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For the past 70 years, the best indicator of life expectancy for a patient with glioblastoma (GBM) -- the most common and the most aggressive brain cancer -- has simply been age at diagnosis. Now, an international team of scientists has experimentally validated a predictor that is not only more accurate but also more clinically relevant: a pattern of co-occurring changes in DNA abundance levels, or copy numbers, at hundreds of thousands of sites across the whole tumor genome.

Patients with the genome-wide pattern survive for a median of one year. However, patients without it survive three times as long, for a median of three years. The results came from a retrospective clinical trial that was published today in the journal Applied Physics Letters (APL) Bioengineering.

Having a predictor of a patient's life expectancy can help inform medical decisions. The GBM pattern can, in principle, be used in this way today. For example, when a patient has magnetic resonance imaging results that are inconclusive such information can help doctors decide whether to perform an intervention.

"The information contained in this pattern, and other patterns that we can discover by using the same mathematical methods, can improve the standard of care of GBM and other diseases," said the team leader Orly Alter, Ph.D., Utah Science, Technology, and Research (USTAR) associate professor of bioengineering and human genetics at the Scientific Computing and Imaging Institute and the Huntsman Cancer Institute at the University of Utah.

Personalizing medicine

Having a predictor that encompasses the whole genome could also help drugs progress to regulatory approval. That is because the cumulative effect of all genes is thought to be involved in the drug response.

"We expect the GBM pattern, for example, to identify the patients who would benefit from a drug in prospective clinical trials," said Sri Priya Ponnapalli, Ph.D., a senior research affiliate and an alumna of Alter's lab, who is the first author of the paper.

"Even if the drug targets just one gene, a patient's response to the drug would depend on the status of the whole genome and not just that one gene," she added. The successful approval of any additional drug would be significant. In GBM, for example, only one drug, which does not cure GBM, has advanced from trials to standard of care over the last 40 years.

The GBM pattern not only predicts survival, but also includes most DNA copy-number alterations that were known and at least as many that were unrecognized in GBM prior to its discovery, including new druggable targets. This enables drug development efforts to directly focus on gene targets that have been shown to correlate with patient outcome.

Finding relationships between patient outcomes and whole genomes

Alter's team were the first to successfully identify, and now to experimentally validate, a relationship between a GBM tumor's DNA copy numbers and a patient's life expectancy. However, researchers have recognized this type of DNA alteration as a hallmark of cancer for more than a century and have observed them in GBM tumors for decades.

The team uncovered the relationship by developing and using new mathematical methods to compare and contrast tumor and normal whole genomes from the Cancer Genome Atlas (TCGA), a publicly open national database. Repeated previous attempts to associate a tumor's DNA copy numbers with a GBM patient's outcome failed, including previous studies of the same data from TCGA that used other methods.

This is the first predictor that encompasses the whole tumor genome.

The new mathematical methods have overcome three distinct challenges that others had not. First, they found consistent patterns across the hundreds of thousands of sites in whole genomes, which have three billion nucleotides. Second, they were able to do that across the tumor and the matching normal genomes simultaneously. Third, they were able to do so in small cohorts of patients, about 100, that are typical in clinical trials.

"Our mathematical methods succeeded because they use the complex structure of the datasets rather than simplifying or standardizing them as is commonly done," said Alter. "This enables the separation of patterns which occur only in the tumor genomes from those that occur in the genomes of normal cells in the body and variations caused by experimental inconsistencies."

These methods can be used with any kind of data, biological and otherwise. They can therefore be used to inform personalized approaches to various health conditions, including infectious disease.

Quantum entanglement is a process by which microscopic objects like electrons or atoms lose their individuality to become better coordinated with each other. Entanglement is at the heart of quantum technologies that promise large advances in computing, communications and sensing, for example detecting gravitational waves.

Entangled states are famously fragile: in most cases even a tiny disturbance will undo the entanglement. For this reason, current quantum technologies take great pains to isolate the microscopic systems they work with, and typically operate at temperatures close to absolute zero. The ICFO team, in contrast, heated a collection of atoms to 450 Kelvin, millions of times hotter than most atoms used for quantum technology. Moreover, the individual atoms were anything but isolated; they collided with each other every few microseconds, and each collision set their electrons spinning in random directions.

The researchers used a laser to monitor the magnetization of this hot, chaotic gas. The magnetization is caused by the spinning electrons in the atoms, and provides a way to study the effect of the collisions and to detect entanglement. What the researchers observed was an enormous number of entangled atoms - about 100 times more than ever before observed. They also saw that the entanglement is non-local - it involves atoms that are not close to each other. Between any two entangled atoms there are thousands of other atoms, many of which are entangled with still other atoms, in a giant, hot and messy entangled state.

What they also saw, as Jia Kong, first author of the study, recalls, "is that if we stop the measurement, the entanglement remains for about 1 millisecond, which means that 1000 times per second a new batch of 15 trillion atoms is being entangled. And you must think that 1 ms is a very long time for the atoms, long enough for about fifty random collisions to occur. This clearly shows that the entanglement is not destroyed by these random events. This is maybe the most surprising result of the work".

The observation of this hot and messy entangled state paves the way for ultra-sensitive magnetic field detection. For example, in magnetoencephalography (magnetic brain imaging), a new generation of sensors uses these same hot, high-density atomic gases to detect the magnetic fields produced by brain activity. The new results show that entanglement can improve the sensitivity of this technique, which has applications in fundamental brain science and neurosurgery.

