Tag: Science

Astronomers discover unusual monster galaxy in the very early universe

Photo by Suzy Hazelwood on Pexels.com

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.”

Help with Heavy Menstrual Bleeding

In women with uterine fibroids, the drug elagolix suppresses ovarian hormone production and prevents heavy menstrual bleeding

About 50 % of women with uterine fibroids—non-cancerous muscle tumors that grow in the uterus—experience heavy menstrual bleeding and other symptoms.  Surgery is commonly recommended when these symptoms are severe enough to prompt a woman to seek treatment.  The most common surgery used to treat fibroids is removal of the uterus (hysterectomy), though in some cases, removal of the fibroids and repair of the uterus (myomectomy) are performed.  Surgery is usually extensive in both cases.  Long-acting hormone injections can reduce symptoms such as heavy bleeding in women with fibroids, but side effects can be significant and it can take months for the effects of the medications to wear off.

In a study published in the New England Journal of Medicine on January 23, 2020, researchers reported on the effectiveness of a new, rapidly reversible oral pill that was used to reduce heavy menstrual bleeding in women with uterine fibroids. The study, which included a large group of researchers from across the country, was led by Dr. William Schlaff, Chair of the Department of Obstetrics and Gynecology at the Sidney Kimmel Medical College at Thomas Jefferson University.

A total of 790 women, ages 18-51, with heavy bleeding due to fibroids, were enrolled into one of three study arms. One group received the oral pill, elagolix, which reduces the production of the hormones estrogen and progesterone normally produced by a woman’s ovaries.  When these hormones are suppressed, fibroids usually get smaller and bleeding is reduced.  A second group received elagolix plus a low dose of estrogen and progestin (“add-back” therapy) with the hope that the additional hormones would produce the same benefit but reduce the side effects of elagolix used alone (like hot flushes and bone loss).  A third group received identical placebo pills that did not contain elagolix or the “add back” hormones.  All of the women enrolled in the two identical trials reported by these researchers were confirmed to have uterine fibroids by ultrasound and heavy menstrual bleeding (more than 80mLs of blood loss per cycle) for at least two cycles. 

The results showed that 80.4% of the women treated with elagolix alone had a reduction of menstrual bleeding of 50% or more compared to 9.6% of the women in the placebo group.  Of those women treated with elagolix plus “add back” therapy, 72% had a reduction of 50% or more.  Women treated with elagolix alone had significantly more loss of bone mineral as compared with the women treated with placebo, a known and clinically significant side effect of this class of medications.  However, there was no difference between the loss of bone mineral in the group treated with elagolix and “add-back” as compared to those in the placebo group. 

For many women with fibroids, severe symptoms like bleeding have a major impact on the quality of life.  Surgery and long-acting injectable medications are acceptable treatments for many, but certainly not all women in this situation. 

“The potential value of an oral, easily reversible medication that can be combined with low-dose hormonal “add back” to reduce heavy menstrual bleeding while avoiding problematic symptoms and side effects could be a major step forward,” says Dr. Schlaff.

AbbVie Inc. funded these studies and participated in the study design, research, analysis, data collection, interpretation of data, reviewing and approval of the publication. Consult article reference for complete list of disclosures.

Article reference: William Schlaff et al., “Elagolix Therapy for Heavy Menstrual Bleeding in Women with Uterine Fibroids,” New England Journal of Medicine, DOI: 10.1056/NEJMoa1904351, 2019.

Rethinking interactions with mental health patients

Credit: Pixabay

New research overturns the belief that people with severe mental illness are incapable of effective communication with their psychiatrist, and are able to work together with them to achieve better outcomes for themselves.

“Interviews are a critical part of assessing people suffering from thought disorder (TD), and deciding what the best therapy is for them,” says Professor Cherrie Galletly from the Adelaide Medical School, University of Adelaide.

“Clinical interactions with people suffering with severe mental illness can be challenging, especially if the patient has disordered communication.”

Published in the journal Australian Psychiatry the study analysed 24 routine clinical interviews between psychiatrists and inpatients, with a mean age of just under 30 years, who were suffering from TD.

“The study, the first of its kind, examined the expertise with which psychiatrists conducted clinical interviews of people suffering from TD, and the shared goals that were accomplished,” says Professor Galletly.

“When interviewing people with TD psychiatrists need to adopt a mindset that the information the patient provides in that particular moment is, for them, meaningful, truthful, relevant and clear.

