Culture

New study examines what human physiology can tell us about how animals cope with stress

How we respond to stress has been a source of scientific research since the term was introduced more than 70 years ago. While the analysis of human stress response has provided valuable insight, new work from University of South Florida researchers is offering a novel perspective on how other vertebrates may regulate flexibility in coping with stress.

When a person experiences stress, a variety of physiological responses kick in through a combination of molecular regulation, hormone secretion and the activation of the hypothalamic pituitary adrenal axis. These responses lead to changes in certain physical characteristics, such as increased blood pressure and heart rate, as well as thought responses that affect how a person perceives and reacts to a stressful situation.

These physiological patterns are well-studied in human beings and have provided tremendous advancements in our understanding of the human body, as well as the long-term impact stress can have on mental health. It's insight that USF postdoctoral researcher Cedric Zimmer hopes to advance in other vertebrates dealing with a variety of environmental stressors in nature.

Zimmer is the lead author of a new paper published this week in the prestigious journal, BioScience. It examines the role a specific molecule, FKBP5, plays in the flexible regulation of stress response.

That focus on flexibility, as it pertains to stress, is a key component in this latest USF project and represents a still-emerging area of stress research. Flexibility refers to an organism's ability to produce and implement best coping strategies based on the current situation and past experiences. Researchers believe the molecule, FKBP5, has a fundamental role in this process.

"This molecule plays a critical function in a person's ability to cope with stress and the flexibility of this response in order to appropriately respond to a current stressful situation," Zimmer said. "So, what we've done is really bring together a tremendous amount of that academic research to develop a new framework for how any vertebrate deals with stress and their propensity to flexibly cope with these stressors."

This work was published through a collaboration between several USF College of Public Health research groups led by Lynn "Marty" Martin, Monica Uddin and Derek Wildman.

While this publication provides an early framework for continued research, Martin believes it could be crucial in understanding the broader impacts of human influence on the environment. When humans and animals interact in ways they haven't before, that can have obvious effects on nature, but also unintended consequences to us.

"Stress influences the immune systems of animals, which then changes the way they pump out pathogens into the environment," Martin said. "And when those pathogens can also infect humans, as is the case for West Nile virus, Salmonella and many others, the importance of understanding stress in animals is not only critical for their wellbeing, but for ours as well."

Researchers hope this work can help further the understanding of the role FKBP5 molecules play in regulating stress response flexibility and long-term impacts that has on a vertebrate's ability to cope with stress.

Credit: 
University of South Florida

New study suggests crucial role for lymphocytes in asymptomatic COVID-19 infection

Washington, DC - October 9, 2020 - COVID-19 remains stubbornly inconsistent. More than a million people have died and 35 million have been diagnosed, but a large fraction of people infected with the coronavirus--about 45%, according to recent estimates--show no symptoms at all.
 

A retrospective study of 52 COVID-19 patients, published this week in mSphere, an open-access journal of the American Society for Microbiology, may help researchers better understand why not everyone show symptoms of the disease. The study's authors found that asymptomatic patients hosted viral loads comparable to those of symptomatic patients, but asymptomatic patients showed higher levels of lymphocytes (a type of white blood cell responsible for immune responses), cleared the viral particles faster, and had lower risks of long-term complications. Further analyses suggested the interaction between the virus and the immune system likely played a role in that process.
 

"Our findings suggested an important role for lymphocytes, especially T cells, in controlling virus shedding," said virologist Yuchen Xia, Ph.D., at Wuhan University's School of Basic Medical Sciences, in China, who worked on the new study.
 

The wide range of COVID-19 symptoms is well documented. Asymptomatic carriers, on the other hand, often go undiagnosed but can still shed the virus and spread it to others. Understanding why some patients get sick and others don't is one of the most important challenges in curbing the pandemic, Xia said. "They may cause a greater risk of virus transmission than symptomatic patients, posing a major challenge to infection control."
 

Xia and his colleagues studied throat swabs and blood samples collected from patients at Renmin Hospital of Wuhan University, including 27 who had been admitted for complications related to COVID-19 and 25 asymptomatic patients who had been admitted for other reasons but tested positive for the SARS-CoV-2 virus upon arrival. The researchers used the throat swabs to assess viral load, and on the blood samples they ran tests to measure immunoglobins, cytokines, and immune cells.
 

Although both groups of patients had comparable viral loads, asymptomatic patients showed a statistically significant increase in number of CD4+ cells, white blood cells that fight infection, compared to symptomatic patients. Like previous studies, the new analysis also showed that symptomatic patients were more likely to show impaired liver function than asymptomatic patients. In contrast to other work, however, the new research did not find significant differences in cytokine levels between the two groups.
 

Xia's group recently began collaborating on a larger follow-up study with researchers in Germany, analyzing blood samples from more than 100 patients with severe COVID-19 symptoms and 30 patients with mild symptoms. They also plan to conduct animal studies to better understand the role of T cells in viral shedding.
 

Xia said he hopes this study will bring attention to the importance of including transmission from asymptomatic people in widespread efforts to curb the pandemic. "More public health interventions and a broader range of testing may be necessary to control COVID-19," he said.

Credit: 
American Society for Microbiology

Sweetpotato biodiversity can help increase climate-resilience of small-scale farming

image: a. The yellow dots mark the origin of each of the cultivars studied on the test site (the red star). The blue dots indicate the location of the most heat-stress tolerant varieties.
b. Drone maps of the 4,040 test plots on the test site in Piura, Peru.
c. Close-up of the delineated plots of sweet-potato cultivars.
d. High-resolution thermographic image of the temperatures of the crop canopy under conditions of heat stress (lowest temperatures in blue, highest in red).

