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Diabetes is characterized by elevated levels of sugar or glucose (hyperglycemia) in the blood. This occurs due to the lack of the hormone insulin in type 1 diabetes, and to reduced insulin levels in combination with insulin resistance in type 2 diabetes. A recent review of data supports stricter control of hemoglobin A1C levels (HbA1C) among pediatric patients with T1D. This review was led by Dr. Maria J. Redondo, pediatric endocrinologist at Texas Children's Hospital and professor at Baylor College of Medicine, in collaboration with Dr. Sarah Lyons, pediatric endocrinologist at Texas Children's and assistant professor at Baylor College of Medicine, along with other leading endocrinologists and diabetes experts across the U.S.

This article, published in the journal Diabetes Care, presents the evidence used by Redondo and her colleagues at the American Diabetes Association (ADA) Professional Practice Committee to issue the new guidelines for optimal A1C in children with T1D in January 2020. This review is intended to increase awareness, present the strong evidence that was used to issue the new recommendations and to reassure caregivers and family medicine practitioners of the safety of this approach. The ADA's 2021 A1C guidelines will remain the same as the guidelines mentioned in this review, which were set forth this year.

The review highlights mounting evidence that shows chronically elevated levels of blood glucose can cause several detrimental effects including abnormal brain development, increased heart problems (e.g. coronary or peripheral heart diseases, stroke), other diabetes-related complications (e.g. diabetic nephropathy, neuropathy and retinopathy), and mortality rates in children and adolescents with T1D. All of these are reasons for stricter HbA1C control among these patients.

Based on this, the ADA's 2020 Standards of Medical Care now recommends most children with T1D should strive for less than 7% HbA1C levels, instead of 7.5%, as per their 2019 guidelines. They also provide distinct guidelines for patients with other predisposing factors or health status.

"Until recently, there was a mistaken belief that sugar fluctuations in pre-pubescent children do not cause any long-term harm. However, it is increasingly evident that is not true. Moreover, studies show intensive insulin therapy that strives to bring sugar levels close to the normal range, beyond what is needed for controlling hyperglycemia, is the best to reduce the risk of most acute and long-term organ damage and diabetes-related complications in T1D children and teens. However, these stringent measures are not always practiced by caregivers of T1D patients or diabetes providers due to concerns and fear that it may cause sudden or dramatic drops in sugar levels. Historically, lower A1C levels was associated with increased risk of hypoglycemia, which led to guidelines with higher glycemic targets among youth," Redondo said.

Hypoglycemia is accompanied by a host of symptoms including dizziness and can cause serious complications such as seizures, coma and brain damage. The review presents several lines of evidence supporting the fact that incidences of hypoglycemia have been declining in T1D children over the past three decades. Additionally, they found the link between lower glucose targets and hypoglycemia risk has weakened over the past 15 years.

"We now know more about the risk factors for hypoglycemia and how to prevent it. In addition, new innovations such as the development of insulin analogs, and diabetes technologies - such as continuous glucose monitoring, insulin pumps and integrated systems - now allow caregivers and patients to measure and regulate sugar levels in relatively pain-free ways. These have also made it more feasible to maintain glucose levels within a pre-specified target A1C range. This is why, based on overwhelming emerging evidence, the ADA has revised its HbA1C targets several times through the years. It is important to note that these new guidelines reflect similar guidance issued by other diabetes societies worldwide," Redondo said.

As per ADA's 2020 guidance, a higher target A1C of

With these lowered A1C target levels, the goal is for T1D children to have better immediate and long-term health outcomes with fewer complications and reduced mortality rates.

Researchers have shown that the link between physical and mental illness is closer than previously thought. Certain changes in physical health, which are detectable in childhood, are linked with the development of mental illness in adulthood.

The researchers, led by the University of Cambridge, used a sample of over 10,000 people to study how insulin levels and body mass index (BMI) in childhood may be linked with depression and psychosis in young adulthood.

They found that persistently high insulin levels from mid-childhood were linked with a higher chance of developing psychosis in adulthood. In addition, they found that an increase in BMI around the onset of puberty, was linked with a higher chance of developing depression in adulthood, particularly in girls. The results were consistent after adjusting for a range of other possible factors.

The findings, reported in the journal JAMA Psychiatry, suggest that early signs of developing physical health problems could be present long before the development of symptoms of psychosis or depression and show that the link between physical and mental illness is more complex than previously thought.

However, the researchers caution that these risk factors are among many, both genetic and environmental, and that their results do not suggest that one could predict the likelihood of developing adult mental disorders from these physical health measures alone.

The researchers recommend that healthcare professionals should carry out robust physical assessments of young people presenting with symptoms of psychosis or depression, so that early signs of physical illnesses may be diagnosed and treated early. It has been well-established that people with depression and psychosis can have a life expectancy of up to 20 years shorter than the general population, mostly because physical health problems like diabetes and obesity are more common in adults with those mental disorders.

While psychosis and depression in adulthood are already known to be associated with significantly higher rates of diabetes and obesity than the general population, these links are often attributed to the symptoms of the mental disorder itself.

"The general assumption in the past has been that some people with psychosis and depression might be more likely to have a poor diet and lower levels of physical exercise, so any adverse physical health problems are a result of the mental disorder, or the treatment for it," said first author Dr Benjamin Perry from Cambridge's Department of Psychiatry. "In essence, the received wisdom is that the mental disorder comes first. But we've found that this isn't necessarily the case, and for some individuals, it may be the other way around, suggesting that physical health problems detectable from childhood might be risk factors for adult psychosis and depression."

Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a long-term population-representative birth cohort study set in the west of England, Perry and his colleagues found that disruption to insulin levels can be detected in childhood, long before the onset of psychosis, suggesting that some people with psychosis may have an inherent susceptibility to developing diabetes.

They used a statistical method to group individuals based on similar trajectories of change in insulin levels and BMI from age one to 24, and examined how the different groups related to risks of depression and psychosis in adulthood. About 75% of study participants had normal insulin levels, between 15% and 18% had insulin levels which increased gradually over adolescence, and around 3% had relatively high insulin levels. This third group had a higher chance of developing psychosis in adulthood compared with the average group.

The researchers did not find that the group who had persistently high BMI through childhood and adolescence had a significantly increased risk of depression in adulthood, and instead suggest that their findings mean that certain factors around the age of puberty which might cause BMI to increase might be important risk factors for depression in adulthood. The researchers were not able to determine in their study what those factors might be, and future research will be required to find them. These factors might be important targets to reduce the risk of both depression in adulthood.

