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Researchers have developed a machine learning model that uses the assortment of microbes found in wastewater to tease out how many individual people they represent.

Research from the lab of Fangqiong Ling showed earlier this year that the amount of SARS-CoV-2 in a wastewater system was correlated with the burden of disease—COVID-19—in the region it served.

But before that work could be done, Ling needed to know: How can you figure out the number of individuals represented in a random sample of wastewater?

A chance encounter with a colleague helped Ling, an assistant professor in the department of energy, environmental, and chemical engineering at the McKelvey School of Engineering at Washington University in St. Louis, led to the creation of a method to do just that

Going forward, this method may be able to link other properties in wastewater to individual-level data.

The problem was straightforward: “If you just take one scoop of wastewater, you don’t know how many people you’re measuring,” Ling says. This is counter to the way studies are typically designed.

“Usually when you design your experiment, you design your sample size, you know how many people you’re measuring,” Ling says. Before she could look for a correlation between SARS-CoV-2 and the number of people with COVID, she had to figure out how many people were represented in the water she was testing.

Initially, Ling thought that machine learning might be able to uncover a straightforward relationship between the diversity of microbes and the number of people it represented, but the simulations, done with an “off-the-shelf” machine learning, didn’t pan out.

Then Ling had a chance encounter with Likai Chen, an assistant professor of mathematics and statistics. The two realized they shared an interest in working with novel, complex data. Ling mentioned that she was working on a project that Chen might be able to contribute to.

“She shared the problem with me and I says, that’s indeed something we can do,” Chen says. It happened that Chen was working on a problem that used a technique that Ling also found helpful.

The key to being able to tease out how many individual people were represented in a sample is related to the fact that, the bigger the sample, the more likely it is to resemble the mean, or average. But in reality, individuals tend not to be exactly “average.” Therefore, if a sample looks like an average sample of microbiota, it’s likely to be made up of many people. The farther away from the average, the more likely it is to represent an individual.

“But now we are dealing with high-dimensional data, right?” Chen says. There are near-endless number of ways that you can group these different microbes to form a sample. “So that means we have to find out, how do we aggregate that information across different locations?”

Using this basic intuition—and a lot of math—Chen worked with Ling to develop a more tailored machine learning algorithm that could, if trained on real samples of microbiota from more than 1,100 people, determine how many people were represented in a wastewater sample (these samples were unrelated to the training data).

“It’s much faster and it can be trained on a laptop,” Ling says. And it’s not only useful for the microbiome, but also, with sufficient examples—training data—this algorithm could use viruses from the human virome or metabolic chemicals to link individuals to wastewater samples.

“This method was used to test our ability to measure population size,” Ling says. But it goes much further. “Now we are developing a framework to allow validation across studies.”

The research appears in the journal PLOS Computational Biology.

Source: Washington University in St. Louis

People with opioid-use disorder who are pregnant may have more favorable neonatal health outcomes when using buprenorphine compared with methadone, a new study shows.

Buprenorphine is an active ingredient in suboxone and other medications approved for treatment of opioid-use disorder.

The study, published in the New England Journal of Medicine, compared the safety of the two medications—buprenorphine and methadone—used to treat opioid-use disorder during pregnancy.

“Our results may encourage increasing access to buprenorphine treatment specifically among pregnant people,” says lead author Elizabeth Suarez, a pharmacoepidemiologist who is a faculty member at the Center for Pharmacoepidemiology and Treatment Science at the Rutgers Institute for Health, Health Care Policy and Aging Research.

“It’s essential for the general public to understand the importance of opioid-use disorder treatment during pregnancy to avoid harms associated with lack of treatment.”

Overdose deaths from opioids continue to increase and opioid-use disorder remains a prevalent issue in the United States, according to the National Center for Health Statistics and research in Drug and Alcohol Dependence.

People who have untreated opioid-use disorders while pregnant and their infants are at greater risk of harms because of withdrawal, continued opioid use, and overdose. Previous studies found buprenorphine may be safer for the infant than methadone, but results were uncertain.

Using a large national database of people insured by Medicaid, researchers examined maternal outcomes in a sample of pregnant individuals with opioid-use disorder, including delivery by cesarean section and severe pregnancy complications, and infant outcomes, including preterm birth, low birth weight, small size for gestational age, and neonatal abstinence syndrome that occurs when the infant experiences withdrawal after delivery after being exposed to certain drugs in pregnancy.

