Culture

Researchers find evidence of smallpox in the viking age

The fatal disease smallpox is older and more widespread than scientists so far have proved. A new study by an international team of researchers from the University of Copenhagen and the University of Cambridge shows that the Vikings also suffered from smallpox.

Through the ages, the highly infectious disease smallpox has killed hundreds of millions of people. But it is unclear exactly when the disease emerged. There has been found evidence of smallpox from individuals from the 17th century while written records suggest the disease is much older.

Now a new study shows that the disease dates 1,000 years further back in time than previously shown. Researchers from the University of Copenhagen (UCPH) and the University of Cambridge have found proof that smallpox also existed in the Viking Age. The new results have been published in the scientific journal Science.

"We have found the oldest evidence of smallpox. Moreover, it seems to have been surprisingly common as early as in the Viking Age," says Associate Professor Martin Sikora, Globe Institute, UCPH, and the University of Cambridge. He continues:

"Smallpox is the infection in the world that has killed most people. For that reason alone, it is very important and interesting to know how the disease developed. It gives us a unique opportunity to understand the viruses' evolution: How did it change and become the pathogen that we know of today."

Widespread in Northern Europe

The researchers have studied and analysed the DNA of 13 individuals from Northern Europe infected with smallpox. The samples are 1,000 years older than the previous oldest sample known to have been infected based on ancient DNA, and they thus push the timeline for smallpox further back in time.

The study also shows the disease has been more widespread than previously assumed. The general idea used to be that smallpox was not endemic to Northern Europe during that time period.

"We show that not only was it endemic in Europe, but it was actually quite widespread in Northern Europe already at the year 600. That means that the disease was almost certainly far more established at a much earlier age than previously thought," says Professor Eske Willerslev, Globe Institute, UCPH.

The researchers have also discovered that the viruses circulating during the Viking Age were distinct from their modern counterparts, and not directly ancestral to the viruses that caused the last big outbreak of smallpox in the 20th century.

"They share a common ancestor, but they also have unique features that differentiate them from the ones circulating later on in history. It turns out that the viruses we have found were some of these very, very early and different versions of the devastating pathogens known from the 20th century. It is the first time we can trace these early smallpox viruses and compare their genomes and mutations and see how the disease evolved over time," says Eske Willerslev.

Catalogue of Mutations

Even though the disease has been eradicated today, it is still very useful to know how it developed and mutated through the ages.

Smallpox is a so-called poxvirus, a large family of viruses with many different types infecting a diverse set of host species. One such example is monkeypox, which typically infects monkeys but has also been known to cause a disease similar to smallpox in humans. It is therefore useful to known how other types of poxviruses mutate and survive.

"When we know how the disease mutated through time, it gives us an opportunity to put together a catalogue of how these pathogens might mutate in the future: What mutations and combinations make such a pathogen viable and successful? If they had those mutations in the past, they can most likely get them again."

"It is one of a few examples where ancient genetic research has direct implications for present-day and future health," says Martin Sikora.

Smallpox:

It is the variola virus that causes smallpox. It is a so-called poxvirus.

Written records of possible smallpox infections dating at least 3,000 years back.

The disease was declared eradicated in 1980 by WHO.

Smallpox virus still exists in two laboratories in the world: one in the US and one in Russia.

Credit: 
University of Copenhagen - The Faculty of Health and Medical Sciences

New approach simultaneously measures EEG and fMRI connectomes

image: Sepideh Sadaghiani is interested in studying the connectivity and functions of brain networks.

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Photo courtesy the Beckman Institute for Advanced Science and Technology.

New research demonstrates how two vastly different methods of measuring brain activity can provide meaningful data on brain networks simultaneously.

Functional magnetic resonance imaging and electroencephalography are used to provide information on very different aspects of neural communication between brain areas. fMRI captures very slow aspects of this communication based on neurons' energy expenditure, whereas EEG directly measures neurons' rapid communication in real time from the electrical signals of the brain. Researchers from the Beckman Institute for Advanced Science and Technology have developed a new approach to look at both types to measure brain communication simultaneously.

The study "Concurrent EEG- and fMRI-derived functional connectomes exhibit linked dynamics" was published in NeuroImage.

"Over the last two decades it has become more common to look at how different regions across the brain communicate rather than focusing on activation of individual regions. The connectome describes the entirety of connections across all the brain regions," said Sepideh Sadaghiani, an assistant professor of psychology at the University of Illinois at Urbana-Champaign, who leads the CONNECT Lab at the Beckman Institute. "Unfortunately, it has been hard to look at fMRI and EEG connectomes simultaneously."

EEG measures the electrical signals that are generated by neurons across the brain. However, the MRI scanners that are used for fMRI measurements interfere with the EEG signals because the scanners use magnetic fields that generate their own currents. As a result, artifacts are produced.

"We looked at how the fMRI connectome changes over time and whether those changes are accompanied by changes in electrophysiological connectomes, as measured by EEG," Sadaghiani said.

The researchers saw that even though fMRI-derived connectomes have been criticized in the past for noise issues, the changes in the connectome over time relate to actual changes in the neural activity, which were measured by EEG. Similarly, EEG-derived connectomes, previously criticized for spatially imprecise measurements of brain communication, are also meaningful in studying whole-brain connectomes because they correlate with the fMRI connectome changes.

"The correlation confirms that the shortcomings of both methods can be overcome and we can obtain meaningful data," Sadaghiani said.

The researchers are interested in improving the limitations of the two methods further. "fMRI is used to look at very specific regions of the brain that are a couple of millimeters in dimension. On the other hand, EEG signals can only look at large regions of the brain," Sadaghiani said. "If we need to compare connectomes obtained from both sets of data, we lose the spatial precision of fMRI. Conversely, EEG measures very rapid changes in connectomes whereas fMRI is inherently slow. Consequently, when comparing connectomes changes in EEG and fMRI we may lose the temporal resolution of EEG."