As ICREA Prof. at ICFO Morgan Mitchell states, "this result is surprising, a real departure from what everyone expects of entanglement." He adds "we hope that this kind of giant entangled state will lead to better sensor performance in applications ranging from brain imaging to self-driving cars to searches for dark matter."

A Spin Singlet and QND

A spin singlet is one form of entanglement where the multiple particles' spins--their intrinsic angular momentum--add up to 0, meaning the system has zero total angular momentum. In this study, the researchers applied quantum non-demolition (QND) measurement to extract the information of the spin of trillions of atoms. The technique passes laser photons with a specific energy through the gas of atoms. These photons with this precise energy do not excite the atoms but they themselves are affected by the encounter. The atoms' spins act as magnets to rotate the polarization of the light. By measuring how much the photons' polarization has changed after passing through the cloud, the researchers are able to determine the total spin of the gas of atoms.

The SERF regime

Current magnetometers operate in a regime that is called SERF, far away from the near absolute zero temperatures that researchers typically employ to study entangled atoms. In this regime, any atom experiences many random collisions with other neighbouring atoms, making collisions the most important effect on the state of the atom. In addition, because they are in a hot medium rather than an ultracold one, the collisions rapidly randomize the spin of the electrons in any given atom. The experiment shows, surprisingly, that this kind of disturbance does not break the entangled states, it merely passes the entanglement from one atom to another.

What The Study Did: This study compares COVID-19 cases in border counties in Iowa, which didn't issue a stay-at-home order, with cases in border counties in Illinois, which did.

Authors: George L. Wehby, Ph.D., of the University of Iowa in Iowa City, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2020.11102)

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

UC Riverside scientists have solved a 20-year-old genetics puzzle that could result in ways to protect wheat, barley, and other crops from a devastating infection.

Ayala Rao, professor of plant pathology and microbiology, has been studying Brome Mosaic virus for decades. Unlike some viruses, the genetic material of this virus is divided into three particles that until now were impossible to tell apart.

"Without a more definitive picture of the differences between these particles, we couldn't fully understand how they work together to initiate an infection that destroys food crops," Rao said. "Our approach to this problem has brought an important part of this picture into very clear focus."

A paper describing the work Rao's team did to differentiate these particles was recently published in the Proceedings of the National Academy of Sciences.

Inside each of the particles is a strand of RNA, the genetic material that controls the production of proteins. The proteins perform different tasks, some of which cause stunted growth, lesions, and ultimately death of infected host plants.

Two decades ago, scientists used the average of all three particles to create a basic description of their structure. In order to differentiate them, Rao first needed to separate them, and get them into their most pure form.

Using a genetic engineering technique, Rao's team disabled the pathogenic aspects of the virus and infused the viral genes with a host plant.

"This bacterium inserts its genome into the plant's cells, similar to the way HIV inserts itself into human cells," Rao said. "We were then able to isolate the viral particles in the plants and determine their structure using electron microscopes and computer-based technology."

Now that one of the particles is fully mapped, it's clear the first two particles are more stable than the third.

"Once we alter the stability, we can manipulate how RNA gets released into the plants," Rao said. "We can make the third particle more stable, so it doesn't release RNA and the infection gets delayed."

This work was made possible by a grant from the University of California Multicampus Research Program and Initiatives. Professors Wiliam Gelbart and Hong Zhou of UCLA, as well as graduate students Antara Chakravarthy of UCR and Christian Beren of UCLA, made significant contributions to this project.

Moving forward, Rao is hoping to bring the other two viral particles into sharper focus with the expertise of scientists at UCLA and UC San Diego.

Brome Mosaic virus primarily affects grasses such as wheat and barley, and occasionally affects soybeans as well. According to Rao, it is nearly identical to Cucumber Mosaic virus, which infects cucumbers as well as tomatoes and other crops that are important to California agriculture.

Not only could this research lead to the protection of multiple kinds of crops, it could advance the understanding of any virus.

"It is much easier to work with plant viruses because they're easier and less expensive to grow and isolate," Rao said. "But what we learn about the principles of replication are applicable to human and animal viruses too."

(Toronto - May 15, 2020) - An international team of researchers led by Dr. Eleanor Fish, emerita scientist at the Toronto General Hospital Research Institute, University Health Network, and professor in the University of Toronto's Department of Immunology, has shown for the first time that an antiviral drug can help speed up the recovery of COVID-19 patients.

According to the new study, published today in Frontiers in Immunology, treatment with interferon(IFN)- α2b may significantly accelerate virus clearance and reduce levels of inflammatory proteins in COVID-19 patients.

The research team found that treatment with this drug, which has been used clinically for many years, significantly reduced the duration of detectable virus in the upper respiratory tract, on average by about 7 days. It also reduced blood levels of interleukin(IL)-6 and C-reactive protein (CRP), two inflammatory proteins found in COVID-19 patients.

Dr. Fish says that the research team considered IFN-α therapy for COVID-19 after they demonstrated interferon provided therapeutic benefit during the SARS outbreak of 2002 and 2003.

"Rather than developing a virus-specific antiviral for each new virus outbreak, I would argue that we should consider interferons as the 'first responders' in terms of treatment," says Dr. Fish.