Image: 
© Bettina Heider et al. Nature Climate Change

Climate change poses a threat to the world's subsistence crops. Heatwaves, which are likely to intensify according to climate evolution predictions, are generating levels of heat stress that are damaging to agricultural production. Identifying resistant crop varieties is therefore crucial to ensuring people's food security and farmers' resilience. To date, many studies have been conducted on varietal improvement, which involves developing and selecting plants with the required characteristics. Few, however, have examined intraspecific diversity, which is defined as the degree of genetic variety that exists within the same species.

For the present study, the international team focused on the sweetpotato - the fifth most produced crop in the world, after corn, wheat, rice, and cassava. This tuber is grown for its hardiness and tolerance to climatic shocks, and has great potential to help achieve the Sustainable Development Goals (SDGs) adopted by the United Nations as part of the Horizon 2030 Agenda: it is grown in areas prone to erosion to protect agricultural land (SDGs 12 and 15); it has a high nutritional value, as well as higher content than most staple foods in vitamins A and C, calcium, iron, dietary fibre, and protein (SDGs 2 and 3); its flexible planting and harvesting schedules mean it is less labour-intensive to grow and thus is particularly adaptable to human migration (SDGs 10 and 16).

Traditional local varieties perform well under heat stress

As part of CGIAR's research program on roots, tubers and bananas (RTB), the researchers assessed the heat-stress tolerance of 1,973 different varieties of sweetpotato from the CIP's sweet-potato 'genebank'. The collection of cultivars from 50 different countries comprised modern and traditional varieties, as well as breeding lines, developed in vitro and then planted in fields irrigated under controlled conditions on a 2.5 ha test site in the coastal desert region of north Peru. Analysis of the roots and foliage data allowed the effect of repeated exposure to extreme temperatures - greater than 35°C - on the plants' performance to be measured.

Result: "132 cultivars, of which 65.9% were traditional local varieties, demonstrated good heat tolerance. These are therefore promising candidates for selection as high-yield, heat-tolerant varieties," explains Bettina Heider, a researcher with CIP and lead author of the study.

"This mass screening, carried out on an unprecedented geographical scale (America, Africa, Asia), proved crucial to identifying the heat-stress tolerance characteristics of the sweetpotato, for the purpose of a deeper molecular characterization of specific genes," explains Olivier Dangles, an ecologist at IRD and co-author of the study.

"Intraspecific diversity - the result of hundreds of years of co-evolution between farmers and their crops - is proving critical in the face of climate change," he continues. "It emphasizes the role of agrobiodiversity in the resilience of tropical agricultural systems."

Farmers will need help to adapt

"Our results also suggest that the temperature of the canopy and the level of carotenoids could be the appropriate markers for selecting heat-stress tolerant lines," adds Emile Faye, researcher in spatial agroecology at CIRAD. "However, participatory experiments need to be conducted in different contexts, to test the efficacy and economic viability of the varieties identified."

Intraspecific diversity offers more options to farmers, therefore, for managing climate risks and increasing the resilience of their farming systems. The study authors recommend that this knowledge be shared with farmers, so that they adopt high-yield varieties that also offer higher nutritional value.

Credit: 
Institut de recherche pour le développement

Research demonstrates microbiome transmissibility in perennial ryegrass

image: Ian Tannenbaum, first author of paper.

Image: 
Ian Tannenbaum

Scientist Ian Tannenbaum has spent most of his career working in clinical microbiology but was excited to transition to agricultural microbiology when he was offered a chance to conduct the first assessment of the perennial ryegrass microbiome and how it changes during plant maturation and seed production.

"The concepts of the project were very interesting to me and unlike anything I'd previously worked on," said Tannenbaum, who is affiliated with the Centre for AgriBioscience and La Trobe University in Victoria, Australia. "This was my first series of experiments aimed at understanding the natural bacterial assembly of a plant microbiome."

Tannenbaum's most surprising discovery? Finding a stable bacterial microbiome within surface-sterilized ryegrass seeds that almost disappears when the plant matures but returns in a new generation of seed.

"Our findings suggest that a portion of microbiome recruited by the parent plant was inherited by the following generation of seed, which demonstrates microbiome transmissibility," Tannenbaum explained. "The microbiome of the mature plant can be used as a snapshot of the following seed generations."

Working alongside a team of researchers, Tannenbaum found that the microbiome within perennial ryegrass seeds was predominantly comprised of a class of bacteria known as Gammaproteobacteria. In germinated seeds, the bacterial population was influenced by the presence of a resident fungal endophyte, which appeared to impact the abundance of some bacteria strongly enough to result in different seed microbiome between those with the fungal endophyte and those without.

They also compared the impact of soil by studying plants grown in potting mix and a sand/vermiculite mixture. Both soil types were strong determiners of the mature plant microbiomes. Many bacterial species were shared between the two soil types but differed greatly in their relative abundance.

Finally, the team assessed the microbiome of the following generation of seed generated from the plants grown in either mixture. The microbiome profile of the new seed was more reflective of the seed microbiome of the parent. However, additional classes were observed and determined to have been recruited from the growth environment by the parent plant and transmitted to the seed.

Credit: 
American Phytopathological Society

Pharmacist-led digital intervention reduces hazardous prescribing in general practice

A pharmacist-led, new digital intervention that improves patient safety when prescribing medication in general practice reduced rates of hazardous prescribing by more than 40* per cent, 12 months after it had been introduced to 43 GP practices in Salford, finds a new study**. Due to its success, plans are underway to roll it out across Greater Manchester.

