Brain

Some of the most important, and difficult, conversations in healthcare are the ones that happen amid serious and life-threatening illnesses. Discussions of the treatment options and prognoses in these settings are a delicate balance for doctors and nurses who are dealing with people at their most vulnerable point and may not fully understand what the future holds.

Now researchers at the University of Vermont's Vermont Conversation Lab have used machine learning and natural language processing to better understand what those conversations look like, which could eventually help healthcare providers improve their end-of-life communication.

"We want to understand this complex thing called a conversation," says Robert Gramling, director of the lab in UVM's Larner College of Medicine who led the study, published December 9 in the journal Patient Education and Counselling. "Our major goal is to scale up the measurement of conversations so we can re-engineer the healthcare system to communicate better."

Gramling and his colleagues wanted to understand the types of conversations that people have around serious illness, to identify the common features they have and determine if they follow common storylines. To do this they borrowed the techniques used in the study of fiction, in which machine learning algorithms analyze the language of fiction manuscripts to identify different types of stories.

Gramling's team adapted this method to analyze 354 transcripts of palliative care conversations collected by the Palliative Care Communication Research Initiative, involving 231 patients in New York and California. They broke each conversation into 10 parts with an equal number of words in each, and examined how the frequency and distribution of words referring to time, illness terminology, sentiment, and words indicating possibility and desirability changed between each decile.

"We picked up some strong signals," says Gramling.

Conversations tended to progress from talking about the past to talking about the future, and from sadder to happier sentiments. "There was quite a range, they went from pretty sad to pretty happy," says Gramling.

The discussions also progressed from talking about symptoms at the beginning of the conversation, to treatment options in the middle and the prognosis at the end. And the use of modal verbs - words like "can", "might", and "will" that refer to probability and desirability - also increased as the conversation went on. "At the end there was more evaluation than description," says Gramling.

The consistent results across multiple conversations show just how much people make meaning out of stories in healthcare, says Gramling. "What we found supports the importance of narrative in medicine," he says.

More practical applications of the work are still some way off, says Gramling. For now, his team is focused on using it as a tool to identify the different types of conversations that can occur in healthcare. "I think this is going to be a potentially important research tool for us to begin fostering an understanding of a taxonomy of conversations that we have so that we can begin to learn how to improve upon each one of those types," he says.

That knowledge could eventually help healthcare practitioners understand what makes a "good" conversation about palliative care, and how different kinds of conversations might require different responses. That could help create interventions that are matched to what the conversation indicates the patient needs the most.

"One type of conversation may lead to an ongoing need for information, while another may have an ongoing need for functional support," says Gramling. "So one of the ways those types can help us is to identify what are the resources we are going to need for individual patients and families so that we're not just applying the same stuff to everybody."

A deeper understanding of these conversations, which are often freighted with emotion and uncertainty, will also help reveal what aspects or behaviors associated with these conversations are more valuable for patients and families. That will allow educators to target their training of healthcare professionals to provide the skills needed in palliative care.

Gramling says perhaps the most useful application of the work would be at a systemic level that could monitor how hospitals respond to patients in aggregate - and reward those that allow patients to express and deal with their fears in a better way with more funding.

"We already measure other processes of clinical care, we just don't do it routinely for actual communication," he says.

SAN DIEGO, December 6, 2019 -- Schools of fish can scatter sound waves, which has impacts on fish farming. Fisheries acoustics have been studied for over 40 years to assess biomass and optimize aquaculture applications.

The talk "Mesoscopic wave physics in a dense fish school" will be presented Dec. 6 at the 178th Meeting of the Acoustical Society of America as part of a session on general topics in physical acoustics. The convention will be held at the Hotel del Coronado in San Diego.

Benoit Tallon, Philippe Roux, Guillaume Matte and Sergey Skipetrov first examined the phenomenon of how fish scatter acoustic waves in a dense school of fish contained in an open-sea cage. They developed a new approach to help overcome issues encountered in aquaculture relating to the evaluation of the total biomass of dense schools of fish.

"We perform experiments in aquaculture farms, because it permits the characteristics of a school to be well known in advance. However, we can reasonably imagine the use of mesoscopic physics to estimate the biomass of wild fish schools in their natural environment," Tallon said.

The ability of fish in a school to scatter sound is a result of physical characteristics, such as the softness of fish flesh, and the effect of noise on their swim bladder -- a special organ that allows fish to control their buoyancy. The size of the school of fish and its concentration also affects the way sound is scattered.

"In the community, many people are interested in multiple scattering of waves at different scales," said Tallon. "For example, mesoscopic effects were observed from seismic wave transport in earth's crust to light wave propagation through microscopic powders. However, such phenomena have never been reported with living matter."

Tallon's presentation 5aPA4, "Mesoscopic wave physics in a dense fish school," will be at 8:45 a.m. PT, Friday, Dec. 6, in the Wilder room of the Hotel del Coronado in San Diego.

RIVERSIDE, Calif. -- Physicists at University of California, Riverside, have designed an experiment to explain the concept of magnetic resonance. The project was carried out by undergraduate students in collaboration with local high school teachers.

A versatile technique employed in chemistry, physics, and materials research, magnetic resonance describes a resonant excitation of electron or atomic nuclei spins residing in a magnetic field by means of electromagnetic waves. Magnetic resonance also provides the basis for magnetic resonance imaging, or MRI -- the central noninvasive tool in diagnostic medicine and medical research.

"Two of my undergraduate students developed the demonstration experiment based on a compass, an object everybody can relate to," said Igor Barsukov, an assistant professor in the UC Riverside Department of Physics and Astronomy, who supervised the project.

