Culture

Optical imaging enters sub-nanometer era

image: Schematic of the experimental set-up for single-molecule photoluminescence imaging with sub-nanometer resolution

Image: 
YANG Ben, HUANG Wen et al.

Prof. DONG Zhenchao and Prof. HOU Jianguo from University of Science and Technology of China (USTC) of Chinese Academy of Sciences (CAS) improved the spatial resolution from 8 nm to ~8 Å of photoluminescence imaging. It realized sub-molecular resolution with single molecule photofluorescence imaging for the first time.

This study was published in Nature Photonics on August 10.

To reach atomic resolution with light has always been one of the ultimate goals in nano-optics. The advent of scanning near-field optical microscopy (SNOM) kindled hopes for the goal.

Prof. DONG and his colleagues successfully demonstrated sub-nanometer scale spatial resolution in the single-molecule Raman spectroscopy imaging with local enhancement effect of a nanocavity plasmon field in a study in 2013.

However, unlike the Raman scattering process, fluorescence will be quenched in the very immediate vicinity of metals which stops the resolution development of SNOM at around 10 nm.

The radiation properties (fluorescence) of molecules in the metal nanocavity are directly affected by the photon density of the nanocavity , and the photon density of the nanocavity is closely related to the structure of the probe tip. Therefore, it is the key to modify the structure of the probe and the electronic state of the molecules in the nanocavity to avoid the fluorescence quenching and achieve high-resolution photofluorescence imaging.

DONG's team further fine-tuned the plasmon nanocavity, especially in the fabrication and control of the atomic-level structure of the probe tip. They constructed an Ag tip apex with an atomistic protrusion and matched the nanocavity plasmon resonance with the effective energy of the incident laser and molecular luminescence.

Then, the researchers used an ultra-thin dielectric layer (three-atom-thick NaCl) to isolate the charge transfer between the nanocavity molecules and the metal substrate, achieving sub-nanometer resolution of the single-molecule photoluminescence imaging.

They found that with the probe approaching the molecule, even if their distance is less than 1 nm, the intensity of photoluminescence continues increasing monotonously. And the fluorescence quenching disappears completely.

Theoretical simulations showed that when the atomistic protrusion tip and the metal substrate form a plasmon nanocavity, the resonance response of the nanocavity plasmon and the lightning rod effect of the atomistic protrusion structure would have a synergistic effect. The synergistic effect generates a strong and highly localized electromagnetic field compressing the cavity mode volume to below 1 nm3, which greatly increases the localized photon density of states and the molecular radiation decay rate. These effects not only inhibit the fluorescence quenching, but also realize sub-nanometer-resolution photoluminescence imaging.

To achieve sub-nanometer spatial resolution, the size of the tip and the distance between the tip and the sample must be on the sub-nanometer scale.

The researchers further realized sub-molecular-resolved photoluminescence hyperspectral imaging with spectral information, and demonstrated the effects of local plasmon-exciton interaction on fluorescence intensity, peak position and peak width on the sub-nanometer scale.

This research achieved the long-awaited goal of using light to analyze the internal structure of molecules in SNOM, and provided a new technical method for detecting and modulating the localized environment of molecules and light-matter interactions on the sub-nanometer scale.

The reviewers of Nature Photonics say that this paper will be an important article in its field, which has guiding significance for carrying out ultra-sensitive spectroscopic microscopy research with atomic-scale light.

Credit: 
University of Science and Technology of China

New evaluation of universal health coverage, world will likely fall short of WHO goal

SEATTLE (August 27, 2020) - A new study projects that 3.1 billion people will still lack effective health service coverage in 2023, with 968 million of those residing in South Asia. This falls short of the World Health Organization (WHO) goal of 1 billion more people benefiting from universal health coverage (UHC) between 2019 and 2023.

Universal health coverage is defined as all people receiving quality health services without incurring financial hardship. The paper, part of the Global Burden of Disease study, was published today in the international medical journal The Lancet. Researchers focused only on measuring service coverage, developing a new framework to capture how well countries align health services with the needs of the population and how well or poorly those services contribute to people's health.

"Universal health coverage is more than just access to health care," said Dr. Rafael Lozano, the senior author of the study and Director of Health Systems at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington School of Medicine. "Measuring access is necessary but not sufficient to capture health outcomes. By striving to capture potential health gains, we hope to better diagnose and address challenges that impede the ultimate objective of UHC: improving health for all people and leaving no one behind."

Using 23 indicators, the researchers assessed effective coverage by country on a scale of 1-100 and measured progress between 1990 and 2019. Globally, UHC effective coverage performance improved by nearly 15 points over that time period, but large variations remained across countries and regions, ranging from over 96 to below 25. Japan had the highest effective coverage score (96.4) in 2019, followed by Iceland, Norway, Switzerland, and San Marino. The Central African Republic, Somalia, Chad, Guinea, and Vanuatu had the lowest performance on UHC effective coverage.

Sub-Saharan Africa had accelerated gains since 2010 compared to other regions, nearly doubling average annual improvement between 2010 and 2019 compared to 1990-2010. Zimbabwe, eSwatini, the Democratic Republic of the Congo, Guinea-Bissau, and South Africa had the fastest growth in effective coverage performance.

The researchers also found that many countries lagged on performance for non-communicable diseases, compared to communicable diseases and reproductive, maternal, and child health. Globally, non-communicable diseases accounted for a greater proportion of potential health gains in 2019.

However, in some countries, like Kenya, Namibia, and Rwanda, causes beyond non-communicable diseases still have a high level of disease burden (e.g., HIV) and are an important area for policymakers and practitioners to prioritize. The different scenarios highlight the value of measuring effective service coverage, which can help inform UHC priorities that align with a country's health needs and evolve with those needs over time, rather than a one-size-fits-all approach to service coverage.

The study did not measure the financial risk protection component of UHC, but the researchers did look at per capita health spending by country. While they found that increased spending could be important for many countries to improve UHC effective coverage performance, efficiencies in health systems are also an important component.

Health spending and its relationship to universal health effective coverage is also explored in IHME's recently published report on global health financing. Countries with high performance relative to spending levels included Peru, Rwanda, South Korea, Cyprus, and Costa Rica. The United States, Central African Republic, Turkmenistan, and Saudi Arabia were among those countries with low performance relative to spending levels.

"We are seeing countries with varied performance at the same level of spend - an indicator that money spent on health is not being translated as efficiently as it could into gains in UHC effective coverage," said Dr. Christopher Murray, IHME Director and a senior author on the study. "For most countries, increased health spending alone is unlikely to deliver on ambitious UHC targets. Improving alignment of health systems with population health needs and bolstering efficiencies, along with more money, will likely result in faster and more sustained gains."