“They have to piece together snippets of information in order to create and interpret meaning and build respectful relationships by inviting patients to share their perspectives no matter how disordered or delusional their responses appear.”

Thought disorder is common in psychotic disorders. The thoughts and conversation of people suffering from TD appear illogical and lacking in sequence and may be delusional or bizarre in content.

In 2010, 0.3% of Australians aged 18-64 years, had a psychotic illness with men aged 25-34 experiencing the highest rates (0.5%) of illness.

“Patients are positioned as active participants by psychiatrists who adopt a non-confrontational, non-judgemental approach, conveying support and safety, and ask open ended questions which allows the patient to engage, feel listened to, and work with the psychiatrist to achieve a shared understanding,” says Professor Galletly.

“Findings from this study of sample interviews between psychiatrists and their patients highlight the need to rethink the notion that patients experiencing TD are incapable of communicating productively with the people trying to help them.

“Psychiatrists use transactional, relational and interactional techniques when they are talking to patients with thought disorder, which go beyond techniques normally employed in clinical interviews.

“Experienced psychiatrists undertake meaningful interviews with these patients, who in turn respond in ways that belie the notion that effective communication is not possible.

“The findings from this research can be used to develop training resources for clinicians who work with people with psychotic disorders.”

Dinosaur Embryos

Eggs Took 3 to 6 Months to Hatch

Research on the teeth of fossilized dinosaur embryos indicates that the eggs of non-avian dinosaurs took a long time to hatch–between about three and six months. The study, led by scientists at Florida State University, the American Museum of Natural History, and the University of Calgary, was published today in the Proceedings of the National Academy of Sciences and finds that contrary to previous assumptions, dinosaur incubation is more similar to that of typical reptiles than of birds. The work suggests that prolonged incubation may have affected dinosaurs’ ability to compete with more rapidly generating populations of birds, reptiles, and mammals following the mass extinction event that occurred 65 million years ago.

Credit: © AMNH/M. Ellison
This is a photo of a hatchling Protoceratops andrewsi fossil from the Gobi Desert Ukhaa Tolgod, Mongolia.

“We know very little about dinosaur embryology, yet it relates to so many aspects of development, life history, and evolution,” said study co-author Mark Norell, Macaulay Curator of Paleontology at the American Museum of Natural History. “But with the help of advanced tools like CT scanners and high-resolution microscopy, we’re making discoveries that we couldn’t have imagined 20 years ago. This work is a great example of how new technology and new ideas can be brought to old problems.”

Because birds are living dinosaurs, scientists have long assumed that the duration of dinosaur incubation was similar to birds, whose eggs hatch within 11 to 85 days. The research team tested this theory by looking at the fossilized teeth of two extremely well-preserved ornithischian dinosaur embryos on each end of the size spectrum: Protoceratops–a pig-sized dinosaur found by Norell and colleagues in the Mongolian Gobi Desert, whose eggs were quite small at 194 grams, or a little less than half of a pound–and Hypacrosaurus, a very large duck-billed dinosaur found in Alberta, Canada, with eggs weighing more than 4 kilograms, or nearly 9 pounds. First, the researchers scanned the embryonic jaws of the two dinosaurs with computed tomography (CT) at the Museum’s Microscopy and Imaging Facility to visualize the forming dentitions. Then they used an advanced microscope to look for and analyze the pattern of “von Ebner” lines–growth lines that are present in the teeth of all animals, humans included. This study marks the first time that these growth lines have been identified in dinosaur embryos.

“These are the lines that are laid down when any animal’s teeth develops,” said lead author and Florida State University professor Gregory Erickson. “They’re kind of like tree rings, but they’re put down daily. And so we could literally count them to see how long each dinosaur had been developing.”

Using this method, the scientists determined that the Protoceratops embryos were about three months old when they died and the Hypacrosaurus embryos were about six months old. This places non-avian dinosaur incubation more in line with that of their reptilian cousins, whose eggs typically take twice as long as bird eggs to hatch–weeks to many months. The work implies that birds likely evolved more rapid incubation rates after they branched off from the rest of the dinosaurs. The authors note that the results might be quite different if they were able to analyze a more “bird-like” dinosaur, like Velociraptor. But unfortunately, very few fossilized dinosaur embryos have been discovered.