"Interferons have been approved for clinical use for many years, so the strategy would be to 'repurpose' them for severe acute virus infections."

Boosting a natural defense mechanism

Interferons are a group of signaling proteins released by the human body in response to all viruses. As Dr. Fish explains, they are a "first line of defense."

They target different stages of a virus's life cycle, inhibiting them from multiplying. They also boost an immune response by activating different immune cells to clear an infection. Some viruses, however, can block this natural defense mechanism.

"But it is possible to override this block. If a virus blocks interferon production, then treating with interferon can offset this."

Study details

The researchers conducted this exploratory study on a group of 77 patients with COVID-19 in Wuhan, China. These patients were admitted to Union Hospital, Tongii Medical College, between January 16 and February 20, 2020. They represented moderate cases of the disease as none of the patients required intensive care or prolonged oxygen supplementation or intubation.

Despite the study's limitations of a small, non-randomized group of patients, the work provides several important and novel insights into COVID-19 disease, notably that treatment with IFN-α2b can accelerate viral clearance from the upper respiratory tract and also reduce circulating levels of inflammatory factors that are associated with severe COVID-19.

Dr. Fish says a randomized clinical trial is a crucial next step. According to her, a clinical trial with a larger group of infected patients who are randomized to treatment or placebo would further this research.

In the meantime, the findings from this study are the first to suggest therapeutic efficacy of IFN-α2b as an available antiviral intervention for COVID-19, which may also benefit public health measures by shortening the duration of viral clearance and therefore slowing the tide of the pandemic.

High salt intake is a well-known risk factor of hypertension and cardiovascular diseases. Reducing salt intake can significantly lower blood pressure and ameliorate target organ damage caused by hypertension. However, in the past three decades, several strategies have failed to decrease daily salt intake to an optimal level. Therefore, it is important to identify alternative approaches for reducing excessive salt intake and antagonizing high salt-induced hypertension.

Salt taste perception is an important factor in determining salt intake at an individual level. Previous studies have shown that aversion induced by salt beyond the physiological concentration range is mediated by a bitter taste sensor-transient receptor potential channel M5 (TRPM5) in taste receptor cells. High salt stimuli might produce a bitter taste for a defensive response to reduce salt intake. Recently, Professor Zhiming Zhu's team from Army Medical University found that acute high-salt stimulation activated TRPM5-mediated bitter taste and increased aversion reaction. However, long-term high salt intake impairs the activity of the TRPM5 by inhibiting protein kinase C (PKC) activity and PKC-dependent threonine phosphorylation. "The TRPM5-mediated aversion response to high salt is weakened, which results in a progressive increase of high salt intake and increased blood pressure in mice fed with long-term high-salt-diet." Said Dr. Yuanting Cui, the first author of this work. These results were published in Hypertension recently.

On this basis, Professor Zhiming Zhu's team continued to explore how to restore TRPM5 function damage caused by long-term high salt intake. They found that long-term dietary intervention with bitter melon extract (BME) restored the TRPM5-mediated aversion to high salt stimuli in tongue epithelium, thus reduced excessive salt intake, and improved the cardiovascular damage in mice. Mechanistically, dietary BME inhibited high salt-induced RhoA/Rho kinase activation, leading to reduced phosphorylation levels of myosin light chain kinase and myosin phosphatase targeting subunit 1. Furthermore, cucurbitacin E (CuE), the major active compound in BME, also inhibited vasoconstriction by attenuating L-type Ca2+ channel-induced Ca2+ influx in vascular smooth muscle cells. "We found that BME and CuE increased TRPM5 expression and function in tongue epithelium. Therefore, the mice fed with high salt plus BME diet showed a lower salt intake, and improved the high salt-induced hypertension and cardiac hypertrophy compared with mice only fed with high-salt diet." said Dr. Hao Wu, the first author and Prof. Zhiming Zhu, the corresponding author of this work. These results were published in SCIENCE CHINA Life Sciences recently.

These encouraging results from Professor Zhu's team provide further suggestions for promoting the use of dietary factors to reduce salt consumption. Enhancing bitter taste function by dietary bitter melon might provide a promising approach for antagonizing excessive salt intake and preventing of high salt-induced cardiovascular dysfunction.

According to a new study published in De Gruyter's open access journal "Diagnosis", approximately one in 10 people (9.6%) in the United States with symptoms caused by major vascular events, infections, or cancers will be misdiagnosed.

The study's authors, led by David E. Newman-Toker from the Johns Hopkins University School of Medicine and CRICO Strategies, analyzed modern, U.S.-based studies and literature-based estimates to calculate rates of diagnostic error and related harms.

Based on the analysis, the authors provide estimates of diagnostic error and serious misdiagnosis-related harm rates (i.e., misdiagnoses that result in permanent disability or death) for each of the five most frequently misdiagnosed major vascular events, infections, and cancers. In total, these 15 diseases represent roughly half of all diagnostic error-related permanent disabilities or deaths in the U.S. health system and suggest a focal area for quality improvement efforts.

Of the people with the most-commonly misdiagnosed major vascular events, infections, and cancers, roughly half (53.9%) suffer a permanent disability or die because of the error.

According to the study, the most uncommon infections and major vascular events are most likely to be misdiagnosed. Among the 15 diseases analyzed, spinal abscesses (an infection that can compress the spinal cord and cause paraplegia) was the disease most often missed (62.1%). More than one in four aortic aneurysms and dissections have a critical delay in diagnosis (27.9%). More than one in five (22.5%) lung cancer diagnoses are also meaningfully delayed.

