Culture

Computer scientists create a 'laboratory' to improve streaming video

In these days of social distancing, as millions cloister at home to binge-watch TV over the internet, Stanford researchers have unveiled an algorithm that demonstrates a significant improvement in streaming video technology.

This new algorithm, called Fugu, was developed with the help of volunteer viewers who watched a stream of video, served up by computer scientists who used machine learning to scrutinize this data flow in real time, looking for ways to reduce glitches and stalls.

In a scientific paper, the researchers describe how they created an algorithm that pushes out only as much data as the viewer's internet connection can receive without degrading quality.

"In streaming, avoiding stalls depends heavily on these algorithms," says Francis Yan, a doctoral candidate in computer science and first author of the paper, which received the 2020 USENIX NSDI Community Award.

Many of the prevailing systems for streaming video are based on something called the Buffer-Based Algorithm, known as BBA, which was developed seven years ago by then-Stanford graduate student Te-Yuan Huang, along with professors Nick McKeown and Ramesh Johari.

BBA simply asks the viewer's device how much video it has in its buffer. For example, if it has less than 5 seconds stored, the algorithm sends lower quality footage to guard against interruptions. If the buffer has more than 15 seconds stored, the algorithm sends the highest quality video possible. If the number falls in between, the algorithm adjusts the quality accordingly.

Although BBA and similar algorithms are widespread in the industry, there have been repeated attempts by researchers over the years to develop more sophisticated algorithms using machine learning -- a form of artificial intelligence in which computers teach themselves to optimize some process.

But in a modern variation of the old garbage-in-garbage-out computer adage, these machine learning algorithms generally require simulated data to learn from, rather than the real thing delivered over the real internet. Therein lies a problem.

"The internet turns out to be a much messier place than our simulations can model," said Keith Winstein, an assistant professor of computer science who supervised the project and advised Yan along with associate professor of computer science and electrical engineering Philip Levis. "What Francis found is that there can be a gulf between making one of these algorithms work in simulation versus making it work on the real internet."

To create a realistic microcosm of the TV-viewing world, Winstein's team erected an antenna atop Stanford's Packard Building to pull in free, over-the-air broadcast signals which they then compressed and streamed to volunteers who signed up to participate in the research project, known as Puffer.

Starting in late 2018, the volunteers streamed and watched TV programs via Puffer and the computer scientists simultaneously monitored the data stream using their own machine learning algorithm, Fugu, and four other leading contenders, including BBA, that were trained to adjust their performance based on the actual quality conditions the viewers were experiencing.

At the start of their stream, each viewer was randomly assigned one of the five streaming algorithms and the Stanford team recorded streaming data like the average video quality, the number of stalls and the length of time the viewer tuned in.

The results disagreed with some earlier research studies that had been based on simulations or on smaller tests. When the supposedly sophisticated machine learning algorithms were tested against BBA in the real world, the simpler standard held its own. By the end of the trial, however, Fugu had outperformed the other algorithms -- including BBA -- in terms of least interruption time, highest image resolution and the consistency of video quality. What's more, those improvements appear to have the power to keep viewers tuned in. Viewers watching Fugu-fed video streams lingered an average of 5-9% longer than other tested algorithms.

"We've found some surprising ways in which the real world differs from simulation, and how machine learning can sometimes produce misleading results. That's exciting in that it suggests a lot of interesting challenges to be solved," Winstein says.

Credit: 
Stanford University School of Engineering

How SARS-CoV-2 gets into respiratory tissue -- and how it may exploit one of our defenses

What makes SARS-CoV-2, the virus behind COVID-19, such a threat? A new study, led by Jose Ordovas-Montanes, PhD at Boston Children's Hospital and Alex K. Shalek, PhD at MIT, pinpoints the likely cell types the virus infects. Unexpectedly, it also shows that one of the body's main defenses against viral infections may actually help the virus infect those very cells. Findings were published April 21 by the journal Cell.

The peer-reviewed study, published as a preprint, will help focus efforts to understand what SARS-COV-2 does in the body, why some people are more susceptible, and how best to search for treatments, the researchers say.

Multiple research models

When news broke about a new coronavirus in China, Ordovas-Montanes and Shalek had already been studying different cell types from throughout the human respiratory system and intestine. They also had gathered data from primates and mice.

In February, they began diving into these data.

"We started to look at cells from tissues such as the lining of the nasal cavity, the lungs, and gut, based on reported symptoms and where the virus has been detected," says Ordovas-Montanes. "We wanted to provide the best information possible across our entire spectrum of research models."

COVID-19-susceptible cells

Recent research had found that SARS-CoV-2 -- like the closely related SARS-CoV that caused the SARS pandemic, uses a receptor called ACE2 to gain entry into human cells, aided by an enzyme called TMPRSS2. That led Ordovas-Montanes and Shalek and colleagues to ask a simple question: Which cells in respiratory and intestinal tissue express both ACE2 and TMPRSS2?

To address this question, the team turned to single-cell RNA sequencing, which identifies which of roughly 20,000 genes are "on" in individual cells. They found that only a tiny percentage of human respiratory and intestinal cells, often well below 10 percent, make both ACE2 and TMPRSS2. Those cells fall in three types: goblet cells in the nose that secrete mucus; lung cells known as type II pneumocytes that help maintain the alveoli (the sacs where oxygen is taken in); and one type of so-called enterocytes that line the small intestine and are involved in nutrient absorption.

Sampling from non-human primates showed a similar pattern of susceptible cells.

"Many existing respiratory cell lines may not contain the full mix of cell types, and may miss the types that are relevant," Ordovas-Montanes notes. "Once you understand which cells are infected, you can start to ask, 'How do these cells work?' 'Is there anything within these cells that is critical for the virus's life cycle?' With more refined cellular models, we can perform better screens to find what existing drugs target that biology, providing a stepping stone to go into mice or non-human primates."

Interferon: Helpful or harmful?

