Culture

A growth mindset intervention can change students' grades if school culture is supportive

AUSTIN, Texas -- Boosting academic success does not have to derive from new teachers or curriculum; it can also come from changing students' attitudes about their abilities through a short online intervention, according to the latest findings from the National Study of Learning Mindsets published in Nature on Aug. 7.

The experimental study involved more than 12,000 ninth graders in a national, representative sample of 65 public high schools across the United States. It showed that an intervention emphasizing a growth mindset -- the belief that intellectual abilities are not fixed but can be developed -- can improve key predictors of high school graduation and college success, especially when a school's culture supports the treatment message.

"The research cemented a striking finding from multiple earlier studies: A short intervention can change the unlikely outcome of adolescents' grades many months later," said David Yeager, the study's lead author and an associate professor of psychology at The University of Texas at Austin. "It also showed us something new: Higher-achieving students don't get higher grades after the program, but they are more likely to take harder classes that set them up for long-term success."

According to U.S. federal government statistics, nearly 20% of students in the U.S. do not finish high school on time. These students are also at an increased risk of poverty, poor health and early mortality. The transition to high school represents an important transition point in adolescents' paths toward high school completion.

Building on prior research, researchers found that two 25-minute online sessions, administered at the beginning of high school, can help students develop a growth mindset by reshaping their attitudes about their abilities. Researchers found that both lower- and higher-achieving students benefited academically from the program, even into their sophomore year.

On average, lower-achieving students who took the program earned 0.10 higher grade points in core academic subjects such as math, English, science and social studies. Additionally, the intervention reduced the proportion of these students with a D or F average in these courses by more than 5 percentage points.

The intervention also increased the likelihood students took Algebra II or higher in 10th grade by 3 percentage points among both higher- and lower-achieving students.

"These effects are substantial when compared to the most successful large-scale, lengthy and rigorously evaluated interventions with adolescents in the educational research literature," Yeager said. "They are particularly notable given the low cost and high fidelity of the online program. But the growth mindset program isn't a magic bullet. Its effectiveness depends a lot on the school context."

In medium- to low-performing schools with norms that encouraged students to take on more challenging coursework, lower-achieving students who received the intervention improved 0.15 grade points in core courses and 0.17 grade points in STEM courses.

"Motivation and learning don't just happen in a student's head; they depend on the resources and learning opportunities present in the school's environment, including the extent to which challenging coursework is available to students," Yeager said. "A mindset intervention is like planting a seed; it grows to fruition in fertile soil. Now that we have shown this in a national study, it will propel us into a new era of mindset research. That era will focus on both the mindset of the student and the culture and climate of the classroom. We have our eyes set on preparing teachers to support students' beliefs that they can grow and learn."

Credit: 
University of Texas at Austin

Football-related head hits that don't cause concussions can still injure the brain

Measures of the integrity of midbrain white matter in 38 college-level American football players changed after a season of play even though all but two of the athletes did not suffer clinically defined concussions, according to a new study. The results indicate that repeated, subconcussive head hits sustained by players over the course of a typical football game can cumulatively cause brain trauma. The authors say this suggests that catching injury before it manifests as overt signs and symptoms will prove critical in protecting players from long-term neurologic injury. Although the buildup of tau protein in the midbrain is already associated with neurodegenerative diseases such as chronic traumatic encephalopathy (CTE), it has not been definitively known whether structural changes to the midbrain occur during the repetitive head impacts that fall short of the clinical diagnosis for concussion. Adnan Hirad et al. examined the midbrain white matter of players before and after a college football season using an MRI-based imaging technique. They also measured the magnitude, location, and direction of hits experienced on the field with accelerometers attached to the players' helmets. The researchers found that the degree of reduction in midbrain white matter structural integrity was linked to the number of impacts that caused the brain to rotate inside the skull (while impacts that caused the brain to strike the front or rear of the skull were not). Further MRI analysis of white matter structural integrity in a second cohort of 29 patients with clinically defined concussions compared to 58 controls of the same age suggested that changes in the midbrain regions of the concussed group were related to tau accumulation. "The midbrain may be the place to look," the authors sayin a related video, "to predict the injury burden of contact sports in the absence of concussion."

Credit: 
American Association for the Advancement of Science (AAAS)

Persistent inflammation in sepsis survivors linked to higher mortality rates

PITTSBURGH, Aug. 7, 2019 - One out of four sepsis patients who survive their hospital stay have elevated levels of inflammation a year after discharge, and they are at higher risk for major health problems and death, according to a study led by physician-scientists at the University of Pittsburgh School of Medicine and the Veterans Affairs Pittsburgh Healthcare System.

The results, published today in JAMA Network Open, give tantalizing clues to future treatments that may improve outcomes for sepsis survivors.

Sepsis is a life-threatening condition that arises when the body's response to an infection injures its own tissues and organs, and affects more than 30 million people worldwide every year, according to the World Health Organization.

"Sepsis is the leading cause of death among hospitalized patients. Patients discharged from the hospital aren't out of the woods yet. Approximately 1 out of every 3 sepsis survivors will die in the following year," said lead author Sachin Yende, M.D., M.S., professor of critical care medicine and clinical and translational science at Pitt's School of Medicine, and vice president of critical care and deputy chief of staff at the Veterans Affairs Pittsburgh Healthcare System. "Our new findings about chronic inflammation post-discharge suggest that addressing this condition may be important to improve patients' long-term outcomes."