The authors say the study should be used to target efforts to improve diagnosis among these conditions. They note that misdiagnoses of major vascular events, infections, and cancers do not appear to have declined over the last several decades. For some conditions, such as stroke and aortic aneurysms, they may even be rising.

"With this insight, health care leaders and clinicians can focus their resources and interventions to target these vulnerabilities," said Dana Siegal, Director of Patient Safety at CRICO Strategies and study co-author.

Lung cancer patients are at heightened risk for COVID-19 and the reported high mortality rate among lung cancer patients with COVID-19 has given pause to oncologists who are faced with patients with not one, but two severe, life-threatening diseases.

To help oncologists address the many challenges COVID-19-positive lung cancer patients present, a team of global lung cancer specialists this week published a review of lung cancer treatments for patients with COVID-19 in the current issue of the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer (IASLC).

"The purpose of this manuscript is to present a practical multidisciplinary and international overview to assist in treatment for lung cancer patients during this pandemic, with the caveat that evidence is lacking in many areas," said lead author Chandra Belani, MD, chief science officer for the IASLC, Professor of Medicine and Oncology at the Penn State College of Medicine and Penn State Cancer Institute.

As a group, lung cancer patients tend to be older and have an increased risk of relative immunosuppression from the underlying malignancy and from anti-cancer treatments. Furthermore, patients with lung cancer may have additional comorbidities, including a history of smoking and pre-existing lung disease.

"A major consideration in the delivery of cancer care during the pandemic is to balance the risk of patient exposure and infection with the need to provide effective cancer treatment," Belani writes.

The rapid onset of the COVID-19 infection requires careful consideration of urgent decisions to treat lung cancer. Treatment decisions balancing the risk of exposure with effective care require close multidisciplinary discussions and thorough deliberation between caregivers and patients. The duration and severity of the COVID-19 pandemic are unclear, and treatment delay alone will be insufficient to provide optimal treatment to cancer patients.

"In combination with determining a treatment path for lung cancer, physicians should educate patients to help them prevent further spread of COVID-19 according to WHO and CDC guidelines," Belani urged colleagues.

COVID-19 complicates cancer care further by forcing patients into self-isolation to protect themselves, other patients, providers, and family members.

"Self-isolation goes against best practices for treating cancer patients, which often calls for joining support groups, reaching out to loved ones and family members for assistance and remaining active," Belani said. "The decision regarding immediate vs. delayed treatment during the COVID-19 pandemic should balance the delay of treatment in the presence of existing co-morbidities vs. the possible harm from COVID-19."

Belani and his co-authors include advice to clinicians that intersects with virtually all lung cancer patients, including those with early-stage lung cancer, locally advanced lung cancer, COVID-19 and immunotherapy, advanced stage non-small cell lung cancer and small cell lung cancer.

MANHATTAN, KANSAS -- An interdisciplinary team of Kansas State University researchers developed a computer simulation that revealed beef supply chain vulnerabilities that need safeguarding -- a realistic concern during the COVID-19 pandemic.

Caterina Scoglio, professor, and Qihui Yang, doctoral student, both in electrical and computer engineering, recently published "Developing an agent-based model to simulate the beef cattle production and transportation in southwest Kansas" in Physica A, an Elsevier journal publication.

The paper describes a model of the beef production system and the transportation industry, which are interdependent critical infrastructures -- similar to the electrical grid and computer technology. According to the model, disruptions in the cattle industry -- especially in the beef packing plants -- will affect the transportation industry and together cause great economic harm. The disruptions modeled in the simulation share similarities with how the packing plants have been affected during the COVID-19 pandemic.

"When we first started working on this project, there was a lot of emphasis on studying critical infrastructures; especially ones that are interdependent, meaning that they need to work together with other critical infrastructures," Scoglio said. "The idea is if there is a failure in one of the systems, it can propagate to the other system, increasing the catastrophic effects."

The study included a variety of viewpoints to create a realistic and integrated model of both systems. Co-authors on the paper include Don Gruenbacher, associate professor and department head of electrical and computer engineering; Jessica Heier Stamm, associate professor of industrial and manufacturing systems engineering; Gary Brase, professor of psychological sciences; Scott DeLoach, professor and department head of computer science; and David Amrine, research director of the Beef Cattle Institute.

The researchers used the model to evaluate which supply chain components were more robust and which were not. They determined that packing plants are the most vulnerable. Scoglio said that recent events in the middle of the COVID-19 pandemic raise important issues about how to safeguard the system.

"An important message is that after understanding the critical role of these packers, we need to decide how we could protect both them and the people who work there," Scoglio said. "While the plants are a critical infrastructure and need to be protected, taking care of the health of the workers is very important. How can we design a production process that can be flexible and adaptable in an epidemic?"

According to the paper, the beef cattle industry contributes approximately $8.9 billion to the Kansas economy and employs more than 42,000 people in the state. Since trucks are needed to move cattle, any disruption in either cattle production or transportation almost certainly would harm the regional economy, Scoglio said.

"Packers need to be considered as a critical point of a much longer supply chain, which needs specific attention to make sure it will not fail and can continue working," Scoglio said. "Beef packers are a critical infrastructure in the United States."