"These findings are an important reminder that all young people presenting with mental health problems should be offered a full and comprehensive assessment of their physical health in tandem with their mental health," said Perry. "Intervening early is the best way to reduce the mortality gap sadly faced by people with mental disorders like depression and psychosis.

"The next step will be to work out exactly why persistently high insulin levels from childhood increase the risk of psychosis in adulthood, and why increases in BMI around the age of puberty increase the risk of depression in adulthood. Doing so could pave the way for better preventative measures and the potential for new treatment targets."

Philadelphia, January 13, 2021--Researchers at Children's Hospital of Philadelphia and the School of Engineering and Applied Science at the University of Pennsylvania have identified ionizable lipid nanoparticles that could be used to deliver mRNA as part of fetal therapy. The proof-of-concept study, published today in Science Advances, engineered and screened a number of lipid nanoparticle formulations for targeting mouse fetal organs and has laid the groundwork for testing potential therapies to treat genetic diseases before birth.

"This is an important first step in identifying nonviral mediated approaches for delivering cutting-edge therapies before birth," said co-senior author William H. Peranteau, MD, an attending surgeon in the Division of General, Thoracic and Fetal Surgery and the Adzick-McCausland Distinguished Chair in Fetal and Pediatric Surgery at CHOP. "These lipid nanoparticles may provide a platform for in utero mRNA delivery, which would be used in therapies like fetal protein replacement and gene editing."

Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in Penn Engineering's Department of Bioengineering, is the other co-senior author of the study.

Recent advances in DNA sequencing technology and prenatal diagnostics have made it possible to diagnose many genetic diseases before birth. Some of these diseases are treated by protein or enzyme replacement therapies after birth, but by then, some of the damaging effects of the disease have taken hold. Thus, applying therapies while the patient is still in the womb has the potential to be more effective for some conditions. The small fetal size allows for maximal therapeutic dosing, and the immature fetal immune system may be more tolerant of replacement therapy.

Of the potential vehicles for introducing therapeutic protein replacement, mRNA is distinct from other nucleic acids, such as DNA, because it does not need to enter the nucleus and can use the body's own machinery to produce the desired proteins. Currently, the common methods of nucleic acid delivery include viral vectors and nonviral approaches. Although viral vectors may be well-suited to gene therapy, they come with the potential risk of unwanted integration of the transgene or parts of the viral vector in the recipient genome. Thus, there is an important need to develop safe and effective nonviral nucleic acid delivery technologies to treat prenatal diseases.

In order to identify potential nonviral delivery systems for therapeutic mRNA, the researchers engineered a library of lipid nanoparticles, small particles less than 100 nanometers in size that effectively enter cells in mouse fetal recipients. Each lipid nanoparticle formulation was used to encapsulate mRNA, which was administered to mouse fetuses. The researchers found that several of the lipid nanoparticles enabled functional mRNA delivery to fetal livers and that some of those lipid nanoparticles also delivered mRNA to the fetal lungs and intestines. They also assessed the lipid nanoparticles for toxicity and found them to be as safe or safer than existing formulations.

Having identified the lipid nanoparticles that were able to accumulate within fetal livers, lungs, and intestines with the highest efficiency and safety, the researchers also tested therapeutic potential of those designs by using them to deliver erythropoietin (EPO) mRNA, as the EPO protein is easily trackable. They found that EPO mRNA delivery to liver cells in mouse fetuses resulted in elevated levels of EPO protein in the fetal circulation, providing a model for protein replacement therapy via the liver using these lipid nanoparticles.

"A central challenge in the field of gene therapy is the delivery of nucleic acids to target cells and tissues, without causing side effects in healthy tissue. This is difficult to achieve in adult animals and humans, which have been studied extensively. Much less is known in terms of what is required to achieve in utero nucleic acid delivery," said Mitchell. "We are very excited by the initial results of our lipid nanoparticle technology to deliver mRNA in utero in safe and effective manner, which could open new avenues for lipid nanoparticles and mRNA therapeutics to treat diseases before birth."

Fuchs' corneal dystrophy is one of the most common eye diseases diagnosed in almost 5% of the population of Europe aged 40 years or over. It is a hereditary eye disease that causes vision impairment and typically manifests in middle age. The first symptoms of the disease - blisters on the surface of your cornea - resemble cataract at first glance. The disease progresses from the centre of the cornea affecting all layers of the cornea. The progression of the disease varies from individual to individual and in severe cases results in vision loss.

The molecular neurobiology research group led by Professor of Molecular Biology Tõnis Timmusk published an article about Fuchs' dystrophy in the journal Scientific Reports titled "The Fuchs corneal dystrophy-associated CTG repeat expansion in the TCF4 gene affects transcription from its alternative promoters", authored by Alex Sirp, Kristian Leite, Jürgen Tuvikene, Kaja Nurm, Mari Sepp and Tõnis Timmusk.

Professor Timmusk says, "Currently, the only method used to treat Fuchs' corneal dystrophy is a surgical procedure, in the course of which the patient's whole cornea is replaced. However, such a treatment is complicated because it requires availability of donor tissue. To prevent an unpleasant surgical procedure, we are working to better understand the causes of Fuchs' dystrophy and to find ways to prevent it."

The human genome - DNA - is composed of chains of four different types of nucleotides (abbreviated A, T, C and G). Their different combinations make us actually who we are. Repeated sequences occur in DNA, i.e. some combinations in our genome can be repeated tens or hundreds or even thousands of times. Such repeats are unstable, varying in length between individuals as well as in different tissues of the same individual.

"Expansion of certain repeats can cause repeat expansion diseases. In most cases, such diseases are caused by abnormal repeat expansion of three nucleotides, which is why they are known also as trinucleotide repeat disorders," says one of the lead authors of the article, PhD student Alex Sirp.

Trinucleotide repeat disorders are a set of over 40 different disorders, including Huntington's disease, fragile X syndrome, myotonic dystrophy, etc. The Fuchs' endothelial corneal dystrophy is caused by the CTG trinucleotide repeat expansion in Transcription factor 4 (TCF4). While the repeat length in healthy persons remains below 40, the repeat length in persons with visual impairment is above 40 repeats. "TCF4 gene pays an important role in the development and functioning of the human nervous system. Mutations and variations in TCF4 are directly associated with schizophrenia, mental retardation and a very rare disorder called Pitt-Hopkins Syndrome, " says Sirp.
Tõnis Timmusk says, "The results of our study showed that CTG repeat expansion affects the expression of TCF4 in cultured cells. Due to rapid advances in genomic technologies in recent years, we were able to compare expression of the TCF4 gene in the corneal endothelium of healthy persons and patients with Fuchs' dystrophy. The results revealed changes in TCF4 expression levels in case of Fuchs' endothelial corneal dystrophy.

