Faced with new uncertainty, shoppers began stocking up on basic household items — especially toilet paper — to account for the new unknown. This buying frenzy led to shortages, even though, in most cases, there would have been enough to go around if people only purchased what they needed.

According to a study led by UNSW Sydney, reactive behaviour like this isn’t unusual, but a common way to handle unexpected uncertainty.

In fact, unexpected uncertainty is such a powerful motivator for change that it often prompts us to adjust our behaviour — even when it’s not good for us.

“When people experience an unexpected change in their environment, they start looking for ways to lessen that uncertainty,” says lead author of the study Dr Adrian Walker, who completed this research as part of his PhD in psychology at UNSW Science. “They can change their behaviour and decision-making strategies to try and find a way to regain some sense of control.

“Surprisingly, our study found that unexpected uncertainty caused people to change their behaviours even when they would have been better off sticking to an old strategy.”

The behavioural study, recently published in The Journal of Experimental Psychology: Learning, Memory, and Cognition, is the first to show the type of uncertainty we experience — that is, whether it is expected or unexpected — plays a key role in our reaction.

For example, a city worker who knows their morning commute takes anywhere from 30 to 50 minutes wouldn’t be surprised by a 50-minute trip. On the other hand, a country driver would be very surprised if their predictable 30-minute trip suddenly took 50 minutes.

To test how people respond to unexpected change, the researchers tasked study participants with selling a pair of objects to one of two subjects — in this scenario, aliens — in a virtual simulation. Their task was simple: get as many points (or ‘alien dollars’) as possible.

Participants needed to choose which alien to sell a pair of chemicals to, but only one of the chemicals determined how much the alien would pay. They needed to work out which chemical and alien combination would earn them the greatest rewards.

An initial group of 35 participants were familiarised with the task and quickly learnt that one strategy (say, Option A) gave the better offer of 15 points. But midway through the experiment, the reward pattern changed, and Option A now gave a random number between 8 and 22 points.

“As soon as we added an element of uncertainty, the participants started looking for new ways to complete the task,” says Dr Walker. “The kicker is that in all cases, the best thing they could do was use their old strategy.”

Dr Walker says the pandemic — and our different responses to it — is a large-scale example of unexpected uncertainty.

“Everything changed very suddenly at the start of COVID-19,” he says.

“Many of us were suddenly all working from home, changing how we shop, and changing how we socialise. The rules we were living by beforehand no longer applied, and there was — and still is — no clear answer about when or how the pandemic will end.

“Different people tried all sorts of things — like panic shopping — to reduce this new uncertainty and return to ‘normal’. But as we’ve seen, not all of these reactive strategies were good in the long run.”

Boiling frog syndrome

While unexpected uncertainty led to dramatic responses, expected uncertainty had the opposite effect.

During the second phase of the trial, the researchers introduced uncertainty in a gradual way to a different group of 35 participants. Option A’s usual 15 points changed to 14-16 points, then 13-17 points, until the uncertainty rose to 8-22 points.

“The participants’ behaviour didn’t change dramatically, even though the uncertainty eventually reached the same levels as in the first experiment,” says Dr Walker.

“When uncertainty was introduced gradually, people were able to maintain their old strategies.”

While this specific experiment was designed for the original strategy to be the most beneficial, Dr Walker says other research has shown the harm in not changing behaviour when faced with gradual change.

“We can see this pattern in a lot of real-world challenges, like the climate change crisis,” says Dr Walker.

“When change is slow and barely noticeable, there’s no sudden prompt to change our behaviour, and so we hold to old behaviours.

“Trying to get action on climate change is a lot like the boiling frog fable. If you put a frog in a pot and boil the water, it won’t notice the threat because the water is warming gradually. When it finally notices, it is too late to jump out.”

Professor Ben Newell, the Deputy Head of UNSW School of Psychology, was one of the researchers involved in the project. He says an important next step in this research is translating insights about how people react to uncertainty in the lab to engaging people in climate action.