But it was the study's second finding that most intrigues the scientists. They discovered that the ACE2 gene, which encodes the receptor used by SARS-CoV-2 to enter human cells, is stimulated by interferon -- one of the body's main defenses when it detects a virus. Interferon actually turned the ACE2 gene on at higher levels, potentially giving the virus new portals to get in.

"ACE2 is also critical in protecting people during various types of lung injury," notes Ordovas-Montanes. "When ACE2 comes up, that's usually a productive response. But since the virus uses ACE2 as a target, we speculate that it might be exploiting that normal protective response."

Interferons, in fact, are being tested as a treatment for COVID-19. Would they help, or would they do more harm than good? That's not yet clear.

"It might be that in some patients, because of the timing or the dose, interferon can contain the virus, while in others, interferon promotes more infection," says Ordovas-Montanes. "We want to better understand where the balance lies, and how we can maintain a productive antiviral response without producing more target cells for the virus to infect."

ACE inhibitors and cytokine storms

The findings may also raise new lines of inquiry around ACE inhibitors. These drugs are commonly used to treat hypertension, which has been linked to more severe COVID-19 disease. Are ACE inhibitors affecting people's risk?

"ACE and ACE2 work in the same pathway, but they actually have different biochemical properties," Ordovas-Montanes cautions. "It's complex biology, but it will be important to understand the impact of ACE inhibitors on people's physiological response to the virus."

It's also too soon to try to relate the study findings to the "cytokine storm," a runaway inflammatory response that has been reported in very sick COVID-19 patients. Cytokines are a family of chemicals that rally the body's immune responses to fight infections, and interferon is part of the family.

"It might be that we're seeing a cytokine storm because of a failure of interferon to restrict the virus to begin with, so the lungs start calling for more help. That's exactly what we're trying to understand right now."

Future directions

The team also wants to explore what the virus is doing in the cells it targets, and to study tissue samples from children and adults to understand why COVID-19 is typically less severe in younger people. Studies will continue at Boston Children's with the support of Benjamin Raby, MD, MPH, chief of pulmonary medicine, Bruce Horwitz, MD, PhD, in emergency medicine, and Scott Snapper, MD, PhD, chief of gastroenterology.

Carly Ziegler, Samuel Allon, and Sarah Nyquist, of MIT and Harvard, and Ian Mbano of the Africa Health Research Institute were co-first authors on the paper in Cell. The study was done in collaboration with the Human Cell Atlas (HCA) Lung Biological Network group. The authors report no competing interests. See the paper for a full list of funders and authors.

"This has been an incredible community effort -- not just within Boston, but also with collaborators around the world who have all shared their unpublished data to try and make potentially relevant information available as rapidly as possible," says Shalek, who was co-senior author on the paper with Ordovas-Montanes. "It's inspiring to see how much can be accomplished when everyone comes together to tackle a problem."

Credit: 
Boston Children's Hospital

Easing the burden of coronavirus with virtual reality

image: Explores the psychological and social issues surrounding the Internet and interactive technologies.

Image: 
Mary Ann Liebert Inc., publishers

New Rochelle, NY, April 21, 2020--A new article discusses the psychological stresses imposed by the coronavirus pandemic and suggests that virtual reality can help alleviate the psychological impact of the need for social isolation. The article, which provides a link to a free 3-dimensional 360 video and suggestions for how to use it, is published in Cyberpsychology, Behavior, and Social Networking, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article free on the Cyberpsychology, Behavior, and Social Networking website.

Giuseppe Riva, PhD, IRCCS Istituto Auxologico Italiano and Università Cattolica del Sacro Cuore (Milan, Italy), and Journal Editor-in-Chief Brenda Wiederhold, PhD, Virtual Reality Medical Center (La Jolla, CA) and Virtual Reality Medical Institute (Brussels, Belgium), coauthored the article entitled "How Cyberpsychology and Virtual Reality Can Help Us to Overcome the Psychological Burden of Coronavirus."

The coronavirus pandemic is forcing people to manage three different psychological problems at the same time: the stress of the disease, the disappearance of places, and the crisis of the sense of community. The fear of getting sick is making us anxious and the need to quarantine is making us lose our sense of place and community. Virtual reality simulates reality. The cost of virtual reality technology has come down considerably in recent years. Now there is free access to the specialized 360-degree immersive videos that allow a person to feel like they are actually in a virtual space. The article provides a day-by-day suggested plan for how to use the free 360 video.

"As our society continues to face these difficult times, it becomes imperative to address mental well-being. It is uplifting to see practical uses of advanced technologies, such as Virtual Reality, making a positive impact. Although previously characterized by some as isolating, we see this new use of shared virtual spaces becoming increasingly important as a means to bring individuals and families together. We look forward to continued exploration of ways that can enrich our shared human experience," says Editor-in-Chief Brenda K. Wiederhold, PhD, MBA, BCB, BCN, Interactive Media Institute, San Diego, California and Virtual Reality Medical Institute, Brussels, Belgium.

Credit: 
Mary Ann Liebert, Inc./Genetic Engineering News

ASU scientists lead study of galaxy's 'water worlds'

image: In a diamond-anvil cell, two gem quality single crystal diamonds are shaped into anvils (flat top in the photo) and then faced with each other. Samples are loaded between the culets (flat surfaces), then the sample is compressed between the anvils.

Image: 
Dan Shim/ASU

Astrophysical observations have shown that Neptune-like water-rich exoplanets
are common in our galaxy. These "water worlds" are believed to be covered with a thick layer of water, hundreds to thousands of miles deep, above a rocky mantle.

While water-rich exoplanets are common, their composition is very different from Earth, so there are many unknowns in terms of these planets' structure, composition and geochemical cycles.

In seeking to learn more about these planets, an international team of researchers, led by Arizona State University, has provided one of the first mineralogy lab studies for water-rich exoplanets. The results of their study have been recently published in the journal Proceedings of the National Academy of Sciences.