The findings of the research help to understand how these (tri)nucleotide repeats can affect development of a disease through changes in gene expression. These results may also contribute to the development of drugs for the treatment of Fuchs' dystrophy.

"As a next step, we want to determine when and for how long changes in TCF4 level occur in people who later develop Fuchs' endothelial corneal dystrophy. This would make it possible to develop a treatment strategy that would enable regulation of TCF4 levels in the corneal endothelium and thus prevent the disease," says Professor Timmusk.

In three recent publications in Molecular Psychiatry, Brain and JAMA Neurology researchers from the University of Gothenburg provide convincing evidence that an in-house developed blood test for Alzheimer's disease can detect the disease early and track its course, which has major implications for a potential use in clinical practice and treatment trials.

"This is an extremely dynamic research field right now, thanks to the technological development and seminal scientific progress in the past years. The dream scenario is to have a blood test for the early detection and screening of Alzheimer's disease up and running. That would give significantly more people in the world access to testing and future treatments", says Michael Schöll, associate professor and one of the senior authors.

After decades of research, we now know that Alzheimer's disease-related memory problems are just the tip of the iceberg of underlying degenerative processes in the brain that have been silently developing over years or even decades.

These processes result from abnormal aggregation of amyloid and tau proteins in the brain, with these aggregates being the defining pathological features of Alzheimer's disease. Until recently, it was only possible to detect these protein aggregates in the brains of deceased patients at autopsy.

Recent research advances, however, have enabled the accurate detection of amyloid and tau pathology in the brain with imaging methods and in the cerebrospinal fluid of living individuals. These current so-called biomarker methods are either expensive, invasive, or only available at specialized centers; thus, only a fraction of patients suffering from the disease currently benefit from these advances.

An accessible, affordable, and minimally invasive biomarker for Alzheimer's disease would revolutionize care of patients worldwide, as well as boost the development of novel drugs for this presently still incurable disease.

In 2020, researchers at Sahlgrenska Academy, University of Gothenburg, have discovered such a biomarker: a cheap blood test capable to detect the presence of phosphorylated tau protein (p-tau181), a principal, defining hallmark of Alzheimer's disease. Three recent scientific articles from the same study group now focus on the diagnostic performance of this blood marker and how it changes over time during healthy aging and during disease.

The authors demonstrated great potential for the blood test to predict and monitor Alzheimer's disease progression in an unprecedently large study comprising more than 1100 subjects from the Alzheimer's Disease Neuroimage Initiative (ADNI), followed up over several years.

First authors are Thomas Karikari (the article in Molecular Psychiatry) and Alexis Moscoso (Brain and JAMA Neurology).

"The recent development of blood tests sensitive to Alzheimer's disease pathology is likely to provide a solution and has the potential to significantly change the way this disease can be managed in the near future", Moscoso says.

In the publication in Brain the researchers analyzed participants' blood samples acquired at different ages to construct the temporal trajectory of p-tau181 levels in blood across the long course of Alzheimer's disease.

Importantly, they found that the novel blood test could detect abnormalities in p-tau181 levels several years before the onset of memory loss, suggesting enormous potential for early disease detection.

This potential was further confirmed in another publication in Molecular Psychiatry, with first author Thomas Karikari, in which the investigators demonstrated the high clinical utility of p-tau181 in blood for predicting future Alzheimer's disease dementia, even among individuals who had not experienced any memory impairment in the moment of the blood test.

Finally, in the third and most recent publication in JAMA Neurology, the scientists demonstrated that annual increases of p-tau181 in blood were strongly coupled to the loss of nerve cells in Alzheimer's disease as well as to cognitive decline, suggesting not only potential for prediction but also for monitoring and identifying rapidly progressive forms of the disease in an affordable yet effective way. Professor Henrik Zetterberg:

"Our findings have clear and novel implications for the use of these tests, both as diagnostic tools, but also as outcome measures in clinical trials, as we showed that the levels of phosphorylated p-tau181 and Neurofilament light, NfL, in standard blood samples, are reliable biomarkers for Alzheimer's disease, specifically p-tau181, and for neurodegenerative diseases in general, NfL."

Together, these studies represent a crucial step towards the widespread use of biomarkers in clinical routine, making effective blood biomarker testing for Alzheimer's disease a reality for most clinical settings, including primary care. Professor Kaj Blennow:

"This is a major step forward showing that blood tests for tau pathology and neurodegeneration have clinical value to track disease progression in patients with Alzheimer's disease", he says.

PLYMOUTH MEETING, PA [January 13, 2021] -- New research in the January 2021 issue of JNCCN--Journal of the National Comprehensive Cancer Network finds more than a third of eligible people miss timely screening tests for colorectal cancer and at least a quarter appear to miss timely screening tests for breast and cervical cancers. The study comes from the University of Alberta, Faculty of Medicine and Dentistry in Alberta, Canada, with findings based on self-reported results from the Canadian Community Health Survey (CCHS) from 2007-2016. According to the author, the results also point to evidence of screening disparities being linked to lower socioeconomic status and identifiable minority race--echoing a similar study conducted in the United States by the Centers for Disease Control.[1]

"We already have high-quality evidence showing that recommended cancer screening saves lives. From a cost perspective, it is far cheaper to have an efficient cancer screening program and lower cancer-specific mortality than to have a high incidence of advanced incurable cancers that would cost the system much more--not to mention the lost opportunities for healthy, cancer-free individuals to work and contribute to the economy," said Omar M. Abdel-Rahman Abdelsalam, MBBCh, MSc, MD, Assistant Professor of Medical Oncology, University of Alberta. "These findings show we need more measures to eliminate socioeconomic-related health disparities in our communities, even where healthcare is publicly funded. The most powerful intervention to improve screening rates would be to invest more in primary care and make sure every individual is linked to a family physician who can track their adherence to recommended screening tests."

Dr. Abdel-Rahman looked at self-reported data for 99,820 people eligible for colorectal cancer screening, 59,724 people eligible for breast cancer screening, and 46,767 in the cervical cancer screening cohort, based on Canadian guidelines from 2007 through 2016. 43% did not have a timely screening test for colorectal, 35% did not have timely mammography, and 25% did not have a timely PAP smear. There were modest increases in screening compliance throughout the study's duration according to self-reporting within the survey.