Barsukov explained the compass is placed in the middle of a wire coil that is fed with a small alternating voltage. A refrigerator magnet in the vicinity of the compass aligns its needle. When the fridge magnet is brought closer to the compass, the needle starts to oscillate at a "sweet spot." When the magnet is moved away from the sweet spot, the oscillation stops. This oscillation corresponds to magnetic resonance of the compass needle in the magnetic field of the fridge magnet.

"During outreach events for the broader public, people often share with us their concerns about MRI procedures they need to undergo in a hospital," Barsukov said. "They associate it with radiation. We wanted to design a hands-on, table-top experiment to alleviate their concerns and to provide a visual explanation for the underlying physics."

Barsukov's team initiated a collaboration with the Physics Teacher Academy, a UCR-based program providing training for local high school teachers, to ensure it is also suitable for a high-school classroom.

"Close interaction with the teachers changed our perspective on what a good demonstration experiment aimed at improving scientific literacy should be," Barsukov said. "We decided to employ 3D-printing techniques for the experimental setup and smartphone-based voltage generators. It reduces the time burden for instructors and makes the presentation more accessible and appealing to students."

The project was recently published in The Physics Teacher and presented in early November 2019 in the educational section of Magnetism and Magnetic Materials, a major conference in magnetism research.

"The project turned out to be truly synergistic," Barsukov said. "We learned a lot from the high school teachers we worked with and were able to design an exciting tool for outreach, which I can also use in my classes at UCR. Working on this project was a great lab experience for my students."

In 2017, the Heising-Simons Foundation -- a family foundation that works in climate and clean energy, science, education, and human rights -- established the 51 Pegasi b Fellowship to support early-career astronomers engaged in planetary research. Just over a year later, the Foundation announced that it would overhaul the selection process for the program because, out of 12 fellowships awarded in the program's first two years, only two -- one each year -- went to female scientists.

"Even with our good intentions, we find ourselves part of a system that drives to less rather than more diversity," said the Foundation in a statement on its website. "We commit to working to change our Fellowship and that system for the better."

Over the next year, the Foundation worked with Joyce Yen -- director of the University of Washington's ADVANCE Center for Institutional Change, an NSF-funded body to promote female STEM faculty on campus -- to modify the application and evaluation process for the 51 Pegasi b Fellowship based on social science research. The goal: to put male and female scientists on a more equal footing.

The Heising-Simons Foundation used the revised method to choose its next class of fellows. In March of this year, the Foundation announced that six scientists would receive 51 Pegasi b Fellowships in 2019, four of them women.

In a paper published Dec. 6 in the journal Nature Astronomy, Yen shared the changes that the Heising-Simons Foundation implemented, and how its lessons could inform changes in academia, education and philanthropy to boost diversity, equity and inclusion in all STEM fields. Yen sat down with UW News to discuss this unique case study.

This is just one postdoctoral fellowship that researchers in astronomy can apply for. Why is this case so important?

JY: These fellowships have a large impact on career trajectory. When postdoctoral researchers apply for faculty positions, grants or other opportunities, they'll be evaluated in part based on research they've already done and fellowships they've previously earned. So, when the process to award things like postdoctoral fellowships already treats male and female candidates differently, it has an impact not just in regard to diversity, equity and inclusion, but also the demographic makeup of faculty, senior researchers, administrators and mentors.

What prompted the Heising-Simons Foundation to change the way that this fellowship was awarded?

JY: With just two fellowships going to female scientists in its first two years, there were strong reactions from the astronomy and philanthropic communities, all essentially asking: Why is the gender diversity so skewed in these fellowships while we're having these conversations about diversity, equity and inclusion? The Heising-Simons Foundation listened, and asked, "How can we make this better?" They reached out to experts and began a year-long process to change the way that they solicit applications and evaluate candidates.

How did you approach working with the Foundation for this fellowship?

JY: I worked with them to evaluate the application process and as a facilitator during the evaluation and review process. Our goal was to bring changes to the fellowship application and evaluation process that reflected effective practices for diversity, equity and inclusion.

What are some of those best practices?

JY: First, don't narrow the applicant pool any earlier than you need to. That makes it more likely that fellowships will be awarded in a way that addresses diversity, equity and inclusion. Second, ensure that the information collected from applicants actually captures what we want to know about them, and also create an evaluation rubric for reviewers. This avoids situations in which evaluators might "fill in the blanks," read between the lines or make assumptions about applicants that might introduce bias into the selection process. Also, we just want to ensure that we're aware and acknowledge that bias happens to all of us.

So what are some of the changes that the Heising-Simons Foundation put in place to reflect those best practices?

JY: Previously, postdoctoral researchers would apply through the universities that they wanted to work at. The universities would then pick which applications to send to the Heising-Simons Foundation. We changed the process so that postdoctoral researchers would apply directly to the Foundation, which would then forward those applications to the relevant universities. This keeps the universities involved in the selection process, which the Foundation wanted, but also increased the percentage of female applicants from less than 25% under the old system to more than 30%.

What about changes to the information given by applicants?

JY: Research has shown that we're not as good as we think we are in evaluating applications without bias coming into play. This is true even in science. Part of overhauling the process involved changes to the application itself -- the information we're requesting from the applicant. This involved stepping back and asking, "What do we really want?" Do we want someone innovative, for example? If so, how do we collect information that will let us identify innovation, for example, among the pool of applicants? And what criteria will reviewers use to evaluate and score the applications? By starting from those types of goal-oriented questions, we made changes to the application, such as asking for an open-ended statement from the applicants about diversity, equity and inclusion. We also improved the rubric for reviewers to use in evaluating and scoring applications, including justifications for their score.

What about steps to reduce bias in the evaluation and selection process?

