Culture

The cover for issue 31 of Oncotarget features Figure 4, "Concentration dose-response curves of sirolimus effect [55 nM–1 nM] on the number of cells per surviving colony in U2OS cell line after 2 weeks exposure," by Vasuri, et al. which reported that the authors evaluated the long-term effects of sirolimus on three different cell in vitro models, cultured in physiological conditions mimicking sirolimus-eluted stent, in order to clarify the effectiveness of sirolimus in blocking cell proliferation and survival.

Three cell lines were selected and growth in 10 ml of Minimum Essential Medium for 5 weeks with serial dilutions of sirolimus.

The number of colonies and the number of cells per colony were counted.

As a result, the number of WPMY-1 surviving colonies increased in a dose-dependent manner when treated with sirolimus, while the number of U2OS colonies progressively decreased.

In conclusion sirolimus showed the well-known cytostatic effect, but with an effect on clonogenic potential different among the different cell types.

Dr. Gianandrea Pasquinelli from The Bologna University said, "Rapamycin (sirolimus) is a widely used cytostatic drug blocking the cell cycle in the phase G1/S through the inhibition of the mammalian target of Rapamycin (mTOR) pathway, that has found several clinical applications, from immunosuppression in diabetes and organ transplantation to cancer therapy and drug-eluting stents (DES)"

Beside to its cytostatic activity, sirolimus was also discovered to protect normal human oral keratinocytes from apoptosis by activating autophagy, and to act as a basal stem cell keratinocyte-protecting drug in irradiated mice.

The effect of sirolimus on mesenchymal cells is unknown, but it is an important issue, since mesenchymal cells such as myofibroblasts and cells promoting vascular calcification play an important role in atherogenesis and vascular restenosis.

Sirolimus seems to block the proliferation and the migration of vascular smooth muscle cells, but we lack information concerning the effects on other cells composing atherosclerotic plaques.

The aim of the present paper is to evaluate the long-term effects of sirolimus, rather than short-term cell survival, on three different cell in vitro models, cultured in Minimum Essential Medium, which simulates physiological conditions (w/o CO2 and glucose, in order to clarify the effectiveness of sirolimus in blocking cell proliferation and survival.

The Pasquinelli Research Team concluded in their Oncotarget Research Paper that the plaque typology and the different cell composition of the plaque, e. g., the presence of inflammatory cells, angiogenesis, prevalence of fibrosis, presence of osteogenic progenitors, may influence the response to sirolimus.

"The presence of inflammatory cells, angiogenesis, prevalence of fibrosis, presence of osteogenic progenitors, may influence the response to sirolimus"

Moreover, it is known that the clonal capacity varies between cells and we should consider this matter when evaluating the effectiveness of eluted stent.

Finally, additional mechanisms can have a role, such as amitotic cell division.

These mechanisms were also observed in human atherogenesis and could be fundamental to evaluate the in vivo effect of sirolimus too.

Talking to people at gun shows about suicide prevention and the risks of unsecured firearms can lead to safe weapons storage, according to a new study.

The research by Forefront Suicide Prevention at the University of Washington, from visits to 18 gun shows and other community events around Washington state last year, found that engaging people in a community-based setting, in an empathetic conversation focused on safety, resulted in more people locking up their firearms.

The results are promising, lead author and Forefront co-founder Jennifer Stuber said, because they show that meeting people where they're at, physically and psychologically, can lead to behavior change that can prevent tragedy.

"We need to be educating people who own firearms or are considering purchasing them that suicide is a possible risk to take into consideration and to make plans in advance to mitigate these risks. So many people are in crisis today -- from youth, to veterans, to our men in economic distress and in relationship turmoil -- we are all vulnerable. We need to educate firearms owners, both experienced and new, at the point of purchase and other places we can find them to raise awareness," said Stuber, an associate professor of social work at the UW.

The study published Oct. 20 in BMJ Injury Prevention.

According to national and state data, about half of all suicides involve firearms. In Washington state, three-quarters of all firearm fatalities are suicides, which most people aren't aware of when they purchase a firearm, Stuber said. Suicide rates are higher among men than women, and higher among veterans than nonveterans. A 2019 Forefront study focused on the potential role of firearms retailers in preventing suicides, by evaluating store owners' willingness to learn about the issue and train their employees in how to spot and act on suicide warning signs. That study found that many retailers were interested in learning more and adopting prevention strategies among their staff.

The new study tested an outreach strategy created by Forefront known as SAFER, an extension of its multi-faceted Safer Homes, Suicide Aware program, which offers training, education and locking devices for firearms and medications in communities across Washington.

Forefront's trained staff and volunteers regularly provide suicide-prevention trainings tailored to students, teachers, parents, veterans, health care workers and pharmacists. In reaching out to visitors to gun shows -- who are mostly men, often veterans -- Forefront designed the brief, motivational interviewing approach it calls SAFER (Signpost, Assess, Facts, Emotion and Recommend) to both educate and listen with empathy. By talking with a person about their familiarity with issues surrounding suicide and their understanding of the risks of unsecured firearms, the volunteer can deliver a suicide-prevention recommendation that encourages safe firearms storage. The volunteer also provides the person with a free locking device for hand-guns, rifles or AR-15s to take home.

In this study, 1,175 people received the SAFER intervention. They took a short, written survey to assess knowledge of firearms safety and suicide prevention prior to the SAFER conversation. Most SAFER encounters took about 10 to 20 minutes each.

