While searching for primate fossils in northern India, paleontologist Christopher Gilbert noticed something small and shiny poking out of the dirt. It turned out to be a roughly 13-million-year-old molar from a small-bodied ape related to modern gibbons.
The tooth is the oldest known fossil from a gibbon ancestor, says Gilbert, of Hunter College at the City University of New York. He and colleagues assigned the fossil, which was eroding out of previously dated sediment at a site called Ramnagar, to a new genus and species, Kapi ramnagarensis.
This roughly 13-million-year-old molar tooth (shown from above) was found in India and is the oldest known fossil from a gibbon ancestor.C. Gilbert
Until now, the oldest remains of an ancient gibbon species consisted of a small number of teeth found in China, which date from around 7 million to 9 million years ago. Possibly older fossils of a gibbonlike creature are controversial (SN: 10/29/15). Genetic studies of living primates have suggested that gibbon ancestors emerged by at least 20 million years ago in Africa.
After finding the Ramnagar molar in 2015, Gilbert’s team compared it with corresponding teeth of living and extinct apes and monkeys. Features including low, rounded cusps on the edges of the chewing surface link the ancient tooth to modern gibbons and the gibbon predecessor in China, the scientists report September 9 in Proceedings of the Royal Society B.
K. ramnagarensis comes from deposits that previously yielded fossils of an orangutan ancestor, suggesting to Gilbert that both apes reached South Asia from Africa around the same time. “We’re catching a window into that event” as small-bodied gibbons and large-bodied orangutans headed to their recent and current home ranges in East and Southeast Asia, he says.
While acetaminophen is helping you deal with your headache, it may also be making you more willing to take risks, a new study suggests. People who took acetaminophen rated activities like “bungee jumping off a tall bridge” as less risky than people who took a placebo.
In October 2019, a state court determined that North Carolina’s congressional districts had been severely gerrymandered and struck down the state’s map. The court’s ruling was informed, in part, by tens of thousands of alternative maps demonstrating that the district boundaries had very likely been manipulated for political gain, the very definition of gerrymandering.
Researchers had generated a slew of alternative, computer-generated maps designed to help identify potential patterns of bias. The approach is increasingly used, alongside other tests, to ferret out alleged gerrymandering. District manipulations can be so subtle that they’re undetectable just by looking at them. “The eyeball test is no good,” says Jonathan Katz, a political scientist and statistician at Caltech.
U.S. states redraw their district lines every 10 years to adjust for changing demographics picked up by the national census. The last round a decade ago raised eyebrows, most notably for districts drawn in Michigan, North Carolina and Pennsylvania.
“The post-2010 round of redistricting is widely viewed as a time of extreme, even egregious, partisan gerrymandering,” retired political scientist Richard Engstrom wrote in the January 2020 Social Science Quarterly.
A 2017 report by the nonpartisan Brennan Center for Justice at New York University School of Law noted that existing congressional maps were largely biased in favor of the Republican Party. In 26 states, which account for 85 percent of U.S. congressional districts, as many as 17 Republicans in the House of Representatives owe their seats to gerrymandering. In states where Democrats controlled the redistricting process, partisan bias is also a problem, but the effect is smaller because those states are often made up of fewer districts.
Since 2011, legal scholars, political scientists and mathematicians conducting gerrymandering research have served as expert witnesses in more than 250 state and federal court cases regarding redistricting.
With the 2020 U.S. census now under way, legislators will soon be revising electoral districts again. This time around, researchers hope that instead of serving as expert witnesses in court, they can help identify problematic districting before the new maps even go into effect.
“In 2010, the politicians were thinking very hard on how to draw maps,” while the public and academics weren’t paying a lot of attention, says Jon Eguia, an applied game theorist at Michigan State University in East Lansing. “So in 2011, [those politicians] drew a lot of very bad maps in very many states. Now we’re all paying attention.”
Measuring bias
According to the U.S. Constitution and the Voting Rights Act of 1965, a state’s voting districts must each contain about the same number of people and be drawn in a way that doesn’t disenfranchise racial or ethnic minorities. States can have additional rules, such as contiguity of districts or that cities or counties be kept intact.
That leaves two main tactics for gerrymandering: “packing” the opposing political party’s supporters into a few districts in hopes your party dominates the rest, or “cracking” these supporters by spreading them across many districts to dilute their collective voting power. Those skilled in gerrymandering draw district boundaries that ensure decade-long protection for the ruling party.
Early methods to test a state map for gerrymandering, which are still in use today, rely on a concept known as partisan symmetry. If a map provides symmetric, or equal, opportunity for all parties in a contest to convert votes into seats, that map is deemed fair. States with packed and cracked districts won’t pass tests based on symmetry.
Puzzle power
The party that controls the maps can grab power through packing or cracking. In packing, politicians cram voters from the opposing party into just a few districts, securing the remaining districts for their own party. The blue ruling party created one all-red district, and three majority blue districts. In cracking, politicians spread voters from the opposing party across districts, blocking them from gaining a majority. The ruling red party split up blue voters at the “city center” to create three reliably red districts.
Three ways to divide a city’s voters
Competitive
Packing
Cracking
T. Tibbitts
Source: Azavea 2018
Symmetry-based tests gained prominence after LULAC v. Perry, a 2006 Supreme Court case that reviewed a mid-decade redistricting plan in Texas. In that case, scientists entered into evidence a partisan bias test — a simulation of what would have happened in an election if the parties’ vote shares were reversed. For instance, if Party A wins 10 out of 15 seats with 70 percent of the vote in an actual election, then Party B, in a hypothetical election, should win 10 seats if it had 70 percent of the vote. Deviation from that “symmetry” equals the level of partisan bias.
In LULAC, the justices largely upheld Texas’ map. But the court indicated willingness to use a symmetry-based method in a future case, though perhaps not solely the partisan bias test. Justice Anthony Kennedy expressed concerns about that particular test, saying it was unclear how much bias was too much. Kennedy also questioned the method’s reliance on statistical simulations rather than real-world results. “We are wary of adopting a constitutional standard that invalidates a map based on unfair results that would occur in a hypothetical state of affairs,” he wrote in the plurality opinion for LULAC.