"This new finding that both modalities can reliably track changes of brain communication provides a solid foundation for future studies exploring human cognition and brain pathologies," said Jonathan Wirsich, a postdoctoral research associate in the CONNECT lab.

The researchers will conduct future studies at the Biomedical Imaging Center at Beckman to obtain higher quality data. Combined with new analytic approaches, they plan to compare the EEG and fMRI connectomes without losing the advantages of either method.

Credit: 
Beckman Institute for Advanced Science and Technology

Online tools can improve autism diagnosis

image: Online tools and assessments can help speed up diagnosis of autism spectrum disorder (ASD), the first comprehensive survey of research in the field has concluded.

The research was conducted by a team led by experts from Swansea University Medical School.

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Swansea University

Online tools and assessments can help speed up diagnosis of autism spectrum disorder (ASD), the first comprehensive survey of research in the field has concluded.

The survey showed that using internet-based tools in healthcare - a field known as telehealth - has potential to improve services in autism care, when used alongside existing methods.

The research, published today in PLOS ONE, was conducted by a team led by experts from Swansea University Medical School. The results are timely as the Covid-19 pandemic is prompting fresh thinking about providing services online.

Currently it can sometimes take several years after someone first seeks help before ASD diagnosis is confirmed. This can be due to a shortage of expertise, to several appointments being necessary, and the fact that the process can be very stressful for individuals who might later be diagnosed with ASD. As these are specialist services, they can also require lots of travelling for families and experts alike.

Delays in diagnosis can lead to poor outcomes for both the families and individuals.

Telehealth is already used successfully in areas such as radiology, cardiology, mental health, and for monitoring patients with diabetes and hypertension. However, the new study is the first to review the existing literature on the use of telehealth to support ASD diagnostic assessment.

The research team surveyed twenty years' worth of research in fields related to autism and telehealth, narrowing down an initial sample of 3700 articles to a set of ten for close study.

They examined which telehealth approaches have been used in the diagnosis and assessment of ASD in children and adults and how they compare with face-to-face methods.

The review revealed two main approaches to using telehealth:

1 Real-Time method - for example, videoconferencing, which enables a range of health professionals in different areas to meet in real time with the family to assess the child or adult, reducing the need for travel or multiple appointments

2 Store-and-Forward method - this involves providing a way for parents/carers to upload videos of a child's behaviour to a web portal, enabling clinicians to see a child in their everyday surroundings, to better inform the assessment.

The team found evidence that these two approaches:
* are acceptable to both families and clinicians;
* have good diagnostic accuracy;
* enable families from a wider area to access professionals;
* reduce costs for accessing care;
* enable the natural behaviours in the home setting to be observed;
* may enable both parents in divorced families to contribute to the diagnostic process.

Professor Sinead Brophy of Swansea University Medical School said:

"Telehealth can potentially improve the efficiency of the diagnosis process for ASD.

The evidence reviewed in our study shows that it can reduce delays and improve outcomes, when used in conjunction with existing methods. It could be of particular benefit to those with clear autism traits and adults with ASD.

Telehealth methods allow for collaboration and the sharing of experiences between the family, education and ASD experts. They can be just as good as face-to-face methods in terms of satisfaction for the patient, family and clinician."

Manahil Alfuraydan of Swansea University Medical School, primary author of the research, said:

"They reduce the time to diagnosis, particularly for those with more severe autism where there is good agreement in terms of the diagnosis compared to the face to face methods.

Our study highlights the potential of telehealth. Larger randomised controlled trials of this technology in relation to ASD are warranted."

Credit: 
Swansea University

New technology makes homes more energy independent, helps divert power during blackouts

image: Mixed neighborhood used in the researchers' computer simulation. Open circles denote nodes where homes have PINE systems and dark, filled circles are nodes where homes do not have PINE. All homes receive energy from the grid.

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Texas A&M University College of Engineering

In a new study, researchers from Texas A&M University and industry have designed a smart technology that can help utility companies better serve communities affected by blackouts. The researchers said their single device works by improving energy delivery between home solar-power systems and the electrical grid.

"Our innovation lets solar energy consumers be less dependent on the external power grid. The same technology also allows the utility company to control energy distribution, which is particularly useful during power outages caused by storms and other natural disasters," said Dr. Le Xie, professor in the Department of Electrical and Computer Engineering. "So, It's a win-win scenario for both the consumer and the utility company."

The study was published online in the Institute of Electrical and Electronics Engineers' Journal of Emerging and Selected Topics in Power Electronics in April.

Over the last decade, a sharp drop in the cost of solar panels has encouraged more households to adopt solar power systems. In these homes, the current generated by rooftop solar panels is fed into an inverter before the electricity is ready for residential use and charging solar backup batteries. Another set of power electronics connects the solar panels and the batteries back to the grid.

These connections ensure that homes are always connected to the grid as long as the grid is functional. During the day, homes consume more solar energy, and any excess energy is supplied to the grid. At night, homes draw electricity from the grid.

The researchers noted that these conventional systems have many disadvantages. Any voltage fluctuations in the grid, due to damage to the power lines or overloading, affects connected devices in homes. Also, they said the current injected into the grid from solar-powered homes can have certain irregularities, known as harmonics, affecting the quality of the power within the grid.

The researchers said another pertinent problem is there is little that a utility company can do to limit the amount of grid electricity consumed by solar-powered homes. This drawback is particularly harmful during natural disasters where other communities or essential services, like hospitals, need energy support.

"Currently, there's no system in place to regulate or limit energy consumption," said Dr. Prasad Enjeti, TI Professor III in Analog Engineering in the Department of Electrical and Computer Engineering. "End users with solar-powered systems continue drawing electricity from the grid because utility companies have no way of controlling it."

