“Small tweaks in early development can contribute to larger differences in how animals’ bodies are laid out,” explained San Francisco State Professor of Biology Karen Crow.

For Crow and her graduate student John Swenson, now a Ph.D. student at the University of Massachusetts Amherst, the hornlike “cephalic lobes” of manta rays represented a curious problem. All types of fish have two sets of paired appendages, like fins. But somewhere in their evolutionary past, a group of rays appeared to acquire a third set. These cephalic lobes are used for feeding, allowing some species to grapple with shellfish while helping species like manta rays more efficiently hoover up tiny plankton as they flap their way through the open ocean. What wasn’t clear was just where these fleshy face funnels came from.

To investigate, the researchers studied the embryos of cownose rays, the closest relatives of the massive mantas. They took samples of genetic material at different stages of the rays’ growth to see which genes were active during fin development, akin to peeking at the growing ray’s assembly instructions. The team examined hundreds of genes and paid special attention to several “Hox” genes, which contain instructions for growth and development of fins and limbs. It’s a group of genes crucial to development in all animals, including humans.

The team’s results showed that the ray’s horns aren’t a third set of appendages at all — they’re simply the foremost bit of fin, modified for a new purpose. They found that the same Hox genes that guide development of the rays’ cephalic lobes also play the same role in the fins of a closely related ray species, the little skate, which doesn’t have cephalic lobes.

In fact, the way the horns develop is surprisingly simple. All it takes is a tiny notch that deepens and widens as the manta grows, separating each fin into two distinct parts: one for feeding and the remainder for swimming. The team published their results in the journal Frontiers in Ecology and Evolution on Nov. 13.

The researchers say that the findings support a consensus that’s emerging among scientists who study evolution: Strange, novel features in nature can often arise from tiny evolutionary tweaks. “Whatever genetic changes occurred, there were far fewer than what we expected,” said Crow. A devil ray isn’t so different from its hornless cousins. And that lesson applies on a broader scale, too, she explains.

“We share the same genetic toolkit with all the other animals — and we share many of our genes with all living things,” Crow said.

Jeff Klomp, a research associate at the University of North Carolina, Chapel Hill, and Robert Fisher, a marine scientist and fisheries specialist at the College of William and Mary, were co-authors on the study.

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Among pregnant women in all parts of the country, amphetamine-affected births (mostly attributed to methamphetamine) doubled — from 1.2 per 1,000 hospitalizations in 2008-2009 to 2.4 per 1,000 delivery hospitalizations by 2014-2015, the new research finds.

The rate of opioid use also quadrupled from 1.5 per 1,000 delivery hospitalizations in 2004-2005 to 6.5 per 1,000 delivery hospitalizations in 2014-2015, according to the findings published in the American Journal of Public Health. The study sample included about 47million deliveries occurring in U.S. hospitals over the 12-year-period.

For pregnant women with amphetamine use, the risk of severe maternal morbidity and mortality was 1.6 times the rate identified among moms with opioid use. The incidence of preterm delivery, pre-eclampsia or eclampsia, heart failure or heart attack, and need for a blood transfusion were also higher among deliveries to moms with amphetamine use compared to opioid use.

“We know from our previous research on maternal health disparities that there are disproportionately higher rates of substance affected births in rural communities,” says lead author Lindsay Admon, M.D., M.Sc., an obstetrician-gynecologist at University of Michigan Von Voigtlander Women’s Hospital and a graduate of the National Clinician Scholar’s Program at U-M’s Institute for Healthcare Policy and Innovation.

“When we looked at the specific types of substances driving this disparity, we were surprised to find that amphetamine use accounted for such a significant portion,” Admon adds, noting that few, if any, studies have examined the incidence of amphetamine use in pregnancy in the last decade.

“Our findings suggest both amphetamine and opioid use are growing public health crises that affect delivery and birth outcomes.”

Admon, the study’s senior author Tyler Winkelman, M.D., M.Sc., and colleagues also recently examined 1.3 million hospitalizations related to amphetamines in the general adult population, finding that by 2015 amphetamine-related hospitalizations were associated with higher risk for in-hospital mortality and accounted for $2.2 billion dollars in hospital costs.

Geography influences health, recovery

An estimated 82,254 delivery hospitalizations during the decade-long study period included one or more amphetamine use diagnoses and 170,164 included one or more opioid use diagnoses.

By 2014-15, amphetamine use complicated roughly 1 percent of all deliveries in the rural West (11.2 per 1,000 hospital deliveries), which was higher than the incidence of maternal opioid use in most regions. The highest incidence of maternal opioid use was identified in the rural Northeast, complicating nearly 3 percent of all deliveries (28.7 per 1,000 hospital deliveries.)