Real-world symmetry
Kennedy’s feedback on LULAC prompted researchers to develop other symmetry-based tests that used actual election results.
One such approach is the median-mean difference test. That test arises from the basic statistical principle that the difference between the median and the mean indicates the level of skew in the data, with values closer to zero less skewed and vice versa. In 2015 in the Election Law Journal, political scientists Michael McDonald and Robin Best of Binghamton University in New York explained how a median-mean analysis could help identify partisan skew in a state.
A party’s mean vote share comes from averaging vote shares across all districts in a state. A party’s median vote share comes from the district in the middle of a distribution, with the party’s worst-performing district in terms of vote share at one end and the best-performing district at the other. If the difference between a party’s median and mean vote shares is high, that indicates a possibly biased skew, though McDonald and Best noted that some natural skew is inevitable and must be factored into any analysis.
Another approach is called the efficiency gap, which measures the difference in packing and cracking between parties by tallying “wasted” votes. So, if Party A draws an electoral map that spreads Party B’s voters across districts, votes cast for Candidate B in districts won by A are wasted. Conversely, if Party A packs Party B’s voters into a few districts, votes cast for Candidate B beyond the majority needed to win are also wasted. Each party should have about the same number of wasted votes in an election. So the efficiency gap, first described in 2015 in the University of Chicago Law Review, is calculated by taking the difference in wasted votes between parties and dividing that by the total number of votes cast.
PlanScore, a nonpartisan group of legal, political and mapping experts, has shown how the various symmetry tests can be used in tandem to flag possible gerrymandering. In its analysis of the congressional map used in North Carolina’s 2018 congressional elections, where Republicans won 10 seats and Democrats three, PlanScore found bias using all three tests: The partisan bias test showed that in a hypothetical, tied election, Republicans would win 26.9 percent extra seats. In the median-mean test, the median Republican vote share was 5.8 percent higher than its mean vote share. And the efficiency gap was 27.7 percent in favor of Republicans.
Natural advantage
Critics of symmetry-based tests, though, say that the presence of packing and cracking does not prove that the governing party has intentionally gerrymandered the state’s districts. Instead, asymmetries can also arise from natural variations in where voters live. Crucially, Republicans tend to be more dispersed across states while Democrats are concentrated in cities.
“The party that’s more spread out has a geographic advantage,” says applied mathematician Jonathan Mattingly of Duke University. “That’s our system.”
Tests that have emerged over the last few years, known broadly as ensemble methods, accept that natural advantage. These tests rely on computers to generate thousands, or even millions, of possible maps. The programs draw myriad boundary lines around a given district and estimate which party would win that district under each scenario.
Consider a state in which one party wins four to seven seats in almost all maps generated, while the state is using a map that regularly gives that party nine seats, Eguia says. That discrepancy suggests partisan gerrymandering.
Lawyers working on gerrymandering cases tend to use ensemble and symmetry methods in tandem, says Ruth Greenwood, an attorney in Cambridge, Mass., with PlanScore and the nonpartisan nonprofit Campaign Legal Center. That’s because each alternative map can also be evaluated for symmetry using the various tests. Averaging symmetry scores in the ensemble maps and comparing those values with the symmetry scores of the real-life map can illuminate when the difference is stark and therefore can’t be chalked up to any “natural advantage.”
Using all methods together also means that when a map’s fairness is questioned, the lawyers can show that “on any metric, the result is terrible,” Greenwood says.
States at the helm
The issue of gerrymandering was weaving through the federal courts until June 2019, when the Supreme Court ruled 5–4 in Rucho v. Common Cause that partisan gerrymandering fell outside federal jurisdiction. The decision was in response to an appeal challenging a federal court’s January 2018 ruling that North Carolina’s congressional district map had been gerrymandered along partisan lines, giving Republicans 10 out of 13 seats in 2016 and 2018, despite the fact that in both elections Republicans won only about half the popular vote.
By removing the federal court system from gerrymandering cases, the Supreme Court left the issue to the states, a charge a North Carolina state court quickly took up in Harper v. Lewis. The state court relied on much of the same evidence presented in Rucho. That evidence included testimony by Mattingly showing that in a universe with 24,518 alternative congressional district maps, the map North Carolina was using was an egregious outlier. In the maps Mattingly generated, Republicans carried 10 or more seats less than 1 percent of the time.
In October 2019, the three-judge panel in the Harper case ruled that state lawmakers needed to redraw the congressional district map for 2020. Plaintiffs, however, then challenged the state’s remedial map, which would likely result in Republicans winning eight out of 13 seats. Mattingly again provided expert testimony, this time adding 57,202 more maps made using less stringent constraints than the first batch. His research showed a much more purple state, with a 7–6 or 6–7 party split arising in the majority of those alternative maps.
But with the state’s 2020 primary fast approaching, a state court approved the remedial map in December 2019. That new map will stand for only a short time, though. Along with every other state, North Carolina will go through redistricting again in 2021 after the census tallies are in. New Jersey and Virginia — which hold statewide elections in odd years — may struggle to finish their maps before the 2021 elections, since the census was delayed due to the pandemic.
Slightly fairer
For the last decade, Republican legislators in North Carolina have strategically packed and cracked Democratic voters across congressional districts, limiting their voting power. A state court struck down the maps from 2016 and 2018 that created only three Democratic-leaning districts (blue). The 2020 map creates two more blue-leaning districts, but researchers say the new map still gives Republicans an extra one or two seats.
North Carolina congressional map, 2016 and 2018
North Carolina congressional map, 2020
T. Tibbitts
Source: North Carolina General Assembly
Meanwhile, census watchers worry that the Trump administration’s recent decision to move the completion deadline for the population count from October 31 to September 30 could lead to undercounts among hard-to-reach groups, thereby affecting the placement of district boundaries.