Four weeks later, Forefront emailed a survey to people who received the intervention. Of the 372 who completed the survey, 66% said they now kept their firearms secure at home, a 15 percentage-point increase from the 51% who reported doing so during the pre-intervention survey.

"To my knowledge, this is the first study to assess receptiveness to suicide prevention messages and self-reported change in firearm storage behavior at gun shows," said Ali Rowhani-Rahbar, an associate professor of epidemiology and co-director of the Firearm Injury and Policy Research Program at the UW. Prior studies had focused on clinical or other community settings, including those in Washington state. "This study is novel not only due to its outreach to participants in gun shows, but also because of its empathetic approach to engage them in conversations about suicide prevention. It can serve as a model for other regions of the country to use similar approaches and broaden the inclusion of individuals who might be at high risk of suicide in their outreach and prevention programs."

Initially, people may not think suicide-prevention awareness applies to them, Stuber said. But that's a key message of the intervention: Life circumstances can and do change. Even if you never have thoughts of suicide, it's critical to have a plan to protect yourself, your family, even friends or strangers who visit your home by locking up firearms and medications and understanding what to do if you are someone you care about is at risk.

"We're building on the idea that people want to do the right thing here, but they don't necessarily know what the right thing is," Stuber said.

As part of the SAFER intervention, volunteers also offered a locking device for medications. In the pre-intervention survey, 15% of participants said they safely stored medications -- a proportion that grew to about 22% afterward, according to the study. Even a modest increase shows a positive impact, Stuber noted, and provides important information for enhancing the strategy going forward. Currently, the emphasis is on locking up firearms, which is the main goal for the audience and the setting.

Forefront continues to improve SAFER to hone in on the demographics of the person receiving the intervention and to tailor the message accordingly, Stuber said. For example, if the individual has children, the volunteer can focus on the risks of a child gaining access to a firearm and emphasizing the need for a fast-access firearm locking device, which participants also receive education about through a raffle at gun shows.

Another key is to expect emotion, Stuber added. People routinely shared personal experiences with suicide or concerns about friends or relatives, which could end up being an opportunity to counsel or provide resources beyond the individual receiving the SAFER intervention.

"We don't want to firehose people with facts and statistics. We should be listening more than talking," Stuber said.

During the COVID-19 pandemic, Forefront has begun offering a "tele-SAFER" intervention, as well, through individualized Zoom sessions facilitated by veterans organizations and nonprofit groups, Stuber said.

PULLMAN, Wash. - People with obsessive-compulsive disorder, or OCD, report that the severity of their symptoms was reduced by about half within four hours of smoking cannabis, according to a Washington State University study.

The researchers analyzed data inputted into the Strainprint app by people who self-identified as having OCD, a condition characterized by intrusive, persistent thoughts and repetitive behaviors such as compulsively checking if a door is locked. After smoking cannabis, users with OCD reported it reduced their compulsions by 60%, intrusions, or unwanted thoughts, by 49% and anxiety by 52%.

The study, recently published in the Journal of Affective Disorders, also found that higher doses and cannabis with higher concentrations of CBD, or cannabidiol, were associated with larger reductions in compulsions.

"The results overall indicate that cannabis may have some beneficial short-term but not really long-term effects on obsessive-compulsive disorder," said Carrie Cuttler, the study's corresponding author and WSU assistant professor of psychology. "To me, the CBD findings are really promising because it is not intoxicating. This is an area of research that would really benefit from clinical trials looking at changes in compulsions, intrusions and anxiety with pure CBD."

The WSU study drew from data of more than 1,800 cannabis sessions that 87 individuals logged into the Strainprint app over 31 months. The long time period allowed the researchers to assess whether users developed tolerance to cannabis, but those effects were mixed. As people continued to use cannabis, the associated reductions in intrusions became slightly smaller suggesting they were building tolerance, but the relationship between cannabis and reductions in compulsions and anxiety remained fairly constant.

Traditional treatments for obsessive-compulsive disorder include exposure and response prevention therapy where people's irrational thoughts around their behaviors are directly challenged, and prescribing antidepressants called serotonin reuptake inhibitors to reduce symptoms. While these treatments have positive effects for many patients, they do not cure the disorder nor do they work well for every person with OCD.

"We're trying to build knowledge about the relationship of cannabis use and OCD because it's an area that is really understudied," said Dakota Mauzay, a doctoral student in Cuttler's lab and first author on the paper.

Aside from their own research, the researchers found only one other human study on the topic: a small clinical trial with 12 participants that revealed that there were reductions in OCD symptoms after cannabis use, but these were not much larger than the reductions associated with the placebo.

The WSU researchers noted that one of the limitations of their study was the inability to use a placebo control and an "expectancy effect" may play a role in the results, meaning when people expect to feel better from something they generally do. The data was also from a self-selected sample of cannabis users, and there was variability in the results which means that not everyone experienced the same reductions in symptoms after using cannabis.

However, Cuttler said this analysis of user-provided information via the Strainprint app was especially valuable because it provides a large data set and the participants were using market cannabis in their home environment, as opposed to federally grown cannabis in a lab which may affect their responses. Strainprint's app is intended to help users determine which types of cannabis work the best for them, but the company provided the WSU researchers free access to users' anonymized data for research purposes.

Cuttler said this study points out that further research, particularly clinical trials on the cannabis constituent CBD, may reveal a therapeutic potential for people with OCD.

This is the fourth study Cuttler and her colleagues have conducted examining the effects of cannabis on various mental health conditions using the data provided by the app created by the Canadian company Strainprint. Others include studies on how cannabis impacts PTSD symptoms, reduces headache pain, and affects emotional well-being.

