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The University of Rochester research lab that recently used lasers to create unsinkable metallic structures has now demonstrated how the same technology could be used to create highly efficient solar power generators.

In a paper in Light: Science & Applications, the lab of Chunlei Guo, professor of optics also affiliated with Physics and the Material Sciences Program, describes using powerful femto-second laser pulses to etch metal surfaces with nanoscale structures that selectively absorb light only at the solar wavelengths, but not elsewhere.

A regular metal surface is shiny and highly reflective. Years ago, the Guo lab developed a black metal technology that turned shiny metals pitch black. "But to make a perfect solar absorber," Guo says, "We need more than a black metal and the result is this selective absorber."

This surface not only enhances the energy absorption from sunlight, but also reduces heat dissipation at other wavelengths, in effect, "making a perfect metallic solar absorber for the first time," Guo says. "We also demonstrate solar energy harnessing with a thermal electric generator device."

"This will be useful for any thermal solar energy absorber or harvesting device," particularly in places with abundant sunlight, he adds.

The work was funded by the Bill and Melinda Gates Foundation, the Army Research Office, and the National Science Foundation.

The researchers experimented with aluminum, copper, steel, and tungsten, and found that tungsten, commonly used as a thermal solar absorber, had the highest solar absorption efficiency when treated with the new nanoscale structures. This improved the efficiency of thermal electrical generation by 130 percent compared to untreated tungsten.

Co-authors include Sohail Jalil, Bo Lai, Mohamed Elkabbash, Jihua Zhang, Erik M. Garcell, and Subhash Singh of the Guo lab.

The lab has also used the femto-second laser etching technology to create superhydrophobic (water repellent) and superhydrophilic (water-attracting) metals. In November 2019, for example, Guo's lab reported creating metallic structures that do not sink no matter how often they are forced into water or how much it is damaged or punctured.

This new paper, however, expands upon the lab's initial work with femto-second laser etched black metal.

Prior to creating the water attracting and repellent metals, Guo and his assistant, Anatoliy Vorobyev, demonstrated the use of femto-second laser pulses to turn almost any metal pitch black. The surface structures created on the metal were incredibly effective at capturing incoming radiation, such as light. But they captured light over a broad range of wavelengths.

Subsequently, his team used a similar process to change the color of a range of metals to various colors, such as blue, golden, and gray, in addition to the black already achieved. The applications could include making color filters and optical spectral devices, a car factory using a single laser to produce cars of different colors; etching a full-color photograph of a family into the refrigerator door; or proposing with a gold engagement ring that matches the color of your fiancee's blue eyes.

The lab also used the initial black and colored metal technique to create a unique array of nano- and micro-scale structures on the surface of a regular tungsten filament, enabling a light bulb to glow more brightly at the same energy usage.

"We fired the laser beam right through the glass of the bulb and altered a patch on the filament. When we lit the bulb, we could actually see this one patch was clearly brighter than the rest of the filament," Guo said.

Pathogens such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and recently the novel coronavirus in Wuhan, China (2019-nCoV) have been a global threat. Lymph nodes (LNs) fight against infectious diseases by providing a shelter for immune cells to grow and launch an attack against pathogens. However, LNs' particular inner workings are poorly understood.

Scientists led by KOH Gou Young at the Center for Vascular Research, within the Institute for Basic Science (IBS), with collaborators of the Korea Advanced Institute of Science and Technology (KAIST), South Korea, have found that a chain of chemical reactions, known as the Hippo-YAP/TAZ signaling pathway, that plays a dominant role in the formation and maintenance of LNs. Their findings have been reported in the journal Nature Communications.

One of the key components of LNs are fibroblastic reticular cells (FRCs), which form LN's basic infrastructure and trigger immune responses by releasing cytokines, which are proteins important for immunity. Functional FRCs form during LN's development: a poorly defined population of mesenchymal cells differentiate into FRC precursors, which further develop into mature FRCs with immune functions. Whereas the molecular details involved in the latter process, such as lymphotoxin-β receptor (LTβR) signaling, have been thoroughly described, the details of the commitment steps of FRC development are still unclear.

The research team confirmed the importance of the Hippo pathway - a key regulator of cellular proliferation and organ size control - in FRCs' maturation. The researchers used more than 20 different genetically modified mouse models to characterize the Hippo pathway at specific time points, depleting the proteins YAP/TAZ at various stages of FRC development.

"As I witnessed the enriched expression of YAP/TAZ in fibroblastic reticular cells of lymph nodes, I knew there must be a role of the Hippo pathway in FRCs," says CHOI Sung Yong, first co-author of this study.

By performing a careful examination of the mice's LNs, the team found that FRCs transform into fat cells when YAP/TAZ are reduced in FRC precursors.

BAE Hosung, first co-author of this study, explains, "It was like a mathematic equation, when we drew out the findings on the blackboard, we were sure that depleting YAP/TAZ in fibroblastic reticular cell precursors would show an effect on the lymph nodes."

The researchers found that YAP/TAZ binding to p52 is required for maintaining FRC identity. JEONG Sun-Hye, first co-author of this study, notes, "I had this basic instinct that YAP/TAZ should bind with key components that regulate fibroblastic reticular cell identity, such as p52."

Future research will focus on determining whether diseases or conditions that affect systemic immune responses can be linked to alterations in the Hippo signaling pathway in FRCs, and whether modulating Hippo signaling within FRCs could serve as a viable therapeutic option. Beyond their importance in the immune response against flu, FRCs have recently gained considerable recognition for their role in cancer progression and patient outcome. The degree of stromal fibrosis within metastatic LNs is an important prognostic factor that significantly affects disease-free survival of cancer patients. "It definitely warrants more extensive investigation of fibroblastic reticular cells in patients with tumor lymph node metastases prior to clinical investigation," adds Koh.