Prescribing and medication are one of the biggest causes of patient safety incidents and the third WHO Global Patient Safety Challenge is focussed on Medication without Harm***. The SMASH**** intervention addresses this. It was developed by researchers at the National Institute for Health Research Greater Manchester Patient Safety Translational Research Centre (NIHR GM PSTRC), which is a partnership between The University of Manchester and Salford Royal hospital in collaboration with The University of Nottingham.

Pharmacists working in general practice use the SMASH dashboard to identify patients who are exposed to potentially hazardous prescribing. For example, patients with a history of internal bleeding may be prescribed medications such as aspirin which could increase the risk of further internal bleeds without prescribing other treatments to protect them. SMASH identifies this and warns healthcare professionals about it, who can then decide on a possible course of action.

The intervention is unique due to its ability to provide near real time feedback to prescribers as it updates every evening.

Professor Darren Ashcroft, Research Lead for the Medication Safety theme at the GM PSTRC, said: "We worked with the Safety Informatics theme at the GM PSTRC to develop then test SMASH. It is designed to improve patient safety in general practice by reducing potential problems made when prescribing medication and inadequate blood-test monitoring. It brings together people and data to reduce these common medication safety problems that all too often can cause serious harm.

"It works when a GP practice has a clinical pharmacy team. These teams working in general practices across Salford used the insights identified by SMASH to become "Champions for Change". In doing so, they achieved marked improvements in rates of hazardous prescribing over the 12 month study period. Importantly, at the end of the 12 month study the success of the intervention was sustained which is encouraging. Our efforts are now focussed on scaling up the SMASH intervention to benefit the whole Greater Manchester population."

The researchers monitored SMASH in each of the GP practices where it was trialled for a year and evaluated its success.

Professor Niels Peek, Research Lead for the Safety Informatics theme at the GM PSTRC, said: "SMASH capitalises on the unique digital infrastructure that already existed in Salford and will soon be available for 2.8 million people in Greater Manchester. This will create an integrated health system that continuously learns and improves the quality of its services."

The intervention builds on the principles of PINCER, an intervention developed by The University of Nottingham and The University of Manchester, and supported by the GM PSTRC. SMASH uses a set of 13 prescribing safety indicators developed by experts for PINCER. An example is the prescription of an oral non-steroidal anti-inflammatory drug (NSAID), without also prescribing an ulcer healing drug, to a patient aged over 65.

PINCER is proven to reduce hazardous prescribing and has been rolled out by Academic Health Science Networks (AHSNs) to 40% of GP practices in England as part of co-ordinated approach to reduce medication errors in primary care by the national AHSN Network. Due to the success of SMASH in Salford, Health Innovation Manchester, the organisation responsible for accelerating proven innovation into Greater Manchester's health and social care services and part of the AHSN Network, is currently working to roll it out across Greater Manchester.

Amanda Risino, Chief Operating Officer at Health Innovation Manchester, said: "SMASH is a great innovation and there is a huge opportunity to be realised by sharing this innovation across the Greater Manchester city region. Not only will it help patients at direct risk of medication-related harm, but by also using data from multiple health and social care organisations we can drive improvements in prescribing safety and effectiveness across all care settings."

Credit: 
NIHR Greater Manchester Patient Safety Translational Research Centre

World Mental Health Day -- CACTUS releases report of largest researcher mental health survey

image: A report of largest and most diverse global survey on researcher mental health

Image: 
Cactus Communications

London, 13th October 2020: On October 10 2020, on the occasion of World Mental Health Day, Cactus Communications (CACTUS), a technology company accelerating scientific advancement, released its much-anticipated global survey report on mental health, wellbeing, and fulfilment among researchers. The survey, which was conducted from October 2019 to July 2020 in seven languages, saw a phenomenal response of over 13,000 participants globally, with strong representation from the top 10 research-producing countries, making it the largest and most diverse survey of its kind among researchers. With 13 active and former academics as collaborators, the initiative was supported by various research-associated institutes and organizations such as IndiaBioscience, SciELO, and India Alliance, with Shift Learning as the analytics & reporting partner, Dragonfly Mental Health as an independent consultant, and Vitae and Euraxess as report amplification partners.

Commenting on the report, Abhishek Goel, Co-Founder and CEO, CACTUS, said, "While the world is constantly looking at researchers for answers and solutions, especially during a crisis like the ongoing pandemic, there is very little knowledge available about the life of a researcher. Through our conversations with researchers over the years, we understand that the academic environment is harsh, competitive, and rife with failure and rejection, and that mental health in academia is a serious issue that needs a concerted global focus. Through the Cactus Foundation, which aligns with the United Nations Sustainable Development Goals, we hope to create a better world for researchers, and we believe this survey is an important first step. By highlighting the pressures and the joy and stress triggers for researchers at this global scale, we hope this survey can eventually pave the way for a more nurturing and fulfilling research culture."

Speaking about the global diversity of the survey population, Clarinda Cerejo, Senior Director, Thought Leadership, CACTUS, said, "While mental health at the workplace has become a global topic of discussion, this topic is still considered taboo in many countries, and academia in particular has traditionally lacked the structure and organization required to address mental health concerns systemically. While we always thought of the survey as immensely important, we are humbled by the kind of global participation we have received from researchers across career stages and even from regions where mental health discussions are not commonplace. This makes us believe that researchers want to speak up and use their voice to drive change, and that research institutions want to pay heed. We hope that this survey marks the beginning of an important global conversation and that all decision makers working with researchers draw on its insights to implement more researcher-friendly work policies".

