialize in person are on the rise.”

The large study is among the first to explore the wide variety of norms that exist around canceling plans. More than 1,100 participants were surveyed to examine how people prefer to be canceled on by a friend, the negative emotions they feel when being canceled on, and their criteria for good and bad reasons to be canceled on.

The majority of participants, 80%, said that canceling plans would not affect their friendship but that they would be upset if they learned that the reason provided was a lie.

Overall, people reported relatively low levels of distress when canceled on unless it was by a good friend. When explicitly asked how upset they would be if they were canceled on by a good or best friend, most participants said they would be moderately upset.

“The level of investment in the relationship appears to matter,” Chopik says. “Being canceled on by a best friend—presumably a relationship that people have invested a great deal in—was more upsetting than being canceled on by a merely good friend or a casual acquaintance. Being canceled on by those we are close to may be more upsetting because it more clearly violates the norms of friendship and could resemble a form of social rejection.”

When asked about how to go about canceling plans, almost 60% of participants stated that they would like advance notice about the cancellation and would prefer to be told in a relatively quick way, like a brief call or text.

But, surprisingly, Chopik says, only 10% of the participants expected an apology from their friend for canceling on them.

In terms of acceptable reasons for canceling, approximately half of the sample said that health or family-related excuses are the most appropriate. Work- or obligation-related excuses were also seen as appropriate by about 40% of the sample. Having an emergency or something unexpected come up was spontaneously mentioned about 25% of the time.

More than half of the participants indicated that pursuing more rewarding social events or romantic opportunities were among the worst excuses for canceling plans.

“Relationships aren’t taught in the same way as social studies or biology,” Chopik says. “A lot of learning happens ‘on the fly’ as we find ourselves in relationships and either screw things up or have successes. Socializing ourselves to be more responsive to the people in our lives is a worthy goal if we’re trying to have fulfilling, long-lasting relationships. Though society offers information about how to navigate romantic relationships, little is available about navigating friendships, which also is important as more and more people find themselves single and report feeling lonelier than ever before.”

Source: Michigan State University

When you’re in a bad mood, you might want to focus on tasks that are more detail-oriented, such as proofreading, research indicates.

The study, published in Frontiers in Communication, builds on existing research on how the brain processes language.

Vicky Lai, assistant professor of psychology and cognitive science at the University of Arizona, worked with collaborators in the Netherlands to explore how people’s brains react to language when they are in a happy mood versus a negative mood.

“Mood and language seem to be supported by different brain networks. But we have one brain, and the two are processed in the same brain, so there is a lot of interaction going on,” Lai says. “We show that when people are in a negative mood, they are more careful and analytical. They scrutinize what’s actually stated in a text, and they don’t just fall back on their default world knowledge.”

Good mood, bad mood

Lai and coauthors set out to manipulate study participants’ moods by showing them clips from a sad movie—Sophie’s Choice—or a funny TV show—Friends. They used a computerized survey to evaluate participants’ moods before and after watching the clips. While the funny clips did not affect participants’ moods, the sad clips succeeded in putting participants in a more negative mood, the researchers found.

The participants then listened to a series of emotionally neutral audio recordings of four-sentence stories that each contained a “critical sentence” that either supported or violated default, or familiar, word knowledge. That sentence was displayed one word at a time on a computer screen, while participants’ brain waves were monitored by EEG, a test that measures brain waves.

For example, the researchers presented study participants with a story about driving at night that ended with the critical sentence “With the lights on, you can see more.” In a separate story about stargazing, the same critical sentence was altered to read “With the lights on, you can see less.” Although that statement is accurate in the context of stargazing, the idea that turning on the lights would cause a person to see less is a much less familiar concept that defies default knowledge.

The researchers also presented versions of the stories in which the critical sentences were swapped so that they did not fit the context of the story. For example, the story about driving at night would include the sentence “With the lights on, you can see less.”

They then looked at how the brain reacted to the inconsistencies, depending on mood.