The study was completed prior to the COVID-19 pandemic but provides an important benchmark for measuring the impact of the pandemic and progress on UHC in years to come. It also highlights the value of effective data systems.

"Whether it's a rapidly spreading virus or persistent gaps in health service delivery, establishing and maintaining strong data systems are crucial to identifying health needs and effectively responding to them so that all people, within a country and around the world, have the opportunity to live full, healthy lives," said Nancy Fullman, a PhD student in global health at the University of Washington and one of the study's lead authors.

Credit: 
Institute for Health Metrics and Evaluation

Study confirms link between influenza, heart complications

The link between influenza and serious heart conditions just grew stronger.

A CDC study looking at more than 80,000 adult patients hospitalized with flu over eight seasons found that sudden, serious heart complications were common, occurring in 12% of patients, or 1 in 8.

"Previous to our study, there had been suggestions between the link, but our study shows just how common it is," said lead author Eric Chow, an infectious diseases fellow at University of Washington School of Medicine.

The study, published Aug. 25 in the Annals of Internal Medicine, underscores the importance of getting a flu shot early.

"There are few respiratory viruses we have a vaccine for," he said. "Our team motto is 'Get a flu shot.'" Chow previously worked as an epidemic intelligence service officer, or "disease detective," for influenza at the Centers for Disease Control and Prevention.

The study found that 5% of patients hospitalized with the flu had a cardiac complication despite having no documented underlying conditions.

In the last month, there have been cases of otherwise healthy athletes showing signs of heart complications after recovering from COVID-19. For example, 27-year-old Florida State basketball player Michael Ojo, who recovered from COVID-19, died of an apparent heart attack at a practice.

Chow said he is not surprised this is happening to healthy people who have been infected with SARS-CoV-2, the virus that causes COVID-19. The virus can cause damage to the lungs and other organs, including the heart. Inflammation makes hearts vulnerable to potentially fatal arrhythmias during vigorous exercise.

In this study of adults hospitalized with flu, 12% had acute heart complications. Of these, 30% were admitted to the ICU and 7% died while in the hospital.

The CDC recommends that everyone 6 months and older get a flu vaccine every flu season. According to the CDC, flu vaccination is always considered important for people at high risk of developing serious flu complications, including people with heart disease. Flu shots are approved for people with heart disease, but people with heart disease should not receive the live attenuated influenza vaccine (LAIV, also known as the nasal spray flu vaccine). However any intramuscular flu shot, such as any inactivated or recombinant influenza vaccine, would be appropriate.

Credit: 
University of Washington School of Medicine/UW Medicine

The northern quoll: An amazingly versatile survivor?

image: Illustration of northern quolls by Nellie Pease

Image: 
Nellie Pease

The northern quoll, one of Australia's most adorable and endangered native carnivores, appears to be adapted to dramatically different landscapes - which may be key to the species' survival.

University of Queensland PhD candidate Pietro Viacava co-led a study that found similarities between northern quoll skulls across a 5000 kilometre range, which has raised hopes scientists will be able to cross-breed isolated populations.

"Northern quolls are in danger - a lot has been thrown at them," Mr Viacava said.

"They've been victims of a devastating cane toad invasion, increases in bushfires and habitat fragmentation, all while facing stiff competition from other carnivores such as dingoes and cats.

"The problem we are facing with conserving the northern quoll is that there may be too little genetic diversity in these handful of remaining populations, scattered across Australia.

"If we cross-bred them, we might run the risk that they wouldn't be ideally suited to these diverse environments.

"Their skulls, for example, might not be properly adapted to eat local prey, as it differs across Australia.

"Luckily, this doesn't seem to be the case - these quolls seem to be incredibly versatile."

The research team used a technique known as 'geometric morphometrics' to characterise skull shape variation in museum specimens of northern quolls.

They looked for shape differences between populations, or whether environmental conditions coincided with changes in skull shape.

Dr Vera Weisbecker from the Flinders University College of Science and Engineering supervised the study, and said the results appeared to be a win for northern quoll conservation.

"Quoll skull shapes were mostly similar across their entire range, although the shapes did vary with the size of the animals," Dr Weisbecker said.

"This means, for example, that a quoll skull from Pilbara region in WA looked nearly the same as a similar-sized one from south-eastern Queensland, 5000 kilometres apart.

"Although other parts of the animal's body and genetic factors need to be considered, we will most likely be able to breed animals from different populations for conservation without losing adaptations to feeding."

However, there is also a much less positive potential explanation for the results.

"Scientists have long suspected that marsupial mammals - such as quolls, kangaroos and koalas - are seriously limited in the degree to which they can adapt their skull and skeleton," Dr Weisbecker said.

"This is because newborn marsupials require a specifically shaped snout to be able to latch onto the mother's teat.

"In that case, what we see may actually be a serious limitation on the ability of quolls to adapt, rather than the much more hopeful multipurpose solution we propose."

To further explore this possibility, the team is now looking at how closely related species of antechinus - smaller quoll relatives - differ in skull shape.

Credit: 
University of Queensland

COVID-19 less deadly and causes milder symptoms in children

Children and teenagers are less likely than adults to develop severe Covid-19 or die from the disease, according to the world's largest study of hospital patients with Covid-19.

Obesity, Black ethnicity and being under one month old are factors that increased the risk of a child being admitted into intensive care with the condition, the report said.

The findings also identify new symptoms of a severe inflammation syndrome that significantly increases the risk of children with Covid-19 needing intensive care.

Researchers are calling for the WHO's definition of Multisystem Inflammatory Syndrome in Children (MIS-C) to be updated to help doctors identify more children with the condition and improve their treatment.

The team led by researchers from the Universities of Edinburgh and Liverpool, Imperial College London and the Royal Hospital for Children, Glasgow, recruited 651 children and young people aged 19 years or less who had been admitted to hospital with Covid-19.

The study is led by ISARIC4C - a global group of clinicians working to prevent death from respiratory disease - and involved 138 hospitals across England, Wales and Scotland. The ISARIC4C Covid-19 study includes two thirds of all people admitted to hospital with the disease.

The findings suggest that it is rare for young people to end up in hospital with Covid-19. They make up less than one per cent of participants in the ISARIC study.

The typical age of children hospitalised was five-years-old. Some 42 per cent of patients had at least one other condition, the most common included neurological conditions and asthma.

The number of children and young people who died from Covid-19 was relatively low - six in total - when compared with adult deaths.

Three children who died were newborn babies born with other severe health problems. The other three children were aged 15 to 18 years old and also had profound health issues.

