Culture

Lockdown and other restrictions imposed to control the COVID-19 pandemic have had unseen negative effects on the cognitive capacity and mental health of the population. A study led by the UOC's research group Open Evidence, in collaboration with international universities and BDI Schlseinger Group Market Research, has gauged the impact of the measures taken during the first and second waves of the virus on citizens of three European Union countries. The study concludes that the shock produced by the situation has reduced people's cognitive capacity, leading them to take more risks, despite the risk of contagion, and make poorer choices, including a tendency to be less altruistic and the desire to punish others.

The study, published in the open access journal Scientific Reports, published by Nature, analyses the relationship between the negative impact of pandemic control measures and people's cognitive functioning and risk, time and social preferences.

The sample consisted of nearly 5,000 volunteers from Spain, Italy and the United Kingdom - three countries criticized for their poor management of the pandemic, where lockdown has had a greater impact on their populations than in other European states. The participants were asked to respond to questionnaires during the first and second waves of the pandemic.

In the first of the two questionnaires, the researchers collected data on levels of exposure to four types of impacts during lockdown: occupational, health, mental health, and stress. In the second, they measured the cognitive function of the volunteers, as well as a series of parameters related to risk, decision-making, altruism, and reciprocity, among others.

"We wanted to explore the impact of lockdown and other COVID-19-related restrictions on people's lives and how this affected their decision-making," explained Francisco Lupiáñez, professor of Information and Communication Sciences and member of Open Evidence.

The results of the study show that those who were more exposed to the consequences of the effects of lockdown also experienced more diminished cognitive capacity, made riskier decisions, and suffered reduced civic-mindedness.

"People's impaired decision-making abilities were impaired, and their reactions were not those we might have expected," said the researcher. "Instead of being more careful because they were in a pandemic, they were taking risks, because they couldn't take it any more." As for their relations with others