"Studying the chemical reactions and processes is an essential step toward developing an understanding of these common planet types," said co-author Dan Shim, of ASU's School of Earth and Space Exploration.

The general scientific conjecture is that water and rock form separate layers in the interiors of water worlds. Because water is lighter, underneath the water layer in water-rich planets, there should be a rocky layer. However, the extreme pressure and temperature at the boundary between water and rocky layers could fundamentally change the behaviors of these materials.

To simulate this high pressure and temperature in the lab, lead author and research scientist Carole Nisr conducted experiments at Shim's Lab for Earth and Planetary Materials at ASU using high pressure diamond-anvil cells.

For their experiment, the team immersed silica in water, compressed the sample between diamonds to a very high pressure, then heated the sample with laser beams to over a few thousand degrees Fahrenheit.

The team also conducted laser heating at the Argonne National Laboratory in Illinois. To monitor the reaction between silica and water, X-ray measurements were taken while the laser heated the sample at high pressures.

What they found was an unexpected new solid phase with silicon, hydrogen and oxygen all together.

"Originally, it was thought that water and rock layers in water-rich planets were well-separated," Nisr said. "But we discovered through our experiments a previously unknown reaction between water and silica and stability of a solid phase roughly in an intermediate composition. The distinction between water and rock appeared to be surprisingly 'fuzzy' at high pressure and high temperature."

The researchers hope that these findings will advance our knowledge on the structure and composition of water-rich planets and their geochemical cycles.

"Our study has important implications and raises new questions for the chemical composition and structure of the interiors of water-rich exoplanets," Nisr said. "The geochemical cycle for water-rich planets could be very different from that of the rocky planets, such as Earth."

Credit: 
Arizona State University

Researchers uncover mechanisms of protective antibody response during Marburg infection

image: Photomicrograph of the Marburg virus.

Image: 
The University of Texas Medical Branch at Galveston

GALVESTON, Texas - A detailed study of the monoclonal antibodies from a person who survived a Marburg infection led researchers to identify novel mechanisms that contribute protection against the disease, according to the latest findings of a collaborative team led by The University of Texas Medical Branch at Galveston and Vanderbilt University Medical Center. The findings are now available in Cell Host & Microbe.

Certainly, the virus that is on everyone's mind is the novel coronavirus SARS-CoV-2 that causes COVID-19 disease, but there are other viral families that continue to cause deadly human disease. One of these viral families are the filoviruses, which includes Ebola and Marburg viruses. There are currently no vaccines or drugs approved for human use to protect against the Marburg virus, which causes severe and often lethal disease in people. The largest known outbreak of Marburg virus occurred in 2004-2005 in Angola, which had a 90 percent case fatality rate, according to the Centers for Disease Control and Prevention.

"Antibodies are currently the most promising platform for developing post-exposure treatments for Marburg virus infection and are critical tools for design of improved vaccines," said senior author Alex Bukreyev, a UTMB virologist in the departments of Pathology and Microbiology & Immunology who led the UTMB team that performed the study. "Understanding the mechanisms of antibody-mediated protection during Marburg virus infection is also useful for understanding antibody protection against other viral pathogens, including SARS-CoV-2, which causes COVID-19."

In an earlier study, the researchers isolated a large panel of monoclonal antibodies from immune B cells of a person who survived a natural Marburg infection. In the current study, they analysed the monoclonal antibodies and learned that two of them revealed unique biological properties that protect against natural Marburg infection. These monoclonal antibodies bind to the envelope protein of Marburg virus called glycoprotein but do not kill the virus. Instead, they recruit immune cells that contribute by killing infected cells. In addition, one of these antibodies rearranges the glycoprotein in a way that facilitates access for other antibodies that are able to kill the virus, thus strengthening the protective effect.

To study the protective effect of the monoclonal antibodies, mice were infected with Marburg virus and then given a single antibody dose 24 hours later. All of the mice who received the antibodies survived the Marburg infection, which would have otherwise been uniformly lethal.

Credit: 
University of Texas Medical Branch at Galveston

Establish contingency plans to meet COVID-19 surge in urban areas

image: Establish contingency plans to meet COVID-19 surge.

Image: 
ATS

April 21, 2020 - In "Mobilization and Preparation of a Large Urban Academic Center During the COVID-19 Pandemic,"- published online in the Annals of the American Thoracic Society - experts from Philadelphia's Temple University Hospital share their contingency plans for meeting an increased demand for hospitalization, as well as their protocols and training plans to minimize health care staff exposure to COVID-19 and ensure proper active and reserve staffing.

"Logistical deficiencies can stress the health care system, but with adequate preparation, we hope to reduce COVID-19 mortality by ensuring that the standard of care is preserved despite the increase in health care utilization," said first author Junad M. Chowdhury, MD, pulmonary disease & critical care medicine fellow, Division of Thoracic Medicine and Surgery, Temple University Hospital. "In addition, efforts to reduce the possible spread of COVID-19 to patients, visitors and essential health care providers through early detection, isolation and triaging must be emphasized."

The situation the team faced was especially challenging, as the medical center is located in a medically underserved area and ICU beds are typically at 80-90 percent of capacity during normal operations.

Following is a brief overview (discussed in detail here) of the plan Dr. Chowdhury and colleagues developed to address these challenges. Staff training on safety measures was started immediately after the outbreak. An infection control committee drafted PPE protocols, while simulation exercises were conducted on advanced cardiac life support and rapid response. All staff are required to report symptoms online and to have their temperature monitored before and after shifts.

Based on learnings from the COVID outbreak in Wuhan, China, the authors created a screening protocol to stratify patients based on their risk of virus transmission. Inpatients are monitored for COVID-related changes and screened. Patients requiring rapid responses or having cardiac arrest are immediately transferred to the COVID unit, if COVID is suspected.