“If we can identify the triggers for exploring new alternatives, then we might overcome the inertia inherent in developing new, sustainable behaviours,” says Prof. Newell.

Being certain about uncertainty

Uncertainty is something humans face every day, whether it’s how bad traffic will be or what questions might be asked in an exam.

But the COVID-19 pandemic has thrown a new layer of uncertainty to major areas of our lives, like career, health, and living circumstances.

“While this study isn’t the whole picture for human behaviour during the pandemic, it can help explain why so many people looked for new ways to add certainty to their lives,” says Dr Walker, who is now a researcher in the School of Psychiatry at UNSW Medicine & Health.

Co-author Dr Tom Beesley, formerly of UNSW and now based at Lancaster University, says “Dr Walker’s work really helps us understand how people develop a representation of the uncertainty they are facing, and how they might cope, or not cope, with that.

“My lab is trying to formalise this relationship in a computational model of behaviour, so that we can make clearer predictions about what we might expect to happen under different conditions of uncertainty.”

While Dr Walker’s research is now focused on psychiatric epidemiology, he is interested to see where future research in this area goes — especially in predicting individual responses to uncertainty.

“Given how many decisions we make under uncertainty in our everyday lives, the more we can understand about how these decisions are made, the more we hope to enable people to make good decisions,” says Dr Walker.

The primary finding is that pairs of electrons and positrons — particles of matter and antimatter — can be created directly by colliding very energetic photons, which are quantum “packets” of light. This conversion of energetic light into matter is a direct consequence of Einstein’s famous E=mc² equation, which states that energy and matter (or mass) are interchangeable. Nuclear reactions in the sun and at nuclear power plants regularly convert matter into energy. Now scientists have converted light energy directly into matter in a single step.

The second result shows that the path of light traveling through a magnetic field in a vacuum bends differently depending on how that light is polarized. Such polarization-dependent deflection (known as birefringence) occurs when light travels through certain materials. (This effect is similar to the way wavelength-dependent deflection splits white light into rainbows.) But this is the first demonstration of polarization-dependent light-bending in a vacuum.

Both results depend on the ability of RHIC’s STAR detector — the Solenoid Tracker at RHIC — to measure the angular distribution of particles produced in glancing collisions of gold ions moving at nearly the speed of light.

Colliding clouds of photons

Such capabilities didn’t exist when physicists Gregory Breit and John A. Wheeler first described the hypothetical possibility of colliding light particles to create pairs of electrons and their antimatter counterparts, known as positrons, in 1934.

“In their paper, Breit and Wheeler already realized this is almost impossible to do,” said Brookhaven Lab physicist Zhangbu Xu, a member of RHIC’s STAR Collaboration. “Lasers didn’t even exist yet! But Breit and Wheeler proposed an alternative: accelerating heavy ions. And their alternative is exactly what we are doing at RHIC.”

An ion is essentially a naked atom, stripped of its electrons. A gold ion, with 79 protons, carries a powerful positive charge. Accelerating such a charged heavy ion to very high speeds generates a powerful magnetic field that spirals around the speeding particle as it travels — like current flowing through a wire.

“If the speed is high enough, the strength of the circular magnetic field can be equal to the strength of the perpendicular electric field,” Xu said. And that arrangement of perpendicular electric and magnetic fields of equal strength is exactly what a photon is — a quantized “particle” of light. “So, when the ions are moving close to the speed of light, there are a bunch of photons surrounding the gold nucleus, traveling with it like a cloud.”

At RHIC, scientists accelerate gold ions to 99.995% of the speed of light in two accelerator rings.

“We have two clouds of photons moving in opposite directions with enough energy and intensity that when the two ions graze past each other without colliding, those photon fields can interact,” Xu said.

STAR physicists tracked the interactions and looked for the predicted electron-positron pairs.

But such particle pairs can be created by a range of processes at RHIC, including through “virtual” photons, a state of photon that exists briefly and carries an effective mass. To be sure the matter-antimatter pairs were coming from real photons, scientists have to demonstrate that the contribution of “virtual” photons does not change the outcome of the experiment.