Through this survey, CACTUS aims to raise awareness about mental health in academia globally, urging research organizations and universities internationally to openly talk about and address this issue.

The full survey report contains interesting insights about the lives of researchers as well as the overall culture in academia. It offers a global researcher perspective on which aspects of their work bring researchers joy and fulfilment, which ones make them feel stressed and overwhelmed, and the kind of support they would like to receive from universities and research institutions, among other topics. To read the full survey report, you can download it here for free: https://bit.ly/3dlbGsv

Credit: 
Cactus Communications

Scientists identify sensor protein that underlies bladder control

LA JOLLA, CA--A team co-led by scientists at Scripps Research has found that the main sensor protein enabling our sense of touch also underlies the feeling of having a full bladder and makes normal bladder function possible.

The discovery, published Oct. 14 in Nature, marks a key advance in basic neurobiology and may also lead to better treatments for bladder control and urination problems, which are common especially among the elderly.

"We tend to take urination for granted, and it has been under-studied, yet it's a huge burden when something goes wrong with this system," says the study's lead author Kara Marshall, PhD, a postdoctoral research associate in the Department of Neuroscience at Scripps Research. "Now we've identified a crucial part of how urination normally works."

Marshall and her colleagues focused in this study on the PIEZO2 protein, a "mechanosensor" that detects the physical stretching of tissues where it resides. They found that PIEZO2 is expressed in cells of the bladder and is necessary for normal urinary continence and functioning in both mice and humans.

"Who would have imagined that the same mechanosensor protein enabling our sense of touch also alerts us that our bladder is full?" says co-senior author Ardem Patapoutian, PhD, Professor and Presidential Endowed Chair in Neurobiology at the Dorris Neuroscience Center at Scripps Research, and a Howard Hughes Medical Institute investigator.

In 2010, Patapoutian and his lab first identified PIEZO2 and its sister protein PIEZO1 as mechanosensors that sense mechanical distortions of tissues. For that feat, among others, Patapoutian was a co-recipient of the prestigious 2020 Kavli Prize in Neuroscience.

Like most sensor proteins, the PIEZOs are ion-channel proteins, which are embedded in their host cell's outer membrane and, when triggered by a stimulus, allow a flow of charged atoms into the cell. Sensor ion-channel proteins are usually found in sensory neurons in the skin, joints and other organs. On a given neuron, when enough of these channels open to admit ion flows, the neuron will fire a nerve signal to the brain.

For PIEZOs, the stimulus that triggers the opening of the ion channel is the stretching of the cell membrane due to mechanical forces on the local tissue. In studies over the past decade, Patapoutian and his colleagues have shown that PIEZO2 is expressed is different organs and tissues throughout the body. For example, they exist in lung tissues to sense lung stretch and help regulate breathing, in blood vessels to sense blood pressure and in the skin to mediate the sense of touch.

The new study was a collaboration with Alexander Chesler, PhD, and Carsten Bönnemann, MD, senior investigators at the National Institutes of Health. Chesler and Bönnemann, and their colleagues, have been studying people born with genetic mutations that result in the functional loss of PIEZO2. These individuals suffer various impairments in sensory pathways known to be PIEZO2-related.

For the study, NIH investigators found that these PIEZO2-deficient individuals, in addition to their other sensory deficits, lack the normal sense of having a full bladder. They typically urinate on a schedule to avoid incontinence and have trouble completely emptying their bladder when they do urinate.

Patapoutian, Marshall and their colleagues showed in experiments that the loss of PIEZO2 has similar effects in mice. The urinary tract uses PIEZO2 protein in both bladder sensory neurons and in bladder-lining cells called umbrella cells to detect stretch and facilitate urination, indicating a two-part sensor system. As they determined in experiments, bladder neurons in mice normally respond robustly with nerve signals when the bladder is filled but are almost completely silent during bladder filling if they lack PIEZO2.

The mice lacking PIEZO2 in their lower urinary tracts also showed abnormal urination reflexes in the muscles controlling the urethra, the duct in which urine flows from the bladder. That suggests that in mice and most likely in people, the mechanosensor protein is needed both for normal bladder-stretch sensation and for normal urination.

The team is currently following up with research on the distinct roles of bladder neurons and umbrella cells, and how they signal to each other. They are also investigating the possible roles of other mechanosensors, such as PIEZO1, in bladder control and urination.

"Mice without PIEZO2 had clear urination deficits, but ultimately were still able to urinate, so that suggests another mechanosensory protein may be involved," Marshall says.

Credit: 
Scripps Research Institute

Army researchers collaborate on universal antibody test for COVID-19

image: U.S. Army Medical Research Institute of Infectious Diseases researchers Laura Prugar (blue mask), Kathleen Huie (print mask) and Nicole Josleyn (purple mask) use a microneutralization assay and a high-throughput fluorescent imaging system to determine levels of neutralizing antibody to SARS-CoV-2 in convalescent patients.

Image: 
John W. Braun Jr., USAMRIID VIO

ADELPHI, Md. -- Researchers with the U.S. Army Futures Command are part of a team that tested alternative ways to measure COVID-19 antibody levels, resulting in a process that is faster, easier and less expensive to use on a large scale. Their method holds promise for accurately identifying potential donors who have the best chance of helping infected patients through convalescent plasma therapy.

Dr. Jimmy Gollihar, biochemist and biotechnologist for the U.S. Army Combat Capabilities Development Command's Army Research Laboratory at CCDC ARL South in Austin, Texas, and chief technology officer of the Bioindustrial Manufacturing Innovation Institute, in collaboration with Dr. John Dye at the U.S. Army Medical Research Institute of Infectious Diseases, or USAMRIID, and collaborators at Houston Methodist, Pennsylvania State University and the University of Texas at Austin, sought to find alternatives to measuring virus neutralization, or VN, titers. These titers are the gold standard of COVID-19 antibody testing, as VN antibodies in the blood have been shown to correlate with levels of protective immunity.