Nearly all patients with sepsis have increased inflammation in their bloodstream during the first few days of their hospitalization. Whether this inflammation resolves or persists is poorly understood. Yende and his team followed 483 people who had been hospitalized with sepsis at one of 12 U.S. hospitals between 2012 and 2017 and survived to be discharged. Detailed information was gathered on the study participants, and they were contacted by telephone and home visits three, six and 12 months after enrollment for health interviews and a blood sample.

Approximately a quarter of the participants showed persistently elevated levels of inflammation and a half showed elevated levels of immunosuppression biomarkers up to a year after hospitalization. These patients had higher rates of readmission -- particularly due to heart disease and stroke -- and death compared to their peers whose inflammation and immunosuppression biomarkers had returned to normal after hospitalization.

"The participants with increased inflammation had levels that were twice as high as levels in healthy individuals and that elevated inflammation persisted long after hospital discharge," said senior author Derek Angus, M.D., M.P.H., professor and chair of Pitt's Department of Critical Care Medicine and director of Pitt's Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center. "Sepsis increases risk of heart disease and stroke, and, for the first time, we've linked these adverse outcomes to persistent inflammation. This opens the door to future studies into why high levels of inflammation persist for at least a year after hospital discharge and the development of treatments aimed at modifying the inflammation with the hope that will improve health."

The researchers cautioned that they did not have blood tests on the study participants before their sepsis diagnosis. It is possible that they had elevated levels prior to hospitalization that may have contributed to the development of sepsis and continued to persist after hospitalization.

Credit: 
University of Pittsburgh

Transport by mobile stroke units get patients quicker treatment than ambulance

image: Amanda L. Jagolino-Cole, MD, and Alexandra Czap, MD, published research that highlights the advantages of hospital transport in a mobile stroke unit versus a traditional ambulance.

Image: 
J. Daniel Escareño/UTHealth

Every second counts for stroke patients, as studies show they can lose up to 27 million brain cells per minute. Researchers at The University of Texas Health Science Center at Houston (UTHealth) recently published new findings in Stroke that show patients transported to the hospital by mobile stroke unit instead of standard ambulance received a clot-busting procedure an average of 10 minutes faster, which could potentially save up to 270 million neurons per patient.

In 2014, McGovern Medical School at UTHealth was the first in the nation to launch a mobile stroke unit, a specially equipped ambulance for diagnosing and treating stroke rapidly before hospital arrival.

"The quicker we get stroke victims treatment that will restore blood flow, the more brain tissue we can save," said Alexandra Czap, MD, vascular neurology fellow in the Department of Neurology at McGovern Medical School and first author of the paper. "This study shows that mobile stroke units like ours can be effective in streamlining time to treatment, potentially saving neurological function, and ultimately improving quality of life in stroke patients."

The study looked at data from 161 patients from Houston and two other locations from 2014 to 2018 who underwent intra-arterial thrombectomy after suffering an acute ischemic stroke, the most common kind, which is caused by a blockage in a cerebral artery. The only medical therapy known to treat ischemic stroke, tissue plasminogen activator (tPA), is not always able to clear a large clot. To perform the procedure, also known as endovascular thrombectomy, a vascular neurologist threads a catheter usually through a groin artery up to the blockage, where a small device inserted into the catheter is used to remove the clot.

"This is a hallmark paper because it shows that pre-hospital evaluation and management on a mobile stroke unit can significantly reduce time to endovascular treatment for patients with large artery clots," said Amanda L. Jagolino-Cole, MD, a teleneurologist and assistant professor in the Department of Neurology at McGovern Medical School, who was the senior author of the paper.

While on board the unit, an interdisciplinary team can begin the process to assess whether the patient needs a thrombectomy, including diagnostic imaging, neurological exam, and the administration of tPA. That gives the treatment team a head start and upon arrival to the hospital, the patient can be taken quickly to the endovascular suite for the procedure.

"Our mobile stroke unit allows us to bring the hospital to the patient," Czap said. "We can complete the necessary diagnostic testing and notify the hospital that we are coming, so that the appropriate teams can be ready. Streamlining this process allowed for one of our recent mobile stroke unit patients to complete treatment in under two hours from onset of symptoms. Going forward, identification of possible thrombectomy candidates on the unit can increase the accuracy of triage and increase the number of patients having the procedure, which we hope will lead to better patient outcomes."

The paper also shows an overall improvement in endovascular thrombectomy metrics for all patients regardless of how they arrived to the hospital. This is significant because the procedure just started to be recognized as standard management for select stroke patients within the last five years, Jagolino-Cole said.

This research is part of the ongoing BEST-MSU study, a prospective comparative effectiveness trial that investigates the benefits of stroke treatment delivered using a mobile stroke unit compared to standard management by emergency medical services. The primary outcomes are patients' functional status at 90 days and long-term health care utilization. The BEST-MSU study will complete enrollment in 2020.

Credit: 
University of Texas Health Science Center at Houston

Calcium: Good for bones, good for cultural conservation

When it comes to cultural heritage sites, there are few things historians wouldn't do to preserve them for future generations. In particular, stone buildings and sculptures made of plaster and marble are increasingly at risk of damage from air pollution, acid rain and other factors. Researchers now report in ACS Applied Nano Materials a new, calcium-based conservation treatment inspired by nature that overcomes many drawbacks of currently used methods. 