"Dr. Abdel-Rahman's study adds to the literature showing that decreased levels of adherence to common cancer screening practices are associated with social and economic disparities," commented Mark Helvie, MD, Director, Breast Imaging Division, University of Michigan Rogel Cancer Center, Vice-Chair, NCCN Guidelines® Panel for Breast Cancer Screening and Diagnosis, who was not involved with this research. "Colorectal cancer screening had the lowest compliance with over a third reporting not being screened. While important differences exist between the NCCN Guidelines for screening and the Canadian screening guidelines--especially regarding colonoscopy and initiation and frequency of mammography--they all agree there is a need for more targeted efforts, research, and education to understand and improve compliance among all individuals, as illustrated by this study's results."

The research data does not include any impact from the COVID-19 pandemic. However, the publication is particularly timely as doctors report concerning drop-offs of screening numbers, which are projected to possibly result in thousands of excess cancer deaths over the next ten years.[2] The study further highlights how economic and racial disparities contribute to unequal health outcomes and showcases the need for interventions that go beyond coverage for health services alone.

Liver transplant priority in the U.S. goes to the sickest patients, which fails to consider other important factors, including how long patients are likely to survive post-transplant.

Researchers with Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine are collaborating with faculty at the University of Pennsylvania to develop a risk score that more comprehensively prioritizes liver cancer patients for transplantation.

Their paper documenting the development and validation of the LiTES-HCC score to predict post-transplant survival for hepatocellular carcinoma, or liver cancer, patients was published in the highly respected peer-reviewed Journal of Hepatology.

The authors looked retrospectively at national registry data of more than 6,500 adult deceased donor liver transplant recipients and found the 11 variables selected for their scoring system resulted in patient prioritization based on predicted survival and survival benefit, according to the study's lead author, David Goldberg, M.D., MSCE, associate professor of medicine in the Division of Digestive Health and Liver Diseases at the Miller School.

Dr. Goldberg is principal investigator for an ongoing National Institutes of Health grant aimed at redefining liver transplantation prioritization in the U.S.

"There are basically two large subsets of patients awaiting liver transplantation: those who have cirrhosis and complications from that, and then about 20% to 25% of transplants are for people who have liver cancer, which is a known complication of cirrhosis," Dr. Goldberg said. "Cirrhosis is the primary risk factor for developing liver cancer. When it is caught early enough and hasn't gotten too big, transplantation is the best treatment."

Since the early 2000s, patients who meet certain criteria based on tumor number and size get points or priority on the wait list for liver transplant.

"Livers are in short supply for transplantation. We have over 15,000 people waiting for livers," said Ezekiel J. Emanuel, M.D., Ph.D., vice provost for global initiatives and co-director of the Healthcare Transformation Institute at the University of Pennsylvania, who also served as co-author and co-investigator in the study. "As we know, in these circumstances who gets priority is really a life and death matter. We have shown that there are better ways to allocate livers saving more lives."

"For example, you could have a 75-year-old with diabetes, high blood pressure and kidney disease who has a 5 cm tumor have the same priority as someone who is 50, who has autoimmune liver disease and cancer and no other problem, even though the 50-year-old's expected survival is quite different," Dr. Goldberg said.

Researchers have developed other scores attempting to predict who will have better survival, but those scores have focused on tumor characteristics, including tumor size, number of tumors and blood biomarkers, and not on other health problems, such as diabetes or heart disease.

"Ours is the first validated score to predict survival after transplant for people with liver cancer that accounts for both their cancer-related factors but also non-cancer-related factors," Dr. Goldberg said.

Improving on the current system is important because there is a dramatic shortage of organs for transplantation, including livers.

The NIH grant has three aims: The first is the post-transplant research in this paper. Another journal has accepted Dr. Goldberg and colleagues' paper looking at using the score to predict survival in people without liver cancer. And now the researchers are developing a model to predict survival without a transplant.

"The broader goal of our work is to change liver transplant prioritization not just based on survival with the transplant but survival without the transplant. So, if someone is expected to live eight years with the transplant and four years without it, that is vastly different than someone who lives six years with a transplant and three months without," Dr. Goldberg said. "Ultimately, we will put this all together to determine who benefits most from a liver transplantation in order to redefine how we prioritize people for transplantation in the U.S. and maybe the world."

Apart from black holes, magnetars may be the most extreme stars in the universe. With a diameter less than the length of Manhattan, they pack more mass than that of our sun, wield the largest magnetic field of any known object -- more than 10 trillion times stronger than a refrigerator magnet -- and spin on their axes every few seconds.

A type of neutron star -- the remnant of a supernova explosion -- magnetars are so highly magnetized that even modest disturbances in the magnetic field can cause bursts of X-rays that last sporadically for weeks or months.

These exotic, compact stars are also thought to be the source of some types of short gamma ray bursts (GRBs): bright flashes of highly energetic radiation that have puzzled astronomers since they were first detected in the 1970s. Several of these giant magnetar flares have been detected within the Milky Way Galaxy. But because they are so intense that they saturate detectors, and observations within the galaxy are obscured by dust, space scientist Kevin Hurley at the University of California, Berkeley, and an international team of astronomers have been looking for these same flares in galaxies outside our own for a clearer view.

That 45-year effort is paying off. A short gamma ray burst detected last April 15 from a galaxy 11.4 million light years away shows a clear signature that Hurley thinks could help astronomers find magnetar bursts more easily and finally gather the data needed to check the many theories that explain magnetars and their gamma ray flares.

"We have got what we believe are four solid detections since 1979 of extragalactic giant magnetar flares, two of them almost identical bursts from different galaxies," said Hurley, a senior space fellow with UC Berkeley's Space Sciences Laboratory. "It leads us to believe that there may be kind of a template emerging that is going to help us identify them more quickly in the future. My hope is that the pace will now accelerate because we know a lot better what we are looking for."

Hurley and three colleagues will report the GRB discovery by various U.S. and European satellites and its implications at a media briefing on Wednesday, Jan. 13, at the annual meeting of the American Astronomical Society and in three papers appearing simultaneously in the journals Nature and Nature Astronomy.

Giant magnetar bursts

GRBs, the most powerful explosions in the cosmos, can be detected across billions of light-years. Most of those lasting less than about two seconds, called short GRBs, occur when a pair of orbiting neutron stars spiral into each other and merge. Astronomers confirmed this scenario for at least some short GRBs in 2017, when a burst followed the arrival of gravitational waves -- ripples in space-time -- produced when neutron stars merged 130 million light-years away.