According to the researchers, this kind of antibody testing is not widely available as it is technically complex and requires days to set up, run and interpret. Thus, the team looked to another type of test, called enzyme-linked immunosorbent assays, or ELISAs.

According to Gollihar, ELISAs are standard quantitative tests used to measure the amount of antibody to a particular antigen in a given sample.

"ELISAs are standard assays that can be performed in almost any academic or medical laboratory," Gollihar said. "This is important in emergency care centers treating critically ill patients. The assays can also be used for serological monitoring of the disease."

Specifically, scientists looked at the relationship of anti-spike ectodomain, or ECD, and anti-receptor binding domain, or RBD, antibody titers in the bloodstream. The spike ECD and RBD proteins are components of the much-talked-about spike protein made by SARS-CoV-2 and are critical to how the virus enters the body, spreads and causes COVID-19 disease.

Gollihar's specific roles included coordinating the plasma sample delivery from Houston Methodist, scaling production and purification of the antigens, and setting up the collaboration with USAMRIID for live virus neutralization testing under biocontainment conditions. He also helped transition the ELISA assay to Houston Methodist's automation team.Dye and his team performed neutralization assays on all the specimens in a Biosafety Level 3 laboratory at USAMRIID. Their work determined that the relative amount of antibody in the bloodstream of COVID-19 patients is linked to their ability to control viral infection; essentially, the more severe the disease, the higher the levels of neutralizing antibody present. This information provides potential benchmarks for a clinical product for convalescent plasma treatment studies; it could also be used to assess how well a vaccine recipient may respond to a subsequent infection.

The researchers found that the ELISA tests had an 80 percent or greater probability of predicting VN titers at or above the Food and Drug Administration-recommended levels for COVID-19 convalescent plasma.

"In all, we discovered that high titer ELISAs correlate well to virus neutralization and can be used as a surrogate for screening convalescent plasma," Gollihar said.

In addition, the researchers found that convalescent donors maintain high levels of immunity over the course of many weeks, and that frequent plasma donations did not cause a significant decrease in antibody or virus neutralization levels.

Perhaps most surprising, the researchers said, is that they identified 27 individuals from the surveillance cohort with high enough antibody titers to indicate that some asymptomatic individuals may have plasma suitable for therapeutic use and may have a degree of relative immunity against SARS-CoV-2.

"This collaboration between the Army, Houston Methodist and our partners in academia shows the incredible diversity of complementary capabilities we can deploy in responding to a worldwide pandemic," Dye said.

The team's findings are described in a paper titled, "Convalescent plasma anti-SARS-CoV-2 spike protein ectodomain and receptor binding domain IgG correlate with virus neutralization," featured in the Journal of Clinical Investigation.

Credit: 
U.S. Army Research Laboratory

Over 150 million websites among a billion tested include sensitive (and tracked) content

image: A decisive research effort for protecting our privacy on the Web: Privacy law is made for use by humans... how can we teach this law to machines?

Image: 
IMDEA Networks Institute

The European General Data Protection Regulation (GDPR) includes specific clauses that put restrictions on the collection and processing of sensitive personal data, defined as any data revealing racial or ethnic origin, political opinions, religious or philosophical beliefs, or trade union membership, also genetic data, biometric data for the purpose of uniquely identifying a natural person, data concerning health or data concerning a natural person's sex life or sexual orientation...

The After two years of hard work, and having crunched more than one billion web-sites (most of the English speaking web), an international team, with Nikolaos Laoutaris (Research Professor at IMDEA Networks Institute, Madrid), as well as researchers from TU Berlin and the Cyprus University of Technology, has developed specialised machine learning classifiers that are able to identify sensitive URLs on the web and used them to search for such URLs on a corpus of some 1 billion URLs in total. As a main (and disturbing) result, some 150 million of them were find to include sensitive content related to Health, Political Beliefs, Sexual Orientation, etc ... and still be tracked nearly as much as the rest of the web.

A real time detection

Existing legislation about sensitive personal data is targeted mostly for use by humans, e.g., to file complaints, conduct investigations, and even pursue cases in courts of law. With the use of the new automated machine learning classifiers, however, additional proactive measures can also be put in place for the first time. For example, the browser of the user, or an add-on program, can warn him before clicking and following URLs pointing to sensitive content. Upon visiting such sites, trackers can be blocked, and complaints can be automatically filed. Being able to do the above hinges on being able to classify automatically whether a URL is a sensitive one or not, in real time.

The latter is easier said than done. The reason has to do with the ambiguity of terms such as "Health", that are used by legal documents to indicate what types of information are considered as sensitive. Indeed, the word Health can be found in both web-sites about healthy eating, sports, and organic food, but also on web-sites about chronic diseases, sexually transmitted diseases, and cancer. Most of the effort on producing the aforementioned classifier went into collecting sufficient "ground-truth" data for training the classifier and allowing it to distinguish truly sensitive uses of words such as health from less sensitive ones.

The results of the work of the team will be presented, as a scientific paper, in ACM IMC'20 (ACM Internet Measurement Conference 2020, 27-29 October, Pittsburgh, USA). Laoutaris also participates in PIMCity (Building the next generation personal data platforms), the EU-funded project to increase transparency and provide users with control over their data. "Privacy law is made for use by humans -Laoutaris comments-, typically after a privacy breach has occurred - e.g., an illegal processing of such data- ... but how can we teach this law to machines and have them protect us before privacy breaches occur?". The research team is working to bring a technological solution to the user in 2021.