The authors noted, "Initially, all SARS-CoV-2 tests were sent to a third-party diagnostics company, which had a 4-5 day turnaround time. This resulted in an inappropriate use of PPE, delay of discharge of non-COVID patients and ultimately an increase in our total census. We developed our own in-house testing, which yielded results in 5-10 hours." This enabled the team to more effectively triage and discharge patients efficiently.

The team determined that three units were necessary: an isolation unit separate from the main hospital, a unit designated for patients with low probability of COVID infection, and a third unit that functioned as an outpatient COVID screening unit.

Contingency planning included: creating designated backup units, mobilizing ventilators from smaller satellite campuses, asking staff who were not performing essential inpatient services to remain at home on reserve for staffing shortages, creation and enforcement of a strict no-visitor policy, and plans for conservation of PPE and disinfection of solid objects such as phones, glasses and pens.

Dr. Chowdhury and colleagues also developed COVID-specific admission protocols. These covered isolation precautions, specimen collection, imaging and laboratory testing. Once admitted, patients are kept in airborne/droplet isolation and contact isolation until SARS-CoV-2 is ruled out; patients are kept in various states of isolation if they are at varying levels of risk or have a confirmed COVID diagnosis, while COVID-positive patients whose symptoms improve are discharged to home quarantine.

On discharge, close follow-up is done to help assure pandemic mitigation. Discharged COVID-19 positive patients are provided with an online portal, where they are required to log in daily to report their symptoms, and are asked to remain in mandatory quarantine for 14 days. Follow-up with these patients is continued for a month, and then again at three and six months. If they are symptomatic, additional tests are ordered.

The hospital's lung center converted all in-person outpatient appointments to telemedicine visits. All telemedicine patients are asked COVID screening questions when their appointments are made.

As a teaching hospital with a large pulmonary disease and critical care program, program leadership and fellows have worked together to continue lectures, conferences and research meetings via teleconference. Trainees have gained autonomy, experience and knowledge during the pandemic that they would have difficulty obtaining if a pandemic was not in effect.

In conclusion, the authors stated: "Our protocols aim to provide a roadmap for other institutions in the U.S. to deal with this crisis optimally. With COVID-19 essentially a call to arms, we made infrastructural adjustments to identify and triage those with suspected COVID-19 infection, optimize and reconfigure hospital operations to confront the current pandemic, curb viral spread and avoid excessive exposure to the immunocompromised. All institutions should have protocols and measures to mitigate the transmission of the novel coronavirus, while also utilizing available resources appropriately."

Credit: 
American Thoracic Society

LGBTQ military service members at higher risk of sexual harassment, assault, stalking

CORVALLIS, Ore. -- A recent study found that LGBTQ service members face an elevated risk of sexual victimization including harassment, assault and stalking while in the military than their non-LGBTQ counterparts.

The study, one of the first funded by the Department of Defense to look specifically at LGBTQ victimization in the military, aims to inform future polices that will identify vulnerable populations and appropriate interventions to help prevent such experiences going forward.

Previous research has found that experiencing sexual harassment and assault during military service can lead to negative health outcomes including PTSD, depression, substance use and suicidal behavior, all of which are often reported at higher rates among LGBTQ veterans than in the straight cisgender population.

"We're really trying to understand the experiences and well-being of LGBTQ service members and help the military learn how they can improve those experiences," said lead author Ashley Schuyler, a Ph.D. student in OSU'S College of Public Health and Human Sciences. "Our findings suggest that LGBTQ service members do experience an elevated risk of sexual and stalking victimization, even in this post-'don't ask, don't tell' era."

Published in the Journal of Traumatic Stress last month, the study surveyed 544 active-duty service members, ages 18-54, including about 41% who identified as LGBTQ and roughly 10% who identified as trans or gender-nonconforming.

"Don't ask, don't tell," the law that barred openly gay, lesbian and bisexual people from serving in the military, was repealed in 2011, but "it seems like some of those effects could linger, including sexual prejudice and discrimination, which may elevate victimization risk," Schuyler said.

The researchers considered that the culture of the military, with a high value placed on "masculine" ideals such as dominance, aggression and self-sufficiency, may compel some individuals to act out toward people they see as weaker to prove their masculinity to others.

That environment may explain a disparity between men and women in the study: Female service members were more likely to experience sexual harassment than male service members, but the risk of harassment did not increase among women who identified as lesbian or bisexual. Among male service members, however, gay and bisexual men were significantly more likely to experience sexual harassment than straight men.

"Our conclusion was that female service members have such an elevated risk of sexual harassment in general, that being bi or lesbian doesn't increase that risk," Schuyler said.

Among all service members in the sample, those identifying as gay, lesbian or bisexual had an increased risk of sexual harassment, stalking and sexual assault compared to heterosexual service members.

More research is needed on how stalking manifests in the military, Schuyler said. It may look different on board a ship with service members confined in close quarters for months at a time, for example.

"Something the military has started to acknowledge is this idea of a continuum of harm, where if you experience sexual harassment or gender discrimination behaviors, you're at higher risk of more severe encounters down the road, like assault," she said. "We're trying to understand where stalking fits into that spectrum of experiences, so we can intervene to help people who we know experience harassment or stalking and prevent potential assault in the future."

The researchers recommend further investigation into victimization in the military, especially as the policies governing LGBTQ service continue to change. Such research was not possible during the "don't ask, don't tell" era.

Schuyler said they'd like to see military leaders and health care providers be more educated about identifying victimization experiences and providing supports that are inclusive of LGBTQ people who have experienced sexual harassment, assault or stalking. With an increased understanding of those experiences, leaders can pinpoint targets for intervention to help stop sexual violence before it happens.