JY: We did quite a lot. To provide a common context among the reviewers, I provided background research about bias -- that it happens, often in counterintuitive ways, and can affect outcomes like who receives a fellowship. They reviewed applications in-person, and we took concrete steps to avoid introducing bias through things like "decision fatigue." This is a well-documented phenomenon, and happens when you just "plow through" a list of cases with no breaks. Here, we handled the applications in randomized bundles of six, followed by a brief break. This randomized discussion also helped with anchoring bias where we latch onto a first impression -- like an ordinal score or ranking -- that influences our future thinking about that application. On paper, these might look like lots of changes, but they really aren't. They're small changes that required a modest investment in time and resources to come up with and implement. But that investment had a large effect on reducing bias and ensuring that the evaluation and selection process is sensitive to diversity, equity and inclusion. These changes support the overall goal of scientific excellence, noting that excellence has many dimensions.

These changes don't seem specific to astronomy.

JY: That is correct. They're widely applicable to STEM fields, academia and funding organizations. Many types of organizations have made commitments to diversity, equity and inclusion in STEM fields. But it takes a lot of leadership to actually make it happen. The Heising-Simons Foundation said that it wants to make the investment -- caring enough to not just say, "We want to do better," but to actually do better. And even after a change like this, the work is not over. This is an ongoing conversation, and the work must continue.

How would you like to see conversations about diversity, equity and inclusion evolve?

JY: I would like people to consider diversity as part of excellence. People right now want to know what the value of diversity is in an organization. But let's put it another way: What's the value -- or the cost -- of being homogenous?

"It is becoming clear that an acid extracellular pH plays an essential role in cancer cell progression, invasiveness and resistance to therapy," explain Yuri Korchev and Yasufumi Takahashi at Nano Life Science Institute of Kanazawa University and Yanjun Zhang at Imperial College London and colleagues at collaborating institutions in the UK, China, Japan and Russia in a recent paper. Despite the growing recognition of the importance of the pH directly surrounding a cell as an indicator of cell health, techniques to measure it so far remain limited in terms of their sensitivity, the spatial resolution they can offer and the speed of response to pH changes. Reporting in Nature Communications, Zhang, Takahashi and Korchev and colleagues describe a nanopipette pH biosensor that is sensitive to changes in pH of less than 0.01 units with a response time of 2 ms and 50 nm spatial resolution.

The researchers originally designed the sensor as a nanopipette ionic field effect transistor - where gates control the flow of ions in the nanopipette instead of electrons. However, while this tackled issues around pH sensitivity and spatial resolution, the device readings still took a few seconds to respond to pH changes due to ionic Coulomb blockade effects hampering the diffusion rate of ions.

The solution Zhang, Takahashi and Korchev and colleagues now propose is to incorporate a zwitterionic membrane to enable faster responses. By using a twin barrel nanopipette with the membrane in just one of the barrels the researchers were able to use the other barrel as a scanning ionic conductance microscope (SICM) for simultaneous topological measurements.

The team tested the device on live cancer cells and showed how the device could pick up on increases in extracellular pH from invasive phenotypes of breast cancer cells that had been deprived of estrogen. They could also detect pH changes from algae exposed to sunlight, caused by the uptake of inorganic carbon in photosynthesis, as well as identifying heterogeneities in aggressive melanoma cells from high-resolution pH maps.

Highlighting the real-time feedback-controlled dynamic 3D mapping of extracellular pH that their tool allows, and the heterogeneities of cancer cells that it can detect "label-free and at subcellular resolution" they conclude, "This method could help with cancer diagnosis, prognosis, and in evaluating acidic pHe [extracellular pH] targeted therapies."

[Background]

Limitations of previous techniques

The most commonly used pH probes at present are based on microelectrodes that are quite large in comparison to the scale of the pH fluctuations of interest in studies of extracellular pH. Alternatives have been based on changes in the fluorescence of molecules, nuclear magnetic resonance imaging and positron emission computed tomography. However, monitoring fluorescence is subject to background noise and photobleaching, and the other techniques have poor spatial resolution and raise difficulties in quantification because they are based on the distribution of probes within tissue.

By using a nanopipette as an ionic field effect transistor, the researchers were able to overcome most of the issues limiting previous techniques. However mutual same charge repulsion leads to the Coulomb blockade effect, which starts to inhibit the diffusion of positively charged protonated water molecules in the nanopipette and this slows down the response time.

Zwitterionic membrane

A zwitterion is an uncharged molecule containing opposingly charged functional groups. For the zwitterionic membrane in the nanopipette the researchers self-assemble a hydrogel from poly-l-lysine (PLL) and glucose oxidase (GOx), which has advantages in terms of cost and stability. The PLL has positively charged quaternary amine groups and the GOx has a negatively charged carboxylic acid residue group. The presence of glutaraldehyde vapour can then crosslink the resulting PLL/GOx hydrogel.

In neutral pH the zwitterionic membrane presents both positively and negatively charged functional groups but in low pH conditions the positive amine groups dominate so that negative anions preferentially diffuse through the membrane avoiding an ionic Coulomb blockade.

RIVERSIDE, Calif. -- A physicist at the University of California, Riverside, has performed calculations showing hollow spherical bubbles filled with a gas of positronium atoms are stable in liquid helium.

The calculations take scientists a step closer to realizing a gamma-ray laser, which may have applications in medical imaging, spacecraft propulsion, and cancer treatment.

Extremely short-lived and only briefly stable, positronium is a hydrogen-like atom and a mixture of matter and antimatter -- specifically, bound states of electrons and their antiparticles called positrons. To create a gamma-ray laser beam, positronium needs to be in a state called a Bose-Einstein condensate -- a collection of positronium atoms in the same quantum state, allowing for more interactions and gamma radiation. Such a condensate is the key ingredient of a gamma-ray laser.

"My calculations show that a bubble in liquid helium containing a million atoms of positronium would have a number density six times that of ordinary air and would exist as a matter-antimatter Bose-Einstein condensate," said Allen Mills, a professor in the Department of Physics and Astronomy and sole author of the study that appears today in Physical Review A.