Analyzing the language

They found that when participants were in a negative mood, based on their survey responses, they showed a type of brain activity closely associated with re-analysis.

“We show that mood matters, and perhaps when we do some tasks we should pay attention to our mood,” Lai says. “If we’re in a bad mood, maybe we should do things that are more detail-oriented, such as proofreading.”

Study participants completed the experiment twice—once in the negative mood condition and once in the happy mood condition. Each trial took place one week apart, with the same stories presented each time.

“These are the same stories, but in different moods, the brain sees them differently, with the sad mood being the more analytical mood,” Lai says.

The study took place in the Netherlands; participants were native Dutch speakers, and the study was conducted in Dutch. But Lai believes their findings translate across languages and cultures.

By design, the study participants were all women, because Lai and her colleagues wanted to align their study with existing literature that was limited to female participants. Lai says future studies should include more diverse gender representation.

In the meantime, Lai and her colleagues say mood may affect us in more ways than we previously realized.

Coauthors are from Utrecht University and the Max Planck Institute for Psycholinguistics.

Source: University of Arizona

A measure of brain activity known as causal flow can help locate the source of epilepsy seizures before they occur, according to a new study.

The finding could reduce the need for invasive procedures in treating drug-resistant forms of the disorder.

According to the World Health Organization, about 50 million people worldwide live with epilepsy. The neurological disorder is marked by recurrent seizures—sudden bouts of abnormal electrical activity in the brain.

“Seizures are often described as electrical storms in the brain,” says coauthor Mukesh Dhamala, an associate professor in Georgia State University’s Neuroscience Institute and physics and astronomy department. “And that can take over normal functioning. Patients can lose consciousness and control of their behaviors for seconds to minutes.”

While some cases of epilepsy can be treated with medication, about 30% are considered drug-resistant. These cases require surgical intervention on the brain area where the seizure starts, known as the seizure focus.

Neurosurgeons look for areas of abnormal activity using intracranial electroencephalogram (iEEG), a procedure in which electrodes are surgically implanted into the brain for the duration of the test. To work, the patient must have a seizure while the iEEG is recording.

This approach to locating the seizure focus is successful only 40 to 60% of the time for multiple reasons. First, the patient must have a seizure while the iEEG is recording. When seizures occur sporadically and without warning, this can be a problem. Second, the iEEG can miss a focus region or detect multiple regions of abnormal activity. In these cases, it can be difficult—if not impossible—to visually interpret the iEEG recordings.

“That’s where we come in—to help neurosurgeons by analyzing recorded data,” Dhamala says.

Rather than looking at the output from each individual electrode, Dhamala and his team have started to combine data from each point to get a broader picture of the brain’s activity. Like using seismographs to determine the location and strength of an earthquake, these data points can be used to determine causal flow, a measurement that quantifies the activity of this broader network.

Previously, Dhamala and his colleagues used high-frequency activity known to be present during seizures to show that causal flow can locate foci. In its recent study, the team was able to do the same using low-frequency activity, which occurs before a seizure starts. Their findings suggest that using low frequencies to determine causal flow could help locate a seizure long before one occurs.

“The method can potentially open up a whole new possibility of localizing seizures with a… non-invasive approach,” Dhamala says. “That’s the idea.”

In the future, neurosurgeons may be able to locate foci without waiting for patients to have more seizures and do so even with less invasive techniques. The team is now conducting research on the use of functional magnetic resonance imaging, which measures low-frequency activity, as an alternative.

Sushma Ghimire, a recent graduate of the Georgia State doctoral program in physics, and Charles Epstein, a neurophysiologist and professor at Emory University are coauthors of the study, published in the Journal of Clinical Neurophysiology.

Source: Georgia State University

Skin tone shapes the experiences of Mexican immigrants in Atlanta and Philadelphia, research finds.

While racism is often a focus of concern in the United States, skin tone—separate but related to race—plays a lesser known but important role in discrimination, according to the findings.