To do that, the STAR scientists analyzed the angular distribution patterns of each electron relative to its partner positron. These patterns differ for pairs produced by real photon interactions versus virtual photons.

“We also measured all the energy, mass distributions, and quantum numbers of the systems. They are consistent with theory calculations for what would happen with real photons,” said Daniel Brandenburg, a Goldhaber Fellow at Brookhaven Lab, who analyzed the STAR data on this discovery.

Other scientists have tried to create electron-positron pairs from collisions of light using powerful lasers — focused beams of intense light. But the individual photons within those intense beams don’t have enough energy yet, Brandenburg said.

One experiment at the SLAC National Accelerator Laboratory in 1997 succeeded by using a nonlinear process. Scientists there first had to boost the energy of the photons in one laser beam by colliding it with a powerful electron beam. Collisions of the boosted photons with multiple photons simultaneously in an enormous electromagnetic field created by another laser produced matter and antimatter.

“Our results provide clear evidence of direct, one-step creation of matter-antimatter pairs from collisions of light as originally predicted by Breit and Wheeler,” Brandenburg said. “Thanks to RHIC’s high-energy heavy ion beam and the STAR detector’s large acceptance and precision measurements, we are able to analyze all the kinematic distributions with high statistics to determine that the experimental results are indeed consistent with real photon collisions.”

Bending light in a vacuum

STAR’s ability to measure the tiny deflections of electrons and positrons produced almost back-to-back in these events also gave the physicists a way to study how light particles interact with the powerful magnetic fields generated by the accelerated ions.

“The cloud of photons surrounding the gold ions in one of RHIC’s beams is shooting into the strong circular magnetic field produced by the accelerated ions in the other gold beam,” said Chi Yang, a long-time STAR collaborator from Shandong University who spent his entire career studying electron-positron pairs produced from various processes at RHIC. “Looking at the distribution of particles that come out tells us how polarized light interacts with the magnetic field.”

Werner Heisenberg and Hans Heinrich Euler in 1936, and John Toll in the 1950s, predicted that a vacuum of empty space could be polarized by a powerful magnetic field and that such a polarized vacuum should deflect the paths of photons depending on photon polarization. Toll, in his thesis, also detailed how light absorption by a magnetic field depends on polarization and its connection to the refractive index of light in a vacuum. This polarization-dependent deflection, or birefringence, has been observed in many types of crystals. There was also a recent report of the light coming from a neutron star bending this way, presumably because of its interactions with the star’s magnetic field. But no Earth-based experiment has detected birefringence in a vacuum.

At RHIC, the scientists measured how the polarization of the light affected whether the light was “absorbed” by the magnetic field.

This is similar to the way polarized sunglasses block certain rays from passing through if they don’t match the polarization of the lenses, Yang explained. In the case of the sunglasses, in addition to seeing less light get through, you could, in principle, measure an increase in the temperature of the lens material as it absorbs the energy of the blocked light. At RHIC, the absorbed light energy is what creates the electron-positron pairs.

“When we look at the products produced by photon-photon interactions at RHIC, we see that the angular distribution of the products depends on the angle of the polarization of the light. This indicates that the absorption (or passing) of light depends on its polarization,” Yang said.

This is the first Earth-based experimental observation that polarization affects the interactions of light with the magnetic field in the vacuum — the vacuum birefringence predicted in 1936.

“Both of these findings build on predictions made by some of the great physicists in the early 20th century,” said Frank Geurts, a professor at Rice University, whose team built and operated the state-of-the-art “Time-of-Flight” detector components of STAR that were necessary for this measurement. “They are based on fundamental measurements made possible only recently with the technologies and analysis techniques we have developed at RHIC.”

The study looked at how dominant primates behave towards those of lower status, with some demanding deference and punishing challenges from subordinates harshly (despotic), whilst others are more relaxed (tolerant).