"Tracking people -add the researcher- when they visit websites with content that belongs to the GDPR sensitive categories is the true 'Elephant in the Room' of privacy. Most people don´t mind be tracked about things that they consider innocent, but would be very upset to know that their visit to sensitive websites are being logged and released to unknown third parties. Our study is, by far, the biggest study about tracking of sensitive topics on the web. It shows that a good part of the web includes content of sensitive character. Unfortunately, these sensitive pages appear to be as tracked as the rest of the web".

Credit: 
IMDEA Networks Institute

Aerosols vs droplets

Winter is on its way. And in this year of coronavirus, with it comes the potential for a second wave of COVID-19. Add in flu season and our tendency to head inside and close our windows to the cold, wet weather, and it appears the next several months are going to present us with new health challenges.

UC Santa Barbara researchers Yanying Zhu and Lei Zhao hope to arm people with better knowledge of how SARS-CoV-2 spreads as the seasons change. Their new study investigates the secret of this virus's unusual success: its transmissibility, or how it manages to get from host to host. The dominant mode, it turns out, changes according to environmental conditions.

"Back at the beginning of April a lot of people were wondering if COVID would go away in the summer, in the warmer weather," said Zhu, a professor of mechanical engineering and one of the authors of a paper that appears in the journal Nano Letters. "And so we started to think about it from a heat transfer point of view, because that's what our expertise is."

The virus, of course, did not disappear during the summer as hoped, and in fact COVID cases across the country continued to climb. To understand how the novel coronavirus manages to persist in circumstances in which the flu virus fails, Zhu, Zhao and colleagues modeled different temperatures and relative humidities along a continuum from hot and dry to cold and humid in typical indoor spaces, where the virus is distributed by normal speech and breathing -- and, according to the paper, where people "only sneeze or cough into a tissue or their elbows." To these scenarios they added emerging knowledge about the highly contagious microbe; in particular, how long it remains infectious outside a host.

The results are sobering. For one thing, respiratory droplets -- the most common mode of transmission -- don't obey our social distancing guidelines.

"We found that in most situations, respiratory droplets travel longer distances than the 6-foot social distance recommended by the CDC," Zhu said. This effect is increased in the cooler and more humid environments to distances of up to 6 meters (19.7 feet) before falling to the ground in places such as walk-in refrigerators and coolers, where temperatures are low and humidity is high to keep fresh meat and produce from losing water in storage. In addition to its ability to travel farther, the virus is particularly persistent in cooler temperatures, remaining "infectious from several minutes to longer than a day in various environments," according to several published studies.

"This is maybe an explanation for those super-spreading events that have been reported at multiple meat processing plants," she said.

At the opposite extreme, where it is hot and dry, respiratory droplets more easily evaporate. But what they leave behind are tiny virus fragments that join the other aerosolized virus particles that are shed as part of speaking, coughing, sneezing and breathing.

"These are very tiny particles, usually smaller than 10 microns," said lead author Lei Zhao, who is a postdoctoral researcher in the Zhu Lab. "And they can suspend in the air for hours, so people can take in those particles by simply breathing.

"So in summer, aerosol transmission may be more significant compared to droplet contact, while in winter, droplet contact may be more dangerous," he continued. "This means that depending on the local environment, people may need to adopt different adaptive measures to prevent the transmission of this disease." This could mean, for example, greater social distancing if the room is cool and humid, or finer masks and air filters during hot, dry spells.

Hot and humid environments, and cold and dry ones, did not differ significantly between aerosol and droplet distribution, according to the researchers.

The quantitative descriptions of virus propagation under varying local conditions could serve as useful guidance for decision-makers and the general public alike in our efforts to keep the spread to a minimum.

"Combined with our study, we think we can maybe provide design guidelines for the optimal filtering for facial masks," said Zhao, adding that the research could be used to quantify real exposure to the virus -- how much virus could land on one's body over a certain period of exposure. This knowledge could, in turn, lead to better strategies for airflow and ventilation to prevent virus accumulation. In addition, the insights, according to the study, "may shed light on the course of development of the current pandemic, when combined with systematic epidemiological studies."

Credit: 
University of California - Santa Barbara

Therapy plus medication better than medication alone in bipolar disorder

image: Lead author David Miklowitz

Image: 
UCLA Health

A review of 39 randomized clinical trials by scientists from UCLA and their colleagues from other institutions has found that combining the use medication with psychoeducational therapy is more effective at preventing a recurrence of illness in people with bipolar disorder than medication alone.

For the paper, published in JAMA Psychiatry researchers analyzed studies that included adult and adolescent patients currently receiving medication for bipolar disorder who were randomly assigned to either an active family, individual or group therapy, or "usual care," meaning medication with routine monitoring and support from a psychiatrist.

David Miklowitz, PhD, the study's lead author, and a distinguished professor of psychiatry at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, said the studies reviewed followed patients for at least a year, measured rates of recurrence of bipolar disorder, depression and mania symptoms, and included study attrition or dropout rates.

The findings were:

Psychoeducation with guided practice of illness management skills (for example, how to keep regular sleep and wake cycles) in a family or group format was more effective in reducing recurrences of mania and depressive symptoms than the same strategies in an individual therapy format.

Cognitive behavioral therapy, family therapy and interpersonal therapy were better at stabilizing depressive symptoms than other forms of treatment.

Rates of dropout were lower in patients who received family-oriented therapies.