Some 18 per cent of hospitalised children and young people were admitted to intensive care. Experts say children most at risk of needing intensive care were those under one month old and those aged 10 to 14 years old. Similar to adults, obesity and Black ethnicity were also found to be risk factors.

The study also identified 52 patients who had MIS-C an inflammatory syndrome. The researchers found that these children were five times more likely to be admitted to intensive care.

The symptoms usually seen in those with MIS-C include conjunctivitis, a rash or gastrointestinal problems such as abdominal pain, vomiting and diarrhea.

The study found new Covid-19 symptoms in children with MIS-C. These include headaches, tiredness, muscle aches and a sore throat.

The study also found that the number of platelets - a component of the blood involved in clotting - was much lower in the blood of children with MIS-C than in those without the condition.

The combination of symptoms and low platelets may be important in identifying children with MIS-C who may become more unwell, experts say.

This research was funded by UK Research and Innovation (UKRI) and by the Department of Health and Social Care through the National Institute for Health Research (NIHR) as part of the UK Government's Covid-19 rapid research response.

Dr Olivia Swann, lead author and Clinical Lecturer in Paediatric Infectious Diseases at the University of Edinburgh, said: "Researchers often want to call attention to large numbers of patients in their studies, however, we want to highlight that children made up only a fraction of a percent of all Covid-19 admissions across the UK in our study and that severe disease was rare."

Professor Calum Semple, Professor in Child Health and Outbreak Medicine and Consultant Respiratory Paediatrician at the University of Liverpool, said: "The diligent work of our colleagues working in Child Health and the NIHR Clinical Research Network across the UK has led to this report which is the largest and most detailed description of covid-19 and MIS-C in children and young people. We have provided new understanding about MIS-C which will help manage this rare but serious condition, but parents can now be reassured that severe covid-19 is very rare in children."

Dr Louisa Pollock, Consultant in Paediatric Infectious Disease at the Royal Hospital for Children, Glasgow, said: "Parents should be reassured by this study which confirms very few children were seriously affected by Covid-19. As children return to school, and over the winter months, it is important we continue to monitor Covid-19 in children."

Professor Fiona Watt, Medical Research Council Chief Executive, said: "This is a significant study involving 138 hospitals across England, Wales and Scotland showing that children and teenagers are less likely than adults to develop severe COVID-19 or die from the disease. Indeed, the findings suggest it is rare for young people to end up in hospital with COVID-19.

"However, while the overall the risk for young people is lower, the added risks of obesity and ethnicity are shared with adults. We need to understand this, and also why a very small number of children are suffering from an inflammatory syndrome. Obviously the goal is to ensure that everyone who develops COVID-19 has the most appropriate treatment."

Credit: 
University of Edinburgh

Cochlear implants should be recommended for adults more often

An international group of hearing specialists has released a new set of recommendations emphasizing that cochlear implants should be offered to adults who have moderate to severe or worse hearing loss much more often than is the current practice. The group hopes the recommendations help increase usage of such devices, potentially improving hearing and quality of life for millions worldwide.

The consensus statement, published Aug. 27 in JAMA Otolaryngology, was developed by a panel of 31 hearing experts representing more than a dozen countries. Craig A. Buchman, MD, the Lindburg Professor and head of the Department of Otolaryngology-Head & Neck Surgery at Washington University School of Medicine in St. Louis, led the panel.

Unlike hearing aids, which amplify sound for people who retain some ability to hear, cochlear implants help people hear by directly stimulating the auditory nerve.

The committee of hearing experts, which includes otolaryngologists and audiologists, said that the estimated 50 million people living with hearing loss severe enough to negatively affect quality of life could benefit from cochlear implants. The recommendations also are intended to raise awareness among primary care doctors and other health-care providers who potentially could diagnose hearing loss and refer patients to hearing specialists.

"Even though cochlear implants have been approved by the Food and Drug Administration since 1985, less than 10% of adults who could benefit from them actually receive one of these devices," Buchman said. "There may be a misconception that cochlear implants are only for young children born with profound hearing loss. But these devices can be extremely effective for adults who have lost hearing later in life. Adults who have difficulty talking on the phone, for example, are probably candidates for a cochlear implant."

Buchman also said adults and their doctors may turn to hearing aids because they assume such devices will solve the problem and help avoid what is perceived by many to be a major surgery.

"Cochlear implants can be implanted in an outpatient procedure that typically takes about an hour," Buchman said. "It's a safe procedure and highly effective. In addition, hearing aids only work for those who need some amplification. But as hearing diminishes, people start to lose clarity as well. Making unclear speech louder doesn't help with comprehension -- people start to sound like the teacher who mumbles in the Charlie Brown cartoon. At that degree of hearing loss, a cochlear implant is the recommended intervention because it can restore clarity."

The consensus paper reports 20 statements that the panel of experts voted to include in the document. The recommendations, which were arrived upon following a review of scientific literature on cochlear implants, cover seven categories for adults with moderate to severe or worse hearing loss in both ears. They focus on:

Awareness of cochlear implants.

Best practice guidelines for diagnosing hearing loss.

Best practice guidelines for cochlear implant surgery.

Clinical effectiveness of cochlear implants.

Factors linked to outcomes after cochlear implant surgery.

Relationship between hearing loss, depression, social isolation and dementia.

Cost implications for cochlear implants.

Buchman said another possible barrier to wider adoption is that hearing loss is surprisingly difficult to diagnose. Primary care offices do not always have the specialized equipment used to test hearing, and patients are adept at finding ways to cope with diminishing ability to hear.

"During a one-on-one checkup, it's actually quite easy for doctors to miss even severe hearing loss," Buchman said. "Hearing loss can happen gradually, and people may not notice the degree to which they are relying on lip reading and the context of what they can hear to compensate for what they're missing. But to compensate for lost hearing successfully, they need to have face-to-face interactions."

"If you are a doctor having a wellness visit with a patient, a simple way to screen for hearing loss is to go to the sink and wash your hands," he said. "With the water running and your back to the patient, try asking a few questions. If the patient doesn't respond in that situation, it's appropriate to start a conversation about hearing loss with him or her and discuss whether formal hearing tests are appropriate."

Hearing loss has been associated with social isolation, depression and dementia. Though research is ongoing to understand the role of hearing loss in these problems, Buchman and his colleagues said strong evidence suggests that improving hearing can have a significant impact on quality of life.

"Research indicates that hearing loss is the single largest modifiable risk factor for dementia, and cochlear implants can perhaps lessen that risk," he said. "We hope these recommendations will eventually lead to formal clinical practice guidelines. Such guidelines could increase access to cochlear implants worldwide, address disparities in care, and lead to improved hearing and quality of life for adults living with debilitating hearing loss."