CORVALLIS, Ore. -- Proposed hydropower dams in Gabon pose a substantial threat to the African nation's most culturally and economically important fishes, according to a new study.

The study, published today in the journal Ecosphere, is the first of its kind to predict the distribution of fishes throughout central African freshwaters by linking museum records to ecological data. That synthesis allowed the study's authors to infer how the nearly 40 dams planned for construction in Gabon might affect its many fish species.

Many of the culturally and economically important fish species in Gabon move from the ocean into rivers, with some known to swim up to 250 miles upstream into pure freshwaters.

Gabon has some of the world's most pristine unimpeded river systems and high freshwater biodiversity. The proposed dams will block access to much of the freshwater habitat that is also suitable for marine species and will impact at least 350 fish species, said Brian Sidlauskas, study co-author and associate professor at Oregon State University.

"Our modeling found that particularly in Gabon's second-largest river, the Nyanga, dam development could cut marine fishes off from 60% of the most suitable freshwater habitats, representing 392 river kilometers," Sidlauskas said.

Previous research shows that freshwater ecosystems are among the most imperiled in the world and approximately 20% of the assessed freshwater fishes are threatened with extinction, and that dams are causing major shifts in species distribution and abundance, including extinctions.

There are three free-flowing rivers at least 500 kilometers in length in Gabon: the Ivindo, the Nyanga, which is currently undammed, and the Ogooué. While the 38 proposed dams in Gabon, including 28 in the Ogooué watershed, can increase energy production, they would fragment and alter relatively pristine river systems, according to the study co-authors.

Potentially impacted fish species include the Giant African threadfin, snappers, croakers, bonga shad, mullets, Atlantic tarpon and tongue soles. Though these fishes are known to enter rivers regularly as adults or as juveniles, most of the 38 potential dam sites have never been scientifically surveyed for their presence, and no previous formal studies of fish movement within Gabon's freshwater ecosystems had been conducted.

For their study, researchers at OSU and University of California, Santa Cruz, compiled records for fresh and brackish water fishes of Gabon and Equatorial Guinea from three databases, and grouped them by guilds. An ecological guild is any group of species that exploits the same resources, or that exploit different resources in similar ways.

The research team used a geographic information system to record river data to create two connectivity scenarios: one under existing dams and one with the proposed dams.

The model used guild data, which included traits and prevalence; topography, including tree canopy cover, waterfalls or steep changes in elevation, and other hydrological information.

The model predicted marine-associated fishes had a high likelihood of occupying the Nyanga and its major tributaries and much of the Ogooué's main channel, as well as portions of its major tributaries.

Construction of all the proposed dams might lead to a loss of access to 7% of highly suitable habitats, or 466 stream kilometers. These losses were largest on the Nyanga, Ogooué, Mvoung, Lolo, Komo and Okano rivers.

EUGENE, Ore. - Feb. 6, 2020 - The prehistoric collapse of Easter Island's monument-building society did not occur as long thought, according to a fresh look at evidence by researchers at four institutions.

"The general thinking has been that the society that Europeans saw when they first showed up was one that had collapsed," said Robert J. DiNapoli, a doctoral candidate in the University of Oregon's Department of Anthropology who led the analysis. "Our conclusion is that monument-building and investment were still important parts of their lives when these visitors arrived."

Easter Island, a Chilean territory also known as Rapa Nui, is located about 3,000 kilometers (1,864 miles) from South America and 2,000 kilometers (1,242 miles) from any other inhabited island.

Rapa Nui is believed to have been settled in the 13th century by Polynesian seafarers. They soon began building massive stone platforms stacked with megalithic statues and large, cylindrical stone hats that were used for cultural and religious rituals, including burial and cremation. A widely-held narrative is that monument construction stopped around 1600 after a major societal collapse.

In the new research, detailed online ahead of print in the Journal of Archaeological Science, DiNapoli's team presents a chronology for the statue platform construction by integrating existing radiocarbon dates with the order of assembly required to build the monuments and the written records of Dutch, Spanish and English seafarers who began arriving in 1722.

Taken together, DiNapoli said, the integration of data, using Bayesian statistics, brings clarity to radiocarbon-dating at various sites. Rapa Nui islanders, the researchers concluded, continued to build, maintain and use the monuments for at least 150 years beyond 1600.

The project began as part of DiNapoli's dissertation, which is focused on the process of building the monuments' architecture. Looking at 11 sites, the researchers examined the necessary sequence of construction, beginning with building a central platform and then adding different structures and statues.

That helped make sense of differing radiocarbon dates found at various excavation sites. Monument construction, according to the team, began soon after initial Polynesian settlement and increased rapidly, sometime between the early 14th and mid-15th centuries, with a steady rate of construction events that continued well beyond the hypothesized collapse and the European arrival.

When the Dutch arrived in 1722, their written observations reported that the monuments were in use for rituals and showed no evidence for societal decay. The same was reported in 1770, when Spanish seafarers landed on the island.

"Their stays were short and their descriptions brief and limited," DiNapoli said. "But they provide useful information to help us think about the timing of building and using these structures as part of their cultural and religious lives."

However, when British explorer James Cook arrived four years later, in 1774, he and his crew described an island in crisis, with overturned monuments.

"The way we interpret our results and this sequence of historical accounts is that the notion of a pre-European collapse of monument construction is no longer supported," DiNapoli said.

