Culture

Philadelphia, March 31, 2020 - Genetic studies of attention-deficit/hyperactivity disorder (ADHD) show that it takes many common genetic variations combining together in one individual to increase risk substantially. At the same time, neuroimaging experts have found differences in how the brains of people diagnosed with ADHD are functionally connected. However it's unclear how genetic risk might be directly related to altered brain circuitry in individuals diagnosed with ADHD.

A new study in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier, combined genetics and functional brain imaging to find that both genetic and neural factors influence ADHD diagnosis.

In the study, researchers focused their imaging analyses on selected brain regions, looking specifically at the communication between those regions and the rest of the brain in children with the diagnosis. One region's connectivity was linked to a higher risk of ADHD, while a second, different part of the brain seemed to compensate for genetic effects and reduced the chances of an ADHD diagnosis.

The authors believe this research will lead to a better understanding of how genetic risk factors alter different parts of the brain to change behaviors and why some people at higher genetic risk do not exhibit ADHD symptoms.

"We are now in a phase with enough data to answer some questions about the underlying genetics of a disorder that in the past have been difficult to elucidate," said senior author Damien Fair, PhD. "Previous imaging studies had shown different functional connectivity, and we assume those have a genetic basis."

ADHD is a neurodevelopmental psychiatric disorder that affects about 5 percent of children and adolescents and 2.5 percent of adults worldwide. The disorder is characterized by inattentive or hyperactive symptoms with many variations.The paper focuses on 315 children between the ages of 8 and 12 who participated in a longitudinal ADHD study that began in 2008 at the Oregon Health & Science University in Portland, WA, USA, as a collaboration between Dr. Fair, a neuroscientist and imaging researcher, and co-author Joel Nigg, PhD, a pediatric psychologist.

In this study, led by Robert Hermosillo, PhD, a postdoctoral researcher in Fair's lab, the team selected three areas of the brain based on a brain tissue database that showed where ADHD risk genes were likely to alter brain activity. To measure the brain communication to-and-from these regions on each side of the brain, the researchers used resting-state non-invasive magnetic resonance imaging (MRI) scans.

To begin to bridge genetic and neuroimaging studies of ADHD, researchers used MRI to scan the brains of children. Two regions previously associated with ADHD stood out. In one, a higher ADHD genetic risk correlated with a more active brain circuit anchored by the nucleus accumbens (orange arrow). Interestingly a weaker connection anchored by the caudate nucleus (blue arrow) seemed to protect children at high genetic risk from ADHD behaviors.

Next, they calculated a cumulative ADHD genetic risk score in the children, based on recent genome-wide studies, including a dozen higher-risk genetic regions reported two years ago by a large international collaboration called the Psychiatric Genetics Consortium.

In one brain region anchored by the nucleus accumbens, they found a direct correlation with genetics. "Increased genetic risk means stronger communication between the visual areas and the reward centers," explained Dr. Hermosillo.

Another brain region anchored by the caudate yielded more puzzling results until the researchers tested its role as a mediator between genetics and behavior. "The less these two regions talk to each other, the higher the genetic risk for ADHD," said Dr. Hermosillo. "It seems to provide a certain resiliency against the genetic effects of ADHD. Even among those with high risk for ADHD, if these two brain regions are communicating very little, a child is unlikely to end up with that diagnosis."

A third region, the amygdala, showed no correlation between connectivity to the other brain regions and the genetics.

According to the authors, the findings suggest that a genetic score alone will not be enough to predict ADHD risk in individuals because the results show both a genetic and neural contribution toward an ADHD diagnosis. A future diagnostic tool will likely need to combine genetics and brain functional measures. "The brain is not at the mercy of genes," added Dr. Hermosillo. "It's a dynamic system not preprogrammed for disorders. It has the capacity to change."

According to a popular view, creativity is a product of the brain’s right hemisphere – innovative people are considered “right-brain thinkers” while “left-brain thinkers” are thought to be analytical and logical. Neuroscientists who are skeptical of this idea have argued that there is not enough evidence to support this idea and an ability as complex as human creativity must draw on vast swaths of both hemispheres. A new brain-imaging study out of Drexel University’s Creativity Research Lab sheds light on this controversy by studying the brain activity of jazz guitarists during improvisation.

The study, which was recently published in the journal NeuroImage, showed that creativity is, in fact, driven primarily by the right hemisphere in musicians who are comparatively inexperienced at improvisation. However, musicians who are highly experienced at improvisation rely primarily on their left hemisphere. This suggests that creativity is a “right-brain ability” when a person deals with an unfamiliar situation but that creativity draws on well-learned, left-hemisphere routines when a person is experienced at the task.

By taking into consideration how brain activity changes with experience, this research may contribute to the development of new methods for training people to be creative in their field. For instance, when a person is an expert, his or her performing is produced primarily by relatively unconscious, automatic processes that are difficult for a person to consciously alter, but easy to disrupt in the attempt, as when self-consciousness causes a person to “choke” or falter.

In contrast, novices’ performances tend to be under deliberate, conscious control. Thus, they are better able to make adjustments according to instructions given by a teacher or coach. Recordings of brain activity could reveal the point at which a performer is ready to release some conscious control and rely on unconscious, well-learned routines. Releasing conscious control prematurely may cause the performer to lock-in bad habits or nonoptimal technique.

The study was led by David Rosen, PhD, a recent Drexel doctoral graduate and current co-founder and chief operations officer of Secret Chord Laboratories, a music-technology startup company; and John Kounios, PhD, professor of psychology and director of the doctoral program in applied and cognitive brain sciences in Drexel’s College of Arts and Sciences.