They found that using buprenorphine to treat opioid-use disorder during pregnancy may result in better outcomes for the baby than methadone. Buprenorphine use was associated with lower risk of preterm birth, small size for gestational age, low birth weight, and neonatal abstinence syndrome compared with methadone use.

“These results may guide clinical recommendations for people with opioid-use disorder who are pregnant or are hoping to be pregnant,” says Suarez, who also is an instructor of epidemiology with the department of biostatistics and epidemiology at the Rutgers School of Public Health.

Future research should explore whether pregnant people with opioid-use disorder have a better experience taking buprenorphine or methadone and if they are more likely to stay on one medication longer than the other, Suarez says.

Additional coauthors are from Brigham and Women’s Hospital, Harvard Medical School, and Stanford University School of Medicine. The National Institute on Drug Abuse supported the work.

Source: Rutgers University

Researchers have discovered that you can wake up each morning without feeling sluggish by paying attention to three key factors: sleep, exercise, and breakfast.

Do you feel groggy until you’ve had your morning joe? Do you battle sleepiness throughout the workday?

You’re not alone. Many people struggle with morning alertness, but the new study demonstrates that awaking refreshed each day is not just something a lucky few are born with.

“From car crashes to work-related accidents, the cost of sleepiness is deadly.”

The findings come from a detailed analysis of the behavior of 833 people who, over a two-week period, were given a variety of breakfast meals; wore wristwatches to record their physical activity and sleep quantity, quality, timing, and regularity; kept diaries of their food intake; and recorded their alertness levels from the moment they woke up and throughout the day.

The researchers included twins—identical and fraternal—in the study to disentangle the influence of genes from environment and behavior.

The researchers found that the secret to alertness is a three-part prescription requiring substantial exercise the previous day, sleeping longer and later into the morning, and eating a breakfast high in complex carbohydrates, with limited sugar.

The researchers also discovered that a healthy controlled blood glucose response after eating breakfast is key to waking up more effectively.

“All of these have a unique and independent effect,” says Raphael Vallat a postdoctoral fellow at the University of California, Berkeley and first author of the study. “If you sleep longer or later, you’re going to see an increase in your alertness. If you do more physical activity on the day before, you’re going to see an increase. You can see improvements with each and every one of these factors.”

Morning grogginess is more than just an annoyance. It has major societal consequences: Many auto accidents, job injuries, and large-scale disasters are caused by people who cannot shake off sleepiness. The Exxon Valdez oil spill in Alaska, the Three Mile Island nuclear meltdown in Pennsylvania, and an even worse nuclear accident in Chernobyl, Ukraine, are well-known examples.

“Many of us think that morning sleepiness is a benign annoyance. However, it costs developed nations billions of dollars every year through loss of productivity, increased health care utilization, work absenteeism. More impactful, however, is that it costs lives—it is deadly,” says senior author Matthew Walker, professor of neuroscience and psychology and author of Why We Sleep (Simon & Schuster, 2018).

“From car crashes to work-related accidents, the cost of sleepiness is deadly. As scientists, we must understand how to help society wake up better and help reduce the mortal cost to society’s current struggle to wake up effectively each day.”

What you eat

Walker and Vallat teamed up with researchers in the United Kingdom, the US, and Sweden to analyze data acquired by a UK company, Zoe Ltd., that has followed hundreds of people for two-week periods in order to learn how to predict individualized metabolic responses to foods based on a person’s biological characteristics, lifestyle factors, and the foods’ nutritional composition.

The researchers gave participants preprepared meals, with different proportions of nutrients incorporated into muffins, for the entire two weeks to see how they responded to different diets upon waking. A standardized breakfast, with moderate amounts of fat and carbohydrates, was compared to a high protein (muffins plus a milkshake), high carbohydrate, or high sugar (glucose drink) breakfast. The subjects also wore continuous glucose monitors to measure blood glucose levels throughout the day.

“…there are still some basic, modifiable, yet powerful ingredients to the awakening equation that people can focus on…”

The worst type of breakfast, on average, contained high amounts of simple sugar; it was associated with an inability to wake up effectively and maintain alertness. When given this sugar-infused breakfast, participants struggled with sleepiness.