"Once Europeans arrive on the island, there are many documented tragic events due to disease, murder, slave raiding and other conflicts," said co-author Carl Lipo, an anthropologist at Binghamton University in New York.

"These events are entirely extrinsic to the islanders and have, undoubtedly, devastating effects. Yet, the Rapa Nui people - following practices that provided them great stability and success over hundreds of years - continue their traditions in the face of tremendous odds," he said. "The degree to which their cultural heritage was passed on - and is still present today through language, arts and cultural practices - is quite notable and impressive. I think this degree of resilience has been overlooked due to the collapse narrative and deserves recognition."

The approach developed for the research, which was funded by the National Science Foundation, may be useful for testing hypotheses of societal collapse at other complex sites around the world where similar debates on timing exist, the researchers noted.

Strawberry-flavored mousse tastes 10% sweeter when served from a white container rather than a black one. Coffee tastes nearly twice as intense when it is drunk from a white mug rather than a clear glass one. Adding two-and-a-half ounces to the weight of a plastic yogurt container makes the yogurt seem about 25% more filling.

Now, Adriana Madzharov, a sensory marketing researcher and assistant professor at Stevens Institute of Technology, shows that when high self-control individuals touch food directly with their hands (vs. indirectly with a utensil), they not only experience it as tastier and more satisfying, but they eat more of it. The work, published in the Dec. 19 issue of the Journal of Retailing, may not only offer a way to increase the appeal of food but also offers retailers a simple way to make the eating experience more enjoyable for consumers sampling food.

"It's an interesting effect," said Madzharov. "It's such a small tweak but it can change how people evaluate your product. "

In her first experiment, Madzharov had 45 undergraduate students visually inspect and evaluate a cube of Muenster cheese, hold it before eating it and then asked them to answer questions about their eating behavior. Half of the participants sampled a cheese cube with an appetizer pick on it and the other half sampled a cheese cube without a pick. Initially, the two groups - direct touch and indirect touch - did not indicate any difference between the cheese with and without the pick before eating it.

Madzharov found that participants who reported a high degree of self-control when consuming food - individuals who report that they can resist tasty foods and are conscious about what and how much they eat - perceived the cheese as tastier and more appetizing after they ate it. However, that finding did not hold true for individuals who report a low degree of self-control when consuming food.

"These two groups do not appear to process sensory information in the same way," said Madzharov. "Our results suggest that for people who regularly control their food consumption, direct touch triggers an enhanced sensory response, making food more desirable and appealing."

Even when Madzharov manipulated participants' thinking on self-control, goals and food consumption, these findings persisted, suggesting that a high degree of self-control influences how people experience food when they touch it directly with their hands - whether self-control is real or primed.

In this second experiment, Madzharov separated a new set of 145 undergraduate students into two groups. The first group was told to imagine that they had decided to be more careful with their diet and cut back on excessive eating in order to achieve their long-term objective of being fit and healthy. The second, that they had decided to worry less about their weight all the time and allow themselves to indulge in tasty foods more often in order to enjoy life and experience its pleasures.

All participants were given a plastic cup with four mini donuts inside it - half with appetizer picks and half without picks. As in the first experiment, the participants were then asked to visually inspect and evaluate the mini donuts on hedonistic qualities such as texture, freshness, quality and nutrition. She also instructed them to report their level of focus and attention when eating the mini donuts to get a measure of mindfulness and sensory experience.

Madzharov found that when participants were primed with self-control (vs. indulgent) thinking, they evaluated the sampled food more positively when they touched it directly with their hands. It also suggests that the mechanism driving this effect was the enhanced sensory experience that participants reported in the direct touch/self-control condition.

Past research has explored, for example, how the weight and texture of containers and cups influence how people evaluate food of beverage, and has confirmed that tactile input from cues external to the food is important. However, this is the first time that direct touch of food has been evaluated as a way to influence how people experience food, and possibly drive consumer behavior.

Two years ago, Madzharov also found that just the scent of coffee, which has no caffeine in it, appears to boost performance in math.

In the run-up to the 2016 U.S. presidential election, an unusual experiment suggested that it might be possible to influence American voters to adopt less polarized positions.

Posing as political researchers, a research team from McGill and Lund Universities approached 136 voters at the first Donald Trump and Hilary Clinton presidential debate in New York. Participants were asked to compare Trump and Clinton on various leadership traits (such as courage, vision, and analytic skills) by putting an X on a sliding scale.

Using a simple magic trick, the researchers then covertly manipulated the results (by substituting one completed survey sheet for another) so that most of the survey answers appeared moderate, closer to the midpoint between Trump and Clinton. They then presented these more moderate responses to the participants as being their own answers.

Willingness to accept and explain more moderate opinions

Surprisingly, 94 % of the respondents accepted the manipulated responses as being their own answers and readily justified the moderate views. For example, one participant who initially heavily favoured Trump claimed, "I guess I fall somewhere in the middle -- I'd like to think I'm a little moderate. I think at this point it's important to be open-minded" -- even though they had reported more polarized views moments earlier.

The researchers then replicated this study online with nearly 500 participants and found no difference in the results between Clinton and Trump supporters. The majority of the participants were again susceptible to the manipulation and rationalized their ostensibly moderate responses. Afterwards, to ensure that it did not affect the participants' attitudes in the longer term, the researchers debriefed them and explained the manipulation.

"Political surveys try to capture the attitudes of the public, but our study demonstrates that these can be heavily manipulated," said Jay Olson, co-author on the research paper that will be published this week in PLOS ONE. "By making people believe that they wrote down different responses moments earlier, we were able to make them endorse and express less polarized political views. These results offer hope in a divided political climate: even polarized people can become -- at least momentarily -- open to opposing views."