Credit: 
Washington University School of Medicine

Our energy hunger is tethered to our economic past

Just as a living organism continually needs food to maintain itself, an economy consumes energy to do work and keep things going. That consumption comes with the cost of greenhouse gas emissions and climate change, though. So, how can we use energy to keep the economy alive without burning out the planet in the process?

In a paper in PLOS ONE, University of Utah professor of atmospheric sciences Tim Garrett, with mathematician Matheus Grasselli of McMaster University and economist Stephen Keen of University College London, report that current world energy consumption is tied to unchangeable past economic production. And the way out of an ever-increasing rate of carbon emissions may not necessarily be ever-increasing energy efficiency--in fact it may be the opposite.

"How do we achieve a steady-state economy where economic production exists, but does not continually increase our size and add to our energy demands?" Garrett says. "Can we survive only by repairing decay, simultaneously switching existing fossil infrastructure to a non-fossil appetite? Can we forget the flame?"

Thermoeconomics

Garrett is an atmospheric scientist. But he recognizes that atmospheric phenomena, including rising carbon dioxide levels and climate change, are tied to human economic activity. "Since we model the earth system as a physical system," he says, "I wondered whether we could model economic systems in a similar way."

He's not alone in thinking of economic systems in terms of physical laws. There's a field of study, in fact, called thermoeconomics. Just as thermodynamics describe how heat and entropy (disorder) flow through physical systems, thermoeconomics explores how matter, energy, entropy and information flow through human systems.

Many of these studies looked at correlations between energy consumption and current production, or gross domestic product. Garrett took a different approach; his concept of an economic system begins with the centuries-old idea of a heat engine. A heat engine consumes energy at high temperatures to do work and emits waste heat. But it only consumes. It doesn't grow.

Now envision a heat engine that, like an organism, uses energy to do work not just to sustain itself but also to grow. Due to past growth, it requires an ever-increasing amount of energy to maintain itself. For humans, the energy comes from food. Most goes to sustenance and a little to growth. And from childhood to adulthood our appetite grows. We eat more and exhale an ever-increasing amount of carbon dioxide.

"We looked at the economy as a whole to see if similar ideas could apply to describe our collective maintenance and growth," Garrett says. While societies consume energy to maintain day to day living, a small fraction of consumed energy goes to producing more and growing our civilization.

"We've been around for a while," he adds. "So it is an accumulation of this past production that has led to our current size, and our extraordinary collective energy demands and CO2 emissions today."

Growth as a symptom

To test this hypothesis, Garrett and his colleagues used economic data from 1980 to 2017 to quantify the relationship between past cumulative economic production and the current rate at which we consume energy. Regardless of the year examined, they found that every trillion inflation-adjusted year 2010 U.S. dollars of economic worldwide production corresponded with an enlarged civilization that required an additional 5.9 gigawatts of power production to sustain itself . In a fossil economy, that's equivalent to around 10 coal-fired power plants, Garrett says, leading to about 1.5 million tons of CO2 emitted to the atmosphere each year. Our current energy usage, then, is the natural consequence of our cumulative previous economic production.

They came to two surprising conclusions. First, although improving efficiency through innovation is a hallmark of efforts to reduce energy use and greenhouse gas emissions, efficiency has the side effect of making it easier for civilization to grow and consume more.

Second, that the current rates of world population growth may not be the cause of rising rates of energy consumption, but a symptom of past efficiency gains.

"Advocates of energy efficiency for climate change mitigation may seem to have a reasonable point," Garrett says, "but their argument only works if civilization maintains a fixed size, which it doesn't. Instead, an efficient civilization is able to grow faster. It can more effectively use available energy resources to make more of everything, including people. Expansion of civilization accelerates rather than declines, and so do its energy demands and CO2  emissions."

A steady-state decarbonized future?

So what do those conclusions mean for the future, particularly in relation to climate change? We can't just stop consuming energy today any more than we can erase the past, Garrett says. "We have inertia. Pull the plug on energy consumption and civilization stops emitting but it also becomes worthless. I don't think we could accept such starvation."

But is it possible to undo the economic and technological progress that have brought civilization to this point? Can we, the species who harnessed the power of fire, now "forget the flame," in Garrett's words, and decrease efficient growth?

"It seems unlikely that we will forget our prior innovations, unless collapse is imposed upon us by resource depletion and environmental degradation," he says, "which, obviously, we hope to avoid."

So what kind of future, then, does Garrett's work envision? It's one in which the economy manages to hold at a steady state--where the energy we use is devoted to maintaining our civilization and not expanding it.

It's also one where the energy of the future can't be based on fossil fuels. Those have to stay in the ground, he says.

"At current rates of growth, just to maintain carbon dioxide emissions at their current level will require rapidly constructing renewable and nuclear facilities, about one large power plant a day. And somehow it will have to be done without inadvertently supporting economic production as well, in such a way that fossil fuel demands also increase."

It's a "peculiar dance," he says, between eliminating the prior fossil-based innovations that accelerated civilization expansion, while innovating new non-fossil fuel technologies. Even if this steady-state economy were to be implemented immediately, stabilizing CO2 emissions, the pace of global warming would be slowed--not eliminated. Atmospheric levels of CO2 would still reach double their pre-industrial level before equilibrating, the research found.

By looking at the global economy through a thermodynamic lens, Garrett acknowledges that there are unchangeable realities. Any form of an economy or civilization needs energy to do work and survive. The trick is balancing that with the climate consequences.

"Climate change and resource scarcity are defining challenges of this century," Garrett says. "We will not have a hope of surviving our predicament by ignoring physical laws."

Future work

This study marks the beginning of the collaboration between Garrett, Grasselli and Keen. They're now working to connect the results of this study with a full model for the economy, including a systematic investigation of the role of matter and energy in production.

"Tim made us focus on a pretty remarkable empirical relationship between energy consumption and cumulative economic output," Grasselli says. "We are now busy trying to understand what this means for models that include notions that are more familiar to economists, such as capital, investment and the always important question of monetary value and inflation."

Credit: 
University of Utah

Meteorite study suggests Earth may have been wet since it formed

A new study finds that Earth's water may have come from materials that were present in the inner solar system at the time the planet formed -- instead of far-reaching comets or asteroids delivering such water. The findings published Aug. 28 in Science suggest that Earth may have always been wet.

Researchers from the Centre de Recherches Petrographiques et Geochimiques (CRPG, CNRS/Universite de Lorraine) in Nancy, France, including one who is now a postdoctoral fellow at Washington University in St. Louis, determined that a type of meteorite called an enstatite chondrite contains sufficient hydrogen to deliver at least three times the amount of water contained in the Earth's oceans, and probably much more.