In contrast, the high carbohydrate breakfast—which contained large amounts of carbohydrates, as opposed to simple sugar, and only a modest amount of protein—was linked to individuals revving up their alertness quickly in the morning and sustaining that alert state.

“A breakfast rich in carbohydrates can increase alertness, so long as your body is healthy and capable of efficiently disposing of the glucose from that meal, preventing a sustained spike in blood sugar that otherwise blunts your brain’s alertness,” Vallat says

“We have known for some time that a diet high in sugar is harmful to sleep, not to mention being toxic for the cells in your brain and body,” Walker adds. “However, what we have discovered is that, beyond these harmful effects on sleep, consuming high amounts of sugar in your breakfast, and having a spike in blood sugar following any type of breakfast meal, markedly blunts your brain’s ability to return to waking consciousness following sleep.”

How you sleep

It wasn’t all about food, however. Sleep mattered significantly. In particular, Vallat and Walker discovered that sleeping longer than you usually do, and/or sleeping later than usual, resulted in individuals ramping up their alertness very quickly after awakening from sleep.

According to Walker, between seven and nine hours of sleep is ideal for ridding the body of “sleep inertia,” the inability to transition effectively to a state of functional cognitive alertness upon awakening. Most people need this amount of sleep to remove a chemical called adenosine that accumulates in the body throughout the day and brings on sleepiness in the evening, something known as sleep pressure.

“Considering that the majority of individuals in society are not getting enough sleep during the week, sleeping longer on a given day can help clear some of the adenosine sleepiness debt they are carrying,” Walker speculates.

“In addition, sleeping later can help with alertness for a second reason,” he says. “When you wake up later, you are rising at a higher point on the upswing of your 24-hour circadian rhythm, which ramps up throughout the morning and boosts alertness.”

It’s unclear, however, what physical activity does to improve alertness the following day.

“It is well known that physical activity, in general, improves your alertness and also your mood level, and we did find a high correlation in this study between participants’ mood and their alertness levels,” Vallat says. “Participants that, on average, are happier also feel more alert.”

But Vallat also notes that exercise is generally associated with better sleep and a happier mood.

“It may be that exercise-induced better sleep is part of the reason exercise the day before, by helping sleep that night, leads to superior alertness throughout the next day,” Vallat says.

Walker notes that the restoration of consciousness from non-consciousness—from sleep to wake—is unlikely to be a simple biological process.

“If you pause to think, it is a non-trivial accomplishment to go from being nonconscious, recumbent, and immobile to being a thoughtful, conscious, attentive, and productive human being, active, awake, and mobile. It’s unlikely that such a radical, fundamental change is simply going to be explained by tweaking one single thing,” he says. “However, we have discovered that there are still some basic, modifiable, yet powerful ingredients to the awakening equation that people can focus on—a relatively simple prescription for how best to wake up each day.”

It’s under your control

Comparisons of data between pairs of identical and non-identical twins showed that genetics plays only a minor and insignificant role in next-day alertness, explaining only about 25% of the differences across individuals.

“We know there are people who always seem to be bright-eyed and bushy-tailed when they first wake up,” Walker says. “But if you’re not like that, you tend to think, ‘Well, I guess it’s just my genetic fate that I’m slow to wake up. There’s really nothing I can do about it, short of using the stimulant chemical caffeine, which can harm sleep.

“But our new findings offer a different and more optimistic message. How you wake up each day is very much under your own control, based on how you structure your life and your sleep. You don’t need to feel resigned to any fate, throwing your hands up in disappointment because, ‘…it’s my genes, and I can’t change my genes.’ There are some very basic and achievable things you can start doing today, and tonight, to change how you awake each morning, feeling alert and free of that grogginess.”

Walker, Vallat, and their colleagues continue their collaboration with the Zoe team, examining novel scientific questions about how sleep, diet, and physical exercise change people’s brain and body health, steering them away from disease and sickness.

Additional coauthors of the paper are from of King’s College London; Lund University in Malmö, Sweden; Zoe Ltd.; the University of Nottingham in the UK; and Massachusetts General Hospital and Harvard Medical School in Boston. Zoe Ltd. and the Department of Twin Studies at King College London funded the study.

The research appears in Nature Communications.

Source: UC Berkeley