Could a stack of 2D materials allow for supercurrents at ground-breakingly warm temperatures, easily achievable in the household kitchen?

An international study published in August opens a new route to high-temperature supercurrents at temperatures as 'warm' as inside a kitchen fridge.

The ultimate aim is to achieve superconductivity (ie, electrical current without any energy loss to resistance) at a reasonable temperature.

TOWARDS ROOM-TEMPERATURE SUPERCONDUCTIVITY

Previously, superconductivity has only been possible at impractically low temperatures, less than -170°C below zero - even the Antarctic would be far too warm!

For this reason, the cooling costs of superconductors have been high, requiring expensive and energy-intensive cooling systems.

Superconductivity at everyday temperatures is the ultimate goal of researchers in the field.

This new semiconductor superlattice device could form the basis of a radically new class of ultra-low energy electronics with vastly lower energy consumption per computation than conventional, silicon-based (CMOS) electronics.

Such electronics, based on new types of conduction in which solid-state transistors switch between zero and one (ie, binary switching) without resistance at room temperature, is the aim of the FLEET Centre of Excellence.

EXCITON SUPERCURRENTS IN ENERGY-EFFICIENT ELECTRONICS

Because oppositely-charged electrons and holes in semiconductors are strongly attracted to each other electrically, they can form tightly-bound pairs. These composite particles are called excitons, and they open up new paths towards conduction without resistance at room temperature.

Excitons can in principle form a quantum, 'superfluid' state, in which they move together without resistance. With such tightly bound excitons, the superfluidity should exist at high temperatures--even as high as room temperature.

But unfortunately, because the electron and hole are so close together, in practice excitons have extremely short lifetimes--just a few nanoseconds, not enough time to form a superfluid.

As a workaround, the electron and hole can be kept completely apart in two, separated atomically-thin conducting layers, creating so-called 'spatially indirect' excitons. The electrons and holes move along separate but very close conducting layers. This makes the excitons long-lived, and indeed superfluidity has recently been observed in such systems.

Counterflow in the exciton superfluid, in which the oppositely charged electrons and holes move together in their separate layers, allows so-called 'supercurrents' (dissipationless electrical currents) to flow with zero resistance and zero wasted energy. As such, it is clearly an exciting prospect for future, ultra-low-energy electronics.

STACKED LAYERS OVERCOME 2D LIMITATIONS

Sara Conti who is a co-author on the study, notes another problem however: atomically-thin conducting layers are two-dimensional, and in 2D systems there are rigid topological quantum restrictions discovered by David Thouless and Michael Kosterlitz (2016 Nobel prize), that eliminate the superfluidity at very low temperatures, above about -170°C.

The key difference with the new proposed system of stacked atomically-thin layers of transition metal dichalcogenide (TMD) semiconducting materials, is that it is three dimensional.

The topological limitations of 2D are overcome by using this 3D `superlattice' of thin layers. Alternate layers are doped with excess electrons (n-doped) and excess holes (p-doped) and these form the 3D excitons.

The study predicts exciton supercurrents will flow in this system at temperatures as warm as -3°C.

David Neilson, who has worked for many years on exciton superfluidity and 2D systems, says "The proposed 3D superlattice breaks out from the topological limitations of 2D systems, allowing for supercurrents at -3°C. Because the electrons and holes are so strongly coupled, further design improvements should carry this right up to room temperature."

"Amazingly, it is becoming routine today to produce stacks of these atomically-thin layers, lining them up atomically, and holding them together with the weak van der Waals atomic attraction," explains Prof Neilson. "And while our new study is a theoretical proposal, it is carefully designed to be feasible with present technology."

Tsukuba, Japan - While it is known that stem cells have the ability to develop into all tissues in a precisely regulated process, the way environmental cues affect stem cell behavior has remained poorly understood. In a new study, researchers from the University of Tsukuba discovered that neurons producing the neurotransmitter octopamine regulate the behavior of germline stem cells (GSCs) in response to environmental cues, such as mating.

The ovaries of the fruit fly Drosophila melanogaster have been a robust model system for studying the relationship between environmental cues and stem cell biology. In fruit flies, GSCs give rise to eggs and exist in close proximity to somatic cells. Somatic cells comprise several types of cells in support of the budding eggs. As with other stem cells, when GSCs divide, one daughter cell retains its stem cell identity, while the other differentiates into multiple progeny cells. The balance between self-renewal and differentiation is tightly regulated, both by cues within and outside the environment in which GSCs reside (also called a niche). Mating is one such external cue known to increase GSCs.

"It is well known that a molecule called sex peptide from the male seminal fluid activates neurons located in the uterine lumen. We have previously shown that these neurons are essential for stimulating the biosynthesis of ovarian steroid hormones to increase the number of GSCs," says corresponding author of the study Professor Ryusuke Niwa. "The goal of our study was to investigate how the information from mating is transmitted from these neurons to GSCs at the molecular and cellular levels."

To achieve their goal, the researchers took a genetic approach to investigate which gene is responsible for the increase of GSCs upon mating, and found that the octopamine receptor Oamb is the one through which octopamine exerts its effect on GSCs. Through a series of experiments, the researchers then found that Oamb in escort cells, one type of somatic cell adjacent to GSCs, modulates GSC increase after mating and the subsequent release of octopamine by neurons. At the molecular level, Oamb activation by octopamine resulted in an increase in calcium signaling in escort cells. Calcium is a potent biomolecule and changes in cellular calcium levels strongly affect cell behavior.