“A lot is known about growth in dinosaurs in their juvenile to adult years,” said co-author Darla Zelenitsky, from the University of Calgary. “Time within the egg is a crucial part of development with major biological ramifications, but is poorly understood because dinosaur embryos are rare.”

The study also has implications for dinosaur extinction. Prolonged incubation exposed non-avian dinosaur eggs and attending parents to predators, starvation, and environmental disruptions such as flooding. In addition, slower embryonic development might have put them at a disadvantage compared to other animals that survived the Cretaceous-Paleogene extinction event.

Florida State University graduate student David Kay also is an author on this paper.

This work was funded, in part, by the U.S. National Science Foundation, grant # EAR 0959029, the Macaulay Family, and the Natural Sciences and Engineering Research Council of Canada, grant # 327513-09.

AMERICAN MUSEUM OF NATURAL HISTORY (AMNH.ORG)

The American Museum of Natural History, founded in 1869, is one of the world’s preeminent scientific, educational, and cultural institutions. The Museum encompasses 45 permanent exhibition halls, including the Rose Center for Earth and Space and the Hayden Planetarium, as well as galleries for temporary exhibitions. It is home to the Theodore Roosevelt Memorial, New York State’s official memorial to its 33rd governor and the nation’s 26th president, and a tribute to Roosevelt’s enduring legacy of conservation. The Museum’s five active research divisions and three cross-disciplinary centers support approximately 200 scientists, whose work draws on a world-class permanent collection of more than 33 million specimens and artifacts, as well as specialized collections for frozen tissue and genomic and astrophysical data, and one of the largest natural history libraries in the world. Through its Richard Gilder Graduate School, it is the only American museum authorized to grant the Ph.D. degree and the Master of Arts in Teaching degree. Annual attendance has grown to approximately 5 million, and the Museum’s exhibitions and Space Shows can be seen in venues on five continents. The Museum’s website and collection of apps for mobile devices extend its collections, exhibitions, and educational programs to millions more beyond its walls. Visit amnh.org for more information.

Sweating People

Photo by Food Photographer | Jennifer Pallian

When people become stressed, their bodies can respond by sweating. Now, researchers at the University of Missouri are monitoring how much adolescents severely affected by autism sweat in order to better understand when behavioral issues, such as aggression, are likely to occur.

Bradley Ferguson analyzed the stress levels of eight adolescents who are severely affected by autism spectrum disorder at The Center for Discovery, a residential facility in New York that provides advanced care and research for individuals with complex conditions. Using wrist and ankle monitors, Ferguson found that there was a rise in the body’s electrodermal activity – which results from increased levels of sweat – 60% of the time before an individual showed behavioral issues.

“A spike in electrodermal activity is telling us that the individual’s body is reacting physiologically to something that is stressful, which could be their internal state, something in the environment, or a combination of the two,” said Ferguson, assistant research professor in the departments of health psychology, radiology and the Thompson Center for Autism and Neurodevelopmental Disorders. “If parents or caregivers are notified ahead of time that their child’s stress levels are rising, they might have a chance to intervene and de-escalate the situation before problem behaviors occur.”

Ferguson explained that possible intervention methods could include removing the child from the environment or activity that is causing the stress, as well as providing access to an item that the child enjoys interacting with in an effort to calm them.

“Individuals who are severely affected by autism spectrum disorder are often unable to verbally communicate their discomfort when they become stressed,” Ferguson said. “However, their body still responds to stressors just like anyone else. Therefore, being alerted of increases in electrodermal activity can allow parents and caregivers to intervene prior to engagement in problem behavior with the goal of ensuring the health and safety of those involved.”

Ferguson collaborated on the study with David Beversdorf, a professor of radiology, neurology and psychology in the MU College of Arts and Science as well as principal investigator of the Cognitive Neuroscience Laboratory in the MU School of Medicine. Ferguson also collaborated with Theresa Hamlin, Johanna Lantz, and Tania Villavicencio at The Center for Discovery, and John Coles at Calspan-University of Buffalo Research Center and The State University of New York at Buffalo.

“Important work is being done to try to identify predictors for when a person with autism is at greatest risk of having a behavioral episode,” Beversdorf said. “This research highlights the individual variability in this response that must be considered, and may also have implications for individualized treatment approaches moving forward.”

“Examining the association between electrodermal activity and problem behavior in severe autism spectrum disorder: A feasibility study,” was published in Frontiers in Psychiatry.