The team recorded high-density electroencephalograms (EEGs) from 32 jazz guitar players, some of whom were highly experienced and others less experienced. Each musician improvised to six jazz lead sheets (songs) with programmed drums, bass and piano accompaniment. The 192 recorded jazz improvisations (six jazz songs by 32 participants) were subsequently played for four expert jazz musicians and teachers individually so they could rate each for creativity and other qualities.

The researchers compared the EEGs recorded during highly rated performances with EEGs recorded during performances that were rated to be less creative. For highly rated performances compared with less-creative performances, there was greater activity in posterior left-hemisphere areas of the brain; for performances with lower ratings compared with those with higher ratings, there was greater activity in right-hemisphere, mostly frontal, areas.

By themselves, these results might suggest that highly creative performances are associated with posterior left-hemisphere areas and that less-creative performances are associated with right-hemisphere areas. This pattern is misleading, however, according to the researchers, because it does not take experience of the musician into consideration.

Some of these musicians were highly experienced, having given many public performances over decades. Other musicians were much less experienced, having given only a very small number of public performances. When the researchers reanalyzed the EEGs to statistically control for the level of experience of the performers, a very different pattern of results emerged. Virtually all of the brain-activity differences between highly creative and less-creative performances were found in the right hemisphere, mostly in the frontal region.

This finding is in line with the team’s other research that used electrical stimulation to study how creative expression is generated in musicians’ brains and its study of how experienced and inexperienced jazz musicians reacted to being exhorted to play “even more creatively.”

The new study reveals the brain areas that support creative musical improvisation for highly experienced musicians and their less-experienced counterparts and addresses the controversial question of the roles of the left and right hemispheres in creativity. Furthermore, it raises an important issue that goes to the heart of the definition and understanding of creativity.

“If creativity is defined in terms of the quality of a product, such as a song, invention, poem or painting, then the left hemisphere plays a key role,” said Kounios. “However, if creativity is understood as a person’s ability to deal with novel, unfamiliar situations, as is the case for novice improvisers, then the right hemisphere plays the leading role.”

The study, “Dual-Process Contributions to Creativity in Jazz Improvisations: An SPM-EEG Study” was funded by a grant from the National Science Foundation. It was published in the journal NeuroImage. Co-authors included Yongtaek Oh, doctoral student; Brian Erickson, post-doctoral researcher; Fengqing (Zoe) Zhang, PhD; and Youngmoo Kim, PhD, of Drexel.

DOI

10.1016/j.neuroimage.2020.116632

Fast communication between our brain cells - or neurotransmission as it is called - is hugely important for our brain to work properly. Some of the messengers involved in this form of communication are neuropeptides, which are chemicals produced in the brain.

Some of these peptides are involved in causing the feeling of pain. In a new study, researchers from the University of Copenhagen show how the neuropeptide Big Dynorphin binds to a receptor involved in sending pain signals around the brain.

"We have mapped exactly how and where Big Dynorphin binds to this receptor, which can cause a pain signal to be sent inside the body. Big Dynorphin is the most potent regulator of this particular receptor discovered in the human body so far. The painkillers that we use today affect other types of receptors. This means that our discovery could pave the way for a new type of painkilling medicine via this receptor, potentially helping to circumvent some of the typical adverse effects of opioids." says author to the study Stephan Pless, Professor at the Department of Drug Design and Pharmacology.

Relevant for inflammation and chronic pain

The new study is published in PNAS and it investigates the interaction between Big Dynorphin and the receptor called Acid-Sensing Ion Channel (ASIC). The researchers have mapped the interaction and signaling using a wide range of methods.

They made manipulations on the peptide and the receptor using technologies such as electrophysiology, genetically encoded cross-linkers, as well as CRISPR. Normally, the biological interaction within the brain cell occurs very fast, but their approach allowed the researchers to trap the interactions and map them.

"We know that both the receptor and Big Dynorphin are upregulated in patients with inflammation and chronic pain. This means that there are many more of them than under normal conditions. And that, in theory at least, can lead to more pain and the risk of long-lasting negative effect on brain health. This means that our result could have implications for these diseases in terms of drug development," says co-first author of the study Dr Nina Braun.

Potential for pain reduction

Other researchers have previously shown that if they knock out the ASIC receptor, they have been able to reduce pain in mouse models. This underlines the potential of the new findings from the University of Copenhagen.

The researchers are looking forward to exploiting the mechanism pharmacologically in their coming studies. They hope to find relevant compounds that could show potential for pain reduction for these vulnerable patient-groups.

TROY, N.Y. -- The temptation for businesses to use artificial intelligence and other technology to improve performance, drive down labor costs, and better the bottom line is understandable. But before pursuing automation that could put the jobs of human employees at risk, it is important that business owners take careful stock of their operations.

AI should not be applied to every business in the same manner, according to Chris Meyer, professor of practice and the director of undergraduate education at the Lally School of Management at Rensselaer Polytechnic Institute. He details his research on the subject in a new conceptual paper published today in a special issue of the Journal of Service Management on "AI and Machine Learning in Service Management".

"AI has the potential to upend our ideas about what tasks are uniquely suited to humans, but poorly implemented or strategically inappropriate service automation can alienate customers, and that will hurt businesses in the long term," Meyer said.

According to Meyer's findings, the choice to use automation or AI needs to be a strategic decision. If a business competes by offering a substantial amount of human interaction, or has a range of service offerings that change from client to client, the company will have a lower success rate in replacing human professionals with AI technologies. Meyer also found that the opposite is true: Businesses that limit customer choice and interaction will see greater success if they choose to automate.

Business leaders considering a switch to automation must carefully examine their strategies for managing knowledge resources. Before companies invest in AI, they need to understand whether replacing human judgment and interaction with digital technologies and algorithms is a strategically sound idea.

"The ideas are of use to managers, as they suggest where and how to use automation or human service workers based on ideas that are both sound and practical," Meyer said. "Managers need guidance. Like any form of knowledge, AI and all forms of service automation have their place, but managers need good models to know where that place is."