PHILADELPHIA -- Every dollar spent on patients receiving support from Penn Medicine's community health worker (CHW) program resulted in an annual return on investment (ROI) of $2.47 for every dollar invested annually by Medicaid, according to a new study published online today in Health Affairs. The savings are generated by reducing hospitalizations.

Developed at Penn, IMPaCT (Individualized Management for Patient-Centered Targets) addresses unmet social needs such as housing and food insecurity and transportation needs in underserved populations with the goal of improving health. The evidence-based program hires and trains trusted neighborhood residents to become CHWs who carry out culturally appropriate outreach activities, social support, patient advocacy, and health system navigation.

"Within a Medicaid population, we now know that investing in our communities with this type of robust and personalized social support not only adds meaningful health value but also meaningful financial value," said senior author Shreya Kangovi, MD, MSHP, founding executive director of the Penn Center for Community Health Workers and developer of the IMPaCT program. "These results paint a more realistic picture of the return on investment from a community health worker program that past studies haven't accurately shown."

The findings provide the latest round of evidence for state Medicaid programs or health systems looking to invest in proven community health worker programs to improve health and lower health care costs.

The study is the first economic analysis of a health system-based community health worker intervention for adults that used data from a randomized controlled trial. Past economic studies, have either not been rigorous enough or exaggerated savings because the reductions in spending were not attributable to an intervention but rather to random variation, or regression to the mean.

The researchers analyzed inpatient and outpatient costs on 302 patients (150 randomly assigned to the intervention arm and 152 to the control arm) who were treated within the University of Pennsylvania Health System between July 2013 and October 2014, along with the return on investment for a team of six IMPaCT CHWs. The patients were insured by Medicaid or uninsured, residents of high-poverty neighborhoods, and had been diagnosed with at least two chronic diseases (diabetes, obesity, tobacco dependence, or hypertension).

The intervention arm had both fewer and lower cost admissions, with a total inpatient cost of $2.3 million compared with $3.7 million in the control arm. Overall, the intervention arm had 149.6 hospital admissions per CHW team, while the control arm had 212.7 admissions per CHW team.

When outpatient costs were factored in, the total cost of care was $2.5 million for the intervention arm and $3.9 million for the control arm. Thus, the intervention resulted in a 38 percent reduction in cost. Overall, the team of community health workers saved Medicaid $1.4 million over one year. This savings divided by program expenses which fund salaries for CHWs, supervisors, transportation, rent, etc. (about $568,000) yielded a return of $2.47 for every dollar invested.

CHWs from IMPaCT meet with patients regularly to encourage healthier behaviors, and otherwise provide support for the patients' own health goals by addressing social determinants of health. That can include helping them identify and purchase healthy food, connecting them with recreational activities such as urban gardening or simply being a shoulder to lean on.

Importantly, while some community health worker programs focus on patients more likely to incur high costs, IMPaCT casts a wider net to capture patients with not only frequent hospitalizations, for instance, but also other measures, such as patients with chronic diseases who never go to the hospital.

"This proves that even when applied to a broader population, IMPaCT still provided a significant return on investment," Kangovi said. "What's more, the return on investment underestimates the true social return."

The randomized controlled trial not only demonstrated financial ROI, but also improved quality of care, and modest improvements in cigarette smoking, obesity, diabetes severity, and mental health. Two other randomized controlled trials of IMPaCT from Penn Medicine researchers over the past several years have similarly demonstrated its benefit. A 2014 study of hospitalized patients demonstrated improved mental health, quality of care and lower recurrent admissions. A recent multi-center randomized trial found that IMPaCT reduced hospital stays by 65 percent and doubled the rate of patient satisfaction with primary care.

IMPaCT has served more than 12,000 patients in the Philadelphia region, including hundreds of veterans at the Corporal Michael J. Crescenz VA Medical Center. In the last three years, IMPaCT has become the most widely disseminated community health worker program in the United States; it is being replicated by organizations across 18 different states including Veterans Health Administration, state Medicaid programs; integrated healthcare organizations and even retailers such as Walmart.

Penn co-authors of the study include Nandita Mitra, David Grande, Judith A. Long, and David A. Ash.

ADELPHI, Md. (Feb. 5, 2020) - Scientists are closer to understanding exactly what happens inside batteries that make them prone to fire, thanks to a molecular eye of sorts.

Scientists at the U.S. Army Combat Capabilities Development Command's Army Research Laboratory teamed with researchers from the U.S. Department of Energy's Pacific Northwest National Laboratory to study chemical reactions that occur when two key components of battery interface, forming a critical component in battery commonly known as the solid-electrolyte-interphase, or SEI.

Understanding the chemistry and formation mechanism of this SEI holds the key to unlocking future better batteries, reseachers said. This new research, enabled by a technique that serves as a molecular eye, presents a dynamic picture of the chemistry and structure of SEI.

These properties are known to influence the battery charge-discharge rate, especially at low temperature, safety and cycle life, according to Army scientist Dr. Oleg Borodin, a researcher with a team focusing on electrochemistry.

"SEIs are critical for battery properties but elusive to characterize," said Dr. Kang Xu, a principal investigator on this research project. "They dictate how fast a battery could be charged for Warfighters in order to improve operational capabilities as well as preventing slow and abrupt battery failure during mission. But like dark matters, everyone knows they exist but no one knows how they work."