The study was funded by the New York State Center of Excellence, New York State Department of Health and Office for People with Developmental Disabilities, as well as private monies donated to The Center for Discovery. The content is solely the responsibilities of the authors and does not necessarily represent the official views of the funding agencies.

The Department of Health Psychology is in the MU School of Health Professions, and the Department of Radiology is in the MU School of Medicine.

Earliest Signs of Life

Scientists Find Microbial Remains in Ancient Rocks

Scientists have found exceptionally preserved microbial remains in some of Earth’s oldest rocks in Western Australia – a major advance in the field, offering clues for how life on Earth originated.

The UNSW researchers found the organic matter in stromatolites – fossilised microbial structures – from the ancient Dresser Formation in the Pilbara region of Western Australia.

The stromatolites have been thought to be of biogenic origin ever since they were discovered in the 1980s. However, despite strong textural evidence, that theory was unproven for nearly four decades, because scientists hadn’t been able to show the definitive presence of preserved organic matter remains – until today’s publication in prestigious journal Geology.

“This is an exciting discovery – for the first time, we’re able to show the world that these stromatolites are definitive evidence for the earliest life on Earth,” says lead researcher Dr Raphael Baumgartner, a research associate of the Australian Centre for Astrobiology in Professor Martin Van Kranendonk’s team at UNSW.

Professor Van Kranendonk says the discovery is the closest the team have come to a “smoking gun” to prove the existence of such ancient life.

“This represents a major advance in our knowledge of these rocks, in the science of early life investigations generally, and – more specifically – in the search for life on Mars. We now have a new target and new methodology to search for ancient life traces,” Professor Van Kranendonk says.

Drilling deep, looking closely

Ever since the Dresser Formation was discovered in the 1980, scientists have wondered whether the structures were truly microbial and therefore the earliest signs of life.

“Unfortunately, there is a climate of mistrust of textural biosignatures in the research community. Hence, the origin of the stromatolites in the Dresser Formation has been a hotly debated topic,” Dr Baumgartner says.

“In this study, I spent a lot of time in the lab, using micro-analytical techniques to look very closely at the rock samples, to prove our theory once and for all.”

Stromatolites in the Dresser Formation are usually sourced from the rock surface, and are therefore highly weathered. For this study, the scientists worked with samples that were taken from further down into the rock, below the weathering profile, where the stromatolites are exceptionally well preserved.

“Looking at drill core samples allowed us to look at a perfect snapshot of ancient microbial life,” Dr Baumgartner says.

Using a variety of cutting-edge micro-analytical tools and techniques – including high-powered electron microscopy, spectroscopy and isotope analysis – Dr Baumgartner analysed the rocks.

He found that the stromatolites are essentially composed of pyrite – a mineral also known as ‘fool’s gold’ – that contains organic matter.

“The organic matter that we found preserved within pyrite of the stromatolites is exciting – we’re looking at exceptionally preserved coherent filaments and strands that are typically remains of microbial biofilms,” Dr Baumgartner says.

The researchers say that such remains have never been observed before in the Dresser Formation, and that actually seeing the evidence down the microscope was incredibly exciting.

“I was pretty surprised – we never expected to find this level of evidence before I started this project. I remember the night at the electron microscope where I finally figured out that I was looking at biofilm remains. I think it was around 11pm when I had this ‘eureka’ moment, and I stayed until three or four o’clock in the morning, just imaging and imaging because I was so excited. I totally lost track of time,” Dr Baumgartner says.

Clues for search for life on Mars

Just over two years ago, Dr Baumgartner’s colleague Tara Djokic, a UNSW PhD candidate, found stromatolites in hot spring deposits in the same region in WA, pushing back the earliest known existence of microbial life on land by 580 million years.

“Tara’s main findings were these exceptional geyserite deposits that indicate that there have been geysers in this area, and therefore fluid expulsions on exposed land surface,” Dr Baumgartner says.

“Her study was focused on the broader geological setting of the paleo-environment – lending support to the theory that life originated on land, rather than in the ocean – whereas my study really went deeper on the finer details of the stromatolite structures from the area.”

The scientists say that both studies are helping us answer a central question: where did humanity come from?

“Understanding where life could have emerged is really important in order to understand our ancestry. And from there, it could help us understand where else life could have occurred – for example, where it was kick-started on other planets,” Dr Baumgartner says.