Historically, conservation scientists have turned to alkoxysilanes, silicon-based molecules used to consolidate stone and other artworks, in their preservation efforts. However, alkoxysilane treatments do not bond properly with non-silicate surfaces, are prone to cracking and are limited in their ability to repel water. Adding other compounds to this treatment have helped overcome these effects, but only to a point. Instead Encarnación Ruiz Agudo and colleagues looked to nature for inspiration, and found that calcium could be the answer. As a major element of strong, natural structures like bone and kidney stones, the researchers theorized that nanoparticles made from calcium could bolster alkoxysilanes and provide the desired protective effects to conserve historical artifacts. 

The researchers made calcium carbonate and calcium oxalate nanoparticles and included polydimethylsiloxane (PDMS) as a stabilizer. PDMS also likely helps the nanoparticles bond to surfaces. The team added the nanoparticles to traditional alkoxysilane treatments, then applied them to samples of three different building materials: white marble, calcarenite limestone and gypsum plaster, and put the samples through a battery of tests. Overall, the results showed enhanced hydrophobicity, less cracking and improved surface adhesion compared to alkoxysilane treatments alone, with calcium oxalate providing a marked improvement in acid resistance. A minimal color effect was observed, but the researchers say this change was within acceptable values for conservation efforts.

Credit: 
American Chemical Society

Brain stimulation for PTSD patients

image: University of Houston assistant professor of electrical engineering Rose T. Faghih is reporting that a closed-loop brain stimulator, based on sweat response, can be developed for PTSD and an array of neuropsychiatric disorders.

Image: 
University of Houston

For 8-million adults who suffer from post-traumatic stress disorder in any given year, medication and cognitive therapy have been the treatment protocol. Now, University of Houston assistant professor of electrical engineering Rose T. Faghih is reporting in Frontiers in Neuroscience that a closed-loop brain stimulator, based on sweat response, can be developed not only for PTSD patients, but also for those who suffer an array of neuropsychiatric disorders.

"Sweat primarily helps maintain body temperature; however, tiny bursts of sweat are also released in response to psychologically arousing stimuli. Tracking the associated changes in the conductivity of the skin, which can be seamlessly measured using wearables in real-world settings, thus provides a window into a person's emotions," reports Faghih.

For people with movement disorders like Parkinson's disease and essential tremor, who have not responded to medication, application of high-frequency electric current to the brain, or deep brain stimulation, is regarded as most effective. Electrodes are placed in certain areas of the brain to regulate abnormal functions and a pacemaker-like device, placed in the upper chest, controls the amount of stimulation the brain receives. Open-loop stimulators, the most widely-used, deliver continuous stimulation until manually re-adjusted by a physician. Closed-loop stimulators, which provide stimulation in response to biomarkers of pathologic brain activity, have been developed for movement disorders, but are yet to be explored for the treatment of neuropsychiatric disorders.

Signaling the onset of a PTSD episode, skin develops the tiniest sheen of perspiration. That symptom of the body's fight or flight response signals a change in the skin's electrical conductivity and provides a window into the brain's state of emotional arousal. Using skin conductance to create the framework for a deep brain stimulator seemed logical to Faghih after reviewing group studies of Vietnam combat veterans with PTSD. Among the findings, PTSD subjects had the largest skin conductance responses when confronted with combat-related words. In a similar study comparing Vietnam combat veterans with and without PTSD and non-combat controls, PTSD veterans had the highest baseline skin conductance levels.

"Skin conductance additionally has the advantage of being easily measured with wearable devices that afford convenience, seamless integration into clothing and do not involve risk of surgically implanted sensors," said Faghih.

The ultimate goal will be to develop closed-loop prototypes that can eventually be used for treating patients in a variety of neuropsychiatric disorders. Faghih's graduate researchers Dilranjan Wickramasuriya and Md. Rafiul Amin were first and second authors, respectively, of the article.

Credit: 
University of Houston

New test to snare those lying about a person's identity

image: This is Dr. Ailsa Millen, Research Fellow in Psychology at the University of Stirling

Image: 
University of Stirling

A new test developed by the University of Stirling could help police to determine when criminals or witnesses are lying about their knowledge of a person's identity.

A team led by Dr Ailsa Millen, Research Fellow in Psychology at Stirling, conducted a study to establish whether liars could hide their reaction when shown a photograph of a familiar face - and found that they could not.

Dr Millen said: "Police officers routinely use photographs of faces to establish key identities in crimes. Some witnesses are honest - but many are hostile and intentionally conceal knowledge of known identities. For example, criminal networks - such as terrorist groups - might deny knowledge to protect one another, or a victim might be too afraid to identify their attacker.

"Our study tracked people's eye movements when they denied knowledge of someone they knew. Instead of looking for signs of lying directly, we looked for markers of recognition in patterns of eye fixations - such as how individuals looked at a photograph of someone they recognised; compared to someone they did not.

"The main aim was to determine if liars could conceal recognition by following instructions to look at every familiar and unfamiliar face with the same sequence of eye fixations - in short, they could not."

They used a process known as the concealed information test (CIT), in which participants' eye movements are tracked while viewing photographs of familiar and unfamiliar faces on a computer screen. In each test, participants denied knowledge of one familiar identity while correctly rejecting genuinely unfamiliar faces, by pressing a button and saying 'no'.

The team found that most liars could not fully conceal markers of face recognition - either spontaneously, or during explicit strategies to look at every face with the same sequence of eye movements. Moreover, these explicit attempts uncovered more instances of concealment than spontaneous attempts to hide knowledge.