The project was supported by the National Science Foundation and focused on southwest Kansas, but the researchers acknowledge that cattle come from outside the region and interruptions may have larger national effects.

The results of a study conducted by the University of Tartu on the prevalence of the coronavirus were presented to the Government Committee responsible for the emergency situation on Tuesday. The results from the second week of the study continue to confirm the low prevalence of the virus in Estonia.

In two weeks, based on random selection, a total of 6,024 adult residents have been interviewed and 4,728 tested in the course of the study. A total of 12 cases of the coronavirus have been identified, of which seven had been diagnosed with the virus prior to the study and six had recovered by the time of the study.

The results allow to conclude that the infection is not widely spread in the society, and that the prevalence of the coronavirus remains stable over the weeks. The researchers consider the gradual easing of the restrictions justified.

"We will continue our successful cooperation with the researchers of the University of Tartu, whose study helps us assess the prevalence of the virus in the society. This will be even more important in two weeks, when we can evaluate the impact of the easing of restrictions that come into force this week on the wider spread of the infection," said Prime Minister Jüri Ratas.

The prime minister pointed out that yesterday, another group of researchers from the University of Tartu started work on an antibody-based seroepidemiological study in Saaremaa and Õismäe to help estimate the number of people who have been exposed to the coronavirus. "The work of the researchers is extremely important for us to be prepared for the second wave of the virus outbreak as soon as possible and to be able to respond to it promptly and efficiently," said Ratas.

In the second week of the study, 3,135 interviews were conducted and 2,495 adult residents were tested. The testing revealed eight cases of the coronavirus; six of the infected persons had been diagnosed with the virus prior to the study. The results of the first week were retroactively supplemented with 226 tests, one of them positive.

Professor Ruth Kalda, the head of the study of the University of Tartu, explained that when assessing the actual prevalence of the virus, it must be considered that six infected persons had battled the disease in March or early April and were currently considered healthy. Thus, only half of the positive cases were at risk of spreading the infection at the time of the study.

"As we can say on the basis of the first two waves that the prevalence of the virus in Estonia is low at the moment, we can take a two-week break and then see whether the opening of shopping centres has an impact on the spread of the virus. If necessary, we will conduct another wave of the study before the Midsummer's Day and if the epidemiological situation is stable, we will continue monitoring the spread of the virus in autumn," said Kalda.

The next wave of the study is scheduled to take place from 22 May to 28 May, i.e. almost two weeks after the partial reopening of shopping centres.

A parent who knows a child's preferences and participates in the activities can guide the child assertively without diminishing the child's enthusiasm for physical activity and exercise. However, children's enthusiasm to move was most commonly associated with child-centered and stimulating parenting. In an interview study conducted at the Faculty of Sport and Health Sciences of the University of Jyväskylä, children perceived coercion as reducing their motivation for physical activity.

Enthusiasm for physical activity and exercise was most often combined in children's thoughts with parenting that promotes freedom of movement, takes into account interests, offers hobby opportunities, and participates in exercise with the child. Children's enthusiasm for exercise was increased by a parental attitude that showed acceptance for the child's occasional lack of motivation. Parental control, meaning varying degrees of coercion and disregarding the child's role in exercise-related decision-making, was perceived as undesirable and reduced enthusiasm for exercise.

Children aged 7 to 10 years were found to have a clear distinction between parenting that increases and reduces exercise motivation.

"For example, strong, public and overt encouragement in tournaments and games was perceived in some cases as embarrassing and even shameful," explains postdoctoral researcher Arto Laukkanen. "In addition, underestimating and ignoring the temporary cessation of exercise motivation, for example, was perceived as controlling and reducing enthusiasm for exercise."

However, the interviews also highlighted experiences in which the parent's strong guidance and instruction was perceived as acceptable and increasing exercise enthusiasm.

"The children pointed out situations where the parent's actions had initially felt domineering and strict," Laukkanen says. "Common to experiencing such situations positively and strengthening exercise motivation was that the parent participated in the activities with the child. Secondly, these parents sensed the line between coercion and acceptable guidance in the child's mind."

Limiting screen time under the guise of exercise eats up the enthusiasm for exercise

A very typical unpleasant exercise experience for children was related to limiting screen time and the associated command that the child should go out to exercise.

"This is very contradictory, as parents try to take care of the children's screen time and adequate level of exercise, but at the same time they may be contributing to alienation from exercise," Laukkanen says. "Perhaps exercise should not be set in opposition to screen time, but one should strive to organize independent space for both of them in everyday life."

Some of the children's experiences were the opposite. Some felt that they had infinitely flexible and loose boundaries for screen time.

"Limiting screen time independently can be challenging, especially for children," Laukkanen says. "In some cases, children also apply considerable effort and ingenuity to create more screen time for the day."

Combining screen time limitations and adequate physical activity seems like a complex challenge in families with children. Further research on this topic is urgently needed from the perspectives of both children and parents.

The study included 79 first-, second-, and third-grade students. Children's perceptions of parenting that support exercise and physical activity motivation were examined through group interviews. The children participated in audio-recorded interviews lasting about half an hour in groups of an average of five pupils as part of a normal school day. Participation was voluntary.