Just last month, NASA and European Space Agency (ESA) scientists spent as week in the Pilbara with Martin Van Kranendonk for specialist training in identifying signs of life in these same ancient rocks. It was the first time that Van Kranendonk shared the region’s insights with a dedicated team of Mars specialists – a group including the Heads of NASA and ESA Mars 2020 missions.

“It is deeply satisfying that Australia’s ancient rocks and our scientific know-how is making such a significant contribution to our search for extra-terrestrial life and unlocking the secrets of Mars,” says Professor Van Kranendonk.

Harvard University to Launch Center for Autism Research

Autism and related disorders—a constellation of neurodevelopmental conditions affecting one in 59 children in the United States alone—have become one of modern medicine’s most confounding mysteries. The condition is believed to arise from the complex interplay between genes and environment, yet its basic biology remains largely a black box.

Now, a new research effort at Harvard University led by Harvard Medical School is poised to identify the biologic roots and molecular changes that give rise to autism and related disorders with the goal of informing the development of better diagnostic tools and new therapies. Harvard University has received a $20 million gift from philanthropists Lisa Yang and Hock Tan, an alumnus of Harvard Business School, to establish The Hock E. Tan and K. Lisa Yang Center for Autism Research at Harvard Medical School. The latest gift brings the total autism-related research funding provided by Yang and Tan to nearly $70 million.

The center will serve as a hub that brings together the diverse expertise of scientists and clinicians working throughout Harvard University, Harvard Medical School and its affiliated hospitals.

“There is an urgent need to understand the fundamental biology of autism,” said Michael Greenberg, chair of the Department of Neurobiology at Harvard Medical School and the center’s inaugural faculty leader. “I strongly believe that the multidisciplinary expertise convened by this center will propel us into a new era of autism research, enhancing our understanding of the condition and yielding critical new insights into its causes. This generous gift will be transformative for the field.”

Working under the premise that autism’s complexity demands the cross-pollination of diverse expertise across different modes of scientific inquiry, the center will encompass the efforts of basic, translational and clinical scientists from the entire Harvard ecosystem. The center will have its administrative home within the Harvard Brain Science Initiative, which brings together researchers from Harvard Medical School and its affiliated hospitals as well as from the Harvard Faculty of Arts and Sciences, the Harvard T.H. Chan School of Public Health and the Harvard John A. Paulson School of Engineering and Applied Sciences. “Neuroscience has reached a unique inflection point. Advances such as single-cell analysis and optogenetics, coupled with an unprecedented ability to visualize molecular shifts down to the minutest level, will enable today’s researchers to tackle a disorder as dauntingly complex as autism,” said Harvard Medical School Dean George Q. Daley.

“Medical history has taught us that truly transformative therapies flow only from a clear understanding of the fundamental biology that underlies a condition,” Daley added. “This gift will allow our researchers to generate critical insights about autism and related disorders.”

Investigators at the new Harvard University center will collaborate with peer researchers at MIT and complement efforts already underway at The Hock E. Tan and K. Lisa Yang Center for Autism Research at the McGovern Institute for Brain Research at MIT, with the unique strengths of each institution converging toward a shared goal: understanding the roots of autism, explaining the condition’s behavior and evolution and translating those insights into novel approaches to treat its symptoms.

“In a short time, the Tan-Yang Center at the McGovern Institute has supported groundbreaking research we believe will change our understanding of autism,” said Robert Desimone, the director of the sibling center at MIT. “We look forward to joining forces with the new center at Harvard, to greatly accelerate the pace of autism-related research.”

“We are excited and hopeful that these sibling centers at Harvard and MIT—two powerhouses of biomedical research—will continue to collaborate in a synergistic way and bring about critical new insights to our understanding of autism,” Yang said. Yang is a former investment banker who has devoted much of her time to mental health advocacy. Tan is president and CEO of Broadcom, a global infrastructure technology company. 

Autism-spectrum disorders—neurodevelopmental conditions that typically emerge in the first few years of life—are marked by a cluster of symptoms, impaired social interactions and compromised communication skills. Yet exactly what portion of these cases is rooted in genetic mutations and how they are influenced by environmental factors is an area of lingering uncertainty. Another key area of uncertainty is how much of autism’s fundamental features arise in the brain and what influence organs and systems outside of the brain might have.

Two of the new center’s initial areas of inquiry will address these critical gaps in knowledge.