Nearly four years ago, ARL scientists began collaborating with experts "who are not battery people," Xu said, but have unique expertise in advanced characterization techniques. He said Army researchers laid down the basic challenges faced in understanding SEIs, and asked for help. This collaboration resulted in a series of groundbreaking work in SEI, and some of the results have already been published in Nature Chemistry and Nature Nanotechnology in 2018 and 2019.

Their latest work is featured in the article, Real-time mass spectrometric characterization of the solid-electrolyte interphase of a lithium-ion battery, published in the Jan. 27, 2020, Nature Nanotechnology, a peer-reviewed scientific journal.

Scientists from the Environmental Molecular Sciences Laboratory and Pacific Northwest National Laboratory developed this technique, an in situ liquid secondary ion mass spectrometry and partnered with Army scientists to apply this technique on investigating the chemical workings at the electrode-electrolyte interface on a molecular level when the battery was charged in its first hour. They monitored the formation of the SEI and its chemistry variation. The approach allowed them to map the chemical reactions as they occurred. When combined with molecular dynamics simulations, their work revealed something that had only been speculated before.

During initial battery charging, the battery forms an electric double layer at the electrode/electrolyte interface. The creation of this double layer leads to fine structural and chemical variations of SEI, which will eventually dictate the performance of battery itself. The molecular-level understanding of the interface could serve as insightful guide to Army scientists' efforts in designing better batteries.

These researchers find that before any interphasial chemistry occurs (during the initial charging), an electric double layer forms at the electrode/electrolyte interface due to the self-assembly of solvent molecules. The formation of the double layer is directed by Li+ and the electrode surface potential. The structure of this double layer predicts the eventual interphasial chemistry; in particular, the negatively charged electrode surface repels salt anions from the inner layer and results in an inner SEI that is thin, dense and inorganic in nature. It is this dense layer that is responsible for conducting Li+ and insulating electrons, the main functions of the SEI. An electrolyte-permeable and organic-rich outer layer appears after the formation of the inner layer. In the presence of a highly concentrated, fluoride-rich electrolyte, the inner SEI layer has an elevated concentration of LiF due to the presence of anions in the double layer. These real-time nanoscale observations will be helpful in engineering better interphases for future batteries.

For decades, scientists tried to study the SEIs in lithium-ion batteries, with limited success due to the absence of a technique that would allow them to see battery operations at a tiny scale. Such nanoscale observations on a molecular level are needed to understand the chemistry at the interface.

In 2017, Army researchers partnerd with the University of Maryland developed for the first time a lithium-ion battery that uses a water-salt solution as its electrolyte and reaches the 4.0 volt mark desired for household electronics, such as laptop computers, without the fire and explosive risks associated with some commercially available non-aqueous lithium-ion batteries. The majority of commerically-available batteries are different from the aqueous batteries invented by this team. Understanding the SEI could lead to incrementally improving current technology as an immediate solution for many Army applications.

Scientists have found a way to distinguish between two progressive neurodegenerative diseases, Parkinson's disease (PD) and multiple system atrophy (MSA), using a technology developed by a researcher at The University of Texas Health Science Center at Houston (UTHealth). The discovery was published today in Nature.

It is challenging to distinguish between the two diseases because the early signs are similar - disturbances in movement, tremors, uncontrollable movements during sleep, impaired speech, etc. - but the diseases progress differently and can require distinct treatment plans.

PD leads to shaking, stiffness, and difficulty with balance and movement as well as a host of nonmotor symptoms. MSA leads to similar motor impairment, and also earlier and more severe dysfunction of the autonomic nervous system, which controls involuntary actions such as blood pressure, digestion, and urination. MSA progresses quicker and is often mistaken for PD at first.

"It is important for physicians to have an objective way to differentiate between PD and MSA in order to provide patients with the best care. Currently, the only way to differentiate them is to wait and see how the disease progresses, with MSA advancing much more rapidly than PD," said Claudio Soto, PhD, a professor in the Department of Neurology at McGovern Medical School at UTHealth and senior author of the Nature paper. "By the time people show progressed symptoms of MSA, a substantial amount of brain cells are already damaged or dead, and they can't be brought back. It has been difficult to develop treatment for both diseases because of the high rates of misdiagnosis, so we needed to find a way to distinguish between the two at the onset of early symptoms."

Both diseases are characterized by deposits of a protein known as alpha-synuclein (aSyn) in the nervous system. This protein can become corrupted and start to change shape in a process called misfolding. These misfolded proteins will start to clump together and poison the surrounding healthy nerve cells that are responsible for brain functioning, particularly for motor skills.

"The formation of these misfolded clumps will happen for many years, even decades, before enough damage is caused for a person to start showing signs of motor impairment," said Soto, who is also the director of the George and Cynthia Mitchell Center for Research in Alzheimer's Disease and Related Brain Disorders.

Using Protein Misfolding Cyclic Amplification (PMCA) technology developed by Soto that was shown in previous studies to detect misfolded proteins associated with diseases such as Creutzfeldt-Jakob and Alzheimer's disease, researchers targeted misfolded aSyn aggregates as a way of developing a sensitive biochemical diagnosis for PD. Researchers put a small amount of the proteins in question from the patient's cerebrospinal fluid together with normal proteins and watched to see if and how they converted the normal proteins.

Soto's latest research in Nature shows that the aSyn-PMCA can successfully discriminate between PD and MSA with an overall sensitivity of 95.4%, which could allow doctors a look into the future to see which disease they need to address. The study also helps to understand the basis of these diseases at the molecular basis.