Because it had previously been shown that ovarian steroid hormones were involved in the increase of GSCs, the researchers next investigated the relationship between ovarian steroid hormones and the calcium-dependent GSC increase. Their results showed that ovarian steroid hormones are indeed required to increase the number of GSCs. Next, the researchers asked which molecules play a role in stimulation of escort cells by octopamine and found that the protein matrix metalloproteinase 2 is required upon the calcium-dependent GSC increase. Finally, the researchers showed that the neurons projecting to the ovaries to increase GSCs do so via specialized proteins, called nicotinic acetylcholine receptors. These results provide a complete picture as to how neuronal activation results in increased ovarian stem cells.

"These are striking results that show the molecular mechanism underlying the coupling of the nervous system with stem cell behavior in response to environmental cues, such as mating," says Professor Niwa. "Our results could help unravel the conserved systemic and neuronal regulatory mechanisms for stem cell homeostasis in animals."

(Boston)-- Although frequently used to treat painful osteoarthritis of the hip and knee, intra-articular corticosteroid (IACS) injections remain controversial. Questions about whether damage to joints occurs as a result of these injections, which are performed thousands a time each day, persist.

Osteoarthritis of the hip and knee is among the most common joint disorders. A frequently performed treatment for osteoarthritis and other joint related pain syndromes are IACS, yet there is conflicting evidence on their potential benefit and possible negative outcomes following such injections.

"As of today, there is no established recommendation or consensus regarding imaging, clinical,
or laboratory markers before an IACS injection is performed to screen for osteoarthritis-related imaging abnormalities and repeating radiographs before each subsequent IACS injection to detect possible adverse joint findings remains controversial," explains corresponding author Ali Guermazi, MD, PhD, chief of radiology at VA Boston Healthcare System and professor of radiology at Boston University School of Medicine (BUSM).

Guermazi and his colleagues had first reported that accelerated arthritis and joint destruction are observed in some patients who received intra-articular corticosteroid injections. (Radiology/2019) https://pubs.rsna.org/doi/10.1148/radiol.2019190341

In this new study, Guermazi led an international expert panel of researchers who reviewed all published evidence in the literature and found not enough evidence exists to decisively draw a conclusion. However, they did recommend the use of imaging for first time injections or multiple injections with the aim of mitigating the risk for joint collapse and total joint replacement. In addition, the panel reviewed the current understanding of pain in osteoarthritis and summarized current international guidelines regarding indications for IACS injection. They also suggested profiles of those who would likely benefit most from IACS injection and recommended updating patient consent forms until further evidence on the topic is available.

The researchers hope that studies with mid- to long-term follow-up will soon be available and provide data from before and after IACS injection compared to appropriate controls. "Understanding the real benefit of IACS in relieving joint pain is paramount," added Guermazi.

These findings appear online in the journal Radiology.

WASHINGTON, October 20, 2020 -- As the coronavirus has affected more than 30 million people globally, researchers have increasingly focused on the extent to which airborne respiratory droplets carrying the virus travel and contaminate the air after an infected person coughs.

While scientists have studied the properties of air at the mouth, such as volume, temperature, droplet distribution, and humidity, less is known about how these properties change as the cough cloud travels. In Physics of Fluids, by AIP Publishing, researchers estimate the evolving volume of the cough cloud and quantify the reduction in its volume in the presence of a face mask.

"We estimate this volume of the air, which may help to design ventilation of closed spaces and consequently reduce the spread of the disease," said Amit Agrawal, one of the authors.

The researchers also examined the variation in temperature and humidity in the cough cloud as the determinant that impacts the droplet distribution in the cloud.

Using an analysis based on jet theory and experimental data from the literature, they found that it's the first 5 to 8 seconds after coughing that matter for suspending the exhaled droplets in the air and, consequently, for the spread of the disease. After that time, the cough cloud typically starts to disperse.

The scientists found the cloud volume without a mask is about 7 times larger than with a surgical mask and 23 times larger than with an N95 mask.

"We found that anything that reduces the distance traveled by the cloud, such as a mask, handkerchief, or coughing into an elbow, should greatly reduce the region over which the droplets disperse upon coughing and therefore the chances of infection," said Rajneesh Bhardwaj, another author.

Interestingly, the researchers found how hard a person coughs, which impacts the initial velocity and volume of coughing, does not affect the volume in the cough cloud when the person is not wearing a mask, although the initial volume is very important for a person wearing a mask.

The scientists determined the volume of a cough cloud varies as a cube of the total distance traveled by the cloud with the proportionality constant being 1 to 150. This formula will be helpful in determining the maximum number of people that can be accommodated in a hospital ward, and the minimum rate at which air in a room, elevator, cinema hall, car, aircraft cabin, or restaurant needs to be circulated to maintain freshness and reduce the chance of infection.

More than 480,000 U.S. deaths per year, as well as diseases affecting 16 million living Americans, can be attributed to cigarette smoking, according to the Centers for Disease Control and Prevention. In particular, this behavior continues to be overrepresented among those with mental illness, substance use disorders, and socioeconomic disadvantage.

An October 20 study in JAMA Network Open provides evidence that, even in smokers from vulnerable populations, reducing nicotine content to low levels decreases addictiveness - a timely finding as the Food and Drug Administration (FDA) considers a policy to lower nicotine content in all cigarettes sold in the U.S.