Of the findings, Miklowitz said they point to the importance of having a support system.

"Not everyone may agree with me, but I think the family environment is very important in terms of whether somebody stays well," he said. "There's nothing like having a person who knows how to recognize when you're getting ill and can say, 'you're starting to look depressed or you're starting to get ramped up.' That person can remind their loved one to take their medications or stay on a regular sleep-wake cycle or contact the psychiatrist for a medication evaluation."

Miklowitz said the same is true for a patient who may not have close relatives but does have support through group therapy.

"If you're in group therapy, other members of that group may be able to help you recognize that you're experiencing symptoms," he said. "People tend to pair off. It's a little bit like the AA model of having a sponsor."

Credit: 
University of California - Los Angeles Health Sciences

The Lancet: Herd immunity approaches to COVID-19 control are a 'dangerous fallacy', say authors of open letter

A group of 80 researchers warn that a so-called herd immunity approach to managing COVID-19 by allowing immunity to develop in low-risk populations while protecting the most vulnerable is "a dangerous fallacy unsupported by the scientific evidence".

Faced with a second wave of COVID-19, and more than a million recorded deaths worldwide, the authors present their view of the scientific consensus on our understanding of COVID-19, and the strategies that need to be put in place to protect our societies and economies.

The open letter, referred to by its authors as the John Snow Memorandum, is published today by The Lancet. It is signed by 80 international researchers (as of publication) with expertise spanning public health, epidemiology, medicine, paediatrics, sociology, virology, infectious disease, health systems, psychology, psychiatry, health policy, and mathematical modelling [1]. The letter will also be launched during the 16th World Congress on Public Health programme 2020.

They state: "It is critical to act decisively and urgently. Effective measures that suppress and control transmission need to be implemented widely, and they must be supported by financial and social programmes that encourage community responses and address the inequities that have been amplified by the pandemic."

"Continuing restrictions will probably be required in the short term, to reduce transmission and fix ineffective pandemic response systems, in order to prevent future lockdowns. The purpose of these restrictions is to effectively suppress SARS-CoV-2 infections to low levels that allow rapid detection of localised outbreaks and rapid response through efficient and comprehensive find, test, trace, isolate, and support systems so life can return to near-normal without the need for generalised restrictions. Protecting our economies is inextricably tied to controlling COVID-19. We must protect our workforce and avoid long-term uncertainty."

The authors acknowledge that ongoing restrictions have understandably led to widespread demoralisation and diminishing trust among the public, and that in the face of a second wave of infection there is renewed interest in so-called natural herd immunity approaches (allowing a large uncontrolled outbreak in the low-risk population while protecting the vulnerable, which some argue could lead to the development of infection-acquired population immunity in the low-risk population, which will eventually protect the vulnerable). They say any pandemic management strategy relying upon immunity from natural infections for COVID-19 is flawed.

They explain that uncontrolled transmission in younger people risks significant ill-health and death across the whole population - with real-world evidence from many countries showing that it is not possible to restrict uncontrolled outbreaks to certain sections of society, and it being practically impossible and highly unethical to isolate large swathes of the population. Instead, they say that special efforts to protect the most vulnerable are essential, but must go hand-in-hand with multi-pronged population-level strategies.

They also state that there is no evidence for lasting protective immunity to SARS-CoV-2 after natural infection, and warn that this waning immunity as a result of natural infection would not end the COVID-19 pandemic but instead result in repeated waves of transmission over several years. They say that this could place vulnerable populations at risk for the indefinite future, as natural infection-based herd immunity strategies would result in recurrent epidemics, as seen with many infectious diseases before mass vaccination. Instead, the authors call for suppression of the virus until the population can be vaccinated.

The authors also warn that natural infection-based herd immunity approaches risk impacting the workforce as a whole and overwhelming the ability of healthcare systems to provide acute and routine care. They note that we still do not understand who might suffer from 'long COVID', and that herd immunity approaches place an unacceptable burden on healthcare workers, many of whom have died from COVID-19 or experienced trauma as a result of having to practise disaster medicine.

The letter concludes: "The evidence is very clear: controlling community spread of COVID-19 is the best way to protect our societies and economies until safe and effective vaccines and therapeutics arrive within the coming months. We cannot afford distractions that undermine an effective response; it is essential that we act urgently based on the evidence."

Credit: 
The Lancet

Breakthrough blood test developed for brain tumors

BOSTON - Genetic mutations that promote the growth of the most common type of adult brain tumors can be accurately detected and monitored in blood samples using an enhanced form of liquid biopsy developed by researchers at Massachusetts General Hospital (MGH).

Comparing blood samples from patients with gliomas with tumor biopsy tissues from the same patients, Leonora Balaj, PhD, Bob S. Carter, MD, and other MGH investigators in the Department of Neurosurgery found that a novel digital droplet polymerase chain reaction (ddPCR) blood test they pioneered could accurately detect and monitor over time two mutations of the gene TERT. The mutations, labeled C228T and C250T, are known to promote cancer growth and are present in more than 60 percent of all gliomas, and in 80 percent of all high-grade gliomas, the most aggressive and life-threatening type.

Their discovery, which has the potential to substantially improve the diagnosis and monitoring of gliomas, is reported in the journal Clinical Cancer Research.

Gliomas are tumors of glia, central and peripheral nervous system cells that support and protect neurons, the cells that transmit electrical impulses.

Liquid biopsy is a method for detecting cancer by looking for fragments of tumor DNA that circulate in blood. The technique has been shown to be sensitive at detecting the presence of some forms of cancer, but brain tumors have until now posed a formidable barrier.