Higher proportions of patients in both substance use groups were non-Hispanic white, from lower-income communities, and had public insurance compared to other hospital deliveries.

“Early and adequate access to prenatal care for women with substance use has been shown to improve birth outcomes,” Admon says. “However, geographic disparities have a major impact on the health and well-being of pregnant women and infants. There are significant barriers to obstetric care access in many rural communities, particularly for women with substance use.”

Barriers to treatment

Determining treatment specifically for prenatal amphetamine use is also a challenge.

While there’s gold standard medical treatment for maternal opioid use, Admon says, the evidence for amphetamine use disorder treatment among pregnant women is limited. Cessation is associated with improved birth outcomes, but obstetricians could use more guidance on how to promote cessation among their patients.

Federal efforts to curb access to precursor drugs used to make meth in the mid-2000s helped reduce amphetamine use overall, Admon notes. But as new methods were used to make the drug, meth use has again spiked.

Rural areas have the double whammy of greater access to amphetamines but less access to addiction treatment services. Further complicating the matter are laws that criminalize substance use during pregnancy that may discourage women from disclosing the concern to their health provider.

Neonatal intensive care units in rural counties may also not have adequate capacity to care for babies born with neonatal abstinence syndrome, which describe health problems a baby experiences when withdrawing from exposure to narcotics.

“We have seen a significant increase in infants born with symptoms of drug withdrawal,” says Winkelman, of Hennepin Healthcare in Minneapolis and graduate of the National Clinician Scholar’s Program at U-M’s IHPI.

“We need to devote more resources to prevent and treat substance use in pregnancy, especially in low-income and rural communities.”

Neonatal abstinence syndrome accounted for $3 billion in hospital costs between 2004 and 2014, according to another study led by Winkelman and colleagues.

More intervention needed

The new U-M-led study follows Admon’s previous research, which found that pre-existing, chronic conditions among delivering women have increased substantially and are linked to adverse birth outcomes.

Prior work by Admon and colleagues also examined racial and ethnic disparities in the incidence of behavioral health conditions, including substance use disorders. Substance use were less common among African-American and Hispanic women, but, when present, were associated with a higher risk for adverse birth outcomes compared to non-Hispanic white women.

“It is critical that health providers employ universal screening for substance use early in pregnancy,” Admon says. “Optimizing access to prenatal care is a crucial mechanism to connect women with the services they need for their health and their baby’s health.”

“We need to find better ways to prevent, detect, and treat maternal amphetamine and opioid use. Developing treatment programs that can reach women in the geographic areas most affected by these epidemics is key to improving outcomes for mothers and newborns.”

Now, a new assessment by a multi-institutional, CIRES-led team has harnessed a novel, highly detailed dataset to identify the factors that caused the speedup and slowdown. As the glacier flowed faster, it became thinner and more unstable — and then, in a twist, a pileup of thick ice replenished the glacier’s terminus, slowing it down again. The work, published today in the Journal of Glaciology, may help scientists better predict how tidewater glaciers contribute to sea level rise.

“As tidewater glaciers, like Jakobshavn Isbræ, thin they become increasingly sensitive to small variations in ice thickness,” said Ryan Cassotto, CIRES researcher and lead author of the new study, which was conducted while he was a doctoral student at the University of New Hampshire. “This is because water pressure at the base of the glacier counters pressure from the weight of ice above it, which impacts how fast the glacier flows.” For tidewater glaciers grounded deep below sea level, thicker, heavier ice travels slower, and thinner, lighter ice, faster. It’s similar, Cassotto said, to the way different sized cars hydroplane: large, heavy truck tend to be very stable and resist sliding while lightweight, compact cars readily slip.”

Jakobshavn Isbræ, the subject of James Balog’s 2012 documentary “Chasing Ice,” produces some of the largest icebergs and fastest speeds in the Arctic. And since iceberg calving contributes significantly to sea level rise, it’s critical to understand the glacier dynamics and calving events that produce them, the researchers said.

“Over the last two decades, Jakobshavn Isbræ has discharged more ice than any other glacier in Greenland,” said Cassotto. “It alone contributes about three percent of the current rise in global sea level annually.”

The research team, which included coauthors from the University of Alaska Fairbanks, the University of Alaska Southeast, the University of New Hampshire, and The Ohio State University, harnessed new techniques to observe the glacier at a level of detail never seen before. They used instruments called ground-based radar interferometers to observe how the ice surface was deforming, measuring every three minutes. Calving events happen in a matter of minutes and so they often can’t be caught by satellite-based instruments that repeat measurements only every 11 days.

Cassotto and his team found the geometry of the fjord bed is critically important to understanding glacier speed, as others have proposed. The new work shows that even small changes at the ends of glaciers, those last several hundred feet moving out toward the ocean, can profoundly affect speed.

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