"Our latest research shows that the aSyn aggregates of PD and MSA have different properties, so by amplifying the abnormal aggregates we can detect with high efficiency which disease the patient has," Soto said. "This has huge implications both for accurate diagnosis and clinical care of the patient, and the development of new specific treatments for both diseases."

Since cerebrospinal fluid is collected through spinal taps, which are invasive and painful, the hope is that future research would enable optimization of the PMCA test to detect aSyn in blood or urine.

"I envision a world without these diseases, but the only way to achieve that is to couple early diagnosis with good and safe treatment. That means we have to detect the abnormal proteins before they produce diseases and use safe treatment so no one ever develops the disease. Many diseases like smallpox, diphtheria, or polio have been eliminated by scientific advances - I hope the same will happen with devastating brain diseases, like Alzheimer's or Parkinson's," Soto said.

The research was funded in part by grants from The Michael J. Fox Foundation for Parkinson's Research (MJFF) and the National Institute on Aging.

"Objective diagnosis of Parkinson's and MSA - and differential diagnosis between the two - would be game-changing for the many patients and families searching for answers when issues arise and, potentially, would help develop, test, and prescribe early interventions to stop disease before symptoms begin," said Luis Oliveira, PhD, MJFF associate director of research programs. "Our foundation is proud to support this important research."

A prehistoric human skeleton found on the Yucatán Peninsula in southern Mexico is at least 10,000 years old and most likely dates from the end of the most recent ice age, the late Pleistocene. An international research team led by geoscientists from Heidelberg University studied the remains of the approximately 30-year-old woman. The uranium-thorium dating technique was used to determine the age of the fossil record, which provides important clues on the early settlement history of the American continent.

The skeleton was discovered near the city of Tulúm in the Chan Hol cave, which is now water-filled as the result of global warming and sea-level rise approximately 8,000 years ago. Nine other prehistoric skeletons had already been discovered in this intricate submerged cave system near the coast in the eastern part of the peninsula. According to Prof. Dr Wolfgang Stinnesbeck, the leader of the research team, not all of the ten skeletons were complete, but they were well preserved. They offer valuable archaeological, palaeontological and climatic information about the American continent and its first inhabitants, the Paleoindians. The Tulúm skeletons exhibit round-headed - mesocephalic - cranial characteristics different to the long-headed - dolicocephalic - morphology of Paleoindians from Central Mexico and North America, explains Prof. Stinnesbeck, who teaches and conducts research at the Institute of Earth Sciences of Heidelberg University.

To the researchers, the head shape is an indication that two morphologically different groups of Paleoindians must have lived in America at the same time. They may have reached the American continent from different geographical points of origin. Or a small group of early settlers may have been living in isolation on the Yucatán Peninsula and developed a different skull morphology over a short period of time. Prof. Dr Silvia Gonzalez and Dr Sam Rennie, both from Liverpool John Moores University (Great Britain), suggest that the early settlement history of the Americas is therefore more complicated and may date back earlier than commonly believed.

The woman's remains were recovered by Mexican divers Vicente Fito and Iván Hernández and then documented. She was approximately 30 years old at the time of her death. Her skull had multiple injuries, but they may not have been the cause of death. The researchers also discovered signs of a potential treponemal bacterial infection that caused severe alteration of the cranial bones. Like the other Tulúm skeletons, the woman's teeth had cavities, possibly due to a diet high in sugar. In contrast, the teeth of most Paleoindian skeletons from Central Mexico and North American are worn down and cavity-free, suggesting they ate hard food.

To precisely date the find, the researchers used a dating method from physics based on the radioactive decay of uranium and its conversion into thorium. The researchers dated the uranium-thorium isotopes of a lime crust that had grown on the finger bones in the originally dry Chan Hol cave. Prof. Dr Norbert Franck and his team from the Institute of Environmental Physics of Heidelberg University were able to give the skeleton a minimum age of 9,900 years. However, the body was then already skeletonised and the prehistoric find may be older.

In 2017, Wolfgang Stinnesbeck and his team of researchers had already documented another human skeleton from Chan Hol cave, which was then considered to be 13,000 years old based on a stalagmite that had grown on its hip bone. For the researchers, these bone finds prove the unexpectedly early settlement of southern Mexico. Scientists from Germany, Great Britain, and Mexico took part in the research, which was funded by the German Research Foundation (DFG) and the German Federal Ministry of Education and Research (BMBF). The results of the research were published in the journal "PLOS ONE".

RIVERSIDE, Calif. -- An international team of astronomers led by scientists at the University of California, Riverside, has found an unusual monster galaxy that existed about 12 billion years ago, when the universe was only 1.8 billion years old.

Dubbed XMM-2599, the galaxy formed stars at a high rate and then died. Why it suddenly stopped forming stars is unclear.

"Even before the universe was 2 billion years old, XMM-2599 had already formed a mass of more than 300 billion suns, making it an ultramassive galaxy," said Benjamin Forrest, a postdoctoral researcher in the UC Riverside Department of Physics and Astronomy and the study's lead author. "More remarkably, we show that XMM-2599 formed most of its stars in a huge frenzy when the universe was less than 1 billion years old, and then became inactive by the time the universe was only 1.8 billion years old."

The team used spectroscopic observations from the W. M. Keck Observatory's powerful Multi-Object Spectrograph for Infrared Exploration, or MOSFIRE, to make detailed measurements of XMM-2599 and precisely quantify its distance.

Study results appear in the Astrophysical Journal.