But not all short GRBs fit the neutron star merger profile, Hurley said. Specifically, of the 29 magnetars within our Milky Way Galaxy known to exhibit occasional X-ray activity, two have produced giant flares that are different from the bursts from these mergers.

The most recent of these detections was on Dec. 27, 2004, an event that produced measurable changes in Earth's upper atmosphere, despite erupting from a magnetar located about 28,000 light years away.

Since the late 1970s, Hurley has operated the InterPlanetary Network (IPN), a 24/7 effort to plow through data from many spacecraft -- currently five, capturing some 325 gamma bursts per year -- in hopes of finding more giant magnetar flares. That network was key to capturing the April 15, 2020, flare.

Shortly before 4:42 a.m. EDT on that Wednesday, a brief, powerful burst of X-rays and gamma rays swept past Mars, triggering the Russian High Energy Neutron Detector aboard NASA's Mars Odyssey spacecraft, which has been orbiting the planet since 2001. About 6.6 minutes later, the burst triggered the Russian Konus instrument aboard NASA's Wind satellite, which orbits a point between Earth and the sun located about 930,000 miles (1.5 million kilometers) away. After another 4.5 seconds, the radiation passed Earth, triggering instruments on NASA's Fermi Gamma-ray Space Telescope and the European Space Agency's INTEGRAL satellite.

Analysis of data from the Burst Alert Telescope (BAT) on NASA's Neil Gehrels Swift Observatory provided additional insight into the event.

These data showed that the pulse of radiation lasted just 140 milliseconds, the blink of an eye.

Hurley and Dmitry Svinkin of Russia's Ioffe Institute, a member of the IPN team, used the arrival times measured by the Fermi, Swift, Wind, Mars Odyssey and INTEGRAL missions to pinpoint the location of the April 15 burst, called GRB 200415A, squarely in the central region of NGC 253, a bright spiral galaxy located about 11.4 million light-years away in the constellation Sculptor. This is the most precise sky position yet determined for a magnetar located beyond the Large Magellanic Cloud, a satellite of our galaxy and host in 1979 to the first giant flare ever detected.

"This was the most accurately localized magnetar outside of our galaxy so far, and we've really pinned it down now, not just to a galaxy, but a part of a galaxy where we expect star formation is going on, and stars are exploding. That is where the supernovas should be and the magnetars, too," Hurley said. "The April 15 event is a game changer."

Flashes from a lighthouse

The giant flares seen within the Milky Way look a bit different from those from nearby galaxies because of distance. Astronomers have documented that giant flares from magnetars in the Milky Way and its satellites evolve in a distinct way, with a rapid rise to peak brightness followed by a more gradual tail of fluctuating emission. These variations result from the magnetar's rotation, which repeatedly brings the flare location in and out of view from Earth, much like a lighthouse.

Observing this fluctuating tail is conclusive evidence of a giant flare -- a smoking gun, Hurley said. For magnetar flares millions of light-years away, however, this emission is too dim to detect with today's instruments. For this reason, giant flares in our galactic neighborhood may be confused with more distant and powerful merger-type GRBs.

The new observations reveal multiple pulses, with the first one appearing in just 77 microseconds -- about 13 times the speed of a camera flash and nearly 100 times faster than the rise of the fastest GRBs produced by mergers.

"The combination of the rise time and decay time, we think, may be showing us a template, because we have seen it before -- we saw it back in 2005, with another event, almost the carbon copy. And the energy spectrum of the two were also similar," Hurley said.

Fermi's Gamma-ray Burst Monitor also detected rapid variations in energy over the course of the flare that have never been observed before.

"Giant flares within our galaxy are so brilliant that they overwhelm our instruments, leaving them to hang onto their secrets," said Oliver Roberts, an associate scientist at Universities Space Research Association's Science and Technology Institute in Huntsville, Alabama, who led the study of Fermi data. "For the first time, GRB 200415A and distant flares like it allow our instruments to capture every feature and explore these powerful eruptions in unparalleled depth."

Starquakes and magnetic field reconnection

Giant flares are poorly understood, but astronomers think they result from a sudden rearrangement of the magnetar's magnetic field. One possibility is that the field high above the surface may become too twisted, suddenly releasing energy as it settles into a more stable configuration. A mechanical failure of the magnetar's crust -- a starquake -- may trigger the sudden reconfiguration.

"The idea is that you have this superstrong magnetic field coming out of the star, but anchored to the crust, and the magnetic field can twist, exerting pressure on the crust. The crust has an elastic limit, and after you exceed that elastic limit, it cracks. Then, that crack sends out waves into the magnetic field, and those waves disrupt the field, and you can get reconnection and energy release and gamma rays," Hurley said.

Roberts and his colleagues say that the data show some evidence of seismic vibrations during the eruption. The researchers say this emission arose from a cloud of ejected electrons and positrons moving at about 99% the speed of light. The short duration of the emission and its changing brightness and energy reflect the magnetar's rotation, ramping up and down like the headlights of a car making a turn. Roberts describes it as starting off as an opaque blob -- he pictures it resembling a photon torpedo from the "Star Trek" franchise -- that expands and diffuses as it travels.

The torpedo also factors into one of the event's biggest surprises. The highest-energy X-rays recorded by the Gamma-Burst Monitor reached 3 million electron volts (MeV), or about 1 million times the energy of blue light. The satellite's main instrument, the Large Area Telescope (LAT), also detected three gamma rays with energies of 480 MeV, 1.3 billion electron volts (GeV) and 1.7 GeV -- the highest-energy light ever detected from a magnetar giant flare. What's surprising is that all of these gamma rays appeared long after the flare had diminished in other instruments.

Nicola Omodei, a senior research scientist at Stanford University, led the LAT team investigating these gamma rays, which arrived between 19 seconds and 4.7 minutes after the main event. The scientists concluded that this signal most likely also came from the magnetar flare.

A magnetar produces a steady outflow of fast-moving particles. As these particles move through space, they plow into, slow and divert interstellar gas. The gas piles up, becomes heated and compressed, and forms a type of shock wave called a bow shock, like the ripples in front of a moving boat.

In the model proposed by the LAT team, the flare's initial pulse of gamma rays travels outward at the speed of light, followed by the cloud of ejected matter, which is moving nearly as fast. After several days, they both reach the bow shock. The gamma rays pass through. Seconds later, the cloud of particles -- now expanded into a vast, thin shell -- collides with accumulated gas at the bow shock. This interaction creates shock waves that accelerate particles, producing the highest-energy gamma rays after the main burst.