Dr Millen explained: "The harder that individuals tried to conceal knowledge, the more markers of recognition there were. These results suggest that it is difficult to conceal multiple markers of recognition at the same time."

The CIT is used in field practice in Japan to uncover guilty knowledge about a crime, which only the culprit would know, such as a murder weapon. However, little research has examined the process being used with faces.

Credit: 
University of Stirling

Entropy explains RNA diffusion rates in cells

Recent studies have revealed that within cells of both yeast and bacteria, the rates of diffusion of RNA proteins - complex molecules that convey important information throughout the cell - are distributed in characteristic exponential patterns. As it turns out, these patterns display the highest possible degree of disorder, or 'entropy', of all possible diffusion processes within the cell. In new research published in EPJ B, Yuichi Itto at Aichi Institute of Technology in Japan explores this behaviour further by zooming in to study local fluctuations in the diffusion rates of RNA proteins. By associating these small-scale diffusion rates with time-varying values for entropy, he finds that the rates of change of entropy in certain time intervals are larger in areas with higher RNA diffusion rates.

Itto's work provides new insights into the complex biochemical processes that go on inside cells. This work could enable researchers to place more rigorous mathematical constraints on the ways in which they function. He also shows that the diffusive dynamics of RNA are analogous to thermodynamic behaviours in larger systems. His calculations imply that the differences in time-varying entropy in different parts of a cell are directly comparable to the time-varying differences in temperature resulting from the flow of heat throughout thermal systems. Itto derived these behaviours by using a series of mathematical equations. These relate RNA diffusion rates on small scales with their subsequent diffusion-varying rates of entropy.

Thanks to this approach, he has now successfully derived the characteristic exponential patterns of RNA diffusion rates, starting from basic mathematics. For the first time, his findings support previous observations that within yeast and bacteria cells, RNA diffusion represents the maximum possible distribution of entropy.

Credit: 
Springer

Permian lizard-like animal suffered from a bone condition similar to Paget's disease

image: A lizard-like animal that lived 289 million years ago suffered from a bone condition similar to Paget's disease, according to a study published August 7, 2019 in the open-access journal PLOS ONE by Yara Haridy of the Museum für Naturkunde in Berlin and colleagues. This is the most ancient known case of such a disease.

Image: 
Images are provided by: Yara Haridy/Museum für Naturekunde, Berlin

A lizard-like animal that lived 289 million years ago suffered from a bone condition similar to Paget's disease, according to a study published August 7, 2019 in the open-access journal PLOS ONE by Yara Haridy of the Museum für Naturkunde in Berlin and colleagues. This is the most ancient known case of such a disease.

The animal in question belonged to an extinct group of lizard-like creatures called varanopids, relatives of the earliest ancestors of mammals or reptiles. The authors identified the disease in an isolated pair of tail vertebrae discovered in an Early Permian cave at Richards Spur, Oklahoma. Micro-CT scanning allowed examination of both the external and internal structure of the elements, revealing that in some places the bone had been thinned by abnormally high levels of reabsorption, while in other areas excessive bone growth had resulted in abnormal bone thickening and the ultimate fusion of the two vertebrae.

According to the researchers, this condition is most similar to Paget's disease, a bone metabolic disorder marked by a breakdown in communication between bone building cells and bone destroying cells. Paget's disease is commonly seen today in the hips and vertebrae of humans and has been diagnosed in other living mammals and reptiles as well as one Early Jurassic dinosaur fossil. The disease has been linked to both genetic and viral factors, though its precise cause remains controversial.

With only two vertebrae preserved, it is impossible to say how widespread the disease was in this animal's body. If it was restricted to the tail, the animal may only have suffered minor pain and stiffness. This discovery marks the oldest known occurrence of a Paget-like disease and suggests that susceptibility to such disorders was already present in our early Permian cousins.

Haridy adds: "Paleopathology is the study of ancient diseases, here we scanned a pair of fused tail bones from a permian (280 million years ago) Varanopid (a superficially-lizard like animal), what we found was evidence of a bone disease similar to modern day Paget's disease. This enigmatic disease is still not well understood in humans, however finding something similar in an ancient animal likely links it to something deep in our bone biology. This study is a great example of how when palaeontologists have well preserved fossils we can tell a lot more than just what animals were present, we can explore their biology, physiology and even what diseases ailed them!"

Credit: 
PLOS

How much energy storage costs must fall to reach renewable energy's full potential

The cost of energy storage will be critical in determining how much renewable energy can contribute to the decarbonization of electricity. But how far must energy storage costs fall? In a study published August 7 in the journal Joule, MIT researchers answer this question. They quantify cost targets for storage technologies to enable solar and wind energy with storage to reach competitiveness with other on-demand energy sources. They also examine what kinds of batteries and other technologies might reach these targets.

"One of the core sources of uncertainty in the debate about how much renewable energy can contribute to the deep decarbonization of electricity is the question of how much energy storage can be improved" says senior author Jessika Trancik, an associate professor of energy studies at the Massachusetts Institute of Technology. "Different assumptions about the cost of energy storage underlie significant disagreements between a number of assessments, but little was known about what costs would actually be competitive and how these costs compare to the storage technologies currently being developed. So, we decided to address this issue head on."

"Quantifying cost targets for energy storage required a new piece of insight," Trancik says, 'about how patterns of the renewable energy supply, and fluctuations in this supply, compare to electricity demand profiles. Large but infrequent solar and wind shortage events are critical in determining how much storage is needed for renewables to reliably meet demand, and it's important to understand the characteristics of these events."