"In this epoch, very few galaxies have stopped forming stars, and none are as massive as XMM-2599," said Gillian Wilson, a professor of physics and astronomy at UCR in whose lab Forrest works.  "The mere existence of ultramassive galaxies like XMM-2599 proves quite a challenge to numerical models. Even though such massive galaxies are incredibly rare at this epoch, the models do predict them. The predicted galaxies, however, are expected to be actively forming stars. What makes XMM-2599 so interesting, unusual, and surprising is that it is no longer forming stars, perhaps because it stopped getting fuel or its black hole began to turn on. Our results call for changes in how models turn off star formation in early galaxies."

The research team found XMM-2599 formed more than 1,000 solar masses a year in stars at its peak of activity -- an extremely high rate of star formation. In contrast, the Milky Way forms about one new star a year.

"XMM-2599 may be a descendant of a population of highly star-forming dusty galaxies in the very early universe that new infrared telescopes have recently discovered," said Danilo Marchesini, an associate professor of astronomy at Tufts University and a co-author on the study.

The evolutionary pathway of XMM-2599 is unclear.

"We have caught XMM-2599 in its inactive phase," Wilson said. "We do not know what it will turn into by the present day. We know it cannot lose mass. An interesting question is what happens around it. As time goes by, could it gravitationally attract nearby star-forming galaxies and become a bright city of galaxies?"

Co-author Michael Cooper, a professor of astronomy at UC Irvine, said this outcome is a strong possibility.

"Perhaps during the following 11.7 billion years of cosmic history, XMM-2599 will become the central member of one of the brightest and most massive clusters of galaxies in the local universe," he said. "Alternatively, it could continue to exist in isolation. Or we could have a scenario that lies between these two outcomes."

The team has been awarded more time at the Keck Observatory to follow up on unanswered questions prompted by XMM-2599.

"We identified XMM-2599 as an interesting candidate with imaging alone," said co-author Marianna Annunziatella, a postdoctoral researcher at Tufts University. "We used Keck to better characterize and confirm its nature and help us understand how monster galaxies form and die. MOSFIRE is one of the most efficient and effective instruments in the world for conducting this type of research."

What The Study Did: An economic evaluation of 3.3 million drug insurance claims looked at whether implementing reference pricing was associated with physicians and patients adjusting to using the least expensive alternative within a drug class.

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

Authors: James C. Robinson, Ph.D., University of California, Berkeley, School of Public Health, is the corresponding author.

(10.1001/jamanetworkopen.2019.20544)

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

An international team has completed the most comprehensive study of whole cancer genomes to date, significantly improving our fundamental understanding of cancer and signposting new directions for its diagnosis and treatment.

Published today in Nature, more than 700 researchers have analysed more than 2600 samples from 38 cancer types ranging from common cancers like colorectal and breast cancers, to rare cancer types including pancreatic and brain cancers.

This analysis has enabled researchers to create the first complete atlas of genomes to compare the cancers and find the common mutations between them.

The atlas has been created by an effort known as PCAWG - the Pan Cancer Analysis of Whole Genomes or the Pan-Cancer Project - which has been a collaborative effort of groups from the International Cancer Genome Consortium who agreed to put thousands of sets of patient genome data together and reanalyse these samples using cloud computing.

University of Melbourne Professor Sean Grimmond, who holds the Bertalli Chair in Cancer Medicine, led the Australian efforts which contributed approximately 10 per cent of primary samples from a broad range of tumours including pancreatic, melanoma, neuroendocrine, and ovarian cancer.

Researchers found on average any given tumour has four to five key mutations - changes to the genetic blueprint - that are responsible for driving that disease. Those mutations can vary a great deal for each cancer type.

Previously researchers were aware of one or two drivers. Researchers say understanding that number and realising the complexity in each patient is an important step in working out where else to look when diagnosing cancer patients.

Professor Grimmond said this atlas provides a solid foundation to understand which genes and which pathways may be damaged in each cancer type.

"This research will help identify what types of genetic test are needed for each cancer type - filling in potential existing gaps that we did not even know were there," Professor Grimmond said.

"It demonstrates better than ever before how similar damage can cause cancer in different tissues - implications mean that for example a breast cancer drug could be effectively used to treat an oesophageal cancer."

The atlas also provides insight for challenging cancers where the tissue of origin is not known by identifying patterns of damage across various cancer types.

"If we don't understand where a cancer comes from, we can't even rely on traditional clinical approaches to treatment," Professor Grimmond said.

Having a harmonised dataset enables international researchers to learn from one cancer treatment and applies those findings to another using a cloud computing portal.

Researchers say further research with much larger datasets are required to enable precision medicine to truly become a reality.

Dr Peter Campbell, member of the Pan-Cancer Project steering committee and Head of Cancer, Ageing and Somatic Mutation at the Wellcome Sanger Institute in the UK said: "This work is helping to answer a long-standing medical difficulty, why two patients with what appear to be the same cancer can have very different outcomes to the same drug treatment. We show that the reasons for these different behaviours are written in the DNA. The genome of each patient's cancer is unique, but there are a finite set of recurring patterns, so with large enough studies we can identify all these patterns to optimize diagnosis and treatment."

Dr Tom Hudson, Chief Scientific Officer at AbbVie and a founder of the International Cancer Genome Consortium said: "The completion of this project represents the culmination of more than a decade of ground-breaking work in studying the cancer genome. When we launched ICGC in 2007, an initiative of this magnitude was unprecedented. I am thrilled that the scientific community has come together to produce this comprehensive study, which enhances our understanding of cancer and fosters the development of new medicines for cancer patients."

The Australian research groups involved include the University of Melbourne, Peter MacCallum Cancer Centre, QIMR Berghofer, Garvin Institute, University of Queensland, and Melanoma Institute of Australia.