New data suggests that asthma is associated with longer time on ventilators for hospitalized younger patients with COVID-19. Patients with COVID-19 between the ages of 20 and 59 years old who also had asthma needed a ventilator to assist with breathing for five days more on average than non-asthmatic patients with COVID-19, according to researchers at Rush University Medical Center, who published their findings today in The Journal of Allergy and Clinical Immunology: In Practice.

"Among the patients who developed severe respiratory symptoms requiring intubation (the use of a ventilator), asthma was associated with a significantly longer intubation time in the younger group of patients who would seemingly have a better disease course than patients over the age of 65," said Dr. Mahboobeh Mahdavinia, chief of allergy and immunology in the Department of Internal Medicine at Rush University Medical Center.

"Our findings suggest that younger individuals with asthma may require extra attention, as they could develop a sustained pulmonary failure with COVID-19 infection, leading to prolonged mechanical ventilation."

Some signs and symptoms of COVID-19 are similar to worsening of asthma, which can lead to a late diagnosis of COVID-19 in asthmatics. "Therefore, we looked at a large group of patients to understand the impact of preexisting asthma on the outcome of patients with COVID-19," Mahdavinia said.

"We found that asthma and obesity are connected in COVID-19 patients, which means that obesity coupled with asthma puts a patient at a significantly higher risk. This is the first report, to our knowledge, to study the role of asthma on the outcome of COVID-19 patients."

Mahdavinia's team of physician-scientists, medical residents, basic scientists and students used an electronic medical record algorithm created by the information services team at Rush to identify patients with asthma and COVID-19 who were either hospitalized or tested for COVID-19 at Rush between the dates of March 12 and April 3.

IBM SPSS Statistics for Windows was used for analysis of COVID-19 outcomes in association with asthma and were adjusted for demographic variables and body mass index (BMI).

Initially, data emerged for 1,003 patients who tested positive for COVID-19. Complete data on demographic variables, asthma, and COVID-19 management was available in 935 patients, who were used for analysis. Overall, 241 were found to have an established diagnosis of asthma, which were broken into three groups by age range.

Asthma was significantly associated with longer intubation time in patients between 18 and 49 years of age and between 50 and 64 years of age, but not in the age group 65 years of age and older. Duration of hospitalization was longer among patients with a history of asthma compared to those without this history in patients aged 50 to 64 years, but not in the younger or older age groups. The patients aged 50 to 64 on average spent two more days in the hospital than the non-asthmatics in this age group.

Asthma was not associated with a higher rate of death or with acute respiratory distress syndrome among COVID-19 patients.

"In other studies, both obesity and gender have been shown to affect COVID-19 hospitalization," said Mahdavinia. "In our study, asthma was also associated with female gender and higher BMI."

The analysis, which was adjusted for both obesity and gender, indicates that asthma is independently linked to the amount of time patients needed to be on ventilators.

"We were able to confirm asthma in prior clinical documentation among 73% of patients, but some cases were self-reported upon screening. We think that patients with a history of asthma may have sought out COVID-19 testing more than others due to concern and overlapping symptoms," Mahdavinia said.

DALLAS, May 15, 2020 -- When health care providers enrolled in a federal program that provides financial payments for monitoring and reducing cardiovascular risk in high-risk patients, they assessed patient risk and prescribed cholesterol-lowering and blood pressure-lowering medication more often, according to research presented today at the American Heart Association's Quality of Care & Outcomes Research Scientific Sessions 2020. The virtual conference, May 15-16, is a premier global exchange of the latest advances in quality of care and outcomes research in cardiovascular disease and stroke for researchers, healthcare professionals and policymakers.

As part of a broader initiative to prevent one million heart attacks and strokes in the United States over five years, the Centers for Medicare and Medicaid Services launched the Million Hearts Cardiovascular Disease Risk Reduction Model (Million Hearts®). The model pays health care providers for measuring each of their Medicare patients' risk of having a heart attack and stroke over 10 years and for reducing that risk among their high-risk patients.

The model specifically targets Medicare beneficiaries ages 40-79 who have not had a previous heart attack or stroke. As part of a five-year, cluster-randomized trial, providers calculated their Medicare patients' risk of having a heart attack or stroke within 10 years, and received incentives to provide care to reduce the risk among high-risk patients (those with 30% or higher risk of a cardiovascular event at the beginning of the study).

Analysis of the first two years of the Million Hearts program found:

Within six months of enrollment in the program, people identified as high-risk at a Million Hearts® center were more likely to initiate or intensify statin therapy or anti-hypertensive medications compared to high-risk people in the control group (28% vs. 24%, respectively).

Million Hearts® providers indicated they were nearly twice as likely than the control group of providers to assess risk in at least half of their Medicare patients (71% vs. 39%, respectively).

Overall, 300,550 Medicare beneficiaries were enrolled in the study across 516 primary and specialty practices, health centers and hospitals throughout the U.S. Half of the enrolled centers were assigned to the intervention group and utilized the Million Hearts® Model.

The global reach of COVID-19 is unquestionable. Every day, news reports highlight the disease's increasing toll on countries and major cities around the world.

However, little attention is paid to indigenous populations worldwide who may be especially vulnerable to COVID-19 but are largely excluded from most national or regional efforts to curb the spread of the disease. Even in high-income countries, indigenous groups like the Navajo have been hit hard by COVID-19, with per capita infection rates rivaling those of New York and New Jersey.