One group of researchers will focus on understanding precisely what goes awry during critical windows in the first two years of life—a period marked by rapid brain development, great neuroplasticity and intense wiring of the brain’s circuits. This is also the typical window of autism diagnosis. The scientists will try to understand what molecular, cellular or neural-circuitry changes underlie autism-fueling processes during this stage. Identifying such critical changes can help illuminate how experiences modulate brain development in individuals with autism.

Another group of researchers will examine the role of factors arising from organs and organ systems outside the brain that may drive autism risk. For example, the peripheral nervous system—made up of nerve cells throughout the body that act as nodes to collect and transmit signals to the brain—has emerged as a central player in the development of autism.

Heightened sensitivity to even light touch is a common feature in autism and one of the disorder’s many perplexing symptoms. Recent research from neurobiologists and geneticists at Harvard Medical School has not only identified the molecular changes that give rise to heightened touch sensitivity in autism-spectrum disorders but also points to a possible treatment for the condition.

First Large-Scale Study of Universal Screening for Autism Raises Critical Questions about Accuracy, Equity

Researchers urge continued screening for all toddlers, while recommending changes to M-CHAT screening method to improve accuracy, address disparities

Newswise — Philadelphia, September 27, 2019 –

In the first large, real-world study of universal screening for autism spectrum disorder (ASD) in toddlers, researchers at Children’s Hospital of Philadelphia (CHOP) have found that the most widely used and researched screening tool is less accurate than shown in previous studies conducted in research laboratory settings. The new study also revealed significant disparities in detecting early autism symptoms in minority, urban and low-income children. The findings were published online today in the journal Pediatrics.

The American Academy of Pediatrics (AAP) recommends screening all toddlers for ASD at their 18- and 24-month primary care check-ups using the Modified Checklist for Autism in Toddlers with Follow-Up (M-CHAT/F), a two-stage parent survey to determine whether a child may have autism, with the follow-up designed to eliminate false positives. However, most studies to evaluate the accuracy of the M-CHAT/F have been conducted in research settings rather than in real-world clinical settings. Therefore, very little was known about screening in the recommended primary care setting, nor about longer-term outcomes for children who screened negative on the M-CHAT/F. The CHOP study is the first to look at outcomes of truly universal screening in a real-world primary care setting.

“As part of a large pediatric network implementing universal screening, we found ourselves in a unique position to find answers to critical questions about the accuracy of the M-CHAT, and to determine how many children are missed by early, universal screening,” said lead author Whitney Guthrie, PhD, a clinical psychologist specializing in early diagnosis at CHOP’s Center for Autism Research. “Early intervention has been shown to improve outcomes, potentially into adulthood. We know that early and accurate screening and diagnosis is the crucial first step in helping children access those effective, autism-specific therapies.”

The CHOP research team studied the electronic health records (EHR) of 25,999 patients screened in primary care using the M-CHAT/F between the ages of 16 and 26 months, and systematically followed these children until 4 through 8 years of age using the EHR. Ninety-one percent of these children were screened using the M-CHAT/F, meaning that nearly universal screening of all children in primary care was achieved.

The study showed that the M-CHAT/F detected only about 40% of children who went on to be diagnosed with ASD. However, children who screened positive were diagnosed seven months earlier than those who screened negative, suggesting that early screening may facilitate early intervention. Overall, 2.2% of children in the study were ultimately diagnosed with ASD, which is consistent with the Centers for Disease Control and Prevention (CDC) estimates nationally.

“Although our findings reveal significant shortcomings in current screening tools, we want to be clear that we are not recommending that pediatricians stop universal screening,” said Guthrie. “Instead, clinicians should continue to screen using the M-CHAT/F, while being aware that this screening tool does miss some children with ASD. Any clinical or parental concerns should be taken seriously, and warrant continued surveillance even if a child screens negative on the M-CHAT/F. And of course, a screen positive on the M-CHAT/F warrants referral so that children with ASD can be diagnosed and receive early intervention.

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“Pediatricians should also be aware of disparities in screening practices and results in children of color and from low-income backgrounds.”

The CHOP study found that the 9% of children who did not receive screening at 18 or 24 months were disproportionately from racial minority groups; from non-English speaking households; and from households with lower median income and who receive Medicaid. When screening was administered, these same children were more likely to receive a false positive result. The M-CHAT was also less accurate in girls than in boys.