Greenwood expects a spike in lawsuits, though now at the state rather than federal level, challenging the newly drawn maps. And a small cadre of researchers is now ready to serve as expert witnesses in those cases, Eguia says.
The upcoming mapmaking process doesn’t have to repeat the mistakes of a decade ago, he adds. In 2011, lawmakers drew maps largely behind closed doors without researchers present — resulting in a decade of lawsuits, he says. Why not, instead, bring researchers into the room, with their tests and myriad maps, from the get-go? “That’s what the community of experts would prefer,” he says. “That’s what I would advocate for.”
To better understand the effect of the COVID-19 pandemic on cannabis and CBD use, the UCLA Cannabis Research Initiative has launched the Cannabis, CBD and COVID Survey.
In June, a large study in the United Kingdom suggested that the steroid dexamethasone could help reduce the risk of death for critically ill COVID-19 patients. Now, more evidence suggests that steroids are an effective weapon against the coronavirus.
Researchers from the World Health Organization combined data from seven randomized clinical trials for severely or critically ill COVID-19 patients treated with steroids versus standard care or a placebo up to June 9. The trials used the steroids hydrocortisone, dexamethasone or methylprednisolone.
People who were on ventilators when their clinical trial started had a 30 percent chance of dying from the virus if given steroids compared with a 38 percent chance on standard care or a placebo, researchers report September 2 in JAMA. Results were even more promising for critically ill people who were not on ventilators: Those taking steroids had a 23 percent chance of death compared with a 42 percent for people taking a placebo or getting standard care.
Results of three of the studies included in the combined analysis — one from France testing hydrocortisone, a trial of dexamethasone in Brazil and an international study of hydrocortisone — were published at the same time in JAMA. Those and other trials in the WHO analysis were stopped early because it wouldn’t have been ethical to continue and deny some sick patients steroids once the U.K. study found them effective.
Based on the results of the combined analysis, the WHO recommended on September 2 that doctors give dexamethasone or hydrocortisone to severely and critically ill COVID-19 patients, but not to people with milder illness. Giving steroids to people with moderate or mild cases might dampen the immune system too much, allowing the virus to do more damage. The U.S. National Institutes of Health have also recommended use of steroids for hospitalized people who need extra oxygen or are on ventilators.
Don’t let the name fool you. Flamboyant cuttlefish (Metasepia pfefferi) look anything but flashy most of the time. Images and videos of the marine mollusks flashing bright purple and yellow hues litter the internet, perpetuating the idea that these animals are constantly putting on a show in the wild. But a new study proves just the opposite: Flamboyant cuttlefish spend most of their time looking like a pile of mud.
“These animals have superb camouflage,” says Roger Hanlon, a marine biologist at the Marine Biological Laboratory in Woods Hole, Mass. Specialized cells and structures in their skin allow the animals to instantly morph into ostentatious patterns, as well as blend in.
Keen to see how the animals balanced flamboyance with camo in nature, Hanlon organized two field studies in a cuttlefish habitat off the coast of North Sulawesi, Indonesia. Citizen scientist divers scouted the Lembeh Strait area over eight days in 2002 and again for 11 days in 2019, being careful to eavesdrop without disturbing the animals. Video footage collected by the team now reveals intimate details of the species’ mating practices and defensive behaviors as well as what the animals do in their downtime. Hanlon and Gwendolyn McManus, a marine biology student at Northeastern University in Boston, describe the results in the August Journal of Experimental Marine Biology and Ecology.
The solitary species slowly ambles along the seafloor, foraging in a drab region of mud and sand between coral reefs. “It’s like a moonscape or a desert,” says Hanlon. Flamboyant cuttlefish take on the color and texture of their muddy seafloor backdrop and masquerade as a lump of sand or a rock. Like some other cephalopods, these cuttlefish spend most of their time incognito, reserving their displays for special occasions: confusing a predator, courting a mate and sparring with rival suitors.
Contrary to previous studies and scuba diver reports, flamboyant cuttlefish don’t parade around the ocean in full getup (left). They actually spend most days pretending to be rocks (right).L-R: R. Hanlon, F. Bavendam
Flashing their good looks 24/7 would attract unwanted attention. But it comes in handy if their first line of defense — camouflage — fails. Then, both males and females will engage in a campaign of unpredictability. When confronted by a threat, the animal might quickly flash its colors to frighten the predator, sometimes in just 700 milliseconds. Next, it cycles through other confusing behaviors — jetting, shooting ink and reverting to camouflage — until it has eluded the enemy.
Males also show flamboyant displays to attract the ladies. After spotting a female in the distance, a male will flaunt bright colors and undulate their mantle stripes in a move called “the passing cloud.” Researchers also observed two types of gestures during this colorful routine: arm waving (reminiscent of a human bowing) and kissing (a tap on the female’s arm with his arms). “These displays are really elaborate and dynamic,” says Hanlon. “And they’re comparable to what some of the most sophisticated birds do and even some primates.”
Love triangles happen, and males sometimes guard females and fight off other males (SN: 5/12/17). In brawls, male body patterns split flirting and fighting. The side facing the female flashes the bright motif, while the side facing the male takes on an aggressive white pattern.
Video footage from field studies in Indonesia provides an inside look at the lives of flamboyant cuttlefish.
All of this pizzazz can put males at risk. Hanlon recalls an instance where a male swimming backward got scarfed up by a scorpion fish in the midst of his flamboyant display. “There’s the price you pay for displaying to a female not paying attention to where you’re going,” says Hanlon.
But the risk can come with reward — for some lucky guys. Eventually, a female may open her arms and mate for a quick three seconds. Figuring out exactly what flirting tactics a female uses to select her mate requires more data. “Does she focus on the male’s courtship dance? On his ‘kiss’ signal? Or on how bright his passing cloud is? It’s too soon to tell,” says Alex Schnell, a wildlife scientist at Cambridge University who was not affiliated with the study.