Unlike the conventional solar-powered systems that involve many electronics to connect back and forth from the grid, the researchers put together a single device, called the power electronics intelligence at the network edge, or PINE. This device, which is installed outside a home, has three main connections: one going to the home, one to the utility grid and another to the solar panels and batteries. PINE can control the flow of electricity in any one of these directions.

"This device is like an intelligent energy router," said Enjeti. "It regulates the grid voltage, integrates solar energy, which is locally produced, and intelligently manages and routes the energy in all directions."

The researchers designed this device to also be programmable, so that an authorized external user, like the utility company, can control the amount of grid electricity reaching solar-powered homes. Enjeti said PINE systems installed at different homes can also be programmed to communicate with each other and with the distribution operator.

To test if the PINE networks will operate as envisioned, the researchers built a hardware prototype and conducted extensive computer simulations of a mixed neighborhood in which some homes had PINE systems and others did not. The hardware performance along with simulations revealed that the homes with the PINE system had a cleaner, more stable voltage. At the grid level, the injected voltage from these homes was also stable because the PINE system was regulating that as well.

"PINE systems can dynamically and in real time inject different voltage support to the utility grid. So, the utility companies need not spend millions in buying capacitor banks to support the voltage across the feeder lines," said Xie. "During power outages, PINE allows homes to be self-sufficient and use their solar power efficiently. The technology also allows the utility company to wirelessly instruct PINE systems to limit the grid current to solar-powered homes and redirect it to other affected areas."

Credit: 
Texas A&M University

Getting a grip on near-field light

image: Designer landscape of localized light in the shape of an elephant. Guided light is molded by bouncing back and forth between two mode converters.

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(Image courtesy of Second Bay Studios/Harvard SEAS)

There are many types of light -- some visible and some invisible to the human eye. For example, our eyes and brain don't have the tools to process ultraviolet light when it hits our eyes, making it invisible. But there is another type of light that is invisible simply because it never reaches our eyes. When light hits certain surfaces, part of it sticks and remains behind rather than being transmitted or scattered away. This type of light is called near-field light.

Today, near-field light is mostly used for ultra-high-resolution microscopy, known as the near-field scanning optical microscopes (NSOM). However, near-field light also has untapped potential for particle manipulation, sensing, and optical communications. But since near-field light doesn't reach our eyes like far-field light does, researchers haven't developed a comprehensive toolkit to harness and manipulate the near field.

"Today, we have a lot of tools and techniques to design what far-field light looks like," said Vincent Ginis, a visiting professor at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). "We have lenses, telescopes, prisms and holograms. All these things enable us to sculpt freely propagating light in space."

Ginis is also a professor at the Vrije University of Brussel.

Now, SEAS researchers have developed a system to mold near-field light -- opening the door to unprecedented control over this powerful, largely unexplored type of light. The research is published in Science.

"Over the years, our group has developed new powerful techniques to structure propagating light using subwavelength-patterned metasurfaces," said Federico Capasso, the Robert Wallace Professor of Applied Physics and Vinton Hayes Senior Research Fellow in Electrical Engineering, and senior author of the paper. "With this work, we show how to structure the near field at a distance, opening exciting opportunities in science and technology."

In order to manipulate near-field light, the researchers developed a device in which light confined to a waveguide bounces back and forth between two reflectors. After each bounce it changes mode, meaning it propagates with a different spatial pattern. With multiple bounces, these patterns add up to generate a complex light intensity profile along the waveguide. The near field light near the surface of the waveguide also changes. When all the different patterns of the near-field light are superimposed on each other, a specific shape is created. The researchers can pre-program that shape by tailoring the amplitude of the modes of the bouncing light.

"The coexistence of all these modes can be designed to create near-field landscapes at will on the surface of the device," said Marco Piccardo, a research associate at SEAS and co-author of the paper. "The shape of the landscape is determined by the combined properties of the cascading light."

"It's a bit like music," said Ginis. "The music that you are hearing is the superposition of many notes or modes assembled in patterns conceived by the composer. One note alone isn't much but taken together you can generate any type of music. While music operates in time, our near-field generator operates in three-dimensional space and the extra intriguing aspect of our device is that one note generates the other."

Importantly, this molding process happens remotely, meaning no part of the device directly interacts with the near-field light. This reduces interference, which is important for applications such as particle manipulation, and is a major departure from current local methods of sculpting near fields such as shining light on metallic tips and nanoparticles.

To demonstrate their design, the researchers molded near-field light into the shape of an elephant. Or, more specifically, an elephant inside a boa constrictor, an homage to the play on dimensions in Antoine de Saint-Exupéry's classic The Little Prince.

The researchers also shaped the light into a curve, a plateau and a straight line.

"This research provides a new path towards unprecedented three-dimensional control of near-field light," said Capasso. "It is a portent of the exciting discoveries and technology developments I expect to come out of this work in the future."

Credit: 
Harvard John A. Paulson School of Engineering and Applied Sciences

A new approach to aiding black male trauma survivors

image: A new study by researchers at the University of Pennsylvania School of Nursing (Penn Nursing) and Drexel University has explored how Black male survivors of trauma articulate the factors that facilitate or hinder their help-seeking for psychological symptoms after injury.

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Penn Nursing Stock

PHILADELPHIA (July 23, 2020) - Many Black men suffer symptoms of traumatic stress in the aftermath of traumatic injury, and they also often carry social concerns, including experiences of discrimination and stigma. Yet despite their significant needs, underserved populations often have limited access to behavioral health care as well as a lack of financial resources to pay for such care. Because of these barriers, many trauma survivors do not seek professional behavioral health care and instead rely on informal or alternative sources of care.