Led by Stephen T. Higgins, Ph.D., director of the Vermont Center on Behavior and Health at the University of Vermont's (UVM) Larner College of Medicine, in collaboration with colleagues at Brown University and Johns Hopkins University, the study sought to determine if reducing the nicotine content of cigarettes decreases smoking rates and nicotine dependence severity among adults with psychiatric disorders or socioeconomic disadvantage.

Three double-blind, randomized clinical trials were conducted at UVM, Brown, and Johns Hopkins between October 2016 and September 2019, with data analyzed from September 2019 to July 2020. A total of 775 daily smokers with affective disorders, opioid use disorder, or socioeconomic disadvantage who were NOT currently trying to quit smoking were deemed eligible.

Participants were randomly assigned to use research cigarettes for 12 weeks that contained either 0.4 mg nicotine/g tobacco, 2.4 mg nicotine/g tobacco (both known as very low-nicotine content cigarettes or VLNCs), or 15.8 mg nicotine/g tobacco (a level comparable to a standard commercial cigarette). NIH provided the study cigarettes, and all were identical in appearance. Assignment to the two VLNCs decreased daily smoking rate by an average of roughly 30 percent, as well as nicotine dependence severity and biochemical measures of smoke exposure compared to those using the cigarettes with nicotine content at levels in commercial cigarettes.

"We know that lower smoking rate and dependence severity are two important predictors of successful smoking cessation should someone attempt to quit," said Higgins, who is presenting these latest findings to a conference of tobacco researchers and NIH-FDA officials on October 20, 2020. "Our findings in this and earlier studies suggest that lowering the nicotine content in all cigarettes to minimally addictive levels would benefit all smokers, including those most vulnerable to smoking and addiction."

With cases increasing in the UK and elsewhere, and winter approaching, there is an urgent need for reliable models that predict the likely course of Covid-19, to support decisions about shielding, hospital admission, treatment, and vaccinations.

The risk prediction tool (known as QCOVID) uses readily available information about people, such as their age, ethnicity and whether they have certain pre-existing conditions (comorbidities) to help identify individuals at highest risk of developing severe illness. It is designed to be applied across the general adult population in the UK.

The tool provides nuanced information on people's risk of serious illness due to Covid-19 and is designed for use by clinicians with patients to reach a shared understanding of risk.

The tool will need to be updated regularly as the pandemic evolves and its performance closely monitored.

Some previous risk prediction models have been developed. They have been identified as having a high risk of bias, raising concerns that these models may be unreliable when applied in practice.

The UK-wide research group set out to develop and validate a population-based prediction model to estimate the overall risks of becoming infected with and subsequently being admitted to hospital or dying from Covid-19. Steps were taken to mitigate known sources of bias.

Their findings are based on data from more than 8 million patients aged 19-100 years at 1,205 general practices in England, linked to Covid-19 test results and hospital and death registry data.

Data from 6 million patients were used to develop the model over a 97 day period (24 January to 30 April 2020), and a further 2.2 million patients to validate its performance over two separate time periods (24 January to 30 April 2020 and 1 May to 30 June 2020) during the first wave of the pandemic.

To develop the model, known factors such as age, ethnicity, deprivation, body mass index, and a range of comorbidities were used to estimate the probability and timing of hospital admission or death from Covid-19.

Over the study period, 4,384 deaths from Covid-19 occurred in the development group, 1,782 in the first validation time period and 621 in the second validation time period.

The model performed well, predicting 73% and 74% of the variation in time to death from Covid-19 in men and women, respectively.

People in the top 5% for predicted risk of death, accounted for 76% of Covid-19 deaths within the 97-day study period. People in the top 20% for predicted risk of death accounted for 94% of Covid-19 deaths.

The researchers point out that the model aims to provide predictions of risk - it does not aim to provide explanations of which individual factors causally affect risk and the results should not be interpreted in this way.

The absolute risks obtained from the model will change over time, in line with the prevailing Covid-19 infection rate and the extent of social distancing measures in place, so these should also be interpreted with caution. However, the ordering of individuals in terms of their risk is expected to remain relatively stable over time, so that those at highest risk can be identified.

The researchers say that QCOVID represents a robust risk prediction model that has the potential to support public health policy, from enabling shared decisions to mitigate health and workplace risks to targeted recruitment for clinical trials and prioritisation for vaccination.

The model can also be recalibrated for different time periods and has the potential to be updated regularly as the pandemic evolves.

Although QCOVID has been specifically designed to inform UK health policy and interventions to manage Covid-19 related risks, it has international potential, subject to local validation, they conclude.

In a linked editorial, researchers at the University of Manchester agree that QCOVID and the ISARIC (International Severe Acute Respiratory and emerging Infection Consortium) 4C (Coronavirus Clinical Characterisation Consortium) Mortality Score represent steps forward in the quality of Covid-19 prognosis models, but say care must be taken when interpreting the predictions generated by these models.

Given the rapidly changing nature of the disease and its management, they also emphasise the need to update these models regularly and closely monitor their performance over time and space.

They acknowledge that improved data on incident cases of Covid-19 "will allow greater granularity in prediction" and say with these caveats, "we support the continued validation and impact assessment of these models."

WASHINGTON, October 20, 2020 -- Contagion processes, such as opinion formation or disease spread, can reach a tipping point, where the contagion either rapidly spreads or dies out. When modeling these processes, it is difficult to capture this complex transition, making the conditions that affect the tipping point a challenge to uncover.

In the journal Chaos, from AIP Publishing, Nicholas Landry and Juan G. Restrepo, from the University of Colorado Boulder, studied the parameters of these transitions by including three-person group interactions in a contagion model called the susceptible-infected-susceptible model.