The study finds that Mexican immigrants with darker skin tones perceived greater racial discrimination and more frequent discrimination specifically from US-born whites than did Mexican immigrants with lighter skin tones. Those same people with darker skin tones also reported more negative responses to that discrimination, such as pulling inward and struggling internally.

The research, published in Social Psychology Quarterly, also shows that darker skin tone is nearly as strong of a predictor of such increased inner struggle as lack of documentation status.

“Skin tone is uniquely related to how Mexican immigrants are understanding their interactions with and treatment by US-born whites, even after controlling for a range of other demographic and immigration-specific factors,” says study leader Helen B. Marrow, an associate professor of sociology at Tufts University.

Colorism is distinct from racism in that it describes mistreatment based on skin tone rather than ethnic or racial category. For example, two people may both be of the same ethnicity or race, but one may perceive more frequent discrimination due to a darker skin tone.

Ellis Monk, an associate professor of sociology at Harvard University who was not involved in the research, says the new study is an “important extension” of burgeoning research on skin tone and discrimination.

“Trying to get more understanding around how people deal with discrimination is really important,” he says. He adds that “when people feel themselves to be disrespected, it has negative physiological responses for the person that can actually lead them to be physically ill over time.”

The study surveyed 500 foreign-born Mexican immigrants living in 10 counties of metropolitan Atlanta and Philadelphia, and asked participants to identify their own skin tone on a scale of one to seven, with one being “very light,” seven being “very dark,” and four being “medium.” While such measurements are subjective, Marrow says that could be an advantage. “It captures something about how people understand themselves,” she says.

Next, participants described the discrimination they’d experienced in their city since moving there, including questions about how often, where, and by whom they’d been treated well or poorly. The survey also asked participants to identify their typical responses to poor treatment, which could range from defending themselves to reporting the treatment to ignoring the discrimination altogether.

Not only were darker-skinned Mexican participants more likely to perceive discrimination from US-born whites relative to lighter-skinned respondents, but skin tone was a stronger predictor of this outcome than participants’ self-described ethnic or racial identity. The predictive results were similar in both metro areas, even as respondents in Atlanta reported higher levels of discrimination.

Participants with darker skin tones were also more likely to report responding to discrimination by struggling internally but not outwardly saying anything.

According to Marrow, this response to colorism might raise health concerns, which warrants further study.

Both metro areas included in the study are considered “new immigrant destinations” for Mexicans, or areas of the country that began to see an influx of Mexican immigration only after the 1980s. Marrow says sociologists don’t yet know as much about the role skin tone plays in the lived experiences of Mexicans in these new immigrant gateways, while much more research has been done on skin tone among Chicanos and Mexican Americans living in Texas and the Southwest.

One possible factor contributing to the results, according to Marrow, is that the racialization of Latinos living in new immigrant destinations has intensified over the past two decades, especially in the US South, where Atlanta is located. This means that Mexican immigrants’ place within local racial hierarchies has become more strongly racialized than scholars typically documented before 2000, likely affecting their perceptions of their interactions with the US-born.

Marrow says the research, conducted with colleagues at Indiana University and the University of Massachusetts Amherst, is one of the first to examine immigrants’ perceptions of discrimination in new destinations using measures of race/ethnicity and skin tone together in the same study, and to do so with a large, representative sample.

“The big implication of this is that social scientists should pay more attention to skin tone variation within our studies of race-based discrimination,” she says.

Source: Grace van Deelen for Tufts University

An internal circadian clock controls the distinctive concentric rings of flowering in sunflowers, maximizing visits from pollinators, according to a new study.

A sunflower head is made up of hundreds of tiny florets. Because of the way sunflowers grow, the youngest florets are in the center of the flower face and the most mature at the edges, forming a distinctive spiral pattern from the center to the edge.