Enstatite chondrites are entirely composed of material from the inner solar system -- essentially the same stuff that made up the Earth originally.

"Our discovery shows that the Earth's building blocks might have significantly contributed to the Earth's water," said lead author Laurette Piani, a researcher at CPRG. "Hydrogen-bearing material was present in the inner solar system at the time of the rocky planet formation, even though the temperatures were too high for water to condense."

The findings from this study are surprising because the Earth's building blocks are often presumed to be dry. They come from inner zones of the solar system where temperatures would have been too high for water to condense and come together with other solids during planet formation.

The meteorites provide a clue that water didn't have to come from far away.

"The most interesting part of the discovery for me is that enstatite chondrites, which were believed to be almost 'dry,' contain an unexpectedly high abundance of water," said Lionel Vacher, a postdoctoral researcher in physics in Arts & Sciences at Washington University in St. Louis.

Vacher prepared some of the enstatite chondrites in this study for water analysis while he was completing his PhD at Universite de Lorraine. At Washington University, Vacher is working on understanding the composition of water in other types of meteorites.

Enstatite chondrites are rare, making up only about 2 percent of known meteorites in collections.

But their isotopic similarity to Earth make them particularly compelling. Enstatite chondrites have similar oxygen, titanium and calcium isotopes as Earth, and this study showed that their hydrogen and nitrogen isotopes are similar to Earth's, too. In the study of extraterrestrial materials, the abundances of an element's isotopes are used as a distinctive signature to identify where that element originated.

"If enstatite chondrites were effectively the building blocks of our planet -- as strongly suggested by their similar isotopic compositions -- this result implies that these types of chondrites supplied enough water to Earth to explain the origin of Earth's water, which is amazing!" Vacher said.

The paper also proposes that a large amount of the atmospheric nitrogen -- the most abundant component of the Earth's atmosphere -- could have come from the enstatite chondrites.

"Only a few pristine enstatite chondrites exist: ones that were not altered on their asteroid nor on Earth," Piani said. "In our study we have carefully selected the enstatite chondrite meteorites and applied a special analytical procedure to avoid being biased by the input of terrestrial water."

Coupling two analytical techniques -- conventional mass spectrometry and secondary ion mass spectrometry (SIMS) -- allowed researchers to precisely measure the content and composition of the small amounts of water in the meteorites.

Prior to this study, "it was commonly assumed that these chondrites formed close to the sun," Piani said. "Enstatite chondrites were thus commonly considered 'dry,' and this frequently reasserted assumption has probably prevented any exhaustive analyses to be done for hydrogen."

Credit: 
Washington University in St. Louis

A spatial regime shift to stickleback dominance

image: A male stickleback (Gasterosteus aculeatus) during spawning time.

Image: 
Photo: Joakim Hansen/Azote

Large numbers of three-spined stickleback have gradually taken over larger parts of the Baltic Sea's coastal ecosystem, shows a new scientific study. Stickleback is a small prey fish common in aquatic food webs across temperate Europe. The stickleback contributes to local ecosystem 'regime shifts', where young-of-the-year pike and perch decline in individual bays, and these shifts gradually spread like a wave from the outer archipelago into the mainland coast.

This disturbing change is shown in a unique study conducted by researchers from Stockholm University, the Swedish University of Agricultural Sciences and the University of Groningen (Netherlands), which is now published in the scientific journal Communications Biology.

Regime shifts across space, as well as time?

Regime shifts are large, sudden and long-lasting changes in the structure and function of ecosystems, often triggered by human pressures on the environment. Most scientific studies of regime shifts focus on temporal change. Meanwhile, ecological theory predicts that regime shifts in large, heterogeneous ecosystems may start locally, in the most vulnerable areas, and then spread gradually across space. So far, however, proof of such dynamics is very rare.

The stickleback 'explosion'

The small fish three-spined stickleback is an important part of aquatic food webs across the Northern hemisphere. It's eaten by both birds and larger fish. It's also a common model organism in studies of fish behavior and evolution.

"In the Baltic Sea, the number of stickleback has increased dramatically since the 1990s", says Ulf Bergström, the researcher in the project who first documented the increase. Eutrophication, climate change and less predatory fish are at least part of the explanation for the sharp rise in sticklebacks. However, research is underway to investigate the causes further.

At the same time, the recruitment of pike and perch - two large predatory fish that eat stickleback - has decreased in the outer archipelagos and open coastal stretches, where the sticklebacks often reside during spring and summer. Previous studies have shown that the stickleback can eat the eggs and larvae of pike and perch, but it has not been known to what extent this has actually affected their reproduction on a larger scale.

A wave of sticklebacks

To get a better picture of the extent and effects of the stickleback increase, researchers in the project PlantFish compiled and analyzed data from nearly 40 years of fish surveys in almost 500 shallow archipelago bays, along the entire Swedish Baltic Sea coast.

The results showed a large-scale change - a so-called regime shift - from predatory fish to stickleback dominance, which gradually spread from the outer archipelagos and in towards the mainland coast.

"One by one, individual bays shifted to being dominated by sticklebacks instead of predatory fish", says the main author Johan Eklöf. "We spontaneously began to call the pattern the 'stickleback wave', as the shift to stickleback dominance seen from the larger perspective wells up like a slow tsunami towards the coast."

Detailed studies of major ecosystem components in 32 of the bays showed that sticklebacks reduce the number of perch and pike young-of-the-year through predation on eggs and larvae. This is likely to diminish the local predatory fish stock, and further benefit the stickleback.

"We also see the reduction of perch and pike juveniles along the entire coast, and not just in the outer archipelagos and the open coastal stretches. These changes are serious, as they suggest that local stocks of predatory fish can gradually become extinct, which in turn affects the ecosystem as a whole", Johan Eklöf continues.

"Since the stickleback also eats small grazing animals, the shift also intensifies the eutrophication symptoms, as filamentous 'nuisance' algae, which suffocate bladderwrack and other important aquatic plants, are allowed to grow uncontrolled", Johan Eklöf points out.

A symptom revealing deeper problems

The researchers now believe that the large-scale nature of the stickleback wave shows a great need for increased monitoring so that we can detect and counteract this type of change in the future.

"The problem has previously gone under the radar or been judged to be very local, as existing monitoring programs have not focused on small fish and have not made any spatial analyzes", says Ulf Bergström. A better understanding of the connections between the open sea and the coast is now needed, where the stickleback's yearly migrations link the systems. The researchers have already started gaining such knowledge in a new project called "The stickleback wave", funded by the Swedish Research Council Formas.