Males also got shot down a lot, as picky females appear largely unmoved by most of their showmanship. Of 108 kisses observed, only 20 led to something more. The observations hint that the most successful males might be the ones that worked the hardest and remained persistent.
The field observations fill in knowledge gaps about how these animals survive in the wild and contradict two previous studies in a lab and an aquarium, as well as photos and videos from scuba divers, that suggested that the animals displayed their flamboyant patterns more frequently. Looming humans, bright lights and higher density tanks may have shifted the behavior of a species that spends most of its time alone and under the radar.
In the United States, the average wait time for COVID-19 test results is about four days. Even worse, 10 percent of individuals don’t receive lab results for 10 days or more.
Quick reporting of test results helps identify infected individuals so they and anyone they potentially spread the coronavirus to can be isolated, preventing further spread of the virus.
“If you have a 14-day lag to knowing if someone is actually sick and contagious, then they’ll interact with many, many more people in that period than if you have a one-day or a six-hour or one-hour turnaround,” says Omar Abudayyeh, a bioengineer at MIT.
Abudayyeh is among the many researchers and companies racing to develop new and speedier types of diagnostic tests that circumvent clinical labs altogether. Some of these tests complete their analyses in all-in-one machines that are portable enough to be set up in schools, nursing homes and offices. Several companies are developing tests like these that can diagnose COVID-19 in 30 minutes or less, with a level of accuracy comparable to lab tests. Others are harnessing the power of the gene editor CRISPR to deliver rapid results.
And another type of test, made by Abbott Laboratories and granted emergency use authorization by the U.S. Food and Drug Administration on August 26, works more like a pregnancy test. All it requires is a test card the size of a credit card, a few drops of a reaction solution and a sample from a nasal swab. Within 15 minutes, two lines appear on the card if the sample contains the virus; one line appears if it doesn’t.
The gold standard
The current gold standard for accurate COVID-19 testing is PCR, or polymerase chain reaction, which can detect even tiny quantities of the virus’s genetic material, RNA (SN: 3/6/20).
The test requires collecting viral RNA directly from the patient, typically gathered using a swab inserted deep into the nasal cavity. At a clinical laboratory, the virus’s RNA is converted to DNA and then run through a specialized instrument that heats and cools that DNA to multiply copies of it, making it easier to detect. After repeating the process for around an hour, if DNA shows up, the sample is considered positive for SARS-CoV-2, the virus that causes COVID-19.
Such tests are fairly accurate. They miss some people very early in the infection or because of lab errors, producing false negatives, meaning that the test results indicate someone isn’t infected when they really are. False positives — when tests wrongly indicate an uninfected person has the virus — are rare with this type of technology. So if a PCR test indicates a person is infected, they probably do carry the virus. The main drawback is the speed. It typically takes days to get results back, and backups at labs can drag the process out for a week or two.
Some people find the nasal probe uncomfortable, so other lab tests have been developed that rely on less invasive samples. On August 15, the FDA authorized a saliva-based test, SalivaDirect, for emergency use. This isn’t the first test to detect the SARS-CoV-2 virus in saliva, which is easier to collect than samples from nasal passages. But its simplified protocol speeds up sample preparation and bypasses testing supplies that have been in short supply in recent months. SalivaDirect, however, is not a rapid test. It still requires processing by clinical laboratories, which contributes to the wait time between providing a sample and receiving results.
To develop faster tests, companies are taking a variety of approaches. Funding for some of this work comes from the Rapid Acceleration of Diagnostics initiative, or RADx, from the National Institutes of Health, which has invested $248.7 million in seven companies tackling testing challenges.
Compact instruments, such as Mesa Biotech’s Accula test, replace the function of clinical labs and could bring rapid testing to schools, nursing homes and offices.Mesa Biotech
San Diego–based Mesa Biotech, for instance, received RADx funding to manufacture a PCR test that replaces an entire clinical lab with a handheld dock and a single-use cartridge. The company says the proprietary technology in its Accula test, which has already received FDA emergency use authorization, can provide a COVID-19 diagnosis in just 30 minutes.
Turning on the LAMP
Other RADx-funded companies, such as Talis Biomedical, headquartered in Menlo Park, Calif., aren’t using PCR to amplify SARS-CoV-2 viral material. The Talis One system instead uses LAMP, or loop-mediated isothermal amplification. In a typical LAMP assay, a patient’s nasal or oral swab sample is mixed with enzymes and specially designed DNA fragments, then heated to 65° Celsius to copy the viral RNA to DNA and produce many more DNA copies. With the Talis test, samples are placed in a cassette, popped into a specialized dock, and analyzed in just 30 minutes.
As opposed to an instrument that cycles between hot and cold, LAMP heats the reaction to one temperature. “You could run the reaction in a water bath,” says Nathan Tanner, a molecular biologist at New England Biolabs in Ipswich, Mass.
In general, LAMP-based diagnostic tests aren’t quite as sensitive as ones based on PCR, Tanner says, but could be used to test more people, given their simpler requirements. In one newly described LAMP testing method, a solution changes color in the presence of 100 or more SARS-CoV-2 RNA molecules. The authors, who describe the test August 12 in Science Translational Medicine, propose that the approach, which didn’t detect the lowest viral loads, would be suitable for identifying individuals with a moderate to high viral load.
Telltale proteins
A third RADx-funded test provides results in a mere 15 minutes. Rather than detecting viral RNA, the test, by Quidel, based in San Diego, detects proteins from virus particles. These viral proteins are also antigens, meaning they stimulate immune responses when they invade our bodies. Such antigen tests are similar to ones used in doctors’ offices and pharmacies to diagnose people with influenza.
Don’t confuse antigen tests with an antibody test that detects antibodies a person develops in response to an infection (SN: 4/28/20) Much like a pregnancy test, COVID-19 antigen tests use antibodies to detect the viral proteins and give a yes or no answer, says Kim Hamad-Schifferli, a bioengineer at the University of Massachusetts Boston.