Helium, the second-most abundant element in the universe, exists in liquid form only at extremely low temperatures. Mills explained helium has a negative affinity for positronium; bubbles form in liquid helium because helium repels positronium. Positronium's long lifetime in liquid helium was first reported in 1957.

When an electron meets a positron, their mutual annihilation could be one outcome, accompanied by the production of a powerful and energetic type of electromagnetic radiation called gamma radiation. A second outcome is the formation of positronium.

Mills, who directs the Positron Laboratory at UC Riverside, said the lab is configuring an antimatter beam in a quest to produce the exotic bubbles in liquid helium that Mills' calculations predict. Such bubbles could serve as a source of positronium Bose-Einstein condensates.

"Near term results of our experiments could be the observation of positronium tunneling through a graphene sheet, which is impervious to all ordinary matter atoms, including helium, as well as the formation of a positronium atom laser beam with possible quantum computing applications," Mills said.

What The Study Did: Cell phones are mainstays of daily life. This observational study analyzed 20 years of data on people who went to emergency departments with head and neck injuries from cell phone use to estimate the number of injuries, learn what types of injuries there were, and understand how the injuries occurred, such as from distracted driving or walking.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Boris Paskhover, M.D., of Rutgers New Jersey Medical School in Newark, New Jersey, is the corresponding author.

(doi:10.1001/jamaoto.2019.3678)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

A UConn School of Dental Medicine researcher used pregnancy to unlock a missing link between various species of mammals and cancer malignancy--fundamentally changing the way we look at cancer metastasis.

Kshitiz, assistant professor in the department of biomedical engineering - a shared department between the School of Dental Medicine, School of Medicine, and School of Engineering - and Gunter Wagner and Andre Levchenko at Yale University used evolutionary biology to draw the connection in the Nature Ecology & Evolution journal.

In many mammals, the placenta invades the wall of the uterus during pregnancy in the same way that cancer cells invade surrounding tissues. In other mammals--including cows, pigs, and horses--the placenta does not invade as aggressively. Interestingly, in these mammals, tumors rarely metastasize or spread.

Looking at cells from endometrium of various species, Kshitiz found that in order to resist invasion of the placenta, certain species have evolved over time to make their stromal cells--the connective tissue cells in an organ--highly resistant to any invasion. In contrast, humans are particularly vulnerable to cancer metastasis owing to their highly invasive placentation during pregnancy. This study identified the cause linking the curious similarity between pregnancy and cancer invasion across various mammals.

"This work fundamentally changes the way we look at cancer metastasis," said Kshitiz. "Basically, it puts stromal cells at the center of invasion associated with cancer and pregnancy, correlating the two. Who thought that pregnancy and cancer are so similar, and pregnancy in some ways is just controlled invasion?"

Kshitiz continues, "In humans, unfortunately, the invasion in pregnancy as well as by cancer is much less controlled. Interestingly, there are mammals where both pregnancy and cancer malignancy are highly controlled, and now we know why. These mammals (the two hoofed animals: cows, horses, pigs, etc.) have evolved their barrier to invasion."

Kshitiz, Wagner, and Levchenko's research has unveiled the exact genes which are different in the supportive stromal tissue between humans and these animals, opening an entirely new field of changing the stromal surrounding of cancer to limit cancer invasion in a guided way.

The findings can revolutionize our way of thinking about cancer metastasis and allow development of new therapeutics. Making human cells similar to cow cells, for instance, could potentially make humans more resistant to the spread of cancer.

The carnival worker who tries to guess your age relies on aspects of your appearance, such as your posture and whether any wrinkles emanate from the corners of your eyes and lips. If the carny's guess is more than a few years off, you win a stuffed koala.

But a team of Stanford University School of Medicine scientists doesn't need to know how you look to guess your age. Instead, it watches a kind of physiological clock: the levels of 373 proteins circulating in your blood. If the clock is off, you don't win a plush toy. But you may find out important things about your health.

"We've known for a long time that measuring certain proteins in the blood can give you information about a person's health status -- lipoproteins for cardiovascular health, for example," said Tony Wyss-Coray, PhD, professor of neurology and neurological sciences, the D. H. Chen Professor II and co-director of the Stanford Alzheimer's Disease Research Center. "But it hasn't been appreciated that so many different proteins' levels -- roughly a third of all the ones we looked at -- change markedly with advancing age."

Changes in the levels of numerous proteins that migrate from the body's tissues into circulating blood not only characterize, but quite possibly cause, the phenomenon of aging, Wyss-Coray said.

A paper describing the research will be published Dec. 5 in Nature Medicine. Wyss-Coray is the senior author. The lead author is neurology instructor Benoit Lehallier, PhD.

'Proteins are the workhorses'

The researchers analyzed plasma -- the cell-free, fluid fraction of blood -- from 4,263 people ages 18-95. "Proteins are the workhorses of the body's constituent cells, and when their relative levels undergo substantial changes, it means you've changed, too," Wyss-Coray said. "Looking at thousands of them in plasma gives you a snapshot of what's going on throughout the body."

The study's results suggest that physiological aging does not simply proceed at a perfectly even pace, but rather seems to chart a more herky-jerky trajectory, with three distinct inflection points in the human life cycle. Those three points, occurring on average at ages 34, 60 and 78, stand out as distinct times when the number of different blood-borne proteins that are exhibiting noticeable changes in abundance rises to a crest. This happens because instead of simply increasing or decreasing steadily or staying the same throughout life, the levels of many proteins remain constant for a while and then at one point or another undergo sudden upward or downward shifts. These shifts tend to bunch up at three separate points in a person's life: young adulthood, late middle age and old age.

The investigators built their clock by looking at composite levels of proteins within groups of people rather than in individuals. But the resulting formula proved able to predict individuals' ages within a range of three years most of the time. And when it didn't, there was an interesting upshot: People whose predicted age was substantially lower than their actual one turned out to be remarkably healthy for their age.