An individual floret blooms over a couple of days. On the first day, it opens the male part of the flower and presents pollen; on the second day, the female stigma unfold to receive pollen. Somehow, florets coordinate so that they open in concentric rings starting from the edge and moving inward on successive days, with a ring of female flowers always outside the earlier-stage, pollen-bearing male flowers.

Pollinating bees tend to land on the ray petals around a sunflower head and walk toward the center, says Stacey Harmer, professor of plant biology in the College of Biological Sciences at the University of California, Davis and senior author of the paper in eLife.

That means that they will pick up pollen after they have walked over the female florets, then carry it to a different flower head.

Harmer and postdoctoral researcher Carine Marshall wanted to understand how the spiral pattern of florets turns into concentric rings of flowering. Harmer’s lab had previously established that circadian rhythms control how growing sunflowers track the sun during the day.

The internal circadian clock of a plant or animal runs on a cycle of about 24 hours, allowing different genes to be activated at different times of day. Natural day/night cycles keep this internal clock synchronized to actual day time. Changing the length of daylight, or darkness, can reset the clock. In sunflowers, continuous light disrupts the clock entirely.

The researchers took time-lapse videos of sunflowers grown in different light/dark or temperature conditions. They found that the plant’s circadian clock controls the opening of florets. When the clock was disrupted by growing plants in continuous light, florets did not open in concentric rings, but only by age, starting at the edge and moving to the center in a continuous gradient.

When plants that had been grown with a disrupted clock were moved outside, they attracted fewer pollinators than normal sunflowers.

“We think that being able to coordinate in this way makes them a better target for bees,” Harmer says. “It’s a strategy to attract as many insects as possible.”

As farmers adapt to a changing climate, it will become increasingly important to make pollination as efficient as possible in crops that require it, Harmer says.

Understanding how the circadian clock and the environment affect flowering will help breeders develop cultivars that flower at the optimal times of day to promote pollination, despite climate change and declining insect populations, she says.

The National Science Foundation and the US Department of Agriculture-National Institute of Food and Agriculture supported the work.

Source: UC Davis

Pandemic frontline health care workers who have not received a formal post-traumatic stress disorder diagnosis may still experience critical health symptoms that could lead to other health problems, researchers report.

The findings of the study in the Journal of Psychiatric Research show that the pandemic’s mental toll impact extends beyond career burnout.

“While there has been a lot of attention paid to elevated symptom levels indicative of a clinical diagnosis, little attention has been paid to subclinical symptom levels,” says lead author Bryce Hruska, assistant professor of public health in the Falk College at Syracuse University.

Subclinical (or subthreshold) symptoms refer to psychiatric symptoms—PTSD symptoms in the case of this study—that are not severe enough to be considered indicative of a clinical diagnosis.

Hruska and his collaborator, Maria Pacella-LaBarbara at the University of Pittsburgh, examined the prevalence and significance of subthreshold PTSD symptom levels (known as PTSS) in frontline health care workers responding to the pandemic nearly one year after it started, from December 2020 through February 2021. Data from this study were collected from emergency health care workers located primarily in western Pennsylvania and surrounding areas.

“This is an important study that captures what frontline health care workers were experiencing during the pandemic’s second wave and continue to experience as COVID approaches the start of its fourth year in the US. It could not have been possible without the work of many people, including other researchers and medical personnel who assisted with ensuring that these workers’ experiences were represented,” says Hruska.

“In fact, we found that while 5.5% of the health care workers in our sample met criteria for probable PTSD, over half (55.3%) experienced subthreshold symptoms,” he says. “Even though they weren’t reporting symptoms indicative of a clinical diagnosis of PTSD, these workers were still feeling its effects.”

Researchers found that workers experiencing these symptoms levels reported:

• 88% more physical health symptoms (e.g., constant fatigue, weight change, low energy, headache)
• 36% more sleep problems (e.g., daytime sleepiness, difficulty getting things done) than health care workers not experiencing any PTSD symptoms

“This is a big oversight because these subthreshold symptom levels are common and often confer risk for other health problems,” says Hruska, who explains that these subthreshold symptoms are often overlooked. That in turn leads to increased risk for subsequently experiencing clinical symptom levels when another significant trauma, such as the current rise in COVID cases, is experienced.