The new project will also provide knowledge about what measures can be taken to try to reverse the shift. Various measures to strengthen the stocks of predatory fish are already being done, but targeted fishing for large sticklebacks could also be an environmental protection measure. The researchers will evaluate whether stickleback fishing can benefit perch and pike recruitment, but at the same time emphasize that the problem is more complex than the stickleback itself.

"Stickleback fishing may be inevitable to slow down the 'wave', but we must better understand and address the root causes of the major changes in the ecosystem. The stickleback wave is probably just a symptom and not the problem itself", Johan Eklöf concludes.

Credit: 
Stockholm University

The Newtonian gravitational constant: Latest advances of the measurements

image: Schematic diagram of four experimental devices used by the co-author's research team.

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©Science China Press

Newton's law of universal gravitation, which describes the attractive force between two masses separated by the distance, is one of the greatest achievements in the 17th century. The strength of this force is defined by the constant of proportionality G, which is called the gravitational constant, independent of the size, shape, and composition of the objects. G is one of the earliest fundamental constants introduced by human beings, and extensively used in the fields of cosmology and astrophysics, and also plays an important role in many other fields of physics.

However, the measurement precision of G is improved by only about two orders of magnitude through more than two centuries of efforts. Up to now, it remains the least precisely known during all fundamental physical constants, due to the extreme weakness and unshieldability of gravity, and in addition, there is not any quantitative relationship with any other fundamental constants.

The following graph shows latest values of G with high precision which were obtained after the year 2000, the difference between them reaches more than 500 ppm (part per million). This phenomenon of inconsistent measurement results of G value has almost occurred in entire history of G measurement and made so many scientists puzzled. It is most likely that there could be some undiscovered systematic errors in the G measurements.

In a new overview published in the Beijing-based National Science Review, scientists at Sun Yat-sen University (Zhuhai Campus) in Zhuhai, China and Huazhong University of Science and Technology in Wuhan, China present the latest advances in the measurements of G. Co-authors Chao Xue, Jian-Ping Liu, Qing Li, Jun-Fei Wu, Shan-Qing Yang, Qi Liu, Cheng-Gang Shao, Liang-Cheng Tu, Zhong-Kun Hu, and Jun Luo trace the history of the development of the G measurements; they also review the values of G adopted in the Committee on Data for Science and Technology recommended value, CODATA-2014, after the year 2000 and their latest two values published in 2018 using two independent methods. These scientists likewise outline the development directions of future experiments for G.

"Since Cavendish's first laboratory measurement of G value by using torsion balance over 200 years ago, experimenters have devoted tremendous efforts to investigating many possible contributions to the measurement uncertainty, but the relative uncertainty of G has not been greatly improved." they state in an article titled "Precision Measurement of the Newtonian Gravitational Constant"

"With the development of science and technology in recent years, experimenters have performed some novel techniques to improve the sensitivity of experiments." they add. "Unfortunately, there is still a large discrepancy of about 550 ppm among thirteen values of G which are reviewed in this paper, even though the relative standard uncertainties of many results have been less than 50 ppm.".

The measurement process, results and advantages and disadvantages of eleven values of G, which are adopted in CODATA-2014 after the year 2000, are described and analyzed in detail. Meanwhile, the values of G, which were obtained by the co-author's research team, are described systematically and comprehensively, the schematic diagram of four experimental devices are shown as follow. Especially the latest two values published in 2018. "an improved experiment with high accuracy and high confidence level needed to be carried out." they state. "These two G values of HUST-18 experiment with different methods have the smallest uncertainties reported until now, and both agree with each other within a 3σ range. S. Schlamminger from National Institute of Standards and Technology published the views to emphasize that our study was an example of excellent craftsmanship in precision measurements"

"Why is the scatter of the G values so large? In principle, there are two possibilities in science and technology that can explain the obvious inconsistency." They add. "The first is that there could be the systematic errors which are not fully understood exist in some or all of the experiments." "The second possibility is that there might be some unknown physical mechanism to explain the discrepancy of G values."

"For the future development of G measurement, the main target should be to reduce the discrepancy of every values of G." the scientists expect. "Every groups need to repeat their experiments with the same method and the same devices, and should make much more effort to estimate the potential systematic errors." "After that, different groups should strengthen the international cooperation to discuss the possible undiscovered systematic errors among different methods." Finally, they hope that "more and more scientists could be involved in G measurement and the problem of "Big G" can be solved in the near future"

Credit: 
Science China Press

Dealing a blow on monetarism

This year's third issue of the Financial Journal opens with an article by Marina Malkina, Professor at the Department of Economic Theory and Methodology of the UNN Institute of Economics and Entrepreneurship, and Igor Moiseev, research assistant at the Center for Macroeconomics and Microeconomics of the same Institute. Their article entitled "Endogeneity of Money Supply in the Russian Economy in the Context of the Monetary Regime Change" is published in the "Monetary policy" section.

Endogenous money (from Greek "endon", meaning "internal"), according to the established definition, is money created inside the economy as a response to its impulses; the economy in this case is considered a closed and autonomous unit.

"The article deals with the endogeneity of money supply in the Russian economy in the context of the changes made to the rules of monetary regulation. We summarized and analyzed the basic concepts of the modern theory of endogenous money, and described the approaches of various researchers to studying the impact of financial innovations and changes in the principles of monetary regulation on money supply endogeneity," Marina Malkina notes.

In the empirical part of the research, in order to test the hypothesis on the endogenous origin of the money supply in the Russian economy in 2010-2018, the authors applied the Granger causality test and the Johansen cointegration test as well as VAR and VECM models. The study was based on the monthly data for the monetary sphere (M2 monetary aggregate, monetary base, and money multiplier), the banking sphere (loans, deposits, and interest rate) and the transactional sector of the economy (wholesale and retail turnover).

The time series were split into two intervals: 2010-2013 and 2014-2018, when a change in the monetary regime occurred (introduction of the key rate, change in the refinancing system, transition to inflation targeting and floating exchange rate of the rouble).

"As a result of our study, we have obtained evidence of the endogenous origin of the money supply in the Russian economy for both periods of time, and the hypotheses of structuralism and preference for liquidity have been confirmed. In the short term of 2010-2013, it was mainly commercial banks that reacted to an increase in money demand (through money multiplier); however, in the long run the Central Bank of Russia prevailed (through changing the monetary base)", Igor Moiseev continues.

In 2014-2018, the Bank of Russia demonstrated an efficient adjustment of money supply toward money demand, which was reflected in the response of the monetary base in the short term.

Meanwhile, in this period the role of commercial banks in lending was increased through operational managing of their own resources, which was reflected in the reaction of the money multiplier to the growth of business activity in the country.