Furthermore, Meyer determined that in businesses where trust and reputation are critical factors in building and maintaining a client base, people will be more likely to be effective than automated technologies. Conversely, in areas where human biases are particularly harmful to the service provision, AI will be a relatively better tool for companies to employ.

Meyer also asserts that many businesses will ultimately be using a mix of people skills and automation to effectively compete. Even AI, which can handle very sophisticated tasks, works best alongside humans -- and vice versa.

"Automation and human workers can and should be used together," Meyer said. "But the extent of automation must fit with the business's strategic approach to customers."

A novel vaccine against pneumonia that is less expensive and more effective than those currently used in Brazil is being tested in human patients. Developed by researchers at the Butantan Institute (Brazil) and Boston Children's Hospital, part of the Harvard Medical School (USA), the innovation is capable of providing protection against all serotypes of the bacterium Streptococcus pneumoniae.

"We chose a different strategy to activate the immune response. Instead of targeting the polysaccharides present in the bacterial capsule, as currently available vaccines do, we opted for proteins common to all serotypes of the microorganism," said Luciana Cezar de Cerqueira Leite, a researcher in the Butantan Institute's Special Vaccine Development Laboratory.

The initial research was led by Cerqueira Leite and supported by São Paulo Research Foundation - FAPESP. Phase I and II clinical trials were conducted in Africa and coordinated in the US by the Harvard team, with support from the Bill & Melinda Gates Foundation and the Program for Appropriate Technologies in Health (PATH), a Seattle-based nonprofit dedicated to developing innovations that save lives and improve health.

"It took more than ten years of research to arrive at this cellular vaccine," Cerqueira Leite said. "First, we investigated proteins that could be used as targets. The idea of developing a cellular vaccine occurred to us on the way. We designed the production process and changed the adjuvant [an agent used in conjunction with the vaccine antigen to augment the host's immune response] as well as the administration pathway. Initially, we set out to produce an intranasally administered vaccine, but then we realized that the product would be more efficient if it was administered by intramuscular injection."

Polyvalent

Some 90 serotypes of S. pneumoniae are estimated to exist worldwide. In addition to pneumonia, the bacterium causes meningitis, otitis and sinusitis, among other diseases. The serotypes are defined on the basis of the combination of polysaccharides present in the microorganisms' capsule. In conventional vaccines, this combination determines the antigen to be introduced into the organism to stimulate antibody production. The vaccine developed by the Butantan Institute triggers an immune response regardless of the bacterial serotype.

"We cultured the bacterium without its capsule in the lab and used a special technique to kill it without disintegrating it. So, the inactivated bacterium can be administered as a vaccine. We also identified immunogenic proteins that are common to all S. pneumoniae serotypes," Cerqueira Leite said.

In a recent article published in the journal Expert Review of Vaccines, Cerqueira Leite and collaborators stressed the importance of developing an affordable pneumonia vaccine that is effective against all S. pneumoniae serotypes.

"In the specific case of pneumonia, insisting on the inclusion of new serotypes in conjugate vaccines only leads to increased complexity and higher production costs, making already expensive vaccines even less affordable for developing countries like Brazil," Cerqueira Leite said.

The pneumococcal vaccines currently available are effective against between ten and 13 serotypes, she added. A nonconjugate version covers 23 serotypes but is used mainly to immunize adults, as it is not effective in children.

"The first generation of conjugate vaccines was effective against the seven most prevalent serotypes in Europe and the US [7-valent]. However, because prevalence varied from one region to another, in Brazil it wasn't able to provide very good coverage, only about 60%," she said.

As time passed, it became possible to combine more strains, and eventually 10-valent and 13-valent vaccines were produced, "but there's a problem with this strategy," Cerqueira Leite said. "When you take specific serotypes out of circulation, other strains [with different serotypes] emerge naturally, and the existing vaccines lose their efficacy. This is known as serotype substitution."

As well as being more comprehensive than current vaccines, the cellular vaccine developed by the Butantan Institute is not vulnerable to the problem of serotype substitution. Pricing is another advantage, according to Cerqueira Leite. "It's hard to say exactly how much the vaccine will cost before it's even been approved and produced, but we estimate about two dollars. The polysaccharide vaccine [13-valent] currently costs the citizen who uses a private clinic about 60 dollars. Public services [administered under the umbrella of SUS, Brazil's national health system] pay 15 dollars," she said.

The price is lower largely because the production process is less complex. "To make the 13-valent vaccine, each of the 13 different serotypes has to be cultured separately and purified to obtain the polysaccharides. Also, because it's a conjugate vaccine, a reaction has to be produced between the polysaccharide and a carrier protein. There are several stages. It's a laborious process with several stages and takes almost two years," she said.

The new vaccine can be produced in approximately two months, according to Cerqueira Leite.

Phase I and II clinical trials have been completed, analyzing safety and toxicity and validating immunogenicity, respectively. "We plan to hold another phase II trial in the US. This is the stage where you compare the type of immune response produced in the populations of different countries," she said.

Phase III clinical trials involve a larger number of people and test the vaccine's effectiveness by comparing an immunized group with a group that receives a placebo. A phase III trial has yet to be scheduled for the new vaccine.

During the 2016 election cycle, politically polarizing tweets by Russian trolls about vaccination included pro- and anti-vaccination messages targeted at people with specific political inclinations through an assortment of fake persona types, according to a new analysis published this month.

This study encompassed more than 2.8 million tweets published by 2,689 accounts operated by the Russian Internet Research Agency (IRA) from 2015-17. Researchers identified nine types of troll personas, from fake Black Lives Matters activists to fake boosters of Donald Trump, and examined the extent to which those persona types discussed vaccination, and how they did so.