"Liquid biopsy is particularly challenging in brain tumors because mutant DNA is shed into the bloodstream at much lower level than any other types of tumors," Balaj says.

"By 'supercharging' our ddPCR assay with novel technical improvements, we showed for the first time that the most prevalent mutation in malignant gliomas can be detected in blood, opening a new landscape for detection and monitoring of the tumors," she says.

The researchers first tested the performance of the ddPCR assay in tumor tissue and found that the results were in perfect agreement with the results from an independently performed clinical laboratory assessment of TERT mutations in the tumor specimens.

They then looked at samples of blood plasma matched to patient tumors and found that the ddPCR assay could detect TERT mutations both in samples from MGH as well as from similarly matched plasma and tumor samples from collaborators at other institutions.

The ddPCR assay has an overall sensitivity (ability to detect the presence of a glioma) of 62.5 percent, which is a tenfold improvement over any prior assay for TERT mutations in the blood for brain tumors, compared to the standard of tissue-based detection of TERT mutations.

The test is easy to use, quick, and low cost, and could be performed in most laboratories, Balaj says. Importantly, the test can also be used to follow the course of disease. "We envision the future integration of tests like this one into the clinical care of our patients with brain tumors," says Carter, chief of Neurosurgery and co-director of the MGH Brain Tumor Center. "For example, if a patient has a suspected mass on MRI scanning, we can take a blood sample before the surgery and assess the presence of the tumor signature in the blood, and then use this signature as a baseline to monitor as the patient later receives treatment, both to gauge response to the treatment and gain early insight into any potential recurrence."

The team's goal is to expand this blood test to be able to differentiate many types of brain tumors.

Credit: 
Massachusetts General Hospital

Will SARS-CoV-2 become endemic?

To date, a few verified repeat SARS-CoV-2 infections have been documented around the world. "Should reinfection [with SARS-CoV-2] prove commonplace, and barring a highly effective vaccine delivered to most of the world's population, SARS-CoV-2 will likely become endemic," write Jeffrey Shaman and Marta Galanti in this Perspective. For many viruses, a number of processes - particularly insufficient adaptive immune response, waning immunity, and immune escape - can allow subsequent reinfection. In the case of SARS-CoV-2, many questions remain about the nature of these immune responses and trajectories, though, say the authors, insight from other respiratory viruses points to the possibility of reinfection with SARS-CoV-2. If this does happen, the pattern of endemicity that results will depend on the typical time scale at which individuals experience reinfection, seasonal differences in transmissibility, vaccine availability and efficacy, and social, immune, and innate factors that modulate virus transmissibility, say the authors. In addition, the cyclic persistence of SARS-CoV-2 in human populations may be affected by ongoing opportunities for interaction with other respiratory pathogens, say the authors; it is possible infection with a different virus could provide some short-lived protection to SARS-CoV-2. Greater monitoring of the clinical and population-scale interactions of SARS-CoV-2 with other respiratory viruses, particularly influenza viruses, is needed, they write. At the population scale, a possible overlap between influenza and SARS-CoV-2 outbreaks poses a serious threat to public health systems. Conversely, the nonpharmaceutical interventions adopted to mitigate SARS-CoV-2 transmission (personal protective equipment, social distancing, increased hygiene, limited indoor gatherings) may reduce the magnitude of seasonal influenza outbreaks, note Shaman and Galanti. Based on modeling of post-pandemic scenarios for SARS-CoV-2 to date, a duration of immunity similar to that of the other betacoronaviruses (~40 weeks) could lead to yearly outbreaks of SARS-CoV-2, the authors note, whereas a longer immunity profile, coupled with a small degree of protective cross-immunity from other betacoronaviruses, could lead to apparent elimination of the virus followed by resurgence after a few years. "Other scenarios are, of course, possible, because there are many processes at play and much that remains unresolved," say the authors.

Credit: 
American Association for the Advancement of Science (AAAS)

Novel software assesses phonologial awareness

image: The ATLAS program -- the first test of its kind for children with speech and/or language impairment -- can help parents, early childhood teachers and paraeducators more accurately measure progress for children with a range of skill levels.

Image: 
Royalty-free via Pxhere

Understanding sounds in language is a critical building block for child literacy, yet this skill is often overlooked. Researchers from Michigan State University have developed a new software tool to assess children's phonological awareness -- or, how they process the sound structure of words.

The ATLAS, or Access to Literacy Assessment System, program -- the first test of its kind for children with speech and/or language impairment -- can help parents, early childhood teachers and paraeducators more accurately measure progress for children with a range of skill levels.

Research conducted by the MSU ATLAS team, published in the journal Language, Speech and Hearing Services in Schools, demonstrated that the software was effective when tested with over 1,100 children between the ages of 3 and 7 -- both with and without speech and language impairments.

"Phonological awareness is one of the strongest predictors of literacy skill development later in life," said Lori Skibbe, professor of human development and family studies at MSU and study lead author. "It can include rhyming, recognizing how sounds go together to make words and understanding how words can be broken apart into sounds."

Skibbe explained that the software, available free of charge, is adaptive, which means that test items are unique for each child. Children can take the test without speaking, and the test is shorter than many others in the field. ATLAS is also helpful for many children with disabilities, including those with speech and/or language impairment.

"For children with a primary speech and/or language impairment, meeting educational literacy goals can be difficult," Skibbe said. "However, the ATLAS software allows children to demonstrate what they know, even if they struggle to answer questions verbally. This ensures their skills are accurately assessed, and that they receive the right support to keep them on track to meet literacy milestones."

Credit: 
Michigan State University