The Quidel Sofia SARS antigen test has been authorized for emergency use. Like the other RADx-funded rapid tests, it uses a dock and single-use cartridges: Instead of making a line on stick the way a pregnancy test does, the dock detects a fluorescent signal if SARS-CoV-2 proteins are present.
An antigen test by Abbott Laboratories requires only a test card, a swab sample and a few drops of a reaction solution to return a COVID-19 diagnosis in 15 minutes.Abbott
Abbott Laboratories’ test granted emergency use authorization August 26 also is an antigen test and, with its card-based technology, is even simpler. Abbott, based in Abbott Park, Ill., said its test was able to detect 34 of 35 COVID-19-positive patients with symptoms, or 97 percent, in initial studies.
The benefit: An antigen test doesn’t require any specialized lab instruments or enzymes. “It’s all self-contained,” Hamad-Schifferli says. Without a step to amplify viral material, however, an antigen test can be less sensitive than PCR or LAMP and result in a higher rate of false-negative results, up to 20 percent per the FDA’s emergency use authorization guidelines for antigen tests.
That’s because people may produce widely varying amounts of virus, depending on how long has passed since they became infected. In most people, the coronavirus is most abundant from a couple of days after infection to about nine days into the illness (SN: 3/13/20). After that, the immune system kicks in, preventing viruses from being made. On the other hand, viral RNA can be detectable in some people for more than a month. A negative result from an antigen test has a higher chance of being false comfort, so the FDA says that diagnosis may need to be confirmed with another type of test, like PCR.
A new kind of rapid test
Even though antigen tests typically are not as accurate as standard PCR or the new rapid tests, they could play a crucial role helping to end the pandemic — if their use becomes widespread. As of now, though, even Abbott’s 15-minute test still needs to be ordered by a doctor and performed in a health care setting, so that can provide hurdles to its use. But what if people didn’t even have to leave home to get a test?
That’s what Hamad-Schifferli and her colleagues are working on. The idea is to build a cheaper test that doesn’t involve a dedicated instrument — just a paper strip and a signal detectable by eye. Such a simple test could be used more widely by people at home. “It would be a game changer,” she says.
If COVID-19 tests are deployed widely enough, they could serve as a public health measure to identify people with high levels of SARS-CoV-2 and spreading the virus to others, even if they’re not displaying symptoms. That’s because frequent and fast tests can be used to pinpoint outbreaks as they are happening (SN: 7/1/20). If cheap enough, these tests could be used by people daily, catching any missed detections through repeated rounds of testing.
But for daily, population-wide testing that could alert people when they first start transmitting the coronavirus to be adopted, a test needs to be cheap enough — for instance, under a dollar — for many people to use them frequently. Abbott said its tests would cost $5. Quidel’s test cartridges cost $23 apiece and the other RADx-funded rapid tests are likely in a similar price range. Given their higher accuracy, those tests could serve a separate purpose: to conclusively determine if an individual is infected and ensure they receive treatment.
With overwhelming demand for COVID-19 testing, it can take days or even longer than a week for people to receive test results.Hoptocopter/E+/Getty Images
The holy grail of tests may be one that is fast, easy, accurate and inexpensive and that could be used broadly — even by people at home. One group of scientists may be among those nearing that goal. The work is led by Abudayyeh, Jonathan Gootenberg and Feng Zhang, all bioengineers at the McGovern Institute for Brain Research at MIT. Zhang is also at the Broad Institute of MIT and Harvard University.
The team adapted an FDA-authorized test by Sherlock Biosciences in Cambridge, Mass., that uses the gene-editing tool CRISPR. All someone has to do is add a sample — either from a nasal swab or saliva — to a tube with a reaction solution, heat the tube to 60° C for an hour in a pot of water, then add a paper test strip to the tube. If two lines appear, that means SARS-CoV-2 RNA is present.
The readout relies on activity of a CRISPR enzyme, Cas12b. If SARS-CoV-2 RNA is present in the reaction, Cas12b cuts what’s called a reporter, a short piece of DNA that’s labeled on both ends. The two halves of the reporter then wick up the paper strip to different places and appear as two lines. If viral RNA isn’t present, the reporter remains intact and wicks up the strip to one place, showing up as one line.
The new test, STOPCovid, is not yet authorized for clinical use, but based on tests in a small number of patients, it identifies SARS-CoV-2 cases as well as PCR tests, the researchers reported May 8 in a preprint posted at medRxiv.org. It returns results in about an hour and would cost under $10, they say.
Unlike rapid tests relying on docks and cartridges, the STOPCovid test is uniquely designed to scale up to millions of tests per week, says Gootenberg. “There’s never been a demand for millions or tens of millions of tests per week — ever.”
With the development of so many new technologies to test for the coronavirus, “we’re going to come away from the epidemic with a whole new field of diagnostics,” Mina says.
As you drift into unconsciousness before a surgery, general anesthetic drugs flowing through your blood are putting you to sleep by binding mainly to a protein in the brain called the ɣ-aminobutyric acid type A (GABAA) receptor. Now UT Southwestern scientists have shown exactly how anesthetics attach to the GABAA receptor and alter its three-dimensional structure, and how the brain can tell the difference between anesthetics and the psychoactive drugs known as benzodiazepines – which also bind to the GABAA receptor. The findings were published online today in the journal Nature.
As the coronavirus hit communities across the United States over the summer, four overnight camps in Maine successfully kept the virus at bay.
Of 1,022 people who attended the summer camps, which included campers and staff members, only three people tested positive for COVID-19, researchers report August 26 in the Morbidity and Mortality Weekly Report. That’s because the people who came to Maine from 41 U.S. states, Puerto Rico, Bermuda and five other countries diligently followed public health measures put in place to stop transmission, the team says.
The camps’ success, as well as others including child care programs in Rhode Island that limited coronavirus transmission, could point to a path forward for places like schools that are reopening with in-person classes in the face of the ongoing pandemic, though challenges remain.