The analysis was conducted by researchers at the Annenberg Public Policy Center (APPC) of the University of Pennsylvania, Georgia State University, and the University at Buffalo, SUNY. The study, "Russian Twitter Accounts and the Partisan Polarization of Vaccine Discourse, 2015-2017," was published in March in the American Journal of Public Health.

"We demonstrate how IRA accounts discussed vaccines not only to sow discord among people of the United States but also to flesh out the personalities of their 'American' accounts in a credible way," the researchers wrote.

In age of COVID-19, mistrust on vaccination worrisome

Although the vaccination tweets made up a small portion of the messaging from these accounts over the three years, the trolls used pro- and anti-vaccination tweets to help establish realistic-seeming partisan identities. By politicizing vaccination, the Russian trolls could potentially affect attitudes, promote vaccination hesitancy, and magnify health disparities, the researchers said.

"Russian trolls worked to polarize Americans on a health topic that is not supposed to be political," said co-author Yotam Ophir, an assistant professor of communication at the University at Buffalo and a former postdoctoral fellow at APPC. "As our nation deals with the coronavirus pandemic, that type of politicization poisons the well of crisis communications for COVID-19 in ways that create tensions, mistrust and, potentially, a lack of intention to comply with government orders and health directives."

Ophir co-authored the paper with Dror Walter, of Georgia State University, and Kathleen Hall Jamieson, director of the Annenberg Public Policy Center, which supported the research.

Russian tweets targeted to specific groups

The researchers expanded on past studies of Russian attempts to sow discord during the election and IRA tweets on vaccination. The current work included the full set of IRA Twitter activity over the three years, and ultimately included the analysis of 2.8 million tweets. Among those tweets, the researchers identified 1,968 that discussed vaccination.

"We first used unsupervised machine learning to map the various topics IRA accounts were talking about," said Walter, the lead author and an assistant professor of communication at Georgia State University. "We used network analysis to group together accounts that tended to discuss the same topics and used the same language. With this method we were able to identify nine different groups of users, which we call 'thematic personas.' We then analyzed computationally and manually how each group discussed the issue of vaccines."

Among those personas, for instance, were one "thematic community" focused on tweeting links to hard news updates and one focused on soft news; one that was clearly pro-Trump, and one clearly anti-Trump; one that specialized in youth talk and celebrities, one that imitated African American users in topics (Black Lives Matter activism) and language, and one that focused on Ukraine. Others focused on international topics, and retweets and trendy "hashtag games."

The researchers found striking differences in the ways different personas talked about vaccines, with the biggest differences falling across political lines. They said that the trolls attempted to cater to audiences of different political inclinations with targeted messages based on their perceived opinions about vaccines. Simply put, pro-Trump personas and African American personas were much more likely to express anti-vaccine sentiment than the anti-Trump, liberal personas.

Specifically, of the accounts using the pro-Trump persona, 17% mentioned vaccines at least once and more than half of those tweets were anti-vaccination. Among the accounts adopting the liberal, anti-Trump persona, only 2% mentioned vaccines; about half of those tweets were neutral on vaccination and over a third were pro-vaccine.

About 11% of the accounts imitating African American users mentioned vaccines. While the tweets mentioning vaccines made up a very small percentage of the total from these accounts, the sentiment among tweets that did discuss it was balanced, slightly more negative than positive.

Are Russian trolls at work today?

"As COVID-19 spreads disease and death across the globe and scientists race to develop treatments and a vaccine against it, I expect the Russian discourse saboteurs to resurrect the behaviors we isolated in this study," said Jamieson, the author of "Cyberwar: How Russian Hackers and Trolls Helped Elect a President," which was published in 2018 by Oxford University Press and will be released in an updated paperback edition in 2020.

The researchers concluded: "Even if small in magnitude, the intentional Russian spread of antivaccine discourse targeted at specific subpopulations that are susceptible to it (i.e., pro-Trump users and African Americans on Twitter) could be the beginning of a new front in the ongoing informational cyberwar."

Astronomers have found the best evidence for the perpetrator of a cosmic homicide: a black hole of an elusive class known as "intermediate-mass," which betrayed its existence by tearing apart a wayward star that passed too close.

Weighing in at about 50,000 times the mass of our Sun, the black hole is smaller than the supermassive black holes (at millions or billions of solar masses) that lie at the cores of large galaxies, but larger than stellar-mass black holes formed by the collapse of a massive star.

These so-called intermediate-mass black holes (IMBHs) are a long-sought "missing link" in black hole evolution. Though there have been a few other IMBH candidates, researchers consider these new observations the strongest evidence yet for mid-sized black holes in the universe.

It took the combined power of two X-ray observatories and the keen vision of NASA's Hubble Space Telescope to nail down the cosmic beast.

"Intermediate-mass black holes are very elusive objects, and so it is critical to carefully consider and rule out alternative explanations for each candidate. That is what Hubble has allowed us to do for our candidate," said Dacheng Lin of the University of New Hampshire, principal investigator of the study. The results are published on March 31, 2020, in The Astrophysical Journal Letters.

The story of the discovery reads like a Sherlock Holmes story, involving the meticulous step-by-step case-building necessary to catch the culprit.

Lin and his team used Hubble to follow up on leads from NASA's Chandra X-ray Observatory and ESA's (the European Space Agency) X-ray Multi-Mirror Mission (XMM-Newton). In 2006 these satellites detected a powerful flare of X-rays, but they could not determine whether it originated from inside or outside of our galaxy. Researchers attributed it to a star being torn apart after coming too close to a gravitationally powerful compact object, like a black hole.

Surprisingly, the X-ray source, named 3XMM J215022.4?055108, was not located in a galaxy's center, where massive black holes normally would reside. This raised hopes that an IMBH was the culprit, but first another possible source of the X-ray flare had to be ruled out: a neutron star in our own Milky Way galaxy, cooling off after being heated to a very high temperature. Neutron stars are the crushed remnants of an exploded star.