In the paper, Trancik and her colleagues estimated the costs of using storage together with wind and solar energy to supply various output profiles reliably over twenty years. They then estimated cost targets for energy storage that would enable plants to reach cost-competitiveness with traditional electricity sources. They also evaluated current and future energy storage technologies against the estimated cost target.

The researchers' model optimizes storage costs by using whatever combination of storage and solar and wind gives the lowest electricity cost. This often means oversizing solar and wind capacity relative to an intended output, to decrease the amount of storage needed.

The analysis also explored the characteristics that distinguish various storage options. Some technologies are more suited to inexpensively storing large quantities of energies but outputting it slowly, at lower power, while others can cost-effectively store smaller amounts that can be quickly discharged at high power. So the model needed to capture these differences, Trancik says.

The research found that technologies with energy storage capacity costs below $20/kWh could enable cost-competitive baseload power that is available all of the time over a twenty-year period, though this target varies with the target output profile and location. They found that electricity costs respond more to costs of storage energy capacity than power capacity.

The research showed that "it's critical to reduce the costs of the materials and manufacturing that contribute to the cost of the storage energy capacity," Trancik says. "The numerical target we estimate, which varies with location, could mean a 90 percent drop in storage costs relative to today's technologies. It's a large drop but some technologies do tend to improve a lot, as we've seen in the case of solar panels, for example."

"However, and importantly, there is another factor that could raise this target considerably and allow more expensive technologies to cost-competitively store renewable energy, which is to use supplemental technologies for a small percent of the time," Trancik says. Allowing the renewable energy system to fail to meet demand for just five percent of the hours over a twenty year period can halve the cost of renewable electricity, the researchers report.

"The trick there is to figure out how to supply electricity for the remaining 5% hours. That's where we need to focus our efforts. This could potentially be accomplished with supplemental generation technologies, or perhaps demand-side management," Trancik says. Expanding the electricity transmission grid could also help mitigate renewable energy supply fluctuations, she says.

The team is exploring options for low-cost and low-carbon supplemental technologies. They are also working to model how certain research directions and economies of scale can help drive down the costs of battery technologies.

Credit: 
Cell Press

Why so fly: MU scientists discover some fruit flies learn better than others

image: Patricka Williams-Simon, a doctoral fellow in biological sciences at MU who led the study, places fruit flies into a box to study how well they learn and remember. She and the team discovered some fruit flies learn better than others.

Image: 
University of Missouri

Fruit flies could one day provide new avenues to discover additional genes that contribute to a person's ability to learn and remember. Scientists at the University of Missouri are studying genes of fruit flies to explore why an individual fly can be a better learner than another. Many of those genes in fruit flies are similar to those found in people.

Past experiments studying how fruit flies' ability to learn and remember have involved "turning off" a single gene and watching the response. In this study, the scientists took a different approach by placing fruit flies in a box equipped with heating elements. When the heat was turned on, the flies -- uncomfortable in heat -- moved to the far side of the box where it was cooler. A fly's ability to avoid the heat measured how well it learned, and a fly's ability to avoid the hotter side of the box, even when the heat was off, measured its capacity to remember.

"Some flies learn fast and remember to stay away from the heat whereas some flies take longer to figure it out," said Patricka Williams-Simon, a doctoral fellow in biological sciences who led the study. "We repeated the experiment with over 40,000 individual fruit flies from over 700 different genes to establish variation in performance. Then, we focused on the high and the low learning and memory performers."

The scientists then took these results and applied genetic sequencing technology to determine if specific genes were responsible for these observed changes in a fly's behavior. They found nine genes that show a change between high and low performing files when it comes to learning and memory.

"All of these genes are previously known to affect the nervous system or the brain in some way, but none of them had previously been implicated in learning and memory," said Elizabeth King, an assistant professor of biological sciences in the MU College of Arts and Science. "Therefore, they represent novel areas to further investigate these behavioral traits."

While the study is considered basic research, Williams-Simon said their findings are important.

"The better we can understand these traits in fruit flies, the more we can develop targeted studies in humans," Williams-Simon said.

Credit: 
University of Missouri-Columbia

New 'liquid biopsy' blood test improves breast cancer diagnostics

image: Muhammed Murtaza, M.B.B.S., Ph.D., Assistant Professor and Co-Director of TGen's Center for Noninvasive Diagnostics. He also holds a joint appointment on the Research Faculty at Mayo Clinic in Arizona, and is one of the study's senior authors.

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Courtesy of TGen

PHOENIX, Ariz. -- Aug. 7, 2019 -- A new type of blood test for breast cancer could help avoid thousands of unnecessary surgeries and otherwise precisely monitor disease progression, according to a study led by the Translational Genomics Research Institute (TGen) and Mayo Clinic in Arizona.

TGen is an affiliate of City of Hope, which along with The Cancer Research UK Cambridge Institute at Cambridge University and the Biodesign Institute at Arizona State University (ASU) also contributed to this study.

Published today in the premier journal Science Translational Medicine, the study suggests that the test called TARDIS -- TARgeted DIgital Sequencing -- is as much as 100 times more sensitive than other blood-based cancer monitoring tests.

TARDIS is a "liquid biopsy" that specifically identifies and quantifies small fragments of cancer DNA circulating in the patient's bloodstream, known as circulating tumor DNA (ctDNA). According to the study, TARDIS detected ctDNA in as low as 2 parts per 100,000 in patient blood.