At the camps, a combination of testing, social bubbles, social distancing, masks, quarantine and isolation prevented outbreaks.
Before arriving at camp, officials told all 642 children and 380 staff members to quarantine with their households for 10 to 14 days. Attendees were also tested for COVID-19 five to seven days prior to arrival — with the exception of 12 people who had already been previously diagnosed. Four people tested positive for the virus and isolated for 10 days at home before heading off to one of the camps, which were in session at different times from mid-June to mid-August. (Three of the four camps ran for less than 50 days and the other went on for 62 days.)
Once on site, the campers and staff participated in daily symptom checks and activities held largely outdoors. They also hung out in small “bubbles,” or cohorts, that ranged from five to 44 people in size and became like family during the weeks at camp, the researchers say. If people interacted with anyone outside their group, masks and social distancing were required.
“We wanted to give the kids the ability to have a family unit at camp that they didn’t need to be masked or social distanced from,” says Laura Blaisdell, a pediatrician at Maine Medical Center Research Institute in Scarborough who worked on the new report.
Attendees came to Maine via car, bus and plane, and could have been exposed to the virus after their initial test, so officials retested the 1,006 attendees who had never had COVID-19 four to nine days after their arrival.
In that round of testing, two staff members and one camper from three different camps tested positive but never developed symptoms. Their cohorts were quarantined for two weeks, but still “were able to have a camp experience … and continue to have fun and play together,” Blaisdell says. The three positive cases didn’t transmit the virus to anyone else before they were identified. They each remained isolated until they had two negative test results.
Off to camp
More than 1,000 people from 41 U.S. states, as well as Puerto Rico, Bermuda and several other countries, attended summer camps in Maine from mid-June to mid-August. The map shown here indicates which states campers and staff members came from. (No one attended from states colored white.) A fair number of people traveled from states like Texas and Florida that were hit hard over the summer (seven-day daily average rate of coronavirus infection as calculated on July 1, shown), but the camps’ public health measures prevented outbreaks. States with less than 10 cases per 100,000 population are not designated.
Camp population, by home state, and states’ COVID-19 infection rates
L.L. Blaisdell et al/MMWR 2020
L.L. Blaisdell et al/MMWR 2020
Some people traveled to Maine from areas where COVID-19 cases were surging over the summer, including Texas, Arizona and Florida. But rigorous testing quickly identified potential spreaders, and small cohorts allowed officials to quickly identify those most at risk of catching the virus.
In that way, “cohorting is an unsung hero of public health intervention,” Blaisdell says.
While interventions like cohorts, social distancing and wearing masks can help reduce coronavirus transmission on their own to some extent, each method has limitations. Combining such strategies into a layered approach where people follow multiple guidelines to curb the virus’ spread, like the Maine camps did, can further protect the members of a community.
“Every public health layer is like a layer of Swiss cheese with a hole in it,” Blaisdell says. It’s the stacking of “multiple layers of cheese on top of each other that close those holes and makes for a robust [infectious] disease plan.”
By contrast, a summer camp in Georgia faced an outbreak of the virus even after requiring attendees to provide proof of a negative test before arrival. But there, campers were not required to wear masks, weren’t tested after they arrived at camp and participated in both indoor and outdoor activities (SN: 7/31/20).
Still, the isolated nature of the summer camps in Maine likely made creating a relatively COVID-19–free bubble much easier than it might be at K–12 schools or universities around the country, where people come and go and may not live on site (SN: 8/4/20). There were some staff members at the four camps in Maine who went home every day, but those people were required to wear masks at all times and social distance from other attendees. It also likely helped that the amount of coronavirus circulating in Maine was quite low while the camps were running.
What’s more, the larger the school, the harder it will probably be to make sure that public health interventions are being adhered to. “If you follow the rules, then this can absolutely be successful,” says Brian Nichols, a virologist at Seton Hall University in South Orange, N.J. But, “when you scale it up and start looking at public schools and universities, you just have to plan on the fact that some people aren’t going to follow the rules.”
Nevertheless, the success in Maine hints that containing the virus is possible with a targeted, layered approach, Blaisdell says. “As schools and colleges begin to consider opening, they need to look at their community as a bubble,” she says. “We all need to be making contracts with each other about the behaviors that we’re going to do.”
A researcher slips stickers under some colored cups on a lazy Susan, then gives the tray a whirl. When the spinning stops, a preschooler must find the hidden stickers. Most children remember where the stickers are, but a few have to check every single cup.
The game tests working memory, which is among the set of mental skills known as executive function that can be impaired in children who faced trauma early in life.
Adversity wreaks havoc, and from there, “you have a system that responds differently,” says Megan Gunnar, a developmental psychobiologist at the University of Minnesota in Minneapolis who has spent two decades studying the impact of early-life adversity in adopted children. The focus of this work is extreme adversity, such as being orphaned, rather than everyday challenges, which might teach beneficial resilience.
A childhood characterized by hardship, negligence or abuse can also alter the neuroendocrine system that regulates how the body responds to stress. Problems in the stress response can set kids on a path toward behavior struggles along with increased risk for depression, diabetes and a host of other health problems.
But recent studies offer hints that such a difficult future may not be inevitable. As Gunnar and others have shown, impaired stress responses can return to normal during puberty, raising the possibility that imbalances created by early trauma can be erased. The research is prompting a new view of puberty as an opportunity — a chance for people who had a shaky start to reset their physiological responses to stress.
A sense of safety
When the brain perceives a threat — even a temporary one such as a stressful exam or a high-stakes competition — levels of the hormone adrenaline shoot up, setting off the “fight-or-flight” reaction. Breathing and heart rate soar. Palms get sweaty. Sight and other senses sharpen. Before long, the brain sends chemical messengers to stimulate adrenal glands near the kidneys to release cortisol.