Hubble was pointed at the X-ray source to resolve its precise location. Deep, high-resolution imaging provides strong evidence that the X-rays emanated not from an isolated source in our galaxy, but instead in a distant, dense star cluster on the outskirts of another galaxy -- just the type of place astronomers expected to find an IMBH. Previous Hubble research has shown that the mass of a black hole in the center of a galaxy is proportional to that host galaxy's central bulge. In other words, the more massive the galaxy, the more massive its black hole. Therefore, the star cluster that is home to 3XMM J215022.4?055108 may be the stripped-down core of a lower-mass dwarf galaxy that has been gravitationally and tidally disrupted by its close interactions with its current larger galaxy host.

IMBHs have been particularly difficult to find because they are smaller and less active than supermassive black holes; they do not have readily available sources of fuel, nor as strong a gravitational pull to draw stars and other cosmic material which would produce telltale X-ray glows. Astronomers essentially have to catch an IMBH red-handed in the act of gobbling up a star. Lin and his colleagues combed through the XMM-Newton data archive, searching hundreds of thousands of observations to find one IMBH candidate.

The X-ray glow from the shredded star allowed astronomers to estimate the black hole's mass of 50,000 solar masses. The mass of the IMBH was estimated based on both X-ray luminosity and the spectral shape. "This is much more reliable than using X-ray luminosity alone as typically done before for previous IMBH candidates," said Lin. "The reason why we can use the spectral fits to estimate the IMBH mass for our object is that its spectral evolution showed that it has been in the thermal spectral state, a state commonly seen and well understood in accreting stellar-mass black holes."

This object isn't the first to be considered a likely candidate for an intermediate-mass black hole. In 2009 Hubble teamed up with NASA's Swift observatory and ESA's XMM-Newton to identify what is interpreted as an IMBH, called HLX-1, located towards the edge of the galaxy ESO 243-49. It too is in the center of a young, massive cluster of blue stars that may be a stripped-down dwarf galaxy core. The X-rays come from a hot accretion disk around the black hole. "The main difference is that our object is tearing a star apart, providing strong evidence that it is a massive black hole, instead of a stellar-mass black hole as people often worry about for previous candidates including HLX-1," Lin said.

Finding this IMBH opens the door to the possibility of many more lurking undetected in the dark, waiting to be given away by a star passing too close. Lin plans to continue his meticulous detective work, using the methods his team has proved successful. Many questions remain to be answered. Does a supermassive black hole grow from an IMBH? How do IMBHs themselves form? Are dense star clusters their favored home?

The Hubble Space Telescope is a project of international cooperation between NASA and ESA (European Space Agency). NASA's Goddard Space Flight Center in Greenbelt, Maryland, manages the telescope. The Space Telescope Science Institute (STScI) in Baltimore, Maryland, conducts Hubble science operations. STScI is operated for NASA by the Association of Universities for Research in Astronomy in Washington, D.C.

When Spanish invaders arrived in the Americas, they were generally able to subjugate the local peoples thanks, in part, to their superior weaponry and technology. But archeological evidence indicates that, in at least one crucial respect, the Spaniards were quite dependent on an older indigenous technology in parts of Mesoamerica (today's Mexico, Guatemala, Belize, and Honduras).

The invaders needed copper for their artillery, as well as for coins, kettles, and pans, but they lacked the knowledge and skills to produce the metal. Even Spain at that time had not produced the metal domestically for centuries, relying on imports from central Europe. In Mesoamerica they had to depend on local smelters, furnace builders, and miners to produce the essential material. Those skilled workers, in turn, were able to bargain for exemption from the taxes levied on the other indigenous people.

This dependence continued for at least a century, and perhaps as long as two centuries or more, according to new findings published in the journal Latin American Antiquity, in a paper by Dorothy Hosler, professor of archeology and ancient technology at MIT, and Johan Garcia Zaidua, a researcher at the University of Porto, in Portugal.

The research, at the site of El Manchón, in Mexico, made use of information gleaned from more than four centuries worth of archeological features and artifacts excavated by Hosler and her crew over multiple years of fieldwork, as well as from lab work and historical archives in Portugal, Spain, and Mexico analyzed by Garcia.

El Manchón, a large and remote settlement, initially displayed no evidence of Spanish presence. The site consisted of three steep sectors, two of which displayed long house foundations, some with interior rooms and religious sanctuaries, patios, and a configuration that was conceptually Mesoamerican but unrelated to any known ethnic groups such as the Aztec. In between the two was an area that contained mounds of slag (the nonmetallic material that separates out during smelting from the pure metal, which floats to the surface).

The Spanish invaders urgently needed enormous quantities of copper and tin to make the bronze for their cannons and other armaments, Hosler says, and this is documented in the historical and archival records. But "they didn't know how to smelt," she says, whereas archaeological data suggest the indigenous people had already been smelting copper at this settlement for several hundred years, mostly to make ritual or ceremonial materials such as bells and amulets. These artisans were highly skilled, and in Guerrero and elsewhere had been producing complex alloys including copper-silver, copper-arsenic, and copper-tin for hundreds of years, working on a small scale using blowpipes and crucibles to smelt the copper and other ores.

But the Spanish desperately required large quantities of copper and tin, and in consultation with indigenous smelters introduced some European technology into the process. Hosler and her colleagues excavated an enigmatic feature that consisted of two parallel courses of stones leading toward a large cake of slag in the smelting area. They identified this as the remains of a thus-far-undocumented hybrid type of closed furnace design, powered by a modified hand-held European bellows. A small regional museum in highland Guerrero illustrates just such a hybrid furnace design, including the modified European-introduced bellows system, capable of producing large volumes of copper. But no actual remains of such furnaces had previously been found.