A new study by researchers at the University of Pennsylvania School of Nursing (Penn Nursing) and Drexel University has explored how Black male survivors of trauma articulate the factors that facilitate or hinder their help-seeking for psychological symptoms after injury. The objective was to use a novel analytic approach called Qualitative Comparative Analysis (QCA) to understand how traumatic symptoms and social factors combine in complex ways toward the outcome of psychological help-seeking.

The study revealed that severe posttraumatic symptoms create pathways to help-seeking among some Black men who survive trauma exposure, while for others, financial worry and discrimination combine in a pathway toward help-seeking even in the absence of severe psychological symptoms after trauma. Factors combine in ways that reflect a complex intersection between barriers and facilitators.

"The existence of these distinct pathways challenges the tendency to view factors individually and either as barriers or facilitators," explains lead author John A. Rich, MD, MPH, Professor of Health Management and Policy at the Dornsife School of Public Health at Drexel University. "We were able to show that various causal conditions, some classically thought to be facilitators and others thought to be barriers, may combine in different ways toward the outcome of help-seeking among the Black men in this study. This supports our view that causation is complex and often intersectional."

Using fuzzy set QCA, researchers identified three different causal pathways for psychological help?seeking among the injured Black men studied. Two pathways showed that severe psychological symptoms in the absence of financial worry were sufficient for seeking help, whereas the third showed that financial worry and discrimination in the absence of psychological symptoms were sufficient for help?seeking.

The research also identified two causal pathways which negated help-seeking, in which low posttraumatic symptom severity and low levels of discrimination or financial worry were sufficient for not seeking psychological help.

"Our study has implications for future research," said Penn Nursing's Therese S. Richmond, PhD, RN, FAAN, the Andrea B. Laporte Professor of Nursing and Associate Dean for Research & Innovation, "Understanding different pathways to help-seeking behavior may identify new approaches to aiding Black men who are victims of trauma. Somewhat akin to a precision medicine approach, future examination of these pathways may help to develop theories about the utilization of behavioral health services for Black men that are based on their experiences rather than the assumption that all Black men who are trauma survivors have a single perspective on seeking help."

The study also helps highlight that Black men bring more than their race and gender to their experience of trauma exposure, combating the tendency to see Black men only as part of a group, which is problematic from a research perspective.

"We were able to show that various causal conditions, some classically thought to be facilitators and others thought to be barriers, may combine in different ways toward the outcome of help-seeking among the Black men in this study," says co-author Theodore J. Corbin, MD, MPH, Professor of Emergency Medicine at Drexel University College of Medicine and co-director of the Drexel Center for Nonviolence and Social Justice. "Applying similar configurational methods in health research could uncover important causal pathways for health inequalities rather than focusing on race or other demographic categories that are often investigated in isolation of their socioecological context."

Credit: 
University of Pennsylvania School of Nursing

FSU biologists shed light on how cells move resources

image: The structure of the clathrin cage that forms around a vesicle, a fluid-filled package that moves materials between compartments in cells. Florida State University researchers determined this cage structure and what determines its shape and size in a paper published in Science Advances.

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Courtesy of Scott Stagg

Florida State University researchers have new insight into the tiny packages that cells use to move molecules, a structure that is key to cellular metabolism, drug delivery and more.

Their research uncovered more about the proteins that form the outer structure of those cellular packages. The work was published in the journal Science Advances.

"Just like human mail carriers have to transport packages of different shapes and sizes, cells also have to transport a variety of materials to the right compartments within them," said Scott Stagg, associate professor of chemistry and biochemistry and a study co-author. "They need to bring in molecules from outside the cell and transport them between the different cellular compartments, and they have little molecular machines called vesicles that function like postal carriers moving microscopic packages from one compartment to another."

Scientists have previously observed cells create vesicles -- fluid-filled sacks that move materials within a cell or from one cell to another. They have also observed a protein called clathrin form a cage-like arrangement that made up the outside structure of vesicles.

But there were still questions about how exactly clathrin forms those structures and what determines the shapes it can take.

Using high-powered microscopes, the FSU researchers discovered that another protein, known as an adaptor protein, ties multiple clathrin molecules together in a way that allows those structures to take on different sizes.

They also showed that the clathrin coat could make a so-called "basket" shape, and one that scientists had thought the protein could not form, showing that clathrin assembly is more complicated than previously thought.

"We learned a lot about clathrin-coated vesicles by looking at the ones that were made by cells themselves," said Mohammadreza Paraan, a researcher at FSU's Institute of Molecular Biophysics and the study's lead author. "We found new structures and patterns that really surprised us."

The researchers found that the clathrin structures that other researchers formed in a test tube were different from the ones they saw from cells.

"This shows that there are things we don't understand about how clathrin coat assembly is regulated and progresses in cells," Stagg said. "Our hypothesis is that the cargo that vesicles carry has a role in dictating how the coats are made and that explains why we see different structures."

The ability for cells to form vesicles is essential. It is the main route by which molecules like hormones, proteins and viruses enter cells and move within them. If it stops working, cells can die, or disease can take hold in an organism.

Understanding cellular transport is also important because the process is often hijacked by viruses like influenza or the virus that causes COVID-19 to gain entry to the cell.

"Understanding the molecular mechanisms of clathrin-based transport is important because it is such a fundamental process," Stagg said. "It touches on so many cellular processes. The better we understand it, the more likely it is that we can manipulate it to do things like stop virus entry, enhance drug delivery inside cells or modulate neurotransmitter levels in the brain, just to mention a few. It's a really exciting time for clathrin research."

Credit: 
Florida State University

Genetic testing for heart diseases may help patients and families identify risks

DALLAS, July 23, 2020 -- Genetic testing and counseling for inherited cardiovascular diseases may help patients and their families make well-informed decisions about managing their heart health, according to "Genetic Testing for Inherited Cardiovascular Diseases," a new scientific statement from the American Heart Association, published today in the Association's journal Circulation: Genomic and Precision Medicine.