Japanese macaques are an example of a despotic species in this study, while black howler monkeys are an example of a tolerant species.

Researchers say this characteristic called “dominance style” is an important factor in understanding the evolution of communication. They expected that tolerant primates would use more communication than despotic primates to achieve their goals or to maintain their dominant position, instead of using aggression.

Using behavioural data from 26 primate species, the researchers quantified dominance style for the first time in many of these species.

Lead author, Dr Eithne Kavanagh a former PhD student from the Department of Psychology said: “We found evidence that dominance style was related to vocal communication at both individual and species levels.

“Notably, we found that more despotic species had richer repertoires of hierarchy-related calls in their evolved vocal systems, but that individuals who were more tolerant of lower-ranking partners vocalized at a higher rate.

“This indicates that tolerance within a relationship may place pressure on the dominant partner to communicate more during social interactions.”

The study concluded that overall, the findings suggested that the strictness of the dominance relationships of individuals and species provides important context for understanding primate vocal usage and evolution.

Partners in the research included Professor Katie Slocombe from the University of York, Dr Adriano Lameira from University of Warwick and Dr Sally Street from Durham University. This project was only possible with a great collaborative effort, with 64 primate researchers from 59 institutions working together to build the data set necessary to test these ideas.

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This trend is supported by preliminary data recently released by the Centers for Disease Control and Prevention (CDC), which recorded more than 93,000 opioid overdose deaths in 2020. That’s a 29.4% increase from the year prior and the most opioid overdose deaths every recorded in the U.S.

The research was published in the Annals of Emergency Medicine and was presented in June at the AcademyHealth annual research meeting. The research also was presented at the Society for Academic Emergency Medicine’s conference, where it was selected for a plenary session.

“COVID-19, and the disruptions in every part of our social and work lives, made this situation even harder by increasing the risk of opioid misuse and relapse because people were separated from their social support and normal routines,” says Molly Jeffery, Ph.D., a researcher in the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery and senior author. “While institutions across the U.S. are keenly aware that opioid misuse is a major health concern, this shows that there is more work to be done, and it provides an opportunity for institutions and policymakers to expand evidence-based treatments and resources.”

Over 70% of drug overdose deaths in 2019 involved an opioid, according to the CDC, though trends were leveling off before the COVID-19 pandemic. Since then, that trend has reversed significantly, data are showing.

The research team studied visits to 25 emergency departments in six states — Alabama, Colorado, Connecticut, North Carolina, Massachusetts and Rhode Island — from January 2018 through December 2020. Opioid-related overdose visits increased to 3,486 in 2020 from 3,285 and 3,020 in 2019 and 2018, respectively. Previous research by this team found an immediate and significant decrease in emergency department visits during the first few months of the COVID-19 pandemic, a trend that continued throughout 2020.

Despite the increase in opioid-related visits, the researchers say evidence suggests the percentage of people who experience an overdose but choose not to visit the emergency department is likely increasing, suggesting overdose rates may be even higher.

“In the absence of comprehensive, real-time national surveillance data, our results offer evidence that the increases in nonfatal opioid overdose rates are not isolated to specific communities,” the researchers wrote.

Dr. Jeffery says treatments for opioid misuse, such as buprenorphine and methadone, need to be more accessible, as does naloxone, an opioid overdose reversal drug. She says, however, it’s a good sign that telemedicine access for psychiatric care increased during the pandemic and has remained high.

“We think this may be an important way to increase the accessibility of care for many people with opioid misuse disorder or addiction,” Dr. Jeffery says.

The lead author is William Soares, M.D., University of Massachusetts Medical School-Baystate. Co-authors are from the Yale School of Medicine, The University of Alabama at Birmingham, the University of North Carolina School of Medicine, the Warren Alpert Medical School of Brown University, and the University of Colorado School of Medicine.

The research was supported by the National Institute on Drug Abuse, of the National Institutes of Health.