The period when this site was occupied spanned from about 1240 to 1680, Hosler says, and may have extended to both earlier and later times.

The Guerrero site, which Hosler excavated over four field seasons before work had to be suspended because of local drug cartel activity, contains large heaps of copper slag, built up over centuries of intensive use. But it took a combination of the physical evidence, analysis of the ore and slags, the archaeological feature in the the smelting area, the archival work, and reconstruction drawing to enable identification of the centuries of interdependence of the two populations in this remote outpost.

Earlier studies of the composition of the slag at the site, by Hosler and some of her students, revealed that it had formed at a temperature of 1150 degrees Celsius, which could not have been achieved with just the blowpipe system and would have required bellows. That helps to confirm the continued operation of the site long into the colonial period, Hosler says.

Years of work went into trying to find ways to date the different deposits of slag at the site. The team also tried archaeomagnetic data but found that the method was not effective for the materials in that particular region of Mexico. But the written historical record proved key to making sense of the wide range of dates, which reflected centuries of use of the site.

Documents sent back to Spain in the early colonial period described the availability of the locally produced copper, and the colonists' successful tests of using it to cast bronze artillery pieces. Documents also described the bargains made by the indigenous producers to gain economic privileges for their people, based on their specialized metallurgical knowledge.

"We know from documents that the Europeans figured out that the only way they could smelt copper was to collaborate with the indigenous people who were already doing it," Hosler says. "They had to cut deals with the indigenous smelters."

Hosler says that "what's so interesting to me is that we were able to use traditional archeological methods and data from materials analysis as well as ethnographic data" from the furnace in a museum in the area, "and historical and archival material from 16th century archives in Portugal, Spain, and Mexico, then to put all the data from these distinct disciplines together into an explanation that is absolutely solid."

The Ferguson Effect is the idea that increased public criticism and distrust of police following the 2014 shooting of Michael Brown in Ferguson, Missouri, lowered police moral, which caused officers to withdraw from proactive policing and boosted the crime rate in major U.S. cities. A new longitudinal study examined whether this effect was real. The study, of law enforcement officers before and after Ferguson, found little support for the concept, though it did identify a reduction in officers' job satisfaction and an increase in their cynicism.

The study, by researchers at the University of South Florida, appears in Criminology & Public Policy, a publication of the American Society of Criminology.

"Post-Ferguson protests in 2014 did not appreciably worsen police morale, nor did they lead to substantial withdrawal from most police work," notes Chris Marier, a Ph.D. student at the University of South Florida, who led the study. "This suggests that the institution of policing is resilient to external shocks and that criticism of police is not detrimental to policing or public safety."

To examine the veracity of the Ferguson Effect, researchers examined whether widespread criticism of and protests against police following the police-related deaths of Brown and other Black men in late 2014 and early 2015 reduced police morale and led to de-policing (a slowdown of or withdrawal from proactive work, in which police perform their duties but reduce their productivity and efficiency). The researchers also examined whether low morale among police officers was associated with de-policing.

The study examined 18,413 surveys of law enforcement officers in 87 police departments across the United States before and after Brown was shot in Ferguson, a nationally representative sample. Morale was measured by survey items reflecting job satisfaction, burnout, and cynicism. De-policing was measured as a reduction in foot patrols, attendance at community meetings, and the number of citations issued.

The researchers found that after Ferguson, officers were significantly less satisfied with their jobs and more burned out than they were before Ferguson, but the before and after differences were negligible in size. The study also found statistically significant differences between officers' responses before and after Ferguson on several measures of cynicism, but two of the five measures showed improved rather than worsened attitudes, and the magnitude of change was insubstantial.

In addition, while officers surveyed after Ferguson issued fewer citations and conducted fewer foot patrols, the changes were very small in magnitude, suggesting that commitment to proactive community policing remained largely unchanged.

The authors suggest that because low job satisfaction was associated with fewer citations, and cynicism was associated negatively with both the number of citations issued and the rate of attendance at community meetings, police departments need to address officers' attitudes in order to promote proactive policing and community engagement. In fact, they suggest that officers' cynicism, which was high before and after Ferguson, may be an enduring cultural element that merits further attention at any time of stress.

"Although we didn't find strong evidence of de-policing following Ferguson, our results indicate that low morale is associated with reduced police activity by officers," says Lorie Fridell, a professor of criminology at the University of South Florida, who coauthored the study. "Police administrators must address officers' cynicism and distrust regardless of current public sentiment. The implications of our findings extend beyond the Ferguson Effect to a more general understanding of police culture."

The study's authors note a few limitations: First, officers who were most affected by post-Ferguson protests may have been those least likely to respond to the survey, which may mean that the study's results underestimate changes in morale and police activity over time. But officers who felt most aggrieved may have been more likely to respond, which may overestimate changes. And some officers may have provided responses they thought were socially desirable, avoiding responses that appeared unprofessional or unappealing.

WASHINGTON--Patients with extreme obesity are prone to unconscious food impulses and cravings that may make it challenging for them to maintain weight loss after bariatric surgery, according to research that was accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting, and will be published in a special supplemental section of the Journal of the Endocrine Society.

The most effective treatment for severe obesity is bariatric, or weight loss, surgery. People whose body mass index is above 50 kg/m2 meet the criteria for superobesity. Individuals with superobesity seem to be more prone to regain weight following a period of apparent success after bariatric surgery, according to lead researcher Rogerio Friedman, M.D., Ph.D. of Hospital de Clínicas de Porto Alegre in Porto Alegre, Brazil. "The proportion of patients who regain weight after a variable time following bariatric surgery can be as high as 20%," he said.