A spin-the-pots task, with colored cups and hidden stickers, tests working memory, which can be impaired in children who experience early hardship.N.H. Brito et al/Frontiers in Psychology 2014
Cortisol sends sugars into the blood for quick energy. The hormone also slows digestion, immune responses, growth and other processes considered nonessential in a fight-or-flight situation.
When the threat passes, the fight-or-flight response ends, at least in a person whose stress response is working as it should. Adrenaline and cortisol levels fall, heart rate slows and other systems resume business as usual.
When Gunnar started her doctoral work in the 1970s, researchers had already mapped out the key actors in the stress response. The neuro-endocrine signals involved form the HPA axis, short for hypothalamic-pituitary-adrenal. When rodents and monkeys face early-life adversity, the HPA axis gets thrown off-kilter. As methods became available for measuring cortisol from samples of saliva — rather than having to collect blood or urine — Gunnar set out to study how the HPA axis influences the brain and behavior in humans.
From experiments with newborn babies in the mid-1980s, Gunnar showed that having a secure parent relationship is important for a healthy neuroendocrine system and helps babies deal with stressful situations, such as getting immunizations. “You can go to the doctor as a baby and get a big shot in one leg and the other leg, and you’re crying your head off … but [the HPA axis] doesn’t kick off,” Gunnar says. However, shots or no shots, if babies get separated from their parents for even a few minutes, “their HPA axis shoots up like a rocket.”
Gunnar wondered what happens if that sense of safety is disrupted longer-term. She tried studying maltreated and impoverished children, but separating the effects of early hardship from later difficulties is not easy. “The way you start out in life tends to continue,” Gunnar says. A report published last November by the U.S. Centers for Disease Control and Prevention points to the long-term consequences: Compared with their peers, adults who experienced childhood trauma are more likely to smoke, drink heavily, have dropped out of high school and develop heart disease and a host of other chronic conditions.
A trip in the mid-1990s set Gunnar on a new path to answer that tricky research question. She ventured with a research team to an orphanage in eastern Romania, where young children were raised in overcrowded, inhumane conditions. “You walk into these wards, and all of a sudden you’re mobbed by kids saying ‘Mama, mama, mama’ … reaching their arms up to get held,” says Gunnar, who had two school-age sons at the time. “It was awful. I just wanted to bring them all home.”
What she did bring back to Minnesota, along with that searing memory, was a set of small vials, each containing a saliva sample from a 2- or 3-year-old orphan. To her surprise, the children’s cortisol levels — the end product of the neuroendocrine cascade — were lower than the average toddler’s. That finding offered a window into the effects of long-term parental deprivation on stress responses.
Adoptee struggles
To single out the effects of early hardship, Gunnar needed children who had started life in deprivation but then moved into healthy, supportive environments after infancy. Such children would be the ideal human analog for all of the animal studies on early adversity, she thought. It dawned on her that this group exists: adopted orphans.
Gunnar shared her idea with members of the adoption unit at the Minnesota Department of Human Services. With the department’s support and funding, she surveyed Minnesota parents who had adopted children internationally in the 1990s, and invited families to join a university registry and participate in research.
Many parents in the study had noticed early on that their adopted children had behavioral problems. And when the youngsters came to the university lab for problem-solving and sorting tests, including the lazy Susan task and the famous marshmallow test of delayed gratification (SN: 8/4/18, p. 14), the children struggled with attention and self-regulation.
Like the Romanian orphans, these kids had lower cortisol levels than nonadopted children who had no behavioral problems. In the face of sustained hardship, which has the potential to encourage dangerously high levels of cortisol, a weak stress response — that is, producing less cortisol — could be “nature’s way of preserving the brain and body,” Gunnar speculates.
Teen-time shift
Before puberty, adopted children, who grew up with early-life trauma (gray curve), had blunted stress responses relative to kids living with biological parents (blue curve). By the time puberty ended, the adopted children showed normal cortisol patterns before, during and after a stressful task. Saliva was collected 20 minutes and 5 minutes before the task, then 5, 20, 40, 60 and 80 minutes after the task. The researchers converted the data to a logarithmic scale, which shows negative numbers. The actual cortisol levels are between 0 and 1 micrograms per deciliter.
Cortisol stress response in adopted and nonadopted children
T. Tibbitts
T. Tibbitts
Source: C.E. DePasquale, B. Donzella and M.R. Gunnar/J. Child Psychol. Psychiatry 2019
Studying the adoptees over time, she found that preschoolers with low cortisol often entered kindergarten with attention problems. A blunted stress response persisted into middle childhood, even after an average of seven to eight years in a household with healthy caregiving.
That was disheartening, says Russell Romeo, a psychobiologist at Barnard College in New York City. “We’d always thought that maybe if these individuals get out of the adverse situations, they could start recalibrating their stress reactivity.”
But research Romeo had done in the mid-2000s gave Gunnar reason to think she just needed to look further down the road of the children’s lives.
High time for change
Romeo was studying rats to see if stress affects adolescent and adult brains differently. In one set of experiments, he subjected adult rats and prepubescent rats to acute stress — 30 minutes trapped inside a wire mesh container — and recorded their levels of corticosterone (the rat version of cortisol) before, during and after the confinement. Both groups produced similar hormone spikes when stressed, but in the juvenile rats, levels took much longer to return to normal.
When Romeo observed how the animals reacted to extended periods of stress — 30 minutes of restraint each day for seven days — the pattern was different. After the animals were released from the restraints, stress hormones surged higher in young rats than in adults. But the rats that were near puberty returned to baseline more quickly than the older animals. Taken together, Romeo’s studies suggested that neuroendocrine stress responses get shaped during puberty to emerge differently in adulthood.
In earlier work, researchers at McGill University in Montreal showed that moving adolescent rats into “enriched” environments — larger cages with more toys and cagemates — could reset stress responses that had been thrown out of whack by early-life trauma.
These findings heartened Gunnar. “Maybe I should be looking at puberty,” she thought. It could be a time to recalibrate.