The researchers obtained their samples from two large studies. One of them, known as the LonGenity study, has assembled a registry of exceptionally long-lived Ashkenazi Jews. It was able to provide many blood samples from people as old as 95.

On measuring the levels of roughly 3,000 proteins in each individual's plasma, Wyss-Coray's team identified 1,379 proteins whose levels varied significantly with participants' age.

Divergence

A reduced set of 373 of those proteins was sufficient for predicting participants' ages with great accuracy, the study said. But there were cases of substantial divergence between participants' chronological and physiological age -- for example, among the subjects in the LonGenity study, with their genetic proclivity toward exceptionally good health in what for most of us is advanced old age.

"We had data on hand-grip strength and cognitive function for that group of people," Wyss-Coray. "Those with stronger hand grips and better measured cognition were estimated by our plasma-protein clock to be younger than they actually were."

The study also strengthened the case that men and women, who were about equally represented in the study, age differently. Of the proteins the analysis found to change with age, 895 -- nearly two-thirds -- were significantly more predictive for one sex than for the other.

"The differences were striking," Wyss-Coray said. He added that this finding strongly supports the rationale for the National Institutes of Health's policy, instituted in 2016, promoting increased inclusion of women in clinical trials and the demarcating of sex as a biological variable.

Any clinical applications of the technique are a good five to 10 years off, he said. With further validation, though, it could be used not only to identify individuals who appear to be aging rapidly -- and, therefore, at risk of age-linked conditions such as Alzheimer's disease or cardiovascular disease -- but also to find drugs or other therapeutic interventions, like leafy green vegetables, that slow the aging process, or conversely to flash an early warning of a drug's unanticipated tendency to accelerate aging.

"Ideally, you'd want to know how virtually anything you took or did affects your physiological age," Wyss-Coray said.

While the words "373 proteins" may conjure up the image of a transfusion-sized blood extraction, a drop is all it takes for a 373-protein readout.

In fact, a mere nine proteins were enough to do a passable job, Wyss-Coray said. "After nine or 10 proteins, adding more proteins to the clock improves its prediction accuracy only a bit more," he said. "With machine learning, you could potentially make a test with good accuracy based on just those nine proteins."

In the Nadym district of the Yamalo-Nenets Autonomous Okrug, there are so-called "blue lakes". Located in the north-taiga, they are interesting not only for their unusual bright blue color, but also for their peculiar cone hollow with a depth of up to 12 m, the chemical composition of ultra-fresh waters, and the almost complete absence of fish. The flora and fauna of anomalous lakes have not been studied yet, and geological research data is very limited.

Assessing the status of bodies of water is often connected to the analysis of zooplankton -- small animals drifting with the water flow. Such creatures are invisible to the eye, but annually they pass through themselves a volume of water approximately equal to the volume of the World Ocean, furthermore, many aquatic animals feed on them. Thus, it is not surprising that changes occurring with zooplankton are reflected in the state of the entire water reservoir.

Scientists from Tyumen State University studied the variety of species, the abundance, and biomass of zooplankton of the two blue lakes. To do so, they collected animals by filtering water through a special sieve, then they determined the main chemical characteristics, including the content of heavy metals (iron, copper, nickel, and others), analyzed the abundance and the diversity of species of zooplankton. The species composition was represented by 14 different species of organisms, while the similarity index was only 38%. Discovered species are typical for most bodies of water in Western Siberia -- these are cladocerans and copepods, rotifers. The most numerous and constantly appearing species is the crustacean Sida crystalline. Another species, copepod ?nthocyclops vernalis, is considered quite rare in lakes of such type. Notably, the concentration of some heavy metals exceeded the sanitary and hygienic standards, although this feature is characteristic to many bodies of water in the region and is associated with the abundance of swamps and processes in the soil.

"The zooplankton of the examined lakes is very similar to the zooplankton of other reservoirs in the Yamalo-Nenets Autonomous Okrug. Since water invertebrates are good indicators of water quality, the obtained data can be further used for the integrated environmental monitoring of the region's aquatic ecosystems", - comments Andrey Soromotin, doctor of biological sciences, professor, director of the Institute of Ecology and Rational Use of Natural Resources of Tyumen State University, honored ecologist of the Russian Federation, a Fellow Member of the Russian Academy of Natural Sciences

SAN FRANCISCO (December 5, 2019) - In 2019, researchers at the California Academy of Sciences added 71 new plant and animal species to our family tree, enriching our understanding of Earth's complex web of life and strengthening our ability to make informed conservation decisions. The new species include 17 fish, 15 geckos, eight flowering plants, six sea slugs, five arachnids, four eels, three ants, three skinks, two skates, two wasps, two mosses, two corals, and two lizards. More than a dozen Academy scientists--along with many more international collaborators--described the new species discoveries.

Proving that our vast and dynamic planet still contains unexplored places, the scientists discovered these new plants and animals across five continents and three oceans--venturing into Croatian caves, diving to extreme ocean depths, and surveying savanna forests. Their results help advance the Academy's mission to explore, explain, and sustain life.

"Despite decades of tirelessly scouring some of the most familiar and remote places on Earth," says Shannon Bennett, PhD, and Academy Chief of Science, "biodiversity scientists estimate that more than 90% of nature's species remain unknown. A rich diversity of plants and animals is what allows life on our planet to thrive: the interconnectedness of all living systems provides collective resilience in the face of our climate crisis. Each newly discovered species serves as an important reminder of the critical role we play in better understanding and preserving these precious ecosystems."

Below are highlights from the 71 new species described by the Academy in 2019. For a full list of species and hi-res images, please contact press@calacademy.org.