To gain an infinite lifespan, cancer cells need to maintain the ends of their chromosomes, known as telomeres. They achieve this in various different ways. Scientists from the German Cancer Research Center systematically investigated more than 2,500 tumor genomes of 36 types of cancer to find out how these mechanisms are manifest in changes in the DNA. Active lengthening of the telomeres is one of the hallmarks of all cancer cells and hence an important focus in developing targeted treatments. The study is part of the Pan-Cancer Analysis of Whole Genomes (PCAWG).

Healthy body cells have a natural expiry date defined by the length of their telomeres. Telomeres are part of DNA and protect the end of the chromosomes. They become shorter each time the cell divides, however, until a minimum length is reached - the telomere has then been used up so to speak. Stem cells are the only type of cells to produce the 'immortality enzyme' telomerase, which can lengthen the telomeres again. All other cells stop dividing after around 50 cycles.

Cancer cells depend on intact telomeres for unlimited cell division. Earlier studies showed that around 85 percent of all tumors upregulate telomerase via different mechanisms. The remaining tumors use alternative mechanisms to lengthen telomeres.

A team of researchers led by Lars Feuerbach from the German Cancer Research Center (DKFZ) studied more than 2,500 tumor samples to gain a better understanding of these mechanisms, in particular those that have not been well researched to date. The study is part of the Pan-Cancer Analysis of Whole Genomes (PCAWG).

The PCAWG researchers found DNA mutations that point to one of the two known mechanisms of telomere lengthening in only 13 percent of the cases studied. As lead author Lina Sieverling explained, "In the vast majority of the 2,500 cancer cases studied, we observed increased activity of the telomerase gene but without any changes in the genome that could explain this. Epigenetic factors that do not leave any trace in the genome might be partly responsible here."

Of the 13 percent of those tumors whose DNA showed indications of telomere lengthening, only 64 cases pointed to the alternative mechanisms. The researchers discovered two peculiarities in these tumors: Telomeres usually consist of hundreds of repetitions of the same sequence of six DNA bases. In the telomeres with alternative lengthening mechanisms, however, variations of the normal telomere sequences are often found. Moreover, small fragments of the telomeres are very often integrated into other parts of the genome in these tumor cells.

In certain types of cancer, particularly in children, one of the factors that determine the aggressiveness of the tumor is known to be the mechanism by which the telomeres of the cancer cells are lengthened. This is the case in medulloblastomas, for example, which carry a worse prognosis if the cancer cells use the alternative mechanism.

"At the moment, we cannot tell whether and, if so, in what way these two findings are important or whether they affect the course of disease in cancer patients," principal investigator Lars Feuerbach explained. "Active lengthening of the telomeres is one of the weak points in all cancer cells and hence an important focus in developing targeted treatments," he added. "To do so, a precise knowledge of all the underlying molecular processes is vital."

Micro-organisms in the gut support healthy digestion by helping nerve cells within the intestine to regulate the contraction and relaxation of the muscle wall of the colon, according to new research from the Crick and Bern University.

The study, published in Nature, identified how the contraction and relaxation of muscles in the colon, which is regulated by nerve cells and is needed to push food along, is influenced by the bacteria resident in our gut. When such microbes are present, a specific gene called Ahr is activated in intestinal nerves, resulting in healthy contraction and relaxation of the colon (peristalsis). This relationship can be disrupted in cases of intestinal disorders, like irritable bowel syndrome (IBS).

"There is a clear link between the presence of microbes in the colon and the speed at which food moves through the system. If this relationship goes off-kilter it could cause considerable harm," says Yuuki Obata, lead author and postdoc in the Development and Homeostasis of the Nervous System Laboratory at the Crick.

A healthy gut contains trillions of microorganisms which help the digestion of food and promote the fitness of gut tissues, such as the epithelial lining of the lumen and the vast collection of immune and nerve cells within the gut wall. The levels and types of microorganisms in the gut vary from person to person and are affected by diet and commonly used drugs, such as antibiotics, which often result in abnormal gut contractions. The work described in this paper helps us understand how nerve cells sense the microbes in the gut and how they could coordinate their function with other gut tissues.

"Disturbances of intestinal motility are extremely common and cause a lot of suffering in patients after surgical operations or in conditions such as irritable bowel syndrome. This work provides a foundation to unravel why patients that are colonised with different groups of microbes are susceptible to these intestinal problems", explains Andrew Macpherson, Professor of Medicine and Director of Gastroenterology at the University Hospital of Bern.

"By drawing on different teams at the Crick and internationally with Bern University, we've combined expertise on the gut and how environmental signals from microbiota and diet are passed to cells, to gain understanding of how gut physiology and digestion are affected by these signals," says Brigitta Stockinger, co-lead author and group leader in the AhRimmunity Laboratory at the Crick.

"While it's been well-documented that the micro-organisms in our gut influence the function of many organs in our body, including the brain, there's less understanding about the role they play in maintaining the healthy functioning of the millions of nerve cells within digestive system itself. The work we describe here shows that AhR, a molecule which is very important for the function of immune and epithelial cells in the gut, is also used by intestinal nerve cells to sense the presence of microbes and regulate peristalsis, and in doing so, promote healthy digestion," says Vassilis Pachnis, co-lead author and group leader in the Development and Homeostasis of the Nervous System Laboratory at the Crick.

"In the future, the use of microbial products that change the activity of AhR in nerve cells could help us alleviate the consequences of abnormal gut peristalsis that is often associated with gastrointestinal diseases," continues Vassilis.