In this model, an infected person who recovers from an infection can be reinfected. It is often used to understand the propagation of things like the flu but does not typically consider interactions between more than two people.

"With a traditional network SIS model, when you increase the infectivity of an idea or a disease, you don't see the explosive transitions that you often see in the real world," Landry said. "Including group interactions in addition to individual interactions has a profound effect on the system or population dynamics" and can lead to tipping point behavior.

Once the rate of infection or information transfer between individuals passes a critical point, the fraction of infected people explosively jumps to an epidemic for high enough group infectivity. More surprisingly, if the rate of infection decreases after this jump, the infected fraction does not immediately decrease. It remains an epidemic past that same critical point before moving back down to a healthy equilibrium.

This results in a loop region in which there may or may not be high levels of infection, depending on how many people are infected initially. How these group interactions are distributed affects the critical point at which an explosive transition occurs.

The authors also studied how variability in the group connections -- for example, whether people with more friends also participate in more group interactions -- changes the likelihood of tipping point behavior. They explain the emergence of this explosive behavior as the interplay between individual interactions and group interactions. Depending on which mechanism dominates, the system may exhibit an explosive transition.

Additional parameters can be added to the model to tune it for different processes and better understand how much of an individual's social network must be infected for a virus or information to spread.

The work is currently theoretical, but the researchers have plans to apply the model to actual data from physical networks and consider other structural characteristics that real-world networks exhibit.

HAMILTON, ON, Oct. 20, 2020 -- When COVID-19 attacks, the immune system produces a cytokine, or protein, called Interleukin-6 (IL-6), whose concentrations can offer vital information about a patient's level and stage of infection.

But measuring the critical marker has been extremely challenging, given its nearly undetectable presence in the biological stew that makes up human blood. Existing technology has not been accurate or sensitive enough to measure concentrations of IL-6 well enough to be reliable, especially in low concentrations.

Now researchers at McMaster University and SQI Diagnostics have created a surface that repels every other element of human blood except the critical cytokine, opening a timely window for understanding the progress of COVID-19 in individual patients.

The McMaster researchers are working to adapt the technology to the Toronto company's existing testing platforms, in the hope of moving it into clinical use as soon as possible. The same biosensing technology can also be used to measure other infectious and non-infectious diseases, including some cancers.

The innovative surface coating is made to repel every component of blood and other complex fluids such as urine, but is dotted with microscopic islands of molecules that attract IL-6, making it possible to detect and measure IL-6 with unprecedented accuracy and sensitivity, at concentrations as low as 0.5 picograms per mL - or one half of one trillionth of a gram per mL - making it far more sensitive than existing technology.

It is the latest application of smart-surface technology to emerge from the laboratory of Tohid Didar, a mechanical engineering professor at McMaster who has recently been involved in projects to create a reactive tag for food packaging that indicates the presence of harmful pathogens, a form of wrap that can repel antimicrobial-resistant bacteria and a coating for surgical implants that can repel infection while attracting cells that promote integration with surrounding tissue.

"There are so many possibilities for these smart surfaces. We can create them to repel everything, or we can design them to interact in many beneficial ways," Didar says. "Here, we're looking for something, and only that one thing, and this allows us to separate it from everything else in a very complex environment."

The new smart surface for detecting IL-6 can be printed inexpensively onto the inside of test tubes and onto other platforms used in diagnostic testing. After a sample of blood is exposed to the surface and removed, the captured IL-6 can readily be measured.

"The technology was challenging to create, but it is easy to use in many applications, including in testing kits that already exist," says co-author Amid Shakeri, a PhD student in Didar's lab. "I'm very happy that we can actually be involved in something that could be important for humankind, and I'm hopeful we can get this into clinical settings very soon."

"Our partnership with McMaster University has opened up an innovative pathway to a low-cost manufacturing design to enable affordable and accurate diagnostics, especially for testing in the COVID-19 pandemic" said Dr. Eric Brouwer, Chief Scientific Officer of SQI Diagnostics.

A paper introducing the technology is published today in the journal Small.

Cannabinoids have a strong influence on how our brains work and how we behave. Many people are only aware of the recreational aspect of cannabinoids. But in fact these molecules naturally exist in our brains where they participate in various intrinsic processes.

Altered cannabinoid signalling, for instance due to chronic use of marijuana, results in a range of impairments. Similarly, mice lacking cannabinoid receptors exhibit reduced activity levels, as well as deficits in learning and memory.

How do cannabinoids exact their effect on learning? A team led by Megan Carey, a principal investigator at the Champalimaud Centre for the Unknown in Portugal, and Catarina Albergaria, a postdoctoral researcher in the lab, decided to tap into this question by investigating the brain mechanisms involved in a classical learning task called eyeblink conditioning.

The immediate suspect

In eyeblink conditioning, subjects learn to associate the appearance of a sensory stimulus, for example a flash of light, with a subsequent delivery of an airpuff to the eye. Once learned, the subject - in this case a mouse - closes its eyes when the light appears to avoid the airpuff. "It's just like Pavlov's dog and the bell," says Albergaria.

Previous studies had established that this form of learning takes place in a brain structure called the cerebellum, and that it was impaired by altered cannabinoid signaling in both humans and mice. To study the role of cannabinoids in learning, the team used mutant mice lacking cannabinoid receptors, which show impaired eyeblink conditioning.

Why are these mice impaired? When they started, the researchers had an immediate suspect in mind. "Many studies support the idea that cannabinoids mediate neural plasticity, or experience-dependent changes in the connections between neurons," Carey explains. "We therefore first hypothesized that interfering with this process was what was driving the impairments in learning."