Flowering plants in need of protection

Emeritus Curator of Botany Frank Almeda, PhD, described a rare white-blossomed plant Trembleya altoparaisensis this year based on several specimens collected over 100 years ago by the famous 19th-century botanist Auguste Francois Marie Glaziou. As rare now as it was then, the plant proved difficult to find in the wild. "People don't think plants move," says Ricardo Pacifico, a PhD student working with Almeda and visiting researcher at the Academy, "but they do." When an environment changes, plants will move to areas that better suit them. For botanists like Pacifico--who sometimes relies on a single museum specimen collected decades ago to track down a plant's current whereabouts in the field--these migrations can be both challenging and rewarding. Luckily, on a recent expedition to the lush canyons of Chapada dos Veadeiros National Park in Brazil, Pacifico was able to track down a living specimen of Trembleya altoparaisensis to inform Almeda's species description.

Almeda emphasizes the importance of Pacifico's fieldwork to document exactly where these plants thrive in the wild. "Sure, national parks are protected," he says, "but we must ensure we know what grows in the parks." He says that finding and documenting species such as T. altoparaisensis and Gravesia serratifolia--another new species from a national park in Madagascar described by Almeda and his former student, Heritiana Ranarivelo--is crucial for effective management of the parks in the event of wildfires or other disasters.

A long-snout skate with potentially high stakes for steaks

Thanks to a discovery by Ichthyology Research Associate David Ebert, PhD, the Falkland Islands have welcomed a new-to-science skate. Since the 1970s, the Falkland Island fisheries have been one of the largest distributors of skates--cartilaginous ray-like fish that live at depths of up to almost 2000 feet (600 meters). The fish are particularly popular in Korea, where they are fermented or filleted into steaks. Through their research, however, Ebert and his team have shown that some of the skates on the market might not be Dipturus chilensis as previously thought, but are instead the newly described species Dipturus lamillai. Ebert urges fisheries to reevaluate their sustainability and surveying practices in order to prevent overfishing of the newly described species before its population status can be fully evaluated--and to ensure the wrong skate doesn't end up as a steak on a dinner plate.

A menagerie of microendemic and critically endangered reptiles

Academy Research Associate Aaron Bauer, PhD, has described more than 205 reptiles during his career, and this year he adds another 15 mottled day geckos, three island-dwelling skinks, an ostentatiously orange lizard, and a high-altitude girdled lizard to the tree of life. Bauer recommends that many of these reptiles be listed as critically endangered due to their microendemism--a term used to describe species only found in an extremely small geographic range. This restricted distribution means these animals are particularly susceptible to any sort of disturbance, such as deforestation. In the case of the newly described skink Kuniesaurus albiauris, invasive fire ants already threaten its restricted, native habitat in New Caledonia. Bauer says that finding these microendemic species is crucial for conservation. "If we don't explore isolated habitats, like mountaintops," he says, "we would miss a huge part of the biodiversity that's unique to these regions."

Californian corals make a case for conservation

Despite being less than 60 miles off the coast of San Francisco, much of the biodiversity in the Cordell Bank National Marine Sanctuary remains a mystery. This is especially true of deeper-dwelling species. "We know the intertidal zone, but the deep sea is out of sight, out of mind," says Invertebrate Zoology Curator Gary Williams, PhD, who described two new California coral species this year. Williams says that deep-sea surveys using remotely operated vehicles--like the 2018 expedition led by the National Oceanic and Atmospheric Administration that collected a new lemon-yellow octocoral Chromoplexura cordellbankensis--are increasingly important for informing the expansion of marine protected areas and protecting the beautiful biodiversity thriving in the unexplored depths of our own backyard.

A fleet of fish (including a cat-eyed cardinalfish and a fish named C. wakanda)

From the purple, armor-like scales of the vibranium fairy wrasse Cirrhilabrus wakanda to the scintillating stare of the cat-eyed cardinalfish Siphamia arnazae, Academy researchers described 17 stunning new species of fish this year. Many of the colorful creatures come from tropical reefs--ecosystems known for both their biodiversity and their vulnerability to climate change. As the oceans continue to warm, the species that depend on the reef's abundant resources are jeopardized. Efforts to document these species, such as those by Academy researchers and their collaborators, helps to ensure that conservationists, policymakers, local communities, and beyond better understand what is at stake.

Cave-dwelling and ant-loving arachnids

As you move east from the Pyrenees Mountains on the border of Spain and France to the Balkan Mountains outside Bulgaria's capital city of Sofia, a group of related cave-dwelling harvestmen (organisms related to spiders) becomes more adapted to life in the dark. This gradient of traits--known in biology as a character cline--helps researchers better understand the process of how a new species branches off on the tree of life. There is now a new link in this character cline chain thanks to the description of the cave-dwelling harvestman Lola konavoka from Croatia by Academy Curatorial Assistant of Entomology Darrell Ubick.

This year Ubick also co-describes the first--and only--species in a new family of "ant-worshipping" spiders. These curious arachnids spend most of their time underground in ant mounds, although scientists aren't sure why. "The only way to see what they're doing," says Ubick, "is to dig them up. But then they're no longer in their natural state." It wasn't until a recent expedition to Mexico's Chihuahuan desert--the spider's namesake--that scientists were first able to witness the species in the wild. But since they were found scattered around the surface of a collapsed ant nest, their underground behavior remains a mystery.

A stunning assortment of sea slugs

Academy Curator of Invertebrate Zoology Terry Gosliner, PhD, has described about one quarter of colorful sea slug species known to science, but these masquerading marine invertebrates still find ways of surprising him. Parts of Madrella amphora--one of six new species Gosliner describes this year--closely resemble the snail eggs that tend to surround their habitat. "We recently confirmed through genetics that sea slugs mimic the colors of other species" says Gosliner, "but it's rare to see sea slugs mimic other animals entirely." Two of the other new-to-science sea slugs are notable for being unusually small members of a group of typically large nudibranchs known as sea hares--named for two appendages on their head that resemble bunny ears.