These changes indicated an amplification of money supply endogeneity in the Russian economy. In addition to passive adaptation, a particular type of activism was revealed by Lobachevsky University researchers in the monetary sphere: the initiative of money emission came not so much from the monetary authorities as from commercial banks fighting for a market share in the face of intensified banking competition and reduced bank margins.

Credit: 
Lobachevsky University

New genetic markers of glucosinolates in rapeseed may help improve oil composition

image: Population structure of Russian rapeseed lines. Population structure assessed using principal component analysis for the whole cohort (A), spring (B), and winter (C) types separately. Red dots correspond to spring rapeseed accessions. Blue dots correspond to winter rapeseed accessions. Yellow dots correspond to yellow-seeded winter rapeseed accessions. (D) Population clustering of rapeseed lines based on the admixture component of each accession, the bar colors correspond to the dot colors in panel A.

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Rim Gubaev et al./Genes

A group of scientists from Skoltech and Pustovoit All-Russian Research Institute of Oil Crops in Krasnodar performed genetic analysis of the Russian rapeseed collection. The scientists described the genetic diversity of Russian rapeseed lines and discovered new candidate genes that are potentially involved in controlling the content of glucosinolates, toxic secondary metabolites in rapeseed oil. Their findings can be used by crop breeders to improve the rapeseed oil composition. The research was published in the Genes journal.

Rapeseed is the world's second-largest oilseed crop after soybeans. Glucosinolates are secondary metabolites of rapeseed and related cruciferous plants. The content of these glucose-derived sulfur-containing organic substances strongly influences oil quality: if present in large amounts, glucosinolates spoil the taste of rapeseed oil and affect the quality of rapeseed meal, compelling crop breeders to look for ways of reducing their content.

The scientists performed genome-wide genotyping of 90 rapeseed lines and compared the results with the glucosinolate content data for these lines collected over 3 growing seasons. This helped identify both the genetic markers of glucosinolate content in oil and the linked candidate genes potentially involved in regulating the biosynthesis of glucosinolates. Once verified on an independent set of plants, the markers can be readily used for breeding new varieties and hybrids with low glucosinolate content.

"Our research aims to foster marker-assisted crop breeding in Russia by using genetic markers to control the characteristics relevant to cross-breeding processes and progeny analysis. This approach can make the breeding of new varieties much faster. Measuring glucosinolates content is an arduous task that can be made much easier by using the markers we have identified", says Rim Gubaev, the first author of the paper and a PhD student at Skoltech.

Credit: 
Skolkovo Institute of Science and Technology (Skoltech)

Two discoveries boost next-generation organoid development

image: During foregut organogenesis, the research team performed single-cell RNA sequencing (scRNA-seq) of the mouse embryonic foregut at three time points that spanned the period of early patterning and lineage induction. This confocal microscope image shows one of those time points.

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Cincinnati Children's and RIKEN

In back-to-back reports published Aug. 27, 2020, in Nature Communications, a team of scientists from Cincinnati Children's and Japan report discoveries that will be vital to a new wave of more-complex organoid development.

Their findings advance efforts to use human stem cells to grow organs from the fetal foregut including the trachea, esophagus, stomach, liver, gallbladder, bile ducts and pancreas.

"With single-cell analysis of mouse embryos, we defined the complex signaling networks controlling development of mesenchyme cells, which form the smooth muscle and fibroblast tissues that are essential for organ function," says senior author Aaron Zorn, PhD, who leads organoid development at Cincinnati Children's. "We then used this information from the mouse to differentiate the equivalent human tissue in the lab. This is important because up until now all of the liver, lung, stomach and esophagus organoids that we make mostly lack these mesenchyme cell types."

Zorn directs the Center for Stem Cell & Organoid Medicine (CuSTOM) at Cincinnati Children's, which has made groundbreaking advances in stomach, intestine, liver and esophageal organoid development. In 2019, the CuSTOM group launched a formal collaboration with RIKEN, Japan's largest comprehensive research institution, to pursue further organoid innovation.

The papers published in Nature Communications represent the first results of that collaboration.

Decoding foregut development cell-by-cell

In this study, the scientists report detecting a set of signals within the foregut--a proto-organ in very early-stage embryos--that trigger how and when the other organs form. Specifically, they found that the signals are driven by the genes Wnt and SHH, which travel between cells in the endoderm and mesoderm layers of very early embryos.

To define these signals, co-first authors Lu Han, PhD, and Keishi Kishimoto, PhD, collaborated with organoid experts James Wells, PhD, and Takanori Takebe, MD, to develop a high-resolution map of foregut development in mice. They detected an unexpected variety of cells sending a chorus of master signals that trigger formation of the various organs that branch out from the foregut.

This study is the first to pin down the dynamics at play in the embryonic mesoderm, co-authors say.

The action happens very early-between embryonic days 8.5 and 9.5 in mice, which roughly corresponds to days 17 to 23 in human gestation. During this brief window of development, groups of cells at certain spots along the simple foregut tube begin transforming into the sprouts of organs that become the trachea, esophagus, liver and pancreas.

By studying the molecular signaling activity during this period, at a cell-by-cell level, the researchers produced a roadmap that shows how and why the organs sprout where they do. They then used these signals to grow tissue from different organs from human pluripotent stem cells.

In September 2019, Takebe and colleagues reported the world's first success at growing a three-organoid system that included the liver, pancreas and biliary ducts. That breakthrough took five years to achieve and the organoids produced did not possess all the cell types needed for full-sized function.

The new road map will enable CuSTOM scientist to grow more compete interconnected organs, Zorn says.

A deep dive into trachea development

In a parallel paper also appearing in Nature Communications, the RIKEN and CuSTOM teams extended these studies with extensive experiments in mice to further define the mechanisms of trachea formation.

This study led by lung development expert Mitsuru Morimoto, PhD, in Japan used genetically modified mice to learn which cell signals were most important to trachea formation. When these signals fail, the developing embryo does not properly form the cartilage rings and smooth muscle tissues that the trachea needs to pipe air to the lungs.

Cincinnati Children's, which developed the first human esophagus organoid in 2018 has been working with the RIKEN team on this project as part of its involvement with the CLEAR Consortium (Congenital Esophageal and Airway Defect Research).

"This work helps explain what happens when birth defects like esophageal atresia, tracheoesophageal fistula, and tracheomalacia occur," Zorn says. "This work also opens the door to one day generating esophagus and trachea tissue for tissue replacement."

Implications for tissue engineering

The sheer complexity of the new signaling roadmap helps explain why it took so long to make the initial three-organoid breakthrough. For example, the map revealed five distinct populations of mesenchymal cells involved in liver formation alone.