“Persistent racial and economic disparities in autism screening and diagnosis are a cause for great concern, and are consistent with previous research showing that black and Hispanic children tend to be diagnosed years later than white children,” said co-author Kate Wallis, MD, MPH, a developmental pediatrician and researcher at CHOP’s PolicyLab who is also studying disparities in referrals for autism services. “This study revealed important limitations and provides us with new knowledge that we can use to make critical improvements to autism screening tools and screening processes, so pediatricians can properly detect and support more children with autism and reduce disparities in diagnosis and care.”

Guthrie et al, “Accuracy of Autism Screening in a Large Pediatric Network.” Pediatrics, online 27 September 2019. DOI: 10.1542/peds.2019-0925.

About Children’s Hospital of Philadelphia: Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, Children’s Hospital has fostered many discoveries that have benefited children worldwide.  Its pediatric research program is among the largest in the country.  In addition, its unique family-centered care and public service programs have brought the 564-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu

Jurassic fossil

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Discovery of a new fossil in China sheds light on when early mammal ancestors first evolved sophisticated thyroid bones that gave them the ability to swallow food like modern-day mammals.

The 165-million-year-old fossil of Microdocodongracilis, a tiny, shrew-like animal, shows the earliest example of modern hyoid bones in mammal evolution The hyoid bones link the back of the mouth, or pharynx, to the openings of the esophagus and the larynx. The hyoids of modern mammals, including humans, are arranged in a “U” shape, similar to the saddle seat of children’s swing, suspended by jointed segments from the skull. It helps us transport and swallow chewed food and liquid – a crucial function on which our livelihood depends.

Mammals as a whole are far more sophisticated than other living vertebrates in chewing up food and swallowing itone small lump at a time, instead of gulping down huge bites or whole prey like an alligator.

“Mammals have become so diverse today through the evolution of diverse ways to chew their food, weather it is insects, worms, meat, or plants. But no matter how differently mammals can chew, they all have to swallow in the same way,” said Zhe-Xi Luo, PhD, a professor of organismal biology and anatomy at the University of Chicago and the senior author of a new study of the fossil, published this week in Science.

“Essentially, the specialized way for mammals to chew and then swallow is all made possible by the agile hyoid bones at the back of the throat,” Luo said.

‘A pristine, beautiful fossil’

This modern hyoid apparatus is mobile and allows the throat muscles to control the intricate functions to transport and swallow chewed food or drink fluids. Other vertebrates also have hyoid bones, but their hyoids are simple and rod-like, without mobile joints between segments. They can only swallow food whole or in large chunks.

When and how this unique hyoid structure first appeared in mammals, however, has long been in question among paleontologists. In 2014, Chang-Fu Zhou, PhD, from the Paleontological Museum of Liaoning in China, the lead author of the new study, found a new fossil of Microdocodon preserved with delicate hyoid bones in the famous Jurassic Daohugou site of northeastern China.Soon afterwards, Luo and Thomas Martin from the University of Bonn, Germany, met up with Zhou in China to study the fossil.

“It is a pristine, beautiful fossil. I was amazed by the exquisite preservation of this tiny fossil at the first sight. We got a sense that it was unusual, but we were puzzled about what was unusual about it,”Luo said. “After taking detailed photographs and examining the fossil under a microscope, it dawned on us that this Jurassic animal has tiny hyoid bones much like those of modern mammals.”

This new insight gave Luo and his colleagues added context on how to study the new fossil. Microdocodonis a docodont, from an extinct lineage of near relatives of mammals from the Mesozoic Era called mammaliaforms. Previously, paleontologists anticipated that hyoids like this had to be there in all of these early mammals, but it was difficult to identify the delicate bones.  After finding them in Microdocodon, Luo and his collaborators have since found similar fossilized hyoid structures in other Mesozoic mammals.

“Now we are able for the first time to address how the crucial function for swallowing evolved among early mammals from the fossil record,” Luo said. “The tiny hyoids of Microdocodonare a big milestone for interpreting the evolution of mammalian feeding function.”

New insights on mammal evolution as a whole

Luo also worked with postdoctoral scholar Bhart-Anjan Bhullar, PhD, now on the faculty at Yale University, and April Neander, a scientific artist and expert on CT visualization of fossils at UChicago, to study casts of Microdocodonand reconstruct how it lived.

The jaw and middle ear of modern mammals are developed from (or around) the first pharyngeal arch, structures in a vertebrate embryo that develop into other recognizable bones and tissues. Meanwhile, the hyoids are developed separately from the second and the third pharyngeal arches. Microdocodonhas a primitive middle ear still attached to the jaw like that of other early mammals like cynodonts, which is unlike the ear of modern mammals. Yet its hyoids are already like those of modern mammals.