"By precisely measuring ctDNA, this test can detect the presence of residual cancer, and inform physicians if cancer has been successfully eradicated by treatment," said Muhammed Murtaza, M.B.B.S., Ph.D., Assistant Professor and Co-Director of TGen's Center for Noninvasive Diagnostics. He also holds a joint appointment on the Research Faculty at Mayo Clinic in Arizona, and is one of the study's senior authors.

For example, Dr. Murtaza explained, TARDIS is precise enough to tell if early stage breast cancer patients have responded well to pre-operative drug therapy. It is more sensitive than the current method of determining response to drug therapy using imaging.

"This has enormous implications for women with breast cancer. This test could help plan the timing and extent of surgical resection and radiation therapy after patients have received pre-operative therapy," said Dr. Barbara A. Pockaj, M.D., a surgical oncologist who specializes in breast and melanoma cancer patients at Mayo Clinic in Arizona, and is the study's other senior author. Dr. Pockaj is the Michael M. Eisenberg professor of surgery and the chair of the Breast Cancer Interest Group (BIG), a collaboration between researchers at Mayo, TGen and ASU.

Unlike traditional biopsies, which only produce results from one place at one time, liquid biopsies use a simple blood draw, and so could safely be performed repeatedly, as often as needed, to detect a patient's disease status.

This study was performed in collaboration with Carlos Caldas, M.D., Professor of Cancer Medicine at the University of Cambridge and Director of the Breast Cancer Programme at the Cancer Research UK Cambridge Cancer Centre.

"TARDIS is a game changer for response monitoring and residual disease detection in early breast cancer treated with curative intent. The sensitivity and specificity of patient-specific TARDIS panels will allow us to tell very early, probably after one cycle, whether neo-adjuvant (before surgery) therapy is working and will also enable detecting micro-metastatic disease and risk-adapted treatment after completing neo-adjuvant therapy," said Dr. Caldas, who also is Senior Group Leader at the Cancer Research UK Cambridge Institute, and one of the study's contributing authors.

Following further clinical testing and trials, TARDIS could someday be routinely used for monitoring patients during cancer treatment, and discovering when patients are essentially cured and cancer free.

"The results of these tests could be used to individualize cancer therapy avoiding overtreatment in some cases and under treatment in others," Dr. Murtaza said. "The central premise of our research is whether we can develop a blood test that can tell patients who have been completely cured apart from patients who have residual disease. We wondered whether we can see clearance of ctDNA from blood in patients who respond well to pre-surgical treatment."

Current tests and imaging lack the sensitivity needed to make this determination.

"Fragments of ctDNA shed into blood by tumors carry the same cancer-specific mutations as the tumor cells, giving us a way to measure the tumor," said Bradon McDonald, a computational scientist in Dr. Murtaza's lab, and the study's first author.

"The problem is that ctDNA levels can be so low in non-metastatic cancer patients, there are often just not enough fragments of ctDNA in a single blood sample to reliably detect any one mutation. This is especially true in the residual disease setting, when there is no obvious tumor left during or after treatment," McDonald said. "So, instead of focusing on a single mutation from every patient, we decided to integrate the results of dozens of mutations from each patient."

The study results suggest that personalized ctDNA analysis, using TARDIS, is a promising approach to identifying patients with a curative response following pre-surgical drug therapy.

"Together with imaging and tissue-based predictive biomarkers, ctDNA is rapidly becoming a useful diagnostic test to determine individualized decisions about additional treatment," Dr. Murtaza said.

Dr. Pockaj affirmed: "We are excited that TARDIS has the potential to really individualize clinical management of patients with non-metastatic cancer."

Thomas Slavin, M.D., Assistant Clinical Professor at City of Hope National Medical Center, and a contributing author of the study, noted that "reliably identifying, often multiple, circulating tumor mutations in the plasma of patients with non-metastatic breast cancer also holds promise that ctDNA may one day be a great tool for early breast cancer detection."

TGen is now focused on evaluating the best partners to work with to automate and scale TARDIS, so it can be made available broadly to benefit patients in need.

"This data represents an exciting strategy to improve the sensitivities of liquid biopsies, which have been challenging for breast cancer," said Karen Anderson, M.D., Ph.D., a researcher at the Biodesign Institute, a medical oncologist at Mayo Clinic in Arizona, and one of the study's contributing authors. "This work represents highly collaborative efforts across multiple institutions, and with the generosity and foresight of our patients who have contributed to this study."

Credit: 
The Translational Genomics Research Institute

Looking out for the little guys

image: A new study, undertaken by a team of scientists from BIOS, the Bermuda Government Department of Environment and Natural Resources, and the University of Rhode Island, used DNA markers to characterize the genetic diversity of Bermuda's baitfish populations. The island's baitfish, as seen here in a large assemblage referred to as a "bait ball," were shown to exist in highly mixed populations of up to six different species.

Image: 
Joanna Pitt

Small fishes play an important role in the marine food chain, providing food for larger fishes and water birds, but they are also caught for use as bait in both commercial and recreational fisheries. Over the past thirty years, a decline has been noted in some species of baitfish, leading scientists and resource managers to look more closely at the population dynamics of these important fish. However, baitfish tend to congregate in large schools containing multiple species, making it difficult to study individual populations.