The statement summarizes what we know - and do not know - about the genes or combination of genes that may influence inherited heart diseases and also provides suggestions for best practices for genetic testing.

"Although genetic testing has seen explosive growth in the past few years, both in the clinical setting and with direct-to-consumer testing, genetic testing for heart disease should be reserved for specific patients," said Kiran Musunuru, M.D., Ph.D., M.P.H., M.L., FAHA, chair of the writing group for the scientific statement and professor of cardiovascular medicine and genetics at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

According to the statement, cardiovascular conditions that may have an inherited genetic component include:

cardiomyopathies, heart muscle diseases that can lead to heart failure;

thoracic aortic aneurysms and dissections, syndromes that cause the body's major artery to balloon and rupture;

arrhythmic disorders that predispose people to potentially fatal abnormal heart rhythms; and

familial hypercholesterolemia, or highly LDL elevated cholesterol levels that greatly increase the risk of heart attack.

Before considering genetic testing, a health care provider should work with the patient to document their family medical history, ideally, going back three generations, to determine if there is a pattern of certain types of heart disease. Genetic testing should typically be reserved for patients with a confirmed or suspected diagnosis of an inherited cardiovascular disease or for individuals at high risk due to a previously identified disease-causing variant (a gene abnormality that is different from most humans, often responsible for the clinical disease in question) in their family.

Genetic counseling is essential before genetic testing to educate patients on the process and potential results, as well as the potential risks and uncertainties related to testing. Counseling is also critical after genetic testing, so the counselor can explain the results and potential consequences for the patient's health and the health of family members including children.

Since immediate family members - first-degree relatives such as fathers, mothers, siblings or children - might share genetic variants predisposing them to an inherited cardiovascular disease, they are considered to be at higher risk for the same conditions. Once a genetic variant is identified within a family, all first-degree relatives should consider undergoing genetic testing and counseling for that specific mutation whenever possible.

Genetic counselors can also advise and support patients on the best ways to communicate the news of any genetic variants they may discover through genetic testing to other family members. Although privacy laws restrict the ability of health care professionals to disseminate information directly to potentially affected relatives, they can provide written letters that explain the genetic findings, which the patients can give to their family members.

"With most genetic cardiovascular diseases, inheriting a mutation (or variant) from a parent substantially increases the risk of getting the disease but does not guarantee the disease," said Musunuru. "In some cases, it might be possible to act early and prevent the disease. In other cases, having the mutation for a genetically caused cardiovascular condition might lead to different and possibly more aggressive treatment."

Advances in human genetics are improving the understanding of a variety of inherited cardiovascular diseases. However, there are still limitations. Genetic testing might not reveal a cause or confirm a diagnosis of the patient's disease.

In many cases, genetic testing can reveal a mutation that is called "uninterpretable" or a "variant of uncertain significance." A variant of uncertain significance, or VUS, is not considered either definitively pathogenic (disease causing) or benign, meaning that it's unclear if the patient is at increased risk for disease. Since it is unclear whether the VUS increases the risk of disease or not, it can be challenging for doctors to counsel patients on appropriate treatment.

It is also possible that a patient may be diagnosed with an inherited cardiovascular disease, yet genetic testing doesn't reveal any genetic mutations. This makes it difficult to explain why the patient has the disease and whether any of their family members are also at risk.

"Another issue is that we have not yet clarified the full spectrum of genes that are responsible for various inherited cardiovascular diseases - we are still very much in discovery mode, with ongoing research efforts," added Musunuru. "Genetic testing methods are evolving, and reliable classification of variants identified in genetic testing will remain a preeminent challenge for the practice of clinical genetics."

Credit: 
American Heart Association

Big wheel ruts, big economic losses

image: Aerial photo of wheel-traffic compaction on early-season crop stands in western Minnesota.

Image: 
Jodi DeJong-Hughes

Excessively wet field conditions at harvest throughout the North Central and upper Midwest regions resulted in many fields with deep wheel-traffic compaction as evident by deep ruts from combines and grain wagons. Although this is a common occurrence during years with excessive moisture at harvest, the subsequent economic costs are rarely, if ever, projected for large regions.

In an article recently published in Agricultural & Environmental Letters, researchers review the scientific literature on the persistence and quantity of yield reductions due to deep wheel-traffic compaction and then project the state-level economic costs to farmers that may be expect for the upcoming 2020 and 2021 crops in North Dakota and Minnesota.

The researchers estimate a median of 21% yield reduction to the upcoming 2020 and 2021 corn and soybean crops on lands impacted by deep wheel-traffic compaction during the 2019 harvest. Based on these reductions, they project a minimum economic cost of $587 million USD to farmers for every 10% of lands that were compacted during harvest. Moreover, the actual land area may extend up to 30%, resulting in a range of $0-to-$1.76 billion USD of actual costs to North Dakota and Minnesota farmers.

The findings have implications for government policies incentivizing conservation practices, such as diversified crop rotations and inter-seeding cover crops, to either reduce the occurrence of field traffic on wet soils or promote drier soils at harvest.

Credit: 
American Society of Agronomy

Mammal cells could struggle to fight space germs

The immune systems of mammals - including humans - might struggle to detect and respond to germs from other planets, new research suggests.

Microorganisms (such as bacteria and viruses) could exist beyond Earth, and there are plans to search for signs of them on Mars and some of Saturn and Jupiter's moons.

Such organisms might be based on different amino acids (key building blocks of all life) than lifeforms on Earth.

Scientists from the universities of Aberdeen and Exeter tested how mammal immune cells responded to peptides (combinations of amino acids) containing two amino acids that are rare on Earth but are commonly found on meteorites.

The immune response to these "alien" peptides was "less efficient" than the reaction to those common on Earth.

The study - conducted in mice, whose immune cells function in a similar way to those of humans - suggests extra-terrestrial microorganisms could pose a threat to space missions, and on Earth if they were brought back.