“Thus, while the world tries to move on from the pandemic, our health care workers continue to face a significant mental health risk with every surge in cases, as is happening now,” Hruska says.

Source: Syracuse University

The number of times a reusable take-out container gets used is a key factor affecting how sustainable it is, a new study indicates.

In an effort to reduce plastic waste in the restaurant industry—single-use takeout containers, specifically—the researchers compared the lifetime environmental impacts of single-use and reusable take-out food containers.

Depending on the single-use container being replaced, the researchers found that the reusable alternatives—which initially use more energy and generate more climate-altering greenhouse gases—can break even with single-use containers after four to 13 uses.

In 2018, the US generated more than 90 times the amount of plastic municipal solid waste it generated in 1960.

“Reducing the quantity of single-use plastics in the restaurant industry by implementing reusable takeout container systems has the potential to reduce greenhouse gas emissions and save on energy, water, and cost,” says study author Greg Keoleian, director of University of Michigan’s Center for Sustainable Systems (CSS) at the School for Environment and Sustainability. “Our study found that reusable containers can outperform single-use in all impact categories.”

The study, published in the journal Resources, Conservation & Recycling, reports that on a global scale, plastic production has accelerated dramatically over the past decades—leading to a sharp increase in plastic waste.

In the United States alone, more than 90 times the 1960 amount of plastic municipal solid waste was generated in 2018. Single-use packaging contributes millions of tons of plastic waste to that total each year.

In addition to the number of times that a reusable container is reused and the material type (e.g., polypropylene, the bioplastic PLA, aluminum), the study also found that customer behavior will be a significant factor in sustainability performance.

“If 5% of customers make trips by vehicle solely to return used containers, the reusable system has higher life-cycle greenhouse gas emissions than the single use,” says coauthor Christian Hitt, a dual-degree graduate student and Center for Sustainable Systems research assistant.

“We also looked at the water usage of at-home cleaning of the containers,” Hitt says. “Excessive washing can tip the balance against the primary energy impacts of reusable containers.”

According to the study, education will be key in counteracting these potential downsides by encouraging customer best practices. Informational labels on containers, signage in restaurants, employee dialogue with customers, and online information are a few educational tools that the study recommends.

Convenience can also play a part. City-scale systems with common containers across multiple restaurants may prove advantageous, as customers can return containers to different locations, decreasing the likelihood of customer travel for the sole purpose of container return.

Study authors recommend further research on actual customer behavior—including the effectiveness of incentives that encourage best practices, such as discounts to customers wearing bike helmets or meal discounts if returning a container.

It is also possible that container deposits could encourage returns, the study reports, citing the example of plastic bottle recycling rates in states with deposit programs compared to those without them (62% vs. 13%).

As a base for their model, the researchers studied the pilot program for returnable takeout containers launched by the nonprofit organization Live Zero Waste in Ann Arbor. The program, Ann Arbor Reduce, Reuse, Return (A2R3), is now in its second pilot phase and was implemented in partnership with the city of Ann Arbor’s A2ZERO carbon neutrality plan.

The Live Zero Waste website outlines the process: Upon entering a restaurant, customers can scan a QR code to check out a reusable container. After the container is emptied and cleaned at home, the customer returns it to the restaurant. The containers, made of FDA-approved polypropylene material, are then sanitized in the restaurants’ industrial dishwashers prior to reuse.

The research, which was supported by a Morgan Stanley Plastics Waste Reduction Research and Fellowship award, concludes that a reusable container system—as part of a circular economy strategy—offers the chance for significant benefits over time, if customers can be effectively educated to adopt sustainable behaviors.

Jacob Douglas, a research assistant at the Center for Sustainable Systems, is a coauthor of the study.

Source: Denise Spranger for University of Michigan