Credit: 
Oregon State University

COVID-19 news from Annals of Internal Medicine

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

Preparing for Battle: How Hospitalists Can Manage the Stress of COVID-19

During the COVID-19 pandemic, hospitalists are on the front lines. As with other pandemics, COVID-19 presents challenges for the well-being of citizens around the globe, resulting from fear of illness, social distancing measures, isolation and quarantines, and protracted uncertainty. The author of a commentary from the Center for the Study of Traumatic Stress, School of Medicine, Uniformed Services University, Bethesda, Maryland, explains how hospitalists and other health care workers face additional unique challenges related to this pandemic. Read the full text: http://annals.org/aim/article/doi/10.7326/M20-1897.

Credit: 
American College of Physicians

New study shows sharp decrease of intimate partner violence in Nicaragua

image: A researcher conducting interviews with women in Leon, Nicaragua

Image: 
Mary Ellsberg/GWI

WASHINGTON (April 21, 2020)--The percentage of women and girls in Nicaragua's second-largest city who reported experiencing physical violence by their partners during their lifetimes decreased from 55% in 1995 to 28% in 2016, according to a new study published in the journal BMJ Global Health. Researchers at the George Washington University's Global Women's Institute (GWI), in partnership with the Autonomous National University of Nicaragua at León and InterCambios, a Nicaraguan nongovernmental organization, recorded the decline in a follow-up study conducted on intimate partner violence (IPV) in the city of León 20 years after the initial prevalence study.

Led by GWI Director Mary Ellsberg, the research team also found that women and girls reporting physical violence by partners in the 12 months preceding their study interviews decreased from 28% to 8%. The team recorded similar decreases in emotional violence over respondents' lifetimes (from 71% to 42%) as well as the preceding 12-month period (from 43% to 23%) of the study. No significant difference was found in the prevalence of lifetime sexual violence between the two time periods.*

"The only other country to our knowledge with a documented reduction in IPV prevalence is the U.S., where the Justice Department reported a similar decrease in IPV victimization between 1994 to 2012," Dr. Ellsberg said. "That Nicaragua, the second-poorest country in the Western Hemisphere, shows a comparable reduction in IPV to the U.S. is a stunning achievement."

Intimate partner violence is defined as physical violence, sexual violence, stalking or psychological harm by a current or former partner or spouse. Thirty-five percent of women globally experience sexual or physical IPV or nonpartner sexual violence at some point in their lives, according to the World Health Organization. Though efforts to address violence against women and girls around the world increased over the last 25 years, few studies measured a long-enough period to adequately measure large-scale and sustained reductions in IPV and to identify the proven strategies that work to reduce violence.

GWI led the first study to measure population-level change in IPV prevalence over a 20-year period. It conducted the study in León by comparing prevalence of physical, emotional and sexual violence against women and girls between 1995 and 2016. During that time period, the influence of the Nicaraguan women's movement over social policies and the movement's efforts to increase women's knowledge of their rights spurred multiple sectors of Nicaraguan society to address violence against women and girls, resulting in legislative and judicial reforms as well as collaboration among the police, government ministries, civil society organizations and others to protect and support victims.

The study included additional data findings:

Physical IPV

Lifetime (happened at least once during their lifetime) decreased from 55% to 28%.
63% decrease in violence when controlling for possible factors that could influence the results, such as age and education

12-month prevalence (happened in the 12 months preceding study interviews) decreased from 28% to 8%.
71% decrease in violence when controlling for possible factors that could influence the results, such as age and education

Emotional IPV

Lifetime decreased from 71% to 43%.
66% decrease in violence when controlling for possible factors that could influence the results, such as age and education

12-month prevalence decreased from 43% to 23%.
51% decrease in violence when controlling for possible factors that could influence the results, such as age and education

Sexual IPV
Lifetime decreased from 20% to 15%, but that change was not statistically significant.

The researchers noted the reduction in violence was not primarily because of demographic shifts, such as increased education or age, but reflected a true decrease in the prevalence of IPV. They concluded that violence against women and girls is preventable through large-scale, structural interventions undertaken by advocacy groups, civil society organizations, national governments, international donors and other sectors.

Now, however, the ongoing violence in Nicaragua and the COVID-19 crisis may threaten those gains.

"Defenders of women's rights have been prominent in the movement calling for election reforms and justice for those who were killed or arbitrarily detained," Dr. Ellsberg said. "As for COVID-19, we can assume that many more women will experience domestic violence, so the need to reestablish services and support for women and girls suffering from violence is even more critical."

Credit: 
George Washington University

SCAI, ACC, and ACEP release consensus on managing AMI patients during COVID-19

WASHINGTON - The Society for Cardiovascular Angiography and Interventions (SCAI), along with the American College of Cardiology (ACC) and American College of Emergency Physicians (ACEP) have released a consensus statement that provides recommendations for a systematic approach for the care of patients with an acute myocardial infarction (AMI) during the coronavirus disease-2019 (COVID-19) pandemic. The document is jointly published in Catheterization and Cardiovascular Interventions, the official journal of SCAI, and the Journal of the American College of Cardiology.

According to recent studies, cardiovascular disease patients who develop COVID-19 have a higher risk of mortality. However, many patients in need of care for the management of various heart diseases may not be infected with this coronavirus. The document identifies several challenges in providing recommendations for AMI care during the COVID-19 epidemic: cardiovascular manifestations in the COVID-19 patient are complex and variable, the prevalence of COVID-19 in U.S. populations remains unknown, and personal protection equipment (PPE) is not uniformly available.

"During the COVID-19 pandemic we wanted to ensure that patients continue to benefit from the tremendous advances made in the care of patients with cardiovascular disease over the past three decades," said Ehtisham Mahmud, MD, FSCAI, SCAI president and lead author of the writing group. "Primary percutaneous coronary intervention (PCI) is the standard of care for STEMI patients, and in this document, we outline an approach to providing that therapy at PCI-capable hospitals while also ensuring health care worker safety with appropriate PPE."