Friedman and colleagues wanted to find out whether behavioral and cognitive factors before and after bariatric surgery might explain the differences in weight regain. "The intake of food is regulated by brain centers that control appetite and satiety," he said. "Part of our intake is the result of automatic responses, and part comes from conscious, deliberate choices."

The researchers focused on attentional bias, the tendency to pay attention to some things while simultaneously ignoring others. Previous research has found that attentional bias is associated with binge eating and emotional eating, and it can contribute to obesity. "Attentional bias also happens in smokers, and people who abuse drugs and alcohol," Friedman said.

The study included 59 people four years after they had received Roux-en-Y gastric bypass surgery. Half of them had superobesity. The researchers measured attentional bias through a computerized task, where individuals had to indicate the direction of an arrow that appeared immediately after selected images were shown. If a person had a greater number of correct responses for food images, they were determined to have an attentional bias for visual food clues.

The study measured two types of attentional bias: pre-conscious and conscious. "The pre-conscious part or our attention is that millisecond when our eyes are caught by something before we even realize it. It's is highly automatic," Friedman said. Conscious attentional bias lasts long enough for a person to become aware of it. "You realize the image is there, and you have time to think about it--you can make a choice," he said.

The study flashed images for 2 seconds to measure conscious attentional bias, and a half second and one-tenth of a second to measure preconscious attentional bias. All patients maintained a conscious attentional bias for food (meaning that they knew the image was catching their attention), but only the patients with superobesity also had a preconscious attentional bias--the image caught their attention before they even realized it. "This may be a predisposing factor to weight regain," Friedman said.

"The findings suggest that the same cognitive processes that operate in addiction are present in morbid obesity as well," he said. "Cognitive and behavioral phenomena are behind many aspects of obesity; they remain present after bariatric surgery and may at least in part explain the failure of different treatments. As long as our treatment approach keeps failing to address such phenomena, we may be far from successfully controlling the disease."

WASHINGTON--Researchers say they have found a viable new therapeutic strategy for estrogen receptor-positive (ER+) breast cancer, even cancers that are resistant to current standard of care treatments. Their new preclinical study was accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.

In various models of ER+ breast cancer, the most common form (about 75% of cases) of breast cancer, the researchers found that activating the androgen receptor decreased tumor growth, said Wayne Tilley, Ph.D., the study's principal investigator and a professor at the University of Adelaide in Australia. The androgen receptor is a protein in cells in men and women to which testosterone and other "male" reproductive hormones called androgens bind to elicit their effects, he explained. Importantly, androgens are found in women as well as men.

"There is a prevailing assumption that the androgen receptor promotes malignancy in breast cancer, as it does in prostate cancer," Tilley said. "Our study demonstrates that this is not the case for ER-driven breast cancer. Rather, the androgen receptor acts as a tumor suppressor."

ER+ breast cancer needs new drug treatments because as many as 35% of women with this type eventually become resistant to current hormone therapies, Tilley said. He noted that androgen receptor-stimulating drugs are under investigation for various diseases. The researchers tested one of these drugs, enobosarm, from a drug class called selective androgen receptor modulators, or SARMs, in models of ER+ breast cancer. These studies used ER+ breast cancer cell lines that are commercially available as well as tissues taken from breast cancer patients, including those resistant to current therapies. Some cell lines and human tissues were grown in culture dishes, and other cell lines and patient tumors were transplanted into mice to create patient-derived models.

In all models, the researchers found evidence that stimulating androgen receptor activity with enobosarm stopped tumor growth. From the different breast cancer models, they derived a gene "signature" of androgen receptor activity, which predicted cancer survival in participants in large studies of ER+ breast cancer. This androgen receptor signature outperformed other breast cancer prognostic signatures, he said.

When the investigators treated ER+ breast cancer tissues with enobosarm combined with current standard of care breast cancer drugs such as tamoxifen that target the estrogen receptor, Tilley said they observed better reduction in tumor growth than with the standard drug alone. Enobosarm is nonsteroidal and, according to Tilley, other researchers have found it to be safe in patients. Importantly, it does not cause women to develop male characteristics.

"Treatment of ER+ breast cancer with an androgen receptor activator drug could be immediately tested in women," Tilley said.

WASHINGTON--In older individuals, the location of a broken bone can have significant impacts on long-term health outcomes, according to research accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.

The study found older people with broken bones closer to the center of the body, known as proximal fractures (such as upper arm, upper leg, pelvis and ribs) face a greater risk of being admitted to the hospital for major medical conditions and of dying prematurely following their fracture than similarly aged people without fractures.

"It is well-known that a hip fracture can have devastating health implications for older individuals, but less is known about the effects of other fractures in the body," said lead study author Jacqueline R. Center, Ph.D., of the Garvan Institute of Medical Research in Sydney, Australia. "Not only should people be treated for their bone health, but we now have information allowing us to understand why people do badly after a fracture and how we may intervene to improve outcomes."

The researchers used the Danish National Database to study 300,000 patients 50 years or older with a low-trauma fracture (due to falls from a standing height). They examined differences in the reasons for subsequent hospital admission and death patterns between patients with proximal fractures compared with those fractures further away from the center of the body, known as distal bones (such as the wrist, ankle, hand or foot), where there is no increased risk of death. They matched people with fractures to people without fractures who had a similar age and other medical diagnoses.

They found that people with broken bones at proximal sites had a 1.5- to 4-fold greater risk of death over the next two years than their non-fracture counterparts, whether they were admitted to the hospital after their fracture or not. They were also more likely to have an admission to the hospital for cardiovascular disease, cancer, stroke, diabetes, pneumonia and lung disease. By contrast, those people who had a distal fracture had similar or lower risk of death, as well as similar hospital admission patterns as their counterparts with no fractures.

"This research provides important insights as to why people who have a proximal fracture die prematurely," Center said. She said further studies are needed to find specific ways of preventing these premature deaths.