But like a good mystery novel, the immediate suspect turned out to be the wrong one. What was the real culprit? "In a study we published two years ago, we found that the more mice ran, the better they learned", Albergaria explains. The team began to suspect that the difference in learning might instead be due to the reduced activity levels of the mutant mice.

Spotlight on behavioural state

"We wondered whether the mutant mice weren't learning as well simply because they weren't active enough," Albergaria recalls. Today in the journal eLife, the team reports that the altered behavioral state of the mutants fully accounts for their impaired eyeblink conditioning. When the researchers placed the mice on a motorised treadmill that ensured that the mutants walked as much as normal mice, the results were striking: learning was completely restored.

The team also found that other cerebellar behaviors, locomotor coordination and learning, were normal in the cannabinoid mutants. Further, eyeblink conditioning was fully intact in mice that lacked cannabinoid receptors specifically within the cerebellum. "These experiments further supported our hypothesis that disrupted cannabinoid signaling was impairing learning by altering behavioral state, and not through direct effects on neural plasticity in the cerebellum," says Carey.

"There is a growing body of evidence that behavioural state profoundly influences brain function," says Carey. "Our study highlights the need to consider behavioral state as a powerful independent means through which individual genes contribute to complex behaviors."

"We were able to overcome a learning deficit associated with a genetic mutation with a purely behavioral intervention," adds Albergaria, suggesting a potential real-world consequence for these findings.

COLUMBUS, Ohio - A blend of racial prejudice, poor coping and partisan media viewing were found in Americans who stigmatized people of Asian descent during the COVID-19 pandemic, according to a new study.

But it was prejudice against Asian Americans that was most strongly linked to beliefs that Asians were responsible for the pandemic and most at risk for spreading it, results showed.

"It was striking that this general prejudice against Asian Americans appeared to play a powerful role in the stigmatization of this group in the specific context of COVID-19," said Hyunyi Cho, lead author of the study and professor of communication at The Ohio State University.

Findings were published online recently in the journal Ethnicity and Health.

The study comes in the wake of other evidence of prejudice against Asian Americans linked to COVID-19, a virus that was first identified in the Wuhan province of China. An April poll of Americans found that one-third had seen someone blaming Asian people for the pandemic.

"We wanted to see what could explain people of Asian descent being stigmatized for this virus," Cho said.

The researchers conducted a nationwide survey of 842 American adults between May 11 and May 19.

Participants were asked a variety of questions about COVID-19 and how they have been impacted and coped with the pandemic's effects, media use, their views of Asian Americans, and other related issues.

Overall, stereotypical racial beliefs about Asians and envy about the success of some Asian Americans in society were most linked to stigmatization.

"It turned out that the stereotypes and beliefs that people already had about Asian Americans were more powerful in predicting stigmatization than other factors we studied," said Wenbo Li, study co-author and doctoral candidate in communication at Ohio State.

"That is what was most surprising to me."

But other factors did play a role, such as how people were coping with the pandemic.

People who reported higher levels of fear about COVID-19 were more likely to stigmatize. The same went for those who felt most harmed by the pandemic and also reported lower levels of ability to deal with the crisis.

As in many issues in the United States today, ideology played a role in stigmatization.

One example was where people got their news. Findings showed that people who reported more viewing of COVID-19 news on Fox News and social media outlets were more likely to blame Asian Americans and see them as a disease risk than those who got their news from CNN or MSNBC and didn't consume as much social media.

In addition, people who believed the Trump administration was doing a good job responding to the pandemic crisis were more likely to report prejudicial views about Asian Americans.

"We saw evidence in our results that stigmatization of Asian Americans because of COVID-19 can have a political and ideological aspect," Cho said.

But some findings suggested ways to help reduce the stigmatization aimed at people of Asian descent, Cho and Li said.

For example, results showed that people who reported watching more foreign language movies showed less prejudice.

"Being exposed to other cultures, even through media like movies and TV, can help mitigate stereotypes," Cho said.

Most importantly, lower stigmatization was found in people who reported higher levels of what researchers call "collective efficacy." People high in collective efficacy strongly agreed with statements like "I feel that Americans can work together to effectively overcome the current COVID-19 crisis."

"Finding ways to foster collective efficacy can be an antidote to divisive communication on partisan cable television and social media," Li said.

The researchers said they believe this study has implications beyond Asian Americans and COVID-19.

"It is Asian Americans who are targeted in COVID-19. But in another crisis, it may be a different group," Cho said.

"It is about how people make sense of crises like this pandemic and how biases and prejudices can be exacerbated in situations like this."

Programmes to reduce dementia risk by targeting smoking, high blood pressure and hearing loss are likely to be cost-effective and cost saving by reducing dementia rates by 8.5%, finds a new study by UCL and LSE researchers.

The modelling study, published in The Lancet Healthy Longevity, found that the benefits would outweigh the costs of such programmes, and could save £1.86 billion each year in England.

Lead author Dr Naaheed Mukadam (UCL Psychiatry and Camden and Islington NHS Foundation Trust) said: "It is becoming increasingly clear that dementia can be prevented in many cases by addressing various health factors throughout the lifespan. As the number of people with dementia is expected to increase to 131 million worldwide by 2050, there is an urgent need to develop evidence-based interventions to prevent dementia, or delay it to enable more years of healthy life.

"Here, we have found that dementia prevention strategies can be cost-effective and cost saving, and should be implemented to reduce the societal burden of dementia."