In 2017, a team of researchers, with funding from a Darwin Plus grant through the United Kingdom's Department of Environment, Food and Rural Affairs (DEFRA), set out to characterize Bermuda's baitfish populations, with the goal of providing data to improve the management of these species. Currently, regulations are in place that restrict the size of nets that may be used to catch baitfish, while net fishing is prohibited altogether in four inshore bays around the island: Coot Pond, Whalebone Bay, and Shelly Bay in the east end, and Somerset Long Bay in the west end. However, one important question remaining for the research team was whether similar protected bays need to be more evenly distributed around the island.

Gretchen Goodbody-Gringley, a coral reef ecologist at BIOS, and Joanna Pitt, marine resources officer for the Bermuda Government Department of Environment and Natural Resources, led the project, which also included Emma Strand, a former BIOS Research Experiences for Undergraduates (REU) student and a current doctoral student at the University of Rhode Island. Their findings were recently published as a paper in the peer-reviewed scientific journal PeerJ.

"Baitfish depend on shallow inshore areas that are often modified and threatened by a variety of human activities, such as overfishing, pollution, and coastal development," Strand said. "It's important to understand the composition of baitfish assemblages and the distribution of the various species around the island."

During June and July of 2017, the team collected baitfish from ten locations around Bermuda, including both the east and west ends and north and south shores. Using physical characteristics, they identified five of the most common baitfish species in Bermuda: the reef silverside (Hypoatherina harringtonensis), the Bermuda anchovy (Anchoa choerostoma), the dwarf herring (Jenkinsia lamprotaenia), the red ear herring (Harengula humeralis), and the round sardinella or Spanish sardine (Sardinella aurita).

DNA samples were extracted from the muscle of the collected fish and then sequenced, allowing the researchers to look at the genetic makeup of the baitfish populations. The team looked at specific DNA markers found in mitochondria, which are the parts of a cell responsible for converting food into energy. Analysis of mitochondrial DNA helps shed light on how genetically diverse each fish species is at the local level, as well as how genetically connected (or similar) Bermuda's local populations are to populations elsewhere. It also serves as a method for confirming the initial identification of each species, which increases the accuracy of the results.

Based on these genetic analyses, the team realized that the samples included a sixth species, the Atlantic thread, or threadfin, herring (Opisthonema oglinum), highlighting the importance of conducting DNA analyses when characterizing multispecies baitfish assemblages.

"For all six of the species we examined, our results showed a high degree of genetic diversity both within and between baitfish assemblages from different locations around Bermuda," Goodbody-Gringley said. "This tells us that, in terms of management, we should consider Bermuda's baitfish species as highly mixed populations in which individuals from all around the island contribute to a single gene pool."

However, the results also indicated that gene flow, and therefore exchange of individuals, between populations of these species in Bermuda and those in other regions of the Caribbean and Western Atlantic is limited, suggesting that the Bermuda populations are largely locally maintained. From a management perspective, this means that local baitfish populations are not likely to be replenished from populations in the Caribbean or other areas of the Tropical West Atlantic.

"As a resource manager, it's important to be able to balance the ecological sustainability of baitfish populations and their role in commercial and recreational fishing," Pitt said. "In practical terms, these two pieces of information mean that we need to work to conserve our baitfish stocks, but that we don't need to worry about the exact placement of protected areas."

She added that studies such as this demonstrate the value of population genetics for informing and adapting fishery management measures.

Credit: 
Bermuda Institute of Ocean Sciences

Cancer in the oldest old: The fastest growing age group in the US

A new report looks at cancer in adults 85 and older and finds incidence and mortality trends are generally similar to those in people 65 to 84, but screening is unexpectedly high and survival is poorer. The report appears in the American Cancer Society journal, CA: A Cancer Journal for Clinicians.

Adults aged 85 years and older - the "oldest old" - are the fastest-growing age group in the United States, yet relatively little is known about their cancer burden. To learn more, American Cancer Society investigators led by Carol DeSantis, MPH, and supported by leading geriatric oncology experts from City of Hope, University of Rochester Medical Center, and Duke University Medical Center, analyzed data from the National Cancer Institute, the North American Association of Central Cancer Registries, and the National Center for Health Statistics to provide comprehensive information on cancer occurrence in this population.

In 2019, there will be approximately 140,690 cancer cases diagnosed and 103,250 cancer deaths among the 85 and older population in the United States. The most common cancers in these individuals -lung, breast, prostate, and colorectum--are the same as those in the general population. Overall cancer incidence rates peaked in the oldest men and women around 1990 and have subsequently declined, with the pace accelerating during the past decade. This progress reflects declines in cancers of the prostate and colorectum, and more recently lung among men and breast among women.

Among men 85 and older, prostate and lung cancers are the most common causes of cancer death, accounting for 40% of cancer deaths. Among women, lung cancer is the leading cause of cancer death (19%) followed by breast cancer (13%). For men and women, colorectal cancer is the third leading cause of cancer death, representing 9% and 12% of cancer deaths, respectively, in this population.

The authors also note that patients aged 85 years and older are less likely to be diagnosed at an early stage compared to those aged 65 to 84. For example, 57% of breast cancers in the oldest old are diagnosed at a local stage versus 68% in patients 65-84 years; for prostate cancer it is 41% compared to 77%, respectively. Late stage at diagnosis among the oldest old partly reflects less screening, which is generally not recommended for those aged 85 years and older because of diminished life expectancy, the higher prevalence of other serious medical conditions, and limited evidence of survival benefit. For most individuals in this age group, the small potential benefit of extending life is outweighed by the possible harms from screening, which increase with age.