The April 15 flare proves that the 2020 and 2004 events constitute their own class of GRBs, Hurley said.

"A few percent of short GRBs may really be magnetar giant flares," said Eric Burns, an assistant professor of physics and astronomy at Louisiana State University in Baton Rouge who led a study that identified additional extragalactic magnetar suspects. "In fact, they may be the most common high-energy outbursts we've detected so far beyond our galaxy -- about five times more frequent than supernovae."

While bursts near the galaxy M81 in 2005 and the Andromeda galaxy (M31) in 2007 had already been suggested to be giant flares, his team identified a newly reported flare in M83, also seen in 2007. Add to these the giant flare from 1979 and those observed in our Milky Way in 1998 and 2004.

"It's a small sample, but we now have a better idea of their true energies, and how far we can detect them," said Burns, whose study will appear later this year in The Astrophysical Journal Letters.

Primary amoebic meningoencephalitis (PAM), a deadly disease caused by the "brain-eating amoeba" Naegleria fowleri, is becoming more common in some areas of the world, and it has no effective treatment. Now, researchers reporting in ACS Chemical Neuroscience have found that a compound isolated from the leaves of a traditional medicinal plant, Inula viscosa or "false yellowhead," kills the amoebae by causing them to commit cell suicide in lab studies, which could lead to new treatments.

PAM, characterized by headache, fever, vomiting, hallucinations and seizures, is almost always fatal within a couple of weeks of developing symptoms. Although the disease, which is usually contracted by swimming in contaminated freshwater, is rare, increasing cases have been reported recently in the U.S., the Philippines, southern Brazil and some Asian countries. Amphotericin B is the most common therapy given to those with the infection. It can kill N. fowleri in the lab, but it isn't very effective when given to patients, likely because it cannot cross the blood-brain barrier. Ikrame Zeouk, José Piñero, Jacob Lorenzo-Morales and colleagues wanted to explore whether compounds isolated from I. viscosa, a strong-smelling plant that has long been used for traditional medicine in the Mediterranean region, could effectively treat PAM.

The researchers first made an ethanol extract from the herb's leaves, finding that it could kill N. fowleri amoebae. Then, they isolated and tested specific compounds from the extract. The most potent compound, inuloxin A, killed amoebae in the lab by disrupting membranes and causing mitochondrial changes, chromatin condensation and oxidative damage, ultimately forcing the parasites to undergo programmed cell death, or apoptosis. Although inuloxin A was much less potent than amphotericin B in the lab, the structure of the plant-derived compound suggests that it might be better able to cross the blood-brain barrier. More studies are needed to confirm this hypothesis, the researchers say.

The authors acknowledge funding from the European Regional Development Fund, the Spanish Ministry of Economic Affairs and Digital Transformation, the Spanish Ministry of Science, Innovation and Universities, the University of La Laguna and the Augustin de Betancourt Foundation.

The abstract that accompanies this paper is available here.

CORVALLIS, Ore. -- A recent study from Oregon State University found that after Oregon expanded Medicaid in 2014, more women were able to receive insurance coverage for abortion services, rather than paying out of pocket.

In analyzing Medicaid claims data and other medical records, researchers found that the Medicaid-financed share of total abortions increased each of the first three years following the state's Medicaid expansion. The incidence of Medicaid-financed abortions increased 18% in 2014, then 7% each in 2015 and 2016.

The total number of abortions in the state did not rise; rather, the expansion shifted who paid for them.

"According to the literature, there was a 1% decline in the abortion rate in Oregon between 2014 and 2017. During the pre-expansion period women were having to pay for abortions out of pocket, which was taking a lot of money out of their incomes that could have been going to food or clothing or caring for their children," said Lisa Oakley, who co-authored the study as a postdoctoral researcher at OSU's College of Public Health and Human Services. "What the expansion of coverage did was reduce the financial burden for women in this low-income group."

Prior to the 2014 expansion, low-income women in Oregon became eligible for Medicaid if they became pregnant. Oregon is one of 16 states where Medicaid coverage includes abortion services.

The expansion increased eligibility to cover everyone earning less than 138% of the federal poverty level, which granted coverage to an estimated 77,000 women of childbearing age, regardless of pregnancy status.

The expanded eligibility cleared a major barrier for women seeking reproductive health care, said Marie Harvey, lead author of the study and associate dean for research in the College of Public Health and Human Sciences.

"Having to wait to be pregnant to enroll in Medicaid delays access to these services that are needed immediately," Harvey said. "Low-income women are disproportionately impacted by unintended pregnancies, and therefore experience greater need for abortion services. Being able to help these women who are most vulnerable is critical."

Researchers note that greater access to health care overall is likely one reason why the increased share of Medicaid-financed abortions leveled off after the first year of expansion, though more studies are needed.

"Alternatively, Medicaid expansion may eventually result in a measurably decreased need for abortion services if women with low incomes gain access to contraceptive services and experience fewer unintended pregnancies," the authors wrote.

The study also looked at the share of abortions that were performed with medication rather than surgery. Researchers found a 7.4 percentage point increase in women getting medication abortions instead of surgical abortions in the first year of Oregon's Medicaid expansion.

Although all types of abortions in the U.S. are safe, the researchers say, early abortions such as medication abortions have been proven to be safer for women and are less costly. But typically, women can only receive medication abortions up until their 10th week of pregnancy. Before Medicaid expansion in Oregon, because it took so long to complete the Medicaid enrollment process, the choice between abortion types was taken away, Harvey said.

"Access to reproductive health care, including contraceptive and abortion services, is essential for promoting reproductive autonomy and the health of all women," she said.

COLUMBUS, Ohio - While we wait for our turn to get vaccinated against SARS-CoV-2, we could - and probably should - use the time to make sure we bring our healthiest emotional and physical selves to the treatment, a new review of previous research suggests.

Ohio State University researchers reviewed 49 vaccine studies in humans dating back 30 years that document how stress, depression and poor health behaviors can negatively affect the body's immune response to vaccination, and how improving health factors can enhance that response.

The impaired immune responses tended to fall into three categories - interference with the development of antibodies against the pathogen, more rapid erosion of antibody protection that does develop, or intensification of vaccination's side effects.