Now, co-authors say the new roadmap will make the process faster, could expand the types of organs that can be grown together, and will allow researchers to grow sets of organoids engineered to mimic conditions that lead to birth defects or increased disease risk--including some forms of cancer.

"One important outcome of our study was to use the signaling roadmap to direct the development of stem cells into different organ cell types," Takebe says. "This approach may have important applications for tissue engineering."

Short term, such organoid systems can be used to test new medications with far less dependence on animal models, or to evaluate the harms caused by pollution, unhealthy diets, allergens, and so on. Longer term, once expects learn ways to grow organoids to significantly larger sizes, customized lab-grown tissues could be used to repair damaged organs and someday even replace failing ones.

The paper lays out the protocols for other scientists to use to make their own organoid systems. Detailed data collected during the project also can be explored via the interactive website https://research.cchmc.org/ZornLab-singlecell.

Credit: 
Cincinnati Children's Hospital Medical Center

DNA repair - Locating and severing lethal links

Chemical lesions in the genetic material DNA can have catastrophic consequences for cells, and even for the organism concerned. This explains why the efficient identification and rapid repair of DNA damage is vital for survival. DNA-protein crosslinks (DPCs), which are formed when proteins are adventitiously attached to DNA, are particularly harmful. DPCs are removed by the action of a dedicated enzyme - the protease SPRTN - which cleaves the bond between the protein and the DNA. Up to now, how SPRTN recognizes such crosslinks, which can differ significantly in structure, has remained unclear. Now a team led by Professor Julian Stingele (LMU Gene Center), in cooperation with Professor Michael Sattler (Helmholtz Zentrum München and Technical University of Munich), has shown that the enzyme utilizes a modular recognition mechanism to detect such sites, such that it is activated only under highly specific conditions. The new findings appear in the journal Molecular Cell.

DPCs can be created by interactions with highly reactive products of normal metabolism or with synthetic chemotherapeutic agents. These lesions are extremely toxic because they block the replication of DNA - and therefore inhibit cell division. Timely and effective repair of these crosslinks by SPRTN is crucial for cell viability and the suppression of tumorigenesis. In humans, mutations that reduce the activity of the enzyme are associated with a high incidence of liver cancer in early life and markedly accelerate the aging process. "SPRTN has a difficult job to do because, depending on the protein and the DNA subunit involved, the structure of the crosslink can vary widely. So the enzyme has to be able to identify many different structures as aberrant," explains Hannah Reinking, first author of the study. "We therefore asked ourselves what sorts of properties a DPC should have in order to be recognized and cleaved."

To answer this question, Reinking and colleagues constructed model substrates consisting of proteins attached to defined positions within DNA strands, and examined whether the SPRTN protease could repair them in the test-tube. This approach revealed that SPRTN interacts with structures that are frequently found in the vicinity of DPCs. With the aid of nuclear magnetic resonance spectroscopy, they went on to show that SPRTN contains two recognition domains. One binds to double-stranded, and the other to single-stranded DNA. "So the protein uses a modular system for substrate recognition. Only when both domains are engaged is the enzyme active - and DNA in which double-stranded and single-stranded regions occur in close proximity is often found in the vicinity of crosslinks," says Stingele.

These results are also of clinical relevance. The action of many chemotherapeutic drugs depends on their ability to form crosslinks with DNA. Since tumor cells divide more frequently than non-malignant cells, they are particularly sensitive to this type of DNA damage. DNA repair enzymes like SPRTN are therefore of great interest as potential drug targets for use in the context of personalized cancer therapies, and agents that specifically inhibit the protease could eventually be employed to boost the efficacy of chemotherapy. "Our work now makes it possible to conceptualize such therapeutic strategies", says Stingele.

Credit: 
Ludwig-Maximilians-Universität München

UVA-developed artificial pancreas effective for children ages 6-13, study finds

image: The Control-IQ artificial pancreas system was derived from research done at the Center for Diabetes Technology at the University of Virginia.

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Tandem Diabetes Care

An artificial pancreas originally developed at the University of Virginia Center for Diabetes Technology safely and effectively manages blood sugar levels in children ages 6 to 13 with type 1 diabetes, a national clinical trial has found. Data from this and other studies has prompted the U.S. Food and Drug Administration to approve the device for use by children ages 6 and older.

The Control-IQ system, manufactured by Tandem Diabetes Care, is an "all-in-one" diabetes management device that automatically monitors and regulates blood glucose. The artificial pancreas system has an insulin pump that is programmed with advanced control algorithms based on a mathematical model using the person's glucose monitoring information to automatically adjust the insulin dose as needed.

"After the resounding success of the system in adolescents and adults in an earlier study, it is very rewarding to see younger participants in this study benefit as well, and to the same extent," said Marc D. Breton, PhD, a UVA School of Medicine researcher who served as the trial's principal investigator. "We are excited to see the outcome of 15 years of research that led to these results acknowledged in the New England Journal of Medicine."

A Real-World Study

The randomized clinical trial enrolled 101 children ages 6 to 13 at four U.S. sites (UVA, Stanford, Yale and the University of Colorado) and assigned them to either the experimental group, which used the artificial pancreas system, or to the control group, which used a standard continuous glucose monitor and separate insulin pump. Check-ins and data collection were conducted every other week for four months. To provide the best possible real-life test of the artificial pancreas, study participants were instructed to continue their typical daily routines.

The study found that the artificial pancreas did a better job keeping the children's blood glucose in the target range: The average percentage of time in the target range during the day was 7 percentage points higher using the artificial pancreas, while nighttime control was 26 percentage points higher. Nighttime control is particularly important, as severe, unchecked hypoglycemia (very low blood-glucose levels) can lead to seizure, coma or even death.

The average amount of time overall where participants' blood-glucose levels were within the target range was 11 percentage points higher than in the control group, which equals 2.6 more hours per day in range. No cases of severe hypoglycemia or diabetic ketoacidosis (a complication caused by very high blood-glucose levels) occurred during the study.

"We are thrilled with the benefits observed in this study in school-aged children with type 1 diabetes, a population that often struggles with diabetes management for a variety of reasons," said R. Paul Wadwa, MD, the protocol chair for this trial who serves as associate professor of pediatrics at the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus. "Control-IQ technology proved very easy to use for children and their parents and led to improved glucose control during both the day and night."

"We look forward to continue to enable access to this technology to even younger children with type 1 diabetes, and to develop even more advanced systems," Breton said.

Parents interested in the artificial pancreas should discuss whether it is appropriate for their children with their pediatricians.

Credit: 
University of Virginia Health System