The findings are based on extensive evidence, including from studies led by this study's researchers, finding that 12 risk factors can be modified across the life course to prevent 40% of dementia cases.

For the present study, the team reviewed evidence to find effective interventions for individuals targeting some of the dementia risk factors. The interventions included nicotine gum to help older adults quit smoking, medication to treat high blood pressure in mid-life, and hearing aids for people with moderate hearing loss in mid-life.

The researchers found that the three interventions combined would cost £1.08 billion annually in England, while reducing social care costs of dementia by £866 million and family care costs by £1.05 billion. The NHS and social care cost savings from dementia prevention would outweigh the costs of the smoking cessation and hearing loss interventions, while all three interventions would meet cost-effectiveness standards set out by the National Institute for Health and Care Excellence (NICE), as measured by cost per quality-adjusted life-year.

The model considered how well each intervention controlled each factor to reduce dementia risk, and accounted for the clustering of dementia risk factors (as many people are affected by more than one risk factor).

While this study focused on England, the researchers say their findings could likely apply similarly to other countries considering implementing dementia prevention strategies.

Senior author Professor Gill Livingston (UCL Psychiatry and Camden and Islington NHS Foundation Trust) said: "We have found that there's a strong case for implementing dementia prevention programmes. They are cost-saving for their impact on reducing dementia rates alone, without even factoring in the additional benefits in reducing other health issues such as stroke or heart disease."

The study was funded by the Economic and Social Research Council and was a collaboration between researchers at UCL and the London School of Economics and Political Science (LSE).

Fiona Carragher, Director of Research at Alzheimer's Society that funded the lead author said: "The evidence shows it's a no-brainer to invest in programmes to stop smoking, manage blood pressure and treat hearing loss, particularly given the cost of dementia to the economy is set to skyrocket as numbers of people with the condition increase. There isn't a fail-safe way to prevent dementia later in life but taking steps to reduce our risk has the potential to buck this worrying trend and give families the chance to have more precious, healthy years together.

"We look to the Government to act on these findings by making sure everyone knows what steps they can take to reduce their risk of dementia, and at the same time honour their commitment to double dementia research funding so we can continue this life-changing work."

Games and the very act of playing have been around since before the cradle of human civilization. However, games have constantly evolved over time, with various rulesets and modes of play falling in and out of favor throughout history. In turn, this implies that people at different times enjoyed different aspects of each game, which may constitute a vivid reflection of the cultural tendencies of each era. Unfortunately, the attractiveness of games is tied to human psychology, and finding objective evidence in topics related to the realm of the human mind is a difficult task. Could there possibly be a way to quantify universal characteristics of games so as to put them under rigorous mathematical analysis?

Professor Hiroyuki Iida, vice president and trustee of the Japan Advanced Institute of Science and Technology (JAIST), thinks that there is. Under his guidance, the Iida laboratory has put much effort into developing theories and models that explain, using concepts from mathematics and psychology, what players enjoy about different games and why they feel motivated to play. Now, in their most recent study published in IEEE Access, scientists at JAIST have developed a novel approach to quantify the psychological appeal of games from a perspective analogous to the basic laws of motion in physics.

Ms Kang Xiaohan, Ph.D. student and lead author of the study, explains that their research is based on a combination of game refinement theory, reinforcement schedules and 'motion in mind.' Game refinement theory is a methodology for assessing the enjoyment and entertainment value of a game based on variables such as uncertainty, match duration and difficulty. On the other hand, reinforcement schedules are a concept widely studied in psychology that explains how rewards and punishments (and their frequency) motivate specific human behaviors. In this case, a 'reward' in the psychological sense can be winning a game in a given match. Finally, "motion in mind" is a novel theory pioneered at Iida laboratory, which proposes an analogy between physical measures of motion (such as potential energy, force and momentum) and game-related measures perceived by players, including pace of the game, effort required to progress, and randomness.

One key measure in the model of motion in mind is the acceleration or 'gravity in the mind,' in analogy with the earth's gravitational acceleration. In sufficiently refined games, the model establishes a relationship between the effort that the player has to make to advance and the degree of challenge a game represents. The scientists calculated the gravity associated with a wide variety of games as they evolved through history, including classic board games like Chinese Go, Chess and Shogi, popular sports like soccer, tennis and basketball, and videogames, such as fighting games and strategy games.

Surprisingly, they found that the value of gravity in the mind changed, for each type of game, in sync with historical and cultural trends (Figure 1). For example, whereas people living 4000 years ago valued slow-paced games like ancient Go with a long period between rewards, the medieval and industrial era favored more aggressive and mid-paced games like Chess and Shogi (Figure 2). Similar trends were also found for various sports and videogames of the modern era. Excited about the results, Ms Xiaohan comments, "The gravity in the mind seems to be a good indicator of the core culture of people from a specific era or time. We can analyze how it changes to gain insight into people's cultural tendencies based on the type of playing experience they seek and their relative comfort."

The methodology and framework adopted in this study can be equally useful in other contexts where effort and motivation are critical factors, such as gamified activities, education and rehabilitation. It can also be used to analyze the nature of a given game or task so as to identify the psychological requirements for it, as well as the profiles of people that would be most comfortable or satisfied with it. In this regard, Prof Iida concludes, "We think the perspective of game-related research could shift naturally from the psychological realms to a more physical realm, making the generally complicated abstractions of the mind easier to understand." One thing is certain: as our understanding of the appeal of games increases, so does our understanding of ourselves and our history.