The writing group recommends informing the public that exposure to the virus can be minimized, that that patients continue to call the Emergency Medical System when presenting with acute ischemic heart disease symptoms, with the intention of primary PCI when indicated. Fibrinolysis at referral hospitals (non-PCI capable) is appropriate with a plan of care for rescue or pharmacoinvasive PCI. The document also provides strategies for maximizing the safety of medical personnel with appropriate use of personal protection equipment and masking patients.

Credit: 
Society for Cardiovascular Angiography and Interventions

Pulse oximetry monitoring overused in infants with bronchiolitis

Philadelphia, April 21, 2020--Monitoring blood oxygen levels with continuous pulse oximetry is being overused in infants with bronchiolitis who do not require supplemental oxygen, according to a study by researchers at Children's Hospital of Philadelphia (CHOP). The researchers found the use of continuous pulse oximetry occurred frequently and varied widely among hospitals in their sample, despite national recommendations advising against the practice.

The findings were published today in JAMA.

"We all have a tendency to believe that continuous monitoring is something that is always going to provide benefit and safety, and unfortunately that isn't the case," said Christopher P. Bonafide, MD, MSCE, an attending physician at CHOP and first author of the study. "When you monitor patients unnecessarily, it creates risk not only for that patient, in terms of longer hospital stays and increased costs, but also for the entire unit due to the potential for alarm fatigue. Our prior work shows that when alarms go off for both patients who need immediate, life-saving care and those who do not, it diminishes trust in the accuracy of the alarms for signaling true emergencies."

Acute viral bronchiolitis is the leading cause of infant hospitalization and is usually treated with supportive care, including fluids, suctioning, and supplemental oxygen when necessary. The Society of Hospital Medicine Choosing Wisely initiative discourages physicians from using continuous pulse oximetry monitoring in infants with bronchiolitis unless they are on supplemental oxygen, and the American Academy of Pediatrics also recommends against the practice.

To examine the extent to which hospitals were using continuous pulse oximetry in infants with bronchiolitis, the research team conducted an observational study in 56 U.S. and Canadian hospitals in the Pediatric Research in Inpatient Settings Network (PRIS), an independent, hospital-based network. The hospitals in the study included freestanding children's hospitals, children's hospitals within hospitals, and community hospitals. Researchers gathered data throughout one bronchiolitis season, from December 1, 2018 until March 31, 2019 and included 3, 612 patients between the ages of 8 weeks and 23 months.

Of the patients in the study who did not receive any supplemental oxygen, 46% were monitored via continuous pulse oximetry. After standardizing the results to account for differences in variables across hospitals that could have influenced monitoring, researchers found the percentage of patients being unnecessarily monitored ranged from 6% to 82%.

"We were surprised by the huge amount of variation we saw across the hospitals in this study, which shows many institutions are using monitoring unnecessarily as a safety net," Bonafide said. "This study represents an essential first step in phasing out an overused, low-value care practice that does not improve outcomes, raises healthcare costs, and leads to alarm fatigue among healthcare workers."

The CHOP-led study was a collaborative, multi-institutional effort that included researchers from CHOP, University of Pennsylvania, Boston Children's Hospital, and Cincinnati Children's Hospital Medical Center. The research was supported by a cooperative agreement awarded by the National Institutes of Health/National Heart, Lung, and Blood Institute (award number U01HL143475).

Credit: 
Children's Hospital of Philadelphia

Humble bug holds key to relieving millions of allergy sufferers in Europe

image: Leaf beetle Ophraella communa.

Image: 
Professor Heinz Müller-Schärer

CABI has led a team of scientists on new research which reveals that a humble bug can help relieve more than 2 million sufferers of allergies in Europe while also saving more than Euro 1 billion in health costs.

Dr Urs Schaffner, lead author of the study published in Nature Communications, says the leaf beetle Ophraella communa can significantly reduce pollen – which causes a range of symptoms from sneezing to itchy eyes and aggravates conditions such as asthma and eczema – from common ragweed (Ambrosia artemisiifolia).

The interdisciplinary study – the first to quantify the economic benefits of biological control in Europe – also argues that the costs inflicted by invasive species in Europe are ‘most probably seriously underestimated’.

The team of scientists from institutions including the University of Fribourg and ETH Zurich, Switzerland, the University of Worcester, UK, and Leiden University, NL, , suggest countries in the Balkan Peninsula – such as Bulgaria, Romania and Serbia – will benefit most from the leaf beetle as a biological control.

Prior to the accidental arrival of the leaf beetle in 2013, some 13.5 million people suffered from ragweed-induced allergies in Europe, causing economic costs of approximately Euro 7.4 billion annually.

In Europe, common ragweed is considered invasive in more than 30 countries and its spread and impact, the scientists say, is likely to increase with rising temperatures caused by climate change.

Field studies in Italy have proved that the leaf beetle can reduce ragweed pollen by 82 percent. In the Milan area, where the beetle was first detected, up to 100 percent of ragweed plants were attacked and the damage caused was enough to prevent flowering that causes pollen to be released.

Dr Schaffner said, “Our study provides evidence that the impacts of common ragweed on human health and the economy are so far highly underestimated, but that biological control by Ophraella communa might mitigate these impacts in parts of Europe.

“We propose that future assessments of the economic impacts of Invasive Alien Species (IAS) should more thoroughly consider costs related to human health.”

The scientists drew upon information from the European Pollen Monitoring Programme before mapping seasonal total ragweed pollen integrals in Europe during 2004 and 2012 – prior to the introduction of the leaf beetle. They then interpolated data from 296 pollen monitoring sites across Europe.

To validate the estimated number of patients suffering from ragweed pollen allergy, the researchers compared their European-wide assessment with detailed healthcare data from the Rhône-Alpes region in southeastern France.

They then weighted the treatment and lost work time cost at the country level using purchasing power parity – adjusted health expenditures per capita for 2015 – to determine the overall economic costs of healthcare to treat the symptoms and other effects of ragweed pollen.