"The world is now only too aware of the immune challenge posed by the emergence of brand new pathogens," said Professor Neil Gow, Deputy Vice-Chancellor (Research and Impact) at the University of Exeter.

"As a thought experiment, we wondered what would happen if we were to be exposed to a microorganism that had been retrieved from another planet or moon where life had evolved.

"Some very unusual organic building blocks exist outside of the planet Earth, and these could be used to make up the cells of such alien microbes.

"Would our immune system be able to detect proteins made from these non-terrestrial building blocks if such organisms were discovered and were brought back to Earth and then accidently escaped?

"Our paper addresses this hypothetical event."

The study was led by scientists at the MRC Centre for Medical Mycology, which moved from Aberdeen to Exeter last year.

Researchers examined the reaction of T cells, which are key to immune responses, to peptides containing amino acids commonly found on meteorites: isovaline and α-aminoisobutyric acid.

The response was less efficient, with activation levels of 15% and 61% - compared to 82% and 91% when exposed to peptides made entirely of amino acids that are common on Earth.

"Life on Earth relies on essential 22 amino acids," said lead author Dr Katja Schaefer, of the University of Exeter.

"We hypothesised that lifeforms that evolved in an environment of different amino acids might contain them in their structure.

"We chemically synthetised 'exo-peptides' containing amino acids that are rare on Earth, and tested whether a mammal immune system could detect them.

"Our investigation showed that these exo-peptides were still processed, and T cells were still activated, but these responses were less efficient than for 'ordinary' Earth peptides.

"We therefore speculate that contact with extra-terrestrial microorganisms might pose an immunological risk for space missions aiming to retrieve organisms from exoplanets and moons."

The discovery of liquid water at several locations in the solar system raises the possibility that microbial life may have evolved outside Earth, and could therefore be accidently introduced into the Earth's ecosystem.

Credit: 
University of Exeter

Diets high in protein, particularly plant protein, linked to lower risk of death

Diets high in protein, particularly plant protein, are associated with a lower risk of death from any cause, finds an analysis of the latest evidence published by The BMJ today.

The researchers say these findings "support current dietary recommendations to increase consumption of plant proteins in the general population."

Diets high in protein, particularly protein from plants such as legumes (peas, beans and lentils), whole grains and nuts, have been linked to lower risks of developing diabetes, heart disease and stroke, while regular consumption of red meat and high intake of animal proteins have been linked to several health problems.

But data on the association between different types of proteins and death are conflicting.

So researchers based in Iran and the USA set out to measure the potential dose-response relation between intake of total, animal, and plant protein and the risk of death from all causes, cardiovascular disease, and cancer.

They reviewed the results of 32 studies that reported risk estimates for all cause, cardiovascular, and cancer mortality in adults aged 19 or older.

All studies were thoroughly assessed for bias (problems in study design that can influence results).

Mathematical models were then used to compare the effects of the highest versus lowest categories of protein intake, and analyses were done to evaluate the dose-response relations between protein intake and mortality.

During a follow-up period of up to 32 years, 113,039 deaths (16,429 from cardiovascular disease and 22,303 from cancer) occurred among 715,128 participants.

The results show that high intake of total protein was associated with a lower risk of all cause mortality compared with low intake.

Intake of plant protein was associated with an 8% lower risk of all cause mortality and a 12% lower risk of cardiovascular disease mortality. Intake of animal protein was not significantly associated with risk of cardiovascular disease and cancer mortality.

A dose-response analysis of data from 31 studies also showed that an additional 3% of energy from plant proteins a day was associated with a 5% lower risk of death from all causes.

Possible reasons for the beneficial effects of plant proteins include their association with favourable changes in blood pressure, cholesterol and blood sugar levels, which might help to lower the risk of conditions such as heart disease and type 2 diabetes, say the researchers.

They point to some limitations, such as differences in the way studies assessed diet and the possibility that some effects may have been due to unmeasured (confounding) factors. What's more, as most of the included studies were from Western nations, the findings may not be applicable to other countries.

However, strengths include the large number of participants and deaths, providing a detailed insight into the association between intake of dietary protein and risk of mortality based on the current evidence, they write.

"These findings have important public health implications as intake of plant protein can be increased relatively easily by replacing animal protein and could have a large effect on longevity," say the researchers.

While further studies are required, these findings "strongly support the existing dietary recommendations to increase consumption of plant proteins in the general population," they conclude.

Credit: 
BMJ Group

Raising legal age for handgun sales to 21 linked to fewer adolescent suicides

Restricting the sale of handguns to those aged 21 or older is associated with a reduction in suicide rates among adolescents in the United States, finds a study published by The BMJ today.

The researchers estimate that hundreds of suicides could be prevented every year in the US if the 33 states where 18 year olds can still buy handguns raised the age limit to 21 years.

Suicide rates have been increasing in the US, particularly among adolescents, with firearms accounting for more than half of these deaths.

A previous study based on suicide data from 1976 to 2001 found that policies restricting the sale of handguns to those aged 21 or older were associated with reductions in firearm related suicides but not overall suicides among adolescents aged 18 to 20 years.

To fill this evidence gap, a team of US researchers led by Julia Raifman at Boston University School of Public Health, used more recent data to re-investigate the relation between the minimum age of handgun purchase in US states and suicide among adolescents.

Their findings are based on suicide data for over 500 million person years from adolescents aged 13 to 20 years in all 46 US states that did not change their policies on age for handgun sales between 2001 and 2017 (a "person year" is the number of years of follow up multiplied by the number of people in the study).

The researchers found state policies that limited the sale of handguns to those aged 18 or older were associated with an increased suicide rate (average 344 extra deaths) among adolescents aged 18 to 20 years between 2001 and 2017, based on an analysis of suicide rates by age.