The research also was supported by the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery. The center seeks to discover new ways to improve health; translate those discoveries into evidence-based, actionable treatments, processes and procedures; and apply this new knowledge to improve care for patients everywhere.

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Materials provided by Mayo Clinic. Original written by Adam Harringa. Note: Content may be edited for style and length.

“BRCA1-BARD1 is important for DNA repair. It has direct relevance to cancer because hundreds of mutations in the BRCA1 and BARD1 genes have been identified in cancer patients,” says Georges Mer, Ph.D., a Mayo Clinic structural biologist and biochemist who is the lead author of the paper. “But no one knows if these mutations, or variants of unknown significance, are cancer-predisposing or not because we do not know whether the variants are located in a region of BRCA1-BARD1 that is important for function. Now because we can see how BRCA1-BARD1 works, we have a good idea of what regions of BRCA1-BARD1 are important for function.”

In a cell, the complex of DNA and histone proteins are complexed into what’s called chromatin, and packaged into bundles called nucleosomes. DNA damage response proteins need to access chromatin to repair damaged DNA. BRCA1-BARD1 contributes to fixing broken DNA strands, which helps in the maintenance and survival of cells. But it is also a function that could possibly be blocked or inactivated if this is a strategy a cancer cell uses to survive chemotherapy.

Cryo-electron microscopy and nuclear magnetic resonance spectroscopy

“We used two techniques — cryo-electron microscopy and nuclear magnetic resonance spectroscopy — to understand at near-atomic resolution how BRCA1-BARD1 associates with the nucleosome, the repeating unit of chromatin, and how BRCA1-BARD1 modifies chromatin,” explains Dr. Mer.

In cryo-electron microscopy, purified BRCA1-BARD1 bound to nucleosomes, together referred to as macromolecules, are flash-frozen then imaged using an electron microscope. The macromolecules are oriented in various ways within the sample so a computer program evaluates all the orientation data to create a 3D structure. Dr. Mer and his team also examined BRCA1-BARD1 nucleosome complexes with nuclear magnetic resonance spectroscopy, which uses a strong magnet to probe the relative positions of atoms within macromolecules. Using these imaging tools, the scientists could visualize BRCA1-BARD1 in action and uncover a new function of the complex.

“We showed how BRCA1-BARD1 attaches ubiquitin to the nucleosome, but we also determined that BRCA1-BARD1 recognizes ubiquitin already attached to the nucleosome, which serves as a signal for broken DNA,” says Dr. Mer. “We discovered an unexpected cross-talk by which ubiquitin recognition by BRCA1-BARD1 enhances its ubiquitin attachment activity, and this helps us better understand how BRCA1-BARD1 performs its function.”

The researchers created a video from the cryo-electron microscopy data to show where the protein complex interacts with the nucleosome [see link below].

From discovery science to patient care

Dr. Mer and his team expect that high-resolution images of BRCA1-BARD1 can help guide patient care and future treatment of cancer in two ways: classifying variants of unknown significance and directing drug development with more accuracy.

“With these 3D structures, we should be able to convert several variants of unknown significance to likely cancer-predisposing variants,” says Dr. Mer. “This work is also expected to have an impact on drug development in the long term because the 3D structures of BRCA1-BARD1 in complex with the nucleosome we generated may help in the design of small molecules that could, for example, inactivate BRCA1-BARD1.”

In addition to Dr. Mer, other authors on the paper are Qi Hu, Ph.D.; Maria Victoria Botuyan, Ph.D.; Debiao Zhao, Ph.D.; Gaofeng Cui, Ph.D.; and Elie Mer. This research was funded by the National Institutes of Health, Mayo Clinic Cancer Center, Mayo Clinic Center for Biomedical Discovery, and the Ovarian Cancer Research Alliance, and was made possible through cryo-electron microscopy and nuclear magnetic resonance instrumentation at the Pacific Northwest Center for Cryo-EM and Mayo Clinic, respectively.

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Materials provided by Mayo Clinic. Original written by Sara Tiner. Note: Content may be edited for style and length.