“Hyoids and ear bones are all derivatives of the primordial vertebrate mouth and gill skeleton, with which our earliest fishlike ancestors fed and respired,” Bhullar said. “The jointed, mobile hyoid of Microdocodoncoexists with an archaic middle ear — still attached to the lower jaw. Therefore, the building of the modern mammal entailed serial repurposing of a truly ancient system.”

The tiny, shrew-like creature likely weighed only 5 to 9 grams, with a slender body, and an exceptionally long tail. The dimensions of its limb bonesmatch up with those of modern tree-dwellers.

“Its limb bones are as thin as matchsticks, and yet this tiny Mesozoic mammal still lived an active life in trees,” Neander said.

The fossil beds that yielded Microdocodonare dated 164 to 166 million years old. Microdocodonco-existed with other docodonts like the semiaquatic Castorocauda, the subterranean Docofossor, the tree-dwellingAgilodocodon, as well as some mammaliaform gliders.

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The study, “New Jurassic mammaliaform sheds light on early evolution of mammal-like hyoid bones,” was published in Scienceon July 19, 2019. The research was supported by the University of Chicago Division of Biological Sciences (Luo); the Deutsche Forschungsgemeinschaft (Martin); and the National Natural Science Foundation and Ministry of Land Resources of China, Shenyang Normal University, and Shandong University of Science and Technology (Zhou).

Autism rates increasing fastest among black and Hispanic children

Autism rates among racial minorities in the United States have increased by double digits in recent years, with black rates now exceeding those of whites in most states and Hispanic rates growing faster than any other group, according to new University of Colorado Boulder research.

The study, published this month in the Journal of Autism and Developmental Disorders, also found that prevalence of autism among white youth is ticking up again, after flattening in the mid-2000s.

While some of the increase is due to more awareness and greater detection of the disorder among minority populations, other environmental factors are likely at play, the authors conclude.

“We found that rates among blacks and Hispanics are not only catching up to those of whites — which have historically been higher — but surpassing them,” said lead author Cynthia Nevison, an atmospheric research scientist with the Institute of Arctic and Alpine Research. “These results suggest that additional factors beyond just catch-up may be involved.”

For the study, Nevison teamed up with co-author Walter Zahorodny, an autism researcher and associate professor of pediatrics at Rutgers New Jersey Medical School, to analyze the most recent data available from the Individuals with Disabilities Education Act (IDEA) and the Autism and Developmental Disabilities Monitoring (ADDM) Network.

IDEA tracks prevalence, including information on race, among 3-to-5-year-olds across all 50 states annually. ADDM tracks prevalence among 8-year-olds in 11 states every two years.

The new study found that between birth year 2007 and 2013, autism rates among Hispanics age 3-5 rose 73%, while rates among blacks that age rose 44% and rates among whites rose 25%.

In 30 states, prevalence among blacks was higher than among whites by 2012.

In states with “high prevalence,” 1 in 79 whites, 1 in 68 blacks and 1 in 83 Hispanics born in 2013 have been diagnosed with autism by age 3-5.

Other states like Colorado fell in a “low-prevalence” category, but the authors cautioned that differences between states likely reflect differences in how well cases are reported by age 3-5. They also said the real prevalence is substantially higher, as many children are not diagnosed until later in life.

“There is no doubt that autism prevalence has increased significantly over the past 10 to 20 years, and based on what we have seen from this larger, more recent dataset it will continue to increase among all race and ethnicity groups in the coming years,” said Zahorodny.

In 2018, the Centers for Disease Control reported that about 1 in 59 children of all races have been diagnosed with autism and that rates had risen 15 percent overall from the previous two year period, largely due to better outreach and diagnosis among historically underdiagnosed minority populations. The new study challenges that explanation.

“Our data contradict the assertion that these increases are mainly due to better awareness among minority children,” said Zahorodny. “If the minority rates are exceeding the white rates that implies some difference in risk factor, either greater exposure to something in the environment or another trigger.”

Established risk factors associated with autism include advanced parental age, challenges to the immune system during pregnancy, genetic mutations, premature birth and being a twin or multiple.

The authors said that, based on current research, they cannot pinpoint what other environmental exposures might be factoring into the increases in autism. But they would like to see more research done in the field.