Physicians who treat patients with triple negative breast cancer have two new ways to predict which patients may benefit most from the well-established post-surgery treatment known as AC chemotherapy, short for adjuvant doxorubicin and cyclophosphamide.

Investigators from the SWOG Cancer Research Network, a cancer clinical trials network funded by the National Cancer Institute, part of the National Institutes of Health, confirm in research findings published in the Journal of Clinical Oncology that two biomarkers - a 44-gene DNA Damage Response (DDIR) signature and stromal tumor-infiltrating lymphocytes (sTILs) - can serve as prognostic markers in people diagnosed with triple negative breast cancer. These new tests could be used to guide cancer treatment in the same way that cancer stage or tumor size are currently used to personalize care.

"This moves us a little closer to basing triple negative breast cancer treatment on the biology of individual patients," said Priyanka Sharma, M.D., a SWOG investigator and a physician and researcher at University of Kansas Cancer Center. "If you knew, up front, which women would respond well to AC chemotherapy, we could preferentially pick this treatment - and spare them other treatment. With other patients, we would want to investigate different strategies such as immunotherapies or targeted drugs."

Triple negative breast cancers get their name for the common cancer growth factors they lack - estrogen receptors, progesterone receptors, and the HER2 gene. Triple negative breast cancers tend to grow faster and spread more frequently than other types of breast cancer, and many current drugs aren't effective in slowing or stopping their growth. Sharma has spent more than 10 years investigating these cancers, trying to better understand how they work in the body and how they can be treated more effectively. Triple negative breast cancers account for about 15 to 20 percent of all breast cancers diagnosed in the United States each year.

Preliminary research had shown that two biomarkers, the DDIR signature and sTILs, could be used to predict good outcomes after AC chemotherapy in patients with hormone receptor-negative and HER2 negative breast cancers. Sharma and her team wanted to see if they could confirm these findings in patients with triple negative breast cancer. To do so, they dipped into SWOG's vast specimen bank - which contains over 800,000 tissue, blood, and other biological samples. Sharma used tumor samples from patients enrolled in S9313, a SWOG breast cancer trial assessing the effectiveness of AC chemotherapy in patients with high- and moderate-risk breast cancers. S9313 stopped enrolling patients in 1997, but breast tumor tissue from those patients remains, preserved in paraffin wax.

Analyzing these samples, Sharma and her team confirmed 425 cases of triple negative breast cancer. They then conducted two analyses. One was creating a DDIR signature, an RNA-based tumor profile that shows whether a patient's immune system is activated based on the working of 44 different genes. In the other analysis, breast cancer histopathologists counted stromal tumor-infiltrating lymphocytes (sTILs), white blood cells that migrate into tumors.

Here's why these tests matter. Both DDIR status and sTIL density can be gauges of the bodies' ability to repair DNA damage and mount immune response against cancer; AC chemotherapy works best in tumors with DNA repair deficiency. So a positive DDIR status, and a high sTILs density, could be used to predict better outcomes with AC chemo.

That's just what the SWOG team confirmed.

Researchers were able to complete DDIR assessments on tissue from 381 patients. Of those, 62 percent were DDIR positive - and had better outcomes from AC chemotherapy based on the S9313 results. Researchers were able to get sTIL density results from 423 patient samples - and the higher the density, the better the outcomes from AC chemo, their analysis showed. In both cases, AC chemo treated patients with a positive DDIR signature and a higher sTIL density were cancer-free longer and also lived longer.

The results have implications for cancer care and research. DDIR scores could be used to guide treatment for triple negative breast cancer patients. Those with DDIR positivity could be treated with AC chemotherapy alone, while those with DDIR negativity could get alternative therapies alone or in conjunction with AC chemotherapy. In addition, the research showed that the most significant biological process in DDIR-positive tumors was immune system activation, suggesting these tumors may be a good target for immune checkpoint inhibitors - a possible line of investigation for future clinical trials.

A recent study by a team of scientists in Korea reveals new findings about how various systems involved in cellular surveillance interact. This research is the first to identify a "cross-talk" molecule between these systems. Because these pathways are involved in fighting toxic cellular or foreign substances, the study has various potential applications in antiviral development, gene therapy, and agriculture.

The central dogma of molecular biology describes how, in a cell, the double-stranded DNA is transcribed into a single-stranded molecule called RNA, which is ultimately translated into protein. But, this process is not foolproof, and occasionally, it produces RNA or protein molecules containing errors, which can cause harm to the cell. To protect themselves from these potentially harmful molecules, as well as from foreign viral RNA, cells have developed complex surveillance systems to identify and degrade aberrant RNAs and proteins. For example, the RNA quality control (RQC) system targets the cell's own error-containing RNAs, while post-transcriptional gene silencing (PTGS) primarily targets foreign RNAs (such as those of invading viruses) by "silencing" their genes. Similarly, a separate cellular system handles protein quality control. To maintain a proper balance of cellular processes, these surveillance systems must be tightly regulated. For example, as both RQC and PTGS target RNAs, when one process is suppressed, the other gets activated. But, exactly how the systems interact has so far remained a mystery.

In a new study published in Nature Plants, scientists at the Daegu Gyeongbuk Institute of Science and Technology, Korea, led by Prof June M. Kwak, uncovered a new link between the pathways involved in RNA degradation. Talking about the motivation for their research, Prof Kwak says, "We wanted to investigate novel mechanisms controlling gene silencing by small regulatory RNAs."

For their investigation, the scientists designed a cell type-specific genetic system in the plant Arabidopsis, which allowed them to monitor RNA silencing. The green fluorescent protein gene was used as a target--or prey--molecule and was paired with a molecular construct called Orion, which exploits the PTGS system to target and degrade the prey RNA. Plant cells expressing the prey without Orion show green fluorescence, whereas those that express both the prey and Orion, referred to as PORI cells, show virtually no fluorescence.