Professor Heinz Müller-Schärer, of the University of Fribourg, said, “We were not sure as first whether the leaf beetle was useful or harmful. Laboratory tests had shown that it was possible that it was harmful to sunflowers. However, field tests in China and Europe could not confirm this finding.”

Dr Schaffner, Professor Müller-Schärer and the other authors conclude that accurate information of policy and management about the impact of IAS on human health and the potential savings – due to the implementation of mitigation measures – is essential to ensure that reasonable resources are invested and actions coordinated in IAS management.”

Credit: 
CABI

Ultrasound-assisted molecule delivery looks to preserve blood for years

image: Illustration of ultrasound-induced microbubble (MB) rupture causing temporary pores in cell membranes, which enables entry of soluble molecules such as trehalose (not to scale).

Image: 
Jonathan A Kopechek

WASHINGTON, April 21, 2020 -- Ensuring adequate preservation of the millions of units of blood that are donated every year presents a challenge for blood banks, as blood can typically be stored for only six weeks after donation. A potential solution to the problem attempts to dry blood by using a sugar-based preservative that organisms living in some of Earth's most extreme environments produce to weather long periods of dryness. New work in ultrasound technology looks to provide a path to inserting these sugars into human red blood cells, in an effort to help them last for years.

Researchers at the University of Louisville have demonstrated a new way to use ultrasound to create pores in blood cells, which allows the molecule trehalose to enter the cells and prevent their degradation when dried for preservation. Oscillating microscopic bubbles of inert gases with ultrasound provides the microfluidic system with the ability to increase the number of viable cells that can be rehydrated. The researchers discuss their work in this week's Biomicrofluidics, from AIP Publishing.

The approach could lead to ways of increasing the shelf life of blood donations from weeks to the order of years. Such advances would provide a boon to those needing blood in areas where access to donations is difficult, like on the battlefield or in space.

"What's unique about this is there are not many other studies that look at using acoustofluidics to place a molecule like this inside red blood cells," said author Jonathan Kopechek. "It's also interesting, because it allows us to store blood without keeping it cool."

When it's not helping these extremophiles survive, trehalose is a relatively cheap sugar that is so safe that it is used as a preservative for food items, like donut glaze.

The group constructed a spiral-shaped channel that exposed blood cells to trehalose while surrounded by microbubbles. They tuned ultrasonic vibrations using several parameters until the bubbles shook nanosized holes in the membranes of the blood cells, just large enough for trehalose or a closely related fluorescent molecule called fluorescein to enter and just briefly enough to maintain the integrity of the blood.

After confirming that fluorescein could enter cells on test samples, they added trehalose to a new batch of samples, dried the blood, rehydrated it, and performed tests to count how many of the blood cells were still viable after the process.

The ultrasound technique was able to preserve a significantly higher portion of cells by adding trehalose versus leaving the trehalose out.

The group looks to improve on the yield for their technique with the hopes of verifying the effectiveness of dry-preserved blood in patients.

Credit: 
American Institute of Physics

NEI researchers link age-related DNA modifications to susceptibility to eye disease

image: DNA methylation is an epigenetic mechanism essential for normal cell development and differentiation, and is also associated with aging and the formation of cancers. When present, DNA methylation generally represses gene expression.

Image: 
NIH Common Fund, adapted from

National Eye Institute (NEI) researchers profiling epigenomic changes in light-sensing mouse photoreceptors have a clearer picture of how age-related eye diseases may be linked to age-related changes in the regulation of gene expression. The findings, published online April 21 in Cell Reports, suggest that the epigenome could be targeted as a therapeutic strategy to prevent leading causes of vision loss, such as age-related macular degeneration (AMD). NEI is part of the National Institutes of Health.

"Our study elucidates the molecular changes and biological pathways linked with aging of rod photoreceptors, light-sensing cells of the retina. Future investigations can now move forward to study how we can prevent or delay vision loss in aging and hopefully reduce the risk of associated neurodegeneration" said the study's lead investigator, Anand Swaroop, Ph.D., senior investigator and chief of the NEI Neurobiology, Neurodegeneration, and Repair Laboratory.

Each organism is born with a genome, a library of genes that control all the body's cellular and tissue functions. Expression of those genes - when information stored in DNA is converted into instructions for making proteins or other molecules - is modulated and maintained by the organism's epigenome. The epigenome tags the DNA code to modify gene expression in ways that can be favorable and unfavorable for survival.

As it turns out, that interplay between the genome and the epigenome evolves as the organism ages. Scientists therefore study epigenomic DNA modifications for clues about why certain diseases develop with advancing age.

To explore how such DNA modifications might influence visual function as we age, Swaroop's team performed whole genome sequencing of DNA methylation changes in mouse rod photoreceptors at four separate stages over the animal's lifetime. DNA methylation is an epigenetic mechanism essential for normal cell development and differentiation, and is also associated with aging and the formation of cancers. When present, DNA methylation generally represses gene expression.

The sequencing was performed at ages three months (young), 12 months (middle-aged), and 18 and 24 months (older). The average lifespan of a mouse is about two years.

Rod photoreceptors are the predominant type of cell in the retina, the light-sensing tissue at the back of the eye. Rod photoreceptors enable dim-light vision, and are critical for the survival of cone photoreceptors that enable daylight and color vision. Rod dysfunction is common in older human adults and can be an early warning sign of AMD and other retinal degenerative diseases.

The researchers identified 2,054 differentially methylated regions across the four mouse age groups, that is, genomic regions with differences in DNA methylation.

"We know that DNA methylation changes are strongly associated with biological age, but prior to this study we had limited understanding of how these alterations correlated with cellular function," Swaroop said. This is the first study to look at DNA methylation changes as animals age. Very few studies have looked at DNA methylation changes in people with AMD, a leading cause of vision loss in people age 50 and older, which can progress even when vision loss is undetectable.

The researchers then analyzed the differentially methylated regions with RNA sequencing data to look more closely at how the mouse genes were transcribing proteins differently in the retina as the animals aged.