The researchers also found state policies that limited the sale of handguns to those aged 21 or older were associated with an 18% reduction in the suicide rate among adolescents.

This is equivalent to almost two fewer suicides per 100,000 adolescents aged 18 to 20 years, based on analysis of how suicide rates changed before and after states changed the minimum age of handgun purchase.

Further analysis indicated increases in suicide rates in states that lowered the age of handgun sales (Missouri and South Carolina), but no effect was found in states that increased the age of handgun sales (West Virginia and Wyoming) during the study period.

It is possible that the high levels of firearm ownership in Wyoming and West Virginia (66% and 59% of households in 2004, relative to 38% in the 46 comparison states) meant that the change in age of handgun purchases had little effect on access to firearms by adolescents in these states, note the researchers.

This is an observational study, so can't establish cause, and the researchers point to some limitations, such as underreporting of suicides and the possibility that adolescents might cross state lines to buy firearms where age limits are lower.

However, key strengths include use of data on the full population of adolescents in all US states and the complementary, rigorous analytical approaches.

As such, they say "changing the age of handgun sales policies from 18 to 21 years across the country or in the 33 states without such policies might reduce deaths from suicide among adolescents."

Such a change is in keeping with public sentiment, they add, noting that in 2018, 67% of American adults reported support for more policies regulating firearms.

But in a linked editorial, researchers argue that age limits on purchasing won't protect the many young people already living with firearms.

Professor Ann John and colleagues point out that most firearms used by people who die from suicide have been in their homes for years - and that in the US, one in three homes with children contain firearms and in half of these homes, the firearms are not locked up.

They acknowledge that legislation that increases the age at which handguns can be acquired "will likely prevent at least some suicides in young people."

However, they say without accompanying efforts to substantially reduce young people's access to household firearms (both long guns and handguns), "sales laws alone might make us feel better but are unlikely to save many lives."

Credit: 
BMJ Group

New CCC19 data offer insights on COVID treatments for people with cancer

image: Jeremy Warner, MD, MS, associate professor Medicine and Biomedical Informatics at Vanderbilt University, the study's corresponding author.

Image: 
Vanderbilt University Medical Center

Newly released data on treatment outcomes of people with cancer diagnosed with COVID-19 reveal a racial disparity in access to Remdesivir, an antiviral drug that has been shown to shorten hospital stays, and increased mortality associated with dexamethasone, a steroid that has had the opposite effect in the general patient population.

The data on 2,186 adults in the United States by the COVID-19 and Cancer Consortium (CCC19) published July 22 in Cancer Discovery is the largest cancer-specific observational study to date of treatments purported to improve COVID-19 outcomes. The data were published shortly after a keynote address by Solange Peters, MD, PhD, president of the European Society for Medical Oncology and one of the study's lead authors, at the American Association for Cancer Research Virtual Meeting: COVID-19 and Cancer.

In this updated report from CCC19, the consortium's researchers confirm and expand upon earlier observations that there was broad use of unproven COVID-19 therapies, almost all of which were outside of clinical trials.

The steroid dexamethasone lowered the death rate among critically ill patients, according to data from the RECOVERY trial in the United Kingdom, but the CCC19 data indicate an association with increased mortality among cancer patients. In the CCC19 analysis, patients receiving high-dose corticosteroids with any other potential COVID-19 treatment were more than twice as likely to die, as compared to patients treated with other medications or patients not requiring any treatment. There were very small numbers of patients treated just with steroids, making analysis of steroids in isolation difficult.

"There is so much enthusiasm about dexamethasone, but our findings in a relatively small subgroup suggest that steroids could be associated with increased mortality in the cancer population," said Jeremy Warner, MD, MS, associate professor Medicine and Biomedical Informatics at Vanderbilt University, the study's corresponding author. "This does have some rational explanation, since cancer is already an immunocompromised state and steroids could potentially make things worse. The RECOVERY trial is the first to show a survival benefit for any treatment of COVID-19, but that study just published in The New England Journal of Medicine does not provide details for the subgroup of patients with cancer."

Remdesivir, which was primarily available as a clinical trial option, was associated with a lower mortality rate when compared to patients receiving any other potential COVID-19 treatment. Black patients were half as likely to receive Remdesivir as white patients.

"Our study reinforces the finding that most COVID-19 treatment occurs outside the context of a formal clinical trial," Warner said. "The exception to this was the drug Remdesivir, which was given mostly through the clinical trial setting. It appears that Black patients were underrepresented in the clinical trials of Remdesivir, likely due to reasons other than purely clinical factors. The unfortunate conclusion is that racial disparities in access to clinical trials continue to exist, and one of our recommendations is that the necessary steps to address such disparities need to be accelerated, especially given that Black patients and other people of color appear to be taking the brunt of the COVID-19 pandemic."

This is the second study and release of data by CCC19. While the mortality rate among cancer patients affected by COVID-19 was 13% in the prior study of 928 patients, the rate was 16% in the newly published study, which involved 2,186 patients.

Patients on the West Coast were more likely to have received Remdesivir and less likely to have been treated with hydroxychloroquine, which a number of studies have shown to be an ineffective treatment that is associated with higher mortality. One reason could be that the number of cases increased on the West Coast after more information was known about the benefits and risks of the two treatments, Warner said.

"We can be much more definitive in stating the risk and ineffectiveness of hydroxychloroquine with this enhanced analysis," said co-senior author, Gary Lyman, MD, MPH, professor of Public Health Sciences and Clinical Research at Fred Hutchinson Cancer Research Center in Seattle. "This higher mortality association is despite what appears to be rational decision making, such as less utilization of this drug in patients with cardiovascular comorbidities."