A team of anthropologists, physicians and tribal leaders has developed a strategy for mitigating the impact of COVID-19 among the Tsimane, an indigenous population in the Bolivian Amazon. Led by UC Santa Barbara's Michael Gurven and Hillard Kaplan of Chapman University, their multiphase plan brings together relevant stakeholders to best serve Tsmane interests. They hope to provide a general template that can be applied to other indigenous groups, and to promote a wider discussion on how to adapt strategies to local circumstances, with the goal of minimizing harm to indigenous populations due to the SARS-CoV-2 pandemic.

Their work is published in the journal The Lancet.

"In Bolivia, most attention is focused in the cities, where the pandemic first appeared. Indigenous communities have not been part of any organizational plan," said Daniel Eid Rodriguez, the paper's Bolivian co-author and a physician working with the Tsimane Health and Life History Project since 2005. "Although resources in Bolivia and other countries are too limited to create the ideal response plan, there are many people and organizations who are ready to help. Finding and building collaboration is key for the success of any COVID-19 plan."

To reach a wider audience, the authors have published their paper not only in English, but also in Spanish, Portuguese and French -- languages spoken in countries where many indigenous people reside.

"We've been working with the Tsimane and other indigenous groups in Bolivia for almost two decades," said Gurven, co-director of the Tsimane Health and Life History Project. Research operations shut down in mid-March, as did most activity worldwide, but he and his team recognized that indigenous groups living in remote areas may be especially vulnerable to COVID-19, given their limited access to up-to-date information and appropriate health care.

So building on their years of active involvement with Tsimane health care, the researchers initiated conversations with tribal authorities and other local officials. Together, they began working on a plan, first to get folks informed and prepared, and then to act once COVID-19 hit the region.

"After a teenage Yanomami boy died of COVID-19 there was, understandably, a lot of panic about the potential plight of indigenous populations around the world in light of this new, unpredictable threat," Gurven said. "Since our team had already been working with the Tsimane to try and work out a reasonable plan, we thought it would be a great opportunity to move the conversation toward a concrete blueprint that could, hopefully, be adapted to work in similar areas."

While every individual around the world is vulnerable to COVID-19 because it is new and no one has developed any immunity, many indigenous communities are at additional risk because of widespread respiratory illness, including prior history of tuberculosis, bronchitis and lower respiratory tract infections and compromised immune function.

"These could make people more at risk of having COVID-19 complications," said Gurven. According to the World Bank, over 370 million indigenous people inhabit over 90 countries, in both rural and urban areas. Though health clinics may be present in rural areas, access and resources such as medication, portable oxygen and other treatments may be very limited. In Bolivia, the local hospital will likely be overloaded by the time COVID-19 reaches Tsimane villages, and the existing remote health outposts are not yet equipped to diagnose or treat COVID-19.

The potential for higher mortality among infected individuals makes COVID-19 more salient for indigenous populations, Gurven notes, for reasons different from those typically considered. "Indigenous elders are at greater risk because of their age and comorbidity; yet they are crucial for helping to pass on long-standing traditions," Gurven explained. "They are 'walking libraries,' the ones who transmit cultural practices, native language and rituals that are crucial to indigenous identity."

While certain elements of the indigenous populations make them more vulnerable to COVID-19, other factors may foster resilience. "Many indigenous populations maintain the ability to provide their own sustenance through farming, fishing, hunting and foraging activities," said Gurven. "The ability to get food in self-sustaining ways -- both in terms of the know-how and having use rights in native territories -- makes it easier for some indigenous communities to self-isolate and reduce COVID-19 exposure that might otherwise come from visits to nearby town."

"Tribal sovereignty also allows indigenous groups to make their own decisions, especially when it comes to restricting access to their communities," Gurven went on. "Also, strong family bonds and a tradition of community meetings helps provide everyone with the latest COVID-19 information and to coordinate action -- without the kind of political polarization we've seen in the U.S. that seems to shape what people know about COVID-19 and what should be done."

The multiphase plan he and his team developed began taking shape before COVID-19 was confirmed in the Beni region of Bolivia, where the Tsimane reside. The goal of Phase I was education and preparation. "Our team of trained Tsimane visited over 60 villages for awareness campaigns, using a variety of materials such as Centers for Disease Control posters translated to the Tsimane language," Gurven said. "In meetings, each community came up with a specific plan for collective isolation and for quarantining suspected cases."

They also developed a list of material needs to help with the collective isolation of Tsimane communities to minimize reliance on markets and outside merchants. Salt, for example, is used not just to flavor food, but also to preserve meat and fish. "So we made massive deliveries of these items to each community," said Gurven.

Phase II of the plan began when COVID-19 reached the Beni in mid-April. It focuses on implementing collective isolation containment of Tsimane communities, COVID-19 containment and patient management. "Our plan is adapted to a low-tech environment of inadequate hospital facilities and to lower population density where isolation is possible for whole communities," said Kaplan, co-director of the Tsimane Health and Life History Project.

"It prioritizes protecting the elderly, rapid-testing with contact-tracing and patient monitoring with portable oxygen support for those who need it," Kaplan continued. To track the location of disease 'hotspots,' the team will take advantage of a variety of communication methods and their detailed GPS data available on resident structure and social networks.

"Details are likely to change as new ways to diagnose or treat COVID-19 become available," Gurven noted. As of now, he added, no confirmed cases have been reported in the towns closest to Tsimane communities.