Those analyses uncovered distinct shifts in how the genes produced proteins relevant to energy metabolism, mitochondria function, and the longevity of rod photoreceptors, indicating their contribution to age-related disease susceptibility.

Rod photoreceptors require vast amounts of energy to sustain vision and are thus vulnerable to metabolic stresses that accompany aging. Energy deprivation of photoreceptors is believed to be a key driver of neurodegeneration of the retina.

"Neurons, specifically photoreceptors, prefer glucose as a source of energy, but in aging, we surprisingly observed utilization of fatty acids as well. These studies suggest how changes in aging rod functions can make them vulnerable to genetic susceptibility variations and environmental factors, which together cause common blinding aging-associated diseases," Swaroop said.

"Our work provides pivotal connections between aging, the epigenome, dysfunction of the cell's mitochondria, and diseases such as AMD. The findings have broad implications for how we understand age-associated neurodegeneration, not only in the eye, but elsewhere in the body," he said.

"Future studies will assess whether DNA methylation contributes to alterations in the expression of metabolic genes and thus introduce epigenomic editing as a therapeutic possibility for age-related retinal disease," said the study's first author, Ximena Corso-Díaz, Ph.D., a postdoctoral fellow in the Neurobiology, Neurodegeneration, and Repair Laboratory.

Credit: 
NIH/National Eye Institute

HudsonAlpha plant genomics researchers surprised by cotton genome

image: Jane Grimwood, Ph.D., is a faculty investigator and co-director of the HudsonAlpha Genome Sequencing Center.

Image: 
HudsonAlpha Institute for Biotechnology

April 20, 2020 (Huntsville, Ala.) - Plant genomics researchers at HudsonAlpha Institute for Biotechnology announce the surprising results of a cotton sequencing study led by Jane Grimwood, PhD, and Jeremy Schmutz, who co-direct the HudsonAlpha Genome Sequencing Center (HGSC). The goal of the project was to identify differences among wild and domesticated cotton that could be used to reintroduce agriculturally beneficial traits like disease or drought resistance. The results, however, surprised the researchers and led them to unexpected conclusions, as described in their paper in Nature Genetics.

"The importance of this study is that it helps us understand more about cotton fiber development," said Grimwood, who is a faculty investigator at HudsonAlpha. "But perhaps more importantly, it reinforces the surprising concept that wild and domesticated cotton is remarkably similar, leading us to the conclusion that we will need to work on other approaches to generate diversity for cotton species."

For the study, the group sequenced and assembled reference-grade genomes for five different species of allotetraploid cotton and compared them with two diploid cotton genomes. Their genomic analysis showed that two ancestral diploid cotton genomes came together to form what is basically the modern tetraploid cotton between 1 and 1.6 million years ago.

Then, about 8,000 years ago, humans began to domesticate cotton for agriculture. They selected wild plants for cultivation that had desirable traits like stronger fiber or more cotton on each plant. Humans then continued to choose plants for breeding that would improve yield and the quality of the harvested crop.

"When we compared the wild cotton plants to domesticated cotton, we expected to see a genetic bottleneck where many wild traits had been discarded," said Schmutz, a faculty investigator at HudsonAlpha. "What you typically see with these crops is that all the selection has gone into improving production, potentially at the cost of losing beneficial genetic material from the wild species."

What they found, however, surprised them.

The wild and domesticated genomes, it turns out, were incredibly similar.

"In all of the cotton tetraploids, there's less diversity between what are supposed to be different species of cotton than between two humans or even within different cells in a single human body," Schmutz said.

This lack of diversity means that researchers won't be as easily able to reach back into the wild cotton gene pool to introduce lost traits like disease resistance back into cultivated cotton plants.

"We can't only rely on the gene pool to make changes to the plant architecture because those wild genes don't exist. Exploring the route of mining natural diversity won't work. The only real way forward to improve cotton as a crop will be genome editing," Schmutz said.

The result of this surprising discovery has been the launch of new projects for Schmutz, Grimwood and their team at HudsonAlpha. To begin with, they now have complete comparison genomes for multiple species of the same crop plant. This knowledge allows them to "walk" from one species to the other to introduce desirable traits to cultivated cotton.

"We are the first group to do these sorts of large projects where we are sequencing multiple high-quality references from the germplasm with the goal of getting direct comparisons across multiple species," Grimwood said.

"We just sequenced a cotton genome in two days," Schmutz added. "The promise of that speed is that we can start to move from inferred variation where you look at a single reference and infer the variation to looking at multiple references and directly comparing the differences."

One ongoing project in the HGSC in collaboration with Clemson University, then, is trying to accelerate targeted gene editing in cotton. The group is looking at genetic mechanisms that enable fast transformation in cotton so they can bump up the rate of making targeted modifications.

In addition, while the group was surprised to find so much similarity among the cotton genomes, they did find some useful variation. Wild cotton, for instance, does have some more disease resistance triggers than cultivated cotton varieties, which tend to be more vulnerable.

"This is the basis from which we can start to compare what else we can do with existing cotton diversity," Grimwood said. "Breeders have selected for 'improved' strains of cotton based on phenotype changes but they don't necessarily have a full understanding of the changes they are making on the genetic side. With this new information, they can look at what their selections are doing on a genetic level."

Even though the project results were unexpected, the entire team is confident that the newly assembled cotton genomes will lead to direct benefits for cotton producers and the cotton industry.

Don Jones, the Director of Agricultural Research at the nonprofit Cotton Incorporated, said these reference grade assemblies are significant advancements for improving the sustainability of cotton production.

"The results described in this Nature Genetics publication will facilitate deeper understanding of cotton biology and lead to higher yield and improved fiber while reducing input costs. Growers, the textile industry, and consumers will derive benefit from this high impact science for years to come," Jones said.

Credit: 
HudsonAlpha Institute for Biotechnology