Despite these recommendations, data from the National Health Interview Survey indicate unexpectedly high rates of screening in adults aged 85 years and older. In 2015, more than one-third of women aged 85 years and older reported receiving a mammogram within the previous two years, and 18% reported receiving recent cervical cancer screening tests. More than one-half of adults aged 85 years and older reported receiving either a stool screening test within the past year or a sigmoidoscopy or colonoscopy within the past five to ten years. Nearly 30% of men in this age group reported receiving a PSA test within the past year.

People 85 and over are also less likely to receive surgical treatment; only 65% of breast cancer patients aged 85 years and older received surgery compared with 89% of those aged 65 to 84 years. This difference partly reflects the complexities of treating older patients, including the presence of multiple comorbidities, functional declines, and cognitive impairment, but also highlights potential undertreatment of otherwise fit older adults. Overtreatment of vulnerable individuals in this age group is also a concern. The authors note that, importantly, age alone does not predict life expectancy, physical function, or the ability to tolerate treatment and provide information about tools to enable clinicians to evaluate the functional age of patients as part of the treatment decision-making process.

"More research on cancer in the oldest Americans is needed to improve outcomes and anticipate the complex health care needs of this rapidly-growing population," write the authors. "The rapid growth and diversification of the population aged 85 years and older will increase demand and complexities for cancer care and could have a substantial impact on medical care resource allocation. There is an urgent need to develop a more comprehensive evidence base to guide treatment decisions for these understudied patients with cancer through increased enrollment in clinical trials and to leverage research designs and infrastructure for generating evidence on older adults with cancer."

Credit: 
American Cancer Society

A marine microbe could play increasingly important role in regulating climate

A USC-led research team has found that marine microbes with a special metabolism are ubiquitous and could play an important role in how Earth regulates climate.

The study finds bacteria containing rhodopsins, a sunshine-grabbing pigment, are more abundant than once thought. Unlike algae, they don't pull carbon dioxide (CO2) out of the air. And they will likely become more abundant in warming oceans, signaling a shuffling of microbial communities at the base of the food chain where the nitty-gritty work of energy conversion occurs.

"Oceans are important for climate change because they play a key role in the carbon cycle. Understanding how that works, and the marine organisms involved, helps us refine our climate models to predict climate in the future," said Laura Gómez-Consarnau, assistant professor (research) of biology at the USC Dornsife College of Letters, Arts and Sciences.

The study appears today in Science Advances. Gómez-Consarnau is the lead author among an international team of scientists from California, China, the United Kingdom and Spain.

The findings break from the traditional interpretation of marine ecology found in textbooks, which states that nearly all sunlight in the ocean is captured by chlorophyll in algae. Instead, rhodopsin-equipped bacteria function like hybrid cars, powered by organic matter when available -- as most bacteria are -- and by sunlight when nutrients are scarce.

Rhodopsins were discovered 20 years ago, and scientists at USC and elsewhere have been studying their prevalence and metabolism since. These microbes have light-sensitive protein systems in their cell membranes that trap sunlight, an adaptation analogous to how rods and cones in the human eye gather light.

In this study, researchers trolled a 3,000-mile-long swath of the eastern Atlantic Ocean and Mediterranean Sea in 2014. They sampled microorganisms in the water column down to 200 meters in an attempt to find how widespread rhodopsins are and in what conditions they are favored.

They found that rhodopsin photosystems were much more abundant than previously realized and concentrated in nutrient-poor waters. In such oligotrophic zones, they outperform algae at capturing light. While algae use sunlight and CO2 to produce organic material and oxygen, rhodopsin pigments use light to make adenosine triphosphate, the basic energy currency that drives many cellular processes.

"Rhodopsins appear to be more abundant in a nutrient-poor ocean, and in the future, the ocean will be more nutrient poor as temperatures change," Gómez-Consarnau explained. "So, with fewer nutrients near the surface, algae will have limited photosynthesis, and the rhodopsin process will be more abundant. We may have a shift in the future, which means the ocean won't be able to absorb as much carbon as it does today. So more CO2 gas may remain in the atmosphere, and the planet may warm faster."

So far, computer simulations of what global warming could be like in the future do not yet account for this microbial shift.

Previous studies have shown rhodopsins comprise about 80% of the marine bacteria, based on genetic analyses. But this is the first study to actually measure their concentration in the ocean and where they like to congregate.

The study underscores how scientists are learning new pathways by which organisms gain energy to live. For example, they've long known that plants and algae use chlorophyll to convert sunshine and nutrients into sugars; indeed, about half of all photosynthesis on Earth is performed by algae at the ocean surface. And they've discovered bottom-dwelling life supported by chemical energy from minerals and chemical compounds released from deep-ocean volcanic vents. In this research, they've learned that bacteria, long considered mainly decomposers in an ecosystem, can actually function as a main producer of energy at the ocean surface.

"We estimate that, given the concentrations found in seawater, rhodopsins could capture more light energy than chlorophyll in the ocean," Gómez-Consarnau said.

"These findings change the fundamental assumption that the marine biosphere is only powered by sunlight captured by chlorophylls during algal photosynthesis."

It also means that, years in the future, microbial communities will likely shift, resulting in less carbon fixation in the ocean. To fully evaluate how the findings affect the ocean's capacity to absorb greenhouse gases, Gómez-Consarnau said CO2 fluxes in marine systems will need to be reevaluated and future climate models will have to include this bacterial metabolism.

Credit: 
University of Southern California