WASHINGTON-- Adults who need medical maintenance treatment of the growth hormone disorder acromegaly respond well to an investigational oral form of the drug octreotide, investigators of the Chiasma OPTIMAL study reported. Results of the phase 3 randomized controlled clinical trial were accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting, and will be published in the Journal of the Endocrine Society.

Acromegaly is a rare condition resulting from too much growth hormone, which causes large hands and feet, altered facial features and often heavy sweating, according to the Hormone Health Network. It also can lead to high blood pressure and diabetes. Usually a noncancerous tumor in the pituitary gland causes acromegaly.

If surgical removal of the pituitary tumor does not cure the condition, one of the current treatments consists of monthly injections of a drug called a somatostatin analog, said OPTIMAL study principal investigator Susan Samson, M.D., Ph.D., medical director, Pituitary Center, Baylor St. Luke's Medical Center in Houston, Texas. She said these injections can be effective but have limitations, including suboptimal symptom control in some patients, pain at the injection site and lost workdays.

"The results of this study suggest that if oral octreotide capsules are approved by the Food and Drug Administration, this drug has the potential to expand the treatment options for adults with acromegaly beyond injectables," Samson said.

The drug manufacturer, Chiasma in Needham, Mass., reported that the FDA is considering its resubmitted new drug application for octreotide capsules, whose brand name would be MYCAPSSA. If accepted, octreotide capsules would become the first oral somatostatin analog for treatment of acromegaly in adults, according to Chiasma, which funded the OPTIMAL (Octreotide capsules vs. Placebo Treatment In MultinationAL centers) study.

Fifty-six adults with active acromegaly participated in the nine-month study, with 28 patients each randomly assigned to receive either octreotide capsules or placebo (inactive) capsules. Neither the patients nor the investigators knew which treatment they were receiving, and all patients stopped their injections one month before the study.

Excess growth hormone raises levels of IGF-1, a hormone that reflects growth hormone activity better than measuring growth hormone, Samson said. Therefore, the study defined successful maintenance of a response to octreotide capsules as blood values of insulin-like growth factor-1 (IGF-1) being within the upper limit of normal when averaged at 34 and 36 weeks of treatment. Average IGF-1 levels in patients receiving octreotide capsules were in the normal range at the end of treatment but exceeded normal limits in patients receiving placebo, Samson reported.

"Octreotide capsules appeared safe and well tolerated," she said, adding that 90 percent of patients completing oral octreotide therapy chose to continue treatment in a long-term extension study.

Two-thirds of transgender teens have depression, and many also have suicidal thoughts and self-injuring behavior, according to research accepted for presentation at ENDO 2020, the Endocrine Society's annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.

Researchers also found transgender teens had significant improvement in gender dysphoria--the feeling of being uncomfortable with the gender they were assigned--after starting hormone therapy.

Transgender youth are children or adolescents who do not identify with the gender assigned at birth. "An increasing number of transgender youths are seeking therapeutic options to change their bodies and match their gender identity," said lead researcher Veronica Figueredo, M.D., of Nicklaus Children's Hospital in Miami, Fla.

The new study included a review of medical records of 158 transgender teens attending a pediatric endocrinology clinic between 2014 and 2019. The study participants included 107 (67.7%) affirmed males (female to male), 47 (29.7%) affirmed females (male to female), and 4 (2.5%) who considered themselves non-binary.

The median age when gender dysphoria began was lower in affirmed females. Among affirmed males, sexual orientation was self-reported as 38% straight, 47% bisexual, 12% gay, and 1% asexual. Among affirmed females, sexual orientation was reported as 54.3% straight, 37.1% bisexual and 8.6% gay.

Prevalence of psychiatric conditions was 78.5%, with depression being the most frequent diagnosis (66.5%). A history of suicidal thoughts was more common among affirmed males (70.1%) than affirmed females (49%). Self-injuring (cutting) was more common among affirmed males (56.1%) than in affirmed females (25.5%).

Mean age when hormonal treatment began was similar in both groups (15.75 years in affirmed males vs. 15.58 years in affirmed females). Both affirmed males and affirmed females reported markedly lower gender dysphoria after starting hormonal treatment. On a scale of 0 (no dysphoria) to 10 (highest possible dysphoria), gender dysphoria dropped for affirmed males from 8.08 before starting treatment to 3.99 after starting treatment. For affirmed females, gender dysphoria ratings dropped from 7.87 before treatment to 2.96 after treatment began.

WHAT:
Researchers at the National Institutes of Health have discovered a second gene that causes melorheostosis, a rare group of conditions involving an often painful and disfiguring overgrowth of bone tissue. The gene, SMAD3, is part of a pathway that regulates cell development and growth. The researchers are now working to develop an animal model with a mutant version of SMAD3 to test potential treatments for the condition. The study appears in the Journal of Experimental Medicine.

Melorheostosis affects about 1 in 1 million people. Its causes have long been unknown. DNA tests of blood and skin could not identify a mutation. The key to finding the gene was to biopsy the affected bone directly and compare it to unaffected bone. Earlier, the researchers used this method to discover the gene for "dripping candle wax bone disease," a form of melorheostosis in which excess bone growth appears to drip from the bone surface like hot wax. In that study, mutations in the gene MAP2K1 accounted for eight cases of the disease among 15 patients.

In the current study, researchers scanned the exome--the part of the genome that codes for proteins-- and found mutations in the affected bone. These mutations occurred during the patient's lifetime rather than being inherited from parents and are not present in all the cells of the body.

The researchers found SMAD3 mutations in four of the patients who did not have mutations in MAP2K1. SMAD3 is involved in a pathway crucial for skeletal development both before and after birth. The SMAD3 mutations increase the maturation of bone-forming cells and are involved in a cellular pathway distinct from the MAPK2K1 pathway.