Credit: 
Vanderbilt University Medical Center

Mapping the brain's sensory gatekeeper

CAMBRIDGE, MA -- Many people with autism experience sensory hypersensitivity, attention deficits, and sleep disruption. One brain region that has been implicated in these symptoms is the thalamic reticular nucleus (TRN), which is believed to act as a gatekeeper for sensory information flowing to the cortex.

A team of researchers from MIT and the Broad Institute of MIT and Harvard has now mapped the TRN in unprecedented detail, revealing that the region contains two distinct subnetworks of neurons with different functions. The findings could offer researchers more specific targets for designing drugs that could alleviate some of the sensory, sleep, and attention symptoms of autism, says Guoping Feng, one of the leaders of the research team.

"The idea is that you could very specifically target one group of neurons, without affecting the whole brain and other cognitive functions," says Feng, the James W. and Patricia Poitras Professor of Neuroscience at MIT and a member of MIT's McGovern Institute for Brain Research.

Feng; Zhanyan Fu, associate director of neurobiology at the Broad Institute's Stanley Center for Psychiatric Research; and Joshua Levin, a senior group leader at the Broad Institute, are the senior authors of the study, which appears today in Nature. The paper's lead authors are former MIT postdoc Yinqing Li, former Broad Institute postdoc Violeta Lopez-Huerta, and Broad Institute research scientist Xian Adiconis.

Distinct populations

When sensory input from the eyes, ears, or other sensory organs arrives in our brains, it goes first to the thalamus, which then relays it to the cortex for higher-level processing. Impairments of these thalamo-cortical circuits can lead to attention deficits, hypersensitivity to noise and other stimuli, and sleep problems.

One of the major pathways that controls information flow between the thalamus and the cortex is the TRN, which is responsible for blocking out distracting sensory input. In 2016, Feng and MIT Assistant Professor Michael Halassa, who is also an author of the new Nature paper, discovered that loss of a gene called Ptchd1 significantly affects TRN function. In boys, loss of this gene, which is carried on the X chromosome, can lead to attention deficits, hyperactivity, aggression, intellectual disability, and autism spectrum disorders.

In that study, the researchers found that when the Ptchd1 gene was knocked out in mice, the animals showed many of the same behavioral defects seen in human patients. When it was knocked out only in the TRN, the mice showed only hyperactivity, attention deficits, and sleep disruption, suggesting that the TRN is responsible for those symptoms.

In the new study, the researchers wanted to try to learn more about the specific types of neurons found in the TRN, in hopes of finding new ways to treat hyperactivity and attention deficits. Currently, those symptoms are most often treated with stimulant drugs such as Ritalin, which have widespread effects throughout the brain.

"Our goal was to find some specific ways to modulate the function of thalamo-cortical output and relate it to neurodevelopmental disorders," Feng says. "We decided to try using single-cell technology to dissect out what cell types are there, and what genes are expressed. Are there specific genes that are druggable as a target?"

To explore that possibility, the researchers sequenced the messenger RNA molecules found in neurons of the TRN, which reveals genes that are being expressed in those cells. This allowed them to identify hundreds of genes that could be used to differentiate the cells into two subpopulations, based on how strongly they express those particular genes.

They found that one of these cell populations is located in the core of the TRN, while the other forms a very thin layer surrounding the core. These two populations also form connections to different parts of the thalamus, the researchers found. Based on those connections, the researchers hypothesize that cells in the core are involved in relaying sensory information to the brain's cortex, while cells in the outer layer appear to help coordinate information that comes in through different senses, such as vision and hearing.

"Druggable targets"

The researchers now plan to study the varying roles that these two populations of neurons may have in a variety of neurological symptoms, including attention deficits, hypersensitivity, and sleep disruption. Using genetic and optogenetic techniques, they hope to determine the effects of activating or inhibiting different TRN cell types, or genes expressed in those cells.

"That can help us in the future really develop specific druggable targets that can potentially modulate different functions," Feng says. "Thalamo-cortical circuits control many different things, such as sensory perception, sleep, attention, and cognition, and it may be that these can be targeted more specifically."

This approach could also be useful for treating attention or hypersensitivity disorders even when they aren't caused by defects in TRN function, the researchers say.

"TRN is a target where if you enhance its function, you might be able to correct problems caused by impairments of the thalamo-cortical circuits," Feng says. "Of course we are far away from the development of any kind of treatment, but the potential is that we can use single-cell technology to not only understand how the brain organizes itself, but also how brain functions can be segregated, allowing you to identify much more specific targets that modulate specific functions."

Credit: 
Massachusetts Institute of Technology

AJTMH July updates

Below is an update of COVID-19 articles published in the American Journal of Tropical Medicine and Hygiene (AJTMH). We've highlighted below those that we think may of interest for your reporting.

The Origin of COVID-19 - and Why It Matters: Embargoed until July 22, 2020 at 5:00 PM ET. Email press contact for a copy of the study.

This new perspective offers credible, scientific authority to the narrative and ongoing exploration of how COVID-19 began. The exploration of the origins argues that available data establishes that our current pandemic virus emerged directly or indirectly from bats prevalent in Asia.

The authors point out that scientists have warned since at least 2007 about the emergence and re-emergence of SARS-like viruses, yet few preventive actions have been taken. They call for "vigorous scientific, public health, and societal actions, including significantly increased funding for basic and applied research addressing disease emergence, to prevent this tragic history from repeating itself."

Keep Politics out of Funding Decisions for Medical Research and Public Health: Embargoed until July 22, 2020 at 5:00 PM ET. Email press contact for a copy of the editorial.

Members of American Society of Tropical Medicine and Hygiene's Executive Committee wrote an editorial on the value of science and the ways that the current administration is undermining efforts to protect and improve human health. Recent decisions by the White House are detrimental to human health, especially during the pandemic. The authors urge the President to reinstate essential funding to research coronaviruses and to continue the United States' relationship with the World Health Organization.

Credit: 
Burness