The steady stress of navigating our disrupted routines and social lives during the pandemic may have set us back when it comes to maintaining healthy behaviors, the researchers say. They report on recent data from across the world documenting higher depressive and anxiety symptoms and more insomnia during lockdown, increased alcohol sales and overeating, and fewer average step counts recorded by Fitbits.

There is good news: The power to make improvements that give us the best chance for a healthy response to the coronavirus vaccine is almost completely in our control. Managing stress through exercise and mindfulness meditation, getting enough sleep, quitting or curbing tobacco use and improving our diets - even in the short term, right around the time of vaccination - could influence how our bodies respond, the evidence suggests. And for those struggling with depression, now would be a good time to seek professional help.

"When we think of vaccine efficacy, we often think of the vaccine itself. My motivation was to draw attention to the fact that we bring important factors to the table as well - and those factors are modifiable," said Annelise Madison, first author of the paper and a graduate student in clinical psychology at Ohio State.

"If we can address them now, when most of the world has yet to receive the vaccine, we have the chance to make our response to the vaccine quicker, more robust and lasting."

A number of the studies reviewed were led by senior author Janice Kiecolt-Glaser, director of Ohio State's Institute for Behavioral Medicine Research and a professor of psychiatry and psychology in the College of Medicine. Kiecolt-Glaser and her late husband, immunologist Ronald Glaser, were pioneers in mind-body research that showed how stress impairs physical health in a variety of ways, primarily by hampering the human immune response.

The review is accepted for publication in the journal Perspectives on Psychological Science.

The studies in this review investigated the effects of psychological factors and behaviors on the immune response to a range of vaccine types, such as influenza, hepatitis B, typhoid and pneumonia. Because many findings have been consistent across responses to different vaccines, the team considered them likely to be relevant to the SARS-CoV-2 vaccine.

Kiecolt-Glaser pointed to a few of her past studies that illustrate the varying effects of different types of stress on human responses to vaccination.

In a study of medical students' immune response to a highly effective hepatitis B vaccine, all students eventually developed antibodies - but the students who were more stressed or anxious about exams coinciding with the inoculations took significantly longer to develop protective antibodies.

Research on older adults' response to a pneumococcal pneumonia vaccine showed that though all study participants initially developed antibodies quickly, the antibody response diminished over the next three to six months in those who were chronically stressed caregivers looking after spouses with dementia.

"These findings suggest that with the COVID-19 vaccine, when people are more stressed and more anxious, it may take a little longer to develop antibodies, so they should probably allow a little more time before they assume they're protected," Kiecolt-Glaser said. "Another possibility is that stress may erode protection more rapidly."

Her lab's past research has also shown that older adults - who are considered at higher risk for severe COVID-19 symptoms - sometimes don't respond well to flu vaccines. In one study, only 20% of stressed adults who were age 71 or older developed antibodies after a flu shot.

Additional studies in her lab showed that people who were depressed experienced post-vaccination side effects of lethargy, malaise and irritability for a longer period of time than people who were not depressed.

Side effects are normal - the vaccination is training the immune system to recognize a pathogen by initiating an inflammatory response that can make us feel sick - but they can cause some people to avoid vaccines.

"Side effects are from an inflammatory response to the vaccine, which is a good thing," Kiecolt-Glaser said. "You want to see a strong response to the vaccine. That's one reason we know the vaccine is effective. On the other hand, the absence of a response doesn't mean it's not effective."

According to previous research, a range of interventions may help us all get the most out of the COVID-19 vaccine: Massage and expressive writing for stress management, short- and long-term physical activity including 25 minutes of arm exercises before injection, and nutritional supplementation all helped increase antibody response or reduce side effects in past studies.

"And when you know you're going to get the vaccine the next day, try to get a good night's sleep. Just one night, and going in fully rested, can be helpful," Kiecolt-Glaser said.

Though we may be suffering from health-advice fatigue 10 months after the first lockdown, Madison said now may be the most important time to heed the experts' recommendations.

"I know it can be difficult day in and day out during the pandemic to keep prioritizing things we know we should do," she said. "But we could use this time as a wake-up call. These are important health behaviors to keep engaging in, especially as we're preparing to get vaccinated - which is a really good thing."

In a study in mice and human cells, Johns Hopkins Medicine researchers say that they have developed a tiny, yet effective method for preventing premature birth. The vaginally-delivered treatment contains nanosized (billionth of a meter) particles of drugs that easily penetrate the vaginal wall to reach the uterine muscles and prevent them from contracting. If proven effective in humans, the treatment could be one of the only clinical options available to prevent preterm labor. The FDA has recommended removing Makena (17-hydroxyprogesterone caproate), the only approved medicine for this purpose, from the market.

The study was published Jan. 13 in Science Translational Medicine.

There are an estimated 15 million premature births each year, making it the number one cause of infant mortality worldwide. Few indicators can predict which pregnancies will result in a pre-term birth, but inflammation in the reproductive tract is a contributing factor in approximately one third of all cases. This symptom not only puts babies at risk of being born with low birth weights and underdeveloped lungs, but also has been linked to brain injuries in the developing fetus.

The newly reported experimental therapy uses technology developed by scientists at the Johns Hopkins Center for Nanomedicine. Its active ingredients are two drugs: progesterone, a hormone that regulates female reproduction, and trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor that regulates gene expression. To prepare the treatment, the drugs are first ground down into miniature crystals, about 200-300nanometers in diameter or smaller than a typical bacteria. Then, the nanocrystals are coated with a stabilizing compound that keeps them from getting caught in the body's protective mucus layers that absorb and sweep away foreign particles.

"This means we can use far less drug to efficiently reach other parts of the female reproductive tract," says Laura Ensign, Ph.D., associate professor of ophthalmology with a secondary appointment in gynecology and obstetrics at the Johns Hopkins University School of Medicine, co-author of the study, and an expert on nanomedicine and drug delivery systems.

To test their therapy, the researchers used mice that were engineered to mimic inflammation-related conditions that would lead to preterm labor in humans. They found that the experimental treatment prevented the mice from entering premature labor. Neurological tests of mouse pups born to mothers that had received the treatment revealed no abnormalities.

The researchers also applied the drug combination to human uterine cells grown in the lab. The drug combination, they report, decreased contractions in the test samples.

Additional laboratory tests of the experimental treatment are planned to evaluate its safety before considering trials in humans.

This article will be featured in the Jan. 19 Johns Hopkins Medicine Research News Tips
Hopkinsmedicine.org/Newsroom

A new study from UBC researchers suggests a strong correlation between following the MIND and Mediterranean diets and later onset of Parkinson's disease (PD). While researchers have long known of neuroprotective effects of the MIND diet for diseases like Alzheimer's and dementia, this study is the first to suggest a link between this diet and brain health for Parkinson's disease (PD).