The authors hope their paper will serve to affect policy and call for action. "Our article is directed toward the heads of state in countries with indigenous peoples, tribal leaders, scientists, health care workers, missionaries and non-governmental organizations that work with tribal peoples," said Kaplan. "We also hope that charitable organizations and ordinary citizens will be inspired to look for ways to help reduce the wave of death that will occur in the face of inaction."

"History teaches us that the effects of a new infectious disease on a vulnerable population can be devastating," said MemorialCare's David Michalik, a co-author of the paper and a specialist in pediatric infectious disease. "Our protocol seeks to augment already existing plans that countries may have in place, and raise awareness that even in 2020, indigenous communities are at risk of being wiped out if nothing is done."

Orange, Calif. - A team of anthropologists, physicians, tribal leaders and local government authorities developed and implemented a multi-phase COVID-19 prevention and containment plan among the Tsimane, an indigenous group of forager-horticulturists in the Bolivian Amazon. The collaborative effort is led by Hillard Kaplan, Ph.D., professor of health economics and anthropology and a member of the Economic Science Institute at Chapman University.

The study, published in The Lancet, proposes that indigenous populations worldwide share characteristics that make them especially vulnerable to COVID-19, including higher rates of extreme poverty, poor healthcare access and infrastructure, and widespread respiratory infections. As of May 7, Bolivia had 2,081 confirmed COVID-19 cases and 102 deaths, largely confined to the Santa Cruz and La Paz provinces. As of now, there are no confirmed cases in the towns closest to the Tsimane communities.

The Tsimane Health and Life History Project has been working with Tsimane communities since 2002, studying health and ageing while providing primary health care and biomedical surveillance. Kaplan, co-director of the project, and his team paused research activity in mid-March to redirect their efforts towards reducing the effects of COVID-19 on the tribal populations with whom they work with.

"The disease is spreading rapidly in Bolivia as is the case in many places throughout the developing world but has not yet reached the tribal territories where we work," said Kaplan, the principal investigator of this study. "It is clear from the painful lessons we have learned in this country and in Europe, advance planning is the key to mitigating the devastating effects of the disease."

"After a teenage Yanomami boy died of COVID-19, there was, understandably, a lot of panic about the potential plight of indigenous populations around the world in light of this new, unpredictable threat," said Michael Gurven, Ph.D., professor of anthropology at UC Santa Barbara and co-director of the Tsimane Project with Kaplan. "Since our team had already been working with the Tsimane to try and work out a reasonable plan, we thought it would be a great opportunity to move the conversation toward a concrete blueprint that could, hopefully, be adapted to work in similar areas."

The researchers believe that their approach with the Tsimane can be adapted more generally to tribal and aboriginal populations throughout the world to prevent widespread mortality, and will continue to adjust their plans according to the local circumstances and future COVID-19 discoveries.

Dr. Kaplan and his team developed their COVID-19 strategy based on two guidelines. The first is that preventative measures before mass infection can greatly reduce the burden of morbidity and mortality. The second is that any effective plan must be collaborative among all stakeholders and should involve the indigenous populations in the decision process.

These tribal communities have unique sources of resilience that can be used to prevent the potentially serious effects of COVID-19. The most pertinent is the group's cultural tradition of collective decision- making, where lively two-way discussions are held during village meetings to allow community members to speak up and contribute to a collective decision. The consensus among the Tsimane is that collective isolation is the most viable strategy for minimizing COVID-19 exposure until vaccines or treatments become available. Researchers utilized these community meetings to communicate best practices in collective isolation with the villages.

The research team has a two-phase plan. Phase I -- focused on education, outreach and preparation -- occurred while the novel coronavirus was spreading quickly in Bolivia but before there were confirmed cases in the Beni region where the Tsimane live.

The research team traveled to around 60 villages to hold community meetings. The researchers sent native speakers of the Tsimane language to these meetings to inform the population about the risks of COVID-19 and promote a collective decision-making process on how best to respond to the epidemic. These meetings lead to unanimous agreement by the Tsimanes to collectively isolate the tribal territory and its constituent communities to prevent interaction with the outside world.

The researchers also worked to translate and adapt U.S. Centers for Disease Control informational posters into the Tsimane language for dissemination.

"While some Tsimane people had heard about the existence of coronavirus, most were unaware of its imminent threat, how it is transmitted, who is most vulnerable or whether there was a cure for the disease," said Kaplan.

The research team is currently in Phase II: containment, patient management and quarantine strategies. This is being accomplished through ongoing radio communications about the current rates and areas of infection, coordination of rapid testing and contact-tracing and the provisioning of personal protective equipment for local health care workers. Phase II began in mid-April when COVID- 19 was diagnosed and confirmed in the Beni region.

"Our plan is adapted to a low-tech environment of inadequate hospital facilities and to lower population density where isolation is possible for whole communities and for families and individuals within communities," said Gregory Thomas, MD, a medical director of the Long Beach MemorialCare Heart and Vascular Institute and collaborator of the study.

"The plan places greater emphasis on testing with contact-tracing and whole-family approaches to isolation. For the management and treatment of COVID-19 cases, it emphasizes patient monitoring, especially blood oxygen, and portable oxygen support for those who need it," added David Michalik, MD, pediatric infectious disease specialist at MemorialCare Miller Women's and Children's Hospital Long Beach.