Closer to normal
During a stressful activity (giving a speech, for example), saliva cortisol levels rose temporarily and returned to normal in those children who lived with their biological parents. Children who were adopted after starting life in an orphanage (an early-life trauma), had blunted cortisol responses during stages 1 to 2 of puberty. But at the tail end of puberty, stages 4 and 5, adopted children’s stress responses normalized.
Stages of puberty and cortisol stress reaction
T. Tibbitts
T. Tibbitts
Source: M.R. Gunnar et al/PNAS 2019
So her team invited 280 7- to 14-year-olds — 122 children adopted from institutions and 158 from socioeconomically comparable biological families — into the lab to complete two stressful tasks. One involved challenging mental math. For the second task, each child prepared a five-minute speech introducing themselves to a new class of students. The children were told that their speech, given in front of a video camera and a mirror, would be rated by judges. Some kids spoke with confidence, while others looked nervous. “We did have one who burst into tears,” Gunnar says. But “we don’t torture them. If we think they’re too nervous, we help them quit.”
Before and after the speech and math tasks, researchers collected saliva samples from each child to measure cortisol levels. Participants’ pubertal status was assessed on a 1-to-5 scale: Stage 1 meant no noticeable body changes and stage 5 meant sexual maturation was complete.
Among kids in early puberty (stages 1–2), adopted kids had blunted cortisol levels before and after the tasks compared with children who lived with their biological parents. This result confirmed Gunnar’s previous research on preschool-aged international adoptees. In the late puberty group (stages 4–5), cortisol patterns looked similar for adopted and nonadopted kids.
To confirm HPA recalibration had occurred within the same child, rather than just comparing across age groups, Gunnar and colleagues brought participants in for the same tests one and two years later, for a total of three annual sessions.
The results, reported in the Nov. 26 Proceedings of the National Academy of Sciences, show the body can recalibrate its response to stressors during puberty. In other words, something happens in puberty — but not earlier in childhood — that allows the brain to shift back to normal stress responses that had been skewed by early trauma.
Matthew Duggan, a therapist in Long Beach, Calif., who specializes in childhood and adolescence, is encouraged by the findings and thinks they could apply to a wide range of children who have trouble managing their emotions and connecting with others because caretakers abused or ignored them early in life. There may be “a window … where things might be able to change,” Duggan says. “And we have some data here to suggest that at a biological level, that is a possibility. For me, that’s really hopeful to see.”
Duggan says Gunnar’s study would have been even more useful if it had assessed participants’ behavior change — for example, by interviewing parents, teachers or the adolescents themselves.
How might puberty combine with better caregiving and support to reshape neuroendocrine stress responses? Romeo speculates that it stems from the fact that the hypothalamus and other brain areas, such as the prefrontal cortex, that control our reactions to stress are among the regions that rewire and strengthen connections during adolescence.
Whether those changes in the stress response will ultimately harm or help a young person is hard to predict, Gunnar says. Mental health and resilience emerge from an ever-changing combination of genes and life experiences — some of which set the body awry early on. But adolescence could potentially erase some of the damage, her research shows. Gunnar and others hope to reveal more of the underlying biology behind the reboot.
Is there a sweet spot for early adversity?
Hardships early in life can mean a difficult road ahead. But some small amount of stress may help kids build mental toughness to handle the stresses of everyday life, such as big exams or performances (SN: 6/8/19, p. 12).
“We learn to handle stress by handling stress,” says Megan Gunnar, a developmental psychobiologist at the University of Minnesota in Minneapolis.
Early-life stress affects later resilience
T. Tibbitts
Groups of lab monkeys exposed to mild or moderate stress (yellow and red dots) showed lower anxiety later than animals exposed to no stress (blue) or heavy stress (black and white).
Source: K.J. Parker et al/Scientific Reports 2019
If a stressful experience shows “the world is tough but we can deal with it, perhaps with the help of family and friends,” she says, “we are tougher the next time.” On the other hand, feeling crushed by an intense stressor, such as abuse or a parent’s death, can impart a sense of helplessness that leaves young people “fearful of it happening again,” Gunnar says.
In a 2010 study, researchers surveyed 2,398 U.S. adults to understand how pain and stress affect resilience. Participants answered questions about their mental health and overall well-being, and indicated whether they had experienced cumulative lifetime adversities, including a serious illness or divorce in the family. The upshot: People who faced some adversity reported less distress and more life satisfaction compared with those who either experienced heavy adversity or sailed through childhood with ease.
Experiments in monkeys suggest that this is more than a correlation. A team led by David Lyons, a behavioral neuroscientist at Stanford University, reported causal evidence last November in Scientific Reports. Since it can be unethical to randomly assign humans to stressful conditions, the team tested the effects of varying “doses” of stress in squirrel monkeys that had not yet reached puberty.
The monkeys in the control group enjoyed a typical lab life — housed in a cage with mom and siblings, plus plenty of water, food and toys. A second group faced a mild stressor — one hour of separation from siblings once daily for 10 days. The stress dose went up a notch for the third group, which had daily separation from siblings and no access to mom during that hour. Two additional groups experienced daily separation from mother and siblings, plus an injection as an additional stressor.
Ten weeks later, each monkey was moved with its mother to an unfamiliar cage. The researchers assessed the monkeys’ willingness to let go of mom and explore the new digs. The team also analyzed blood levels of the stress hormone cortisol before and after the time spent in the new cage. On the whole, monkeys in the groups that faced one or two stressors clung less to their mothers and more readily explored their new surroundings — showing less anxiety — than both the no-stress and the two high-stress groups.
Cortisol patterns also reflected this trend: Cortisol levels were closer to normal in monkeys exposed to mild or moderate stress than in monkeys from the other groups.
Growing up healthy means “learning how to deal with mild challenge and change,” Lyons says.
To better understand the effect of the COVID-19 pandemic on cannabis and CBD use, the UCLA Cannabis Research Initiative has launched the Cannabis, CBD and COVID Survey.