The MIND diet combines aspects of two very popular diets, the Mediterranean diet and the Dietary Approaches to Stop Hypertension (DASH) diet.

"The study shows individuals with Parkinson's disease have a significantly later age of onset if their eating pattern closely aligns with the Mediterranean-type diet. The difference shown in the study was up to 17 years later in women and eight years later in men," says Dr. Silke Appel-Cresswell of the Pacific Parkinson's Research Centre, the Djavad Mowafaghian Centre for Brain Health and the Division of Neurology in the UBC Faculty of Medicine. "There is a lack of medications to prevent or delay Parkinson's disease yet we are optimistic that this new evidence suggests nutrition could potentially delay onset of the disease."

In a study of 176 participants, researchers looked at adherence to these types of diets, characterized by reduced meat intake and a focus on vegetables, fruits, whole grains and healthy fats, and the age of PD onset. They found that close adherence to these diets coincided with later onset of PD in women of up to 17.4 years, and 8.4 years in men. The MIND diet showed a more significant impact on women's health, whereas the Mediterranean diet did for the men. The differences in these two diets are subtle, but could serve as clues to the impacts specific foods and micronutrients may have on brain health.

The different effects of diet adherence between sexes are noteworthy as approximately 60 per cent of those diagnosed with Parkinson's disease are men.

"If we understand the sex differences between the MIND diet and Mediterranean diet then we might better understand the sex differences that drive Parkinson's disease in the first place," says lead researcher Avril Metcalfe-Roach, a PhD student at UBC's Michael Smith Laboratories.

These findings springboard to other research questions that could have significant impacts on the understanding of PD.

"It drives home the connection between the gut and the brain for this disease," says Dr. Brett Finlay, professor in the departments of biochemistry and molecular biology, and microbiology and immunology at UBC. "It also shows it's not just one disease that healthy eating can affect, but several of these cognitive diseases."

The research team plans to further examine the potential connection between the microbiome and its effect on the brain.

"There is so much benefit to eating healthy," says Metcalfe-Roach. "It is in everybody's best interest to try to keep your microbiome healthy, to try and eat a rich variety of plant-based and other healthy foods. This study provides even more evidence for what we already know--that we should be trying to eat healthy and taking care of ourselves."

BOSTON -- Completing cancer screening tests, such as mammograms, can be challenging for low-income people, who may face such challenges as lack of transportation or inability to take time off work. A team at Massachusetts General Hospital (MGH) explored the possibility of addressing preventive care needs when patients are admitted to the hospital.

The pilot study, published in the Annals of Family Medicine, examined the feasibility of performing mammograms in women insured by Medicaid or both Medicaid and Medicare (dual-eligible patients) while they were hospitalized. "We designed the study to reach the patients who face significant barriers to completing their mammograms in the outpatient setting," says Andrew S. Hwang, MD, MPH, an internist at MGH and first author of the study. "National and local data show that Medicaid and dual-eligible patients have low rates of breast cancer screening. This targeted strategy has the potential to reduce disparities in cancer screening rates by addressing patients' acute medical needs and their preventive care needs simultaneously."

Hwang and his colleagues identified Medicaid and dual-eligible patients who were admitted to MGH's General Medicine service and were overdue for mammograms. The women had primary care physicians affiliated with MGH who would be responsible for following up on abnormal mammogram results in collaboration with the MGH Breast Evaluation Team.

Of the 21 women who were identified as appropriate candidates for an inpatient mammogram, 17 women, who were an average age of 59, successfully completed the mammogram. The other four patients were discharged from the hospital before the mammograms could be coordinated. Of the 17 women who completed an inpatient mammogram, 35% had never had a mammogram and the other women were overdue for their mammograms by four years on average. All the mammograms were negative, except one, which was inconclusive, and additional imaging evaluation was recommended to rule out cancer. Completing a mammogram did not increase the patients' hospital length of stay.

Hwang and his colleagues hope to build on the pilot study by offering inpatient mammograms to Medicaid and dual-eligible patients admitted to other areas of the hospital. They also envision potentially delivering additional preventive care services, such as fecal immunochemical tests for colorectal cancer screening, to low-income hospitalized men and women.

"The patients who participated in our pilot study faced significant psychosocial challenges to completing outpatient prevention tests," says Hwang. "Attaining equitable health outcomes for all patients will require innovative solutions that lower the barriers to care by addressing patients' psychosocial needs. In addition, as our health care system transitions from fee-for-service to value-based payment models, improving health outcomes among underserved patient populations will become increasingly important. Completing preventive screening tests, such as mammograms, during hospitalizations can be one way to help patients who might otherwise miss preventive care."

DES PLAINES, IL -- Among children who were not in an independently verified incident, evaluation for child abuse should be done by specialty consultation in children aged less than three-years old presenting with rib fractures and children aged less than 18-months presenting with humeral or femoral fractures. That is the conclusion of a study titled Identifying Maltreatment in Infants and Young Children Presenting with Fractures: Does Age Matter?, to be published in the January 2021 issue of Academic Emergency Medicine (AEM), a journal of the Society for Academic Emergency Medicine (SAEM).

The lead author of the study is Ian C. Mitchell, MD, a pediatric surgery specialist, Departments of Surgery, University of Texas Health Science Center at San Antonio and Baylor College of Medicine, San Antonio, TX. The findings of the study are discussed in a recent AEM podcast.

According to the study findings, 77 percent of children presenting with rib fractures aged less than three years were abused; when those involved in motor vehicle collisions were excluded, 96% were abused. Abuse was identified in 48% of children less than 18?months with humeral fractures. Among those with femoral fractures, abuse was diagnosed in 34% and 25% of children aged less than 12 and 18?months, respectively.

Commenting on the study is Mark R. Zonfrillo, MD, MSCE, associate professor of emergency medicine and pediatrics at Alpert Medical School of Brown University and Hasbro Children's Hospital:

"Undiagnosed child abuse can lead to subsequent serious injury or death, and understanding injury characteristics that can predict increased risk of an abusive injury is critical. This systematic review identified rib fractures in children younger than three years old and humeral or femoral fractures in children younger than 18 months old, and without an independently verified injury mechanism, as higher risk for abuse. For these patients, the authors recommend diagnostic evaluation and consultation for potential abuse in order to minimize morbidity and mortality from these intentional injuries."