Using this system, the researchers identified a defective PORI plant that nonetheless exhibited fluorescence. This plant carried a mutation in a protein called RPT2a, which is known to be part of the protein quality control system. Further investigations revealed that RPT2a is critical to the cross-talk between RQC and PTGS. Specifically, they found that RPT2a targets RQC proteins for degradation, which reduces the influence of RQC and promotes the role of PTGS. This is particularly beneficial when foreign RNA is present in the cell, as unlike RQC, PTGS includes an amplification process that alerts nearby cells to further silence the foreign RNA.

This study is the first in the world to show the role of RPT2a in maintaining the balance between the two RNA-degrading systems in a cell. Prof Kwak is optimistic about potential implications for this study. He says, "The RNA surveillance machinery involved here is the same used in other plant, animal, and human cells in response to viral infections or any foreign genetic material. Therefore, a better understanding of the working of these systems will be useful for developing new vaccines/antivirals to treat diseases, or implementing genetic manipulation, such as in agriculture or gene therapy."

CHICAGO - Researchers studying the brain found that women taking oral contraceptives, commonly known as birth control pills, had significantly smaller hypothalamus volume, compared to women not taking the pill, according to a new study presented today at the annual meeting of the Radiological Society of North America (RSNA).

Located at the base of the brain above the pituitary gland, the hypothalamus produces hormones and helps regulate essential bodily functions including body temperature, mood, appetite, sex drive, sleep cycles and heart rate.

Structural effects of sex hormones, including oral contraceptive pills, on the human hypothalamus have never been reported, according to the researchers. This may be in part because validated methods to quantitatively analyze MRI exams of the hypothalamus have not been available.

"There is a lack of research on the effects of oral contraceptives on this small but essential part of the living human brain," said Michael L. Lipton, M.D., Ph.D., FACR, professor of radiology at the Gruss Magnetic Resonance Research Center at Albert Einstein College of Medicine and medical director of MRI Services at Montefiore Medical Center in New York City. "We validated methods for assessing the volume of the hypothalamus and confirm, for the first time, that current oral contraceptive pill usage is associated with smaller hypothalamic volume."

Oral contraceptives are among the most popular forms of birth control and are also used to treat a host of conditions, including irregular menstruation, cramps, acne, endometriosis and polycystic ovary syndrome. According to a 2018 report from the Centers for Disease Control and Prevention's National Center for Health Statistics, from 2015 to 2017 approximately 47 million women aged 15-49 in the U.S. reported current use of contraceptives. Of those, 12.6% used the pill.

In his study, Dr. Lipton and colleagues recruited a group of 50 healthy women, including 21 women who were taking oral contraceptives. All 50 women underwent brain MRI, and a validated approach was used to measure hypothalamic volume.

"We found a dramatic difference in the size of the brain structures between women who were taking oral contraceptives and those who were not," Dr. Lipton said. "This initial study shows a strong association and should motivate further investigation into the effects of oral contraceptives on brain structure and their potential impact on brain function."

Other findings from the study, which Dr. Lipton described as "preliminary," were that smaller hypothalamic volume was also associated with greater anger and showed a strong correlation with depressive symptoms. However, the study found no significant correlation between hypothalamic volume and cognitive performance.

December 4, 2019 -- A new study at Columbia University Mailman School of Public Health suggests there is a two-way relationship between bullying perpetration and mental health problems among youth in the U.S. Researchers report that bullying perpetration increased the risk of developing internalizing problems, and having internalizing problems increased the probability of bullying others. While previous research has focused on the causes and consequences of bullying victimization, this is the first study to comprehensively explore the time sequence between bullying perpetration and mental health problems. The results are published online in the Journal of Adolescent Health.

Bullying is defined as any unwanted aggressive behavior by another youth or group of youths, who are not siblings or dating partners, and is repeated multiple times or highly likely to be repeated. In the U.S., it has been estimated that between 18-31 percent of youths are involved in bullying.

"While it is well documented that bullying victimization is associated with immediate and life-long mental health problems, no studies to date have examined the hypothesis that the relationship between bullying perpetration and mental health problems may be bidirectional," said Marine Azevedo Da Silva, PhD, postdoctoral researcher at Columbia Mailman School of Public Health.

The researchers analyzed data from 13,200 youths aged 12 to 17 years in the nationally representative Population Assessment of Tobacco and Health survey to study the bidirectional association between bullying perpetration and internalizing problems. Among them, 79 percent reported they never bullied others, 11 percent reported having bullied others over a year ago, and 10 percent reported having bullied others in the past year. When bullying perpetration was considered as a past month measure, 16 percent reported having bullied others over a month ago, and 5 percent reported having bullied others in the past month.

When the researchers examined the relationship between bullying perpetration as a predictor of internalizing problems, they found that youths who reported being the perpetrators of bullying were more likely to develop a moderate to high incidence of mental health problems compared to those who reported not perpetrating bullying. On the other hand, they found that adolescents who experienced moderate to high internalizing problems had increased risk of bullying others compared to those who reported no or low incidence of having mental health problems.

"The study we designed allowed us to show that the association is likely to be bidirectional between bullying perpetration and internalizing problem. However, it is important to point out that the methods of assessment - including definitions, question wording, and self-report - could overestimate or underestimate the prevalence of bullying and in turn, influence the strength of association between bullying perpetration and internalizing problems.," observed Marine Azevedo Da Silva.

"Our findings provide an important extension to previous literature, and indicate that bullying behaviors prevention and intervention strategies among youth should consider how to take into account and handle negative feelings and mental health problems" said Silvia Martins, MD, PhD, director of the Substance Abuse Epidemiology Unit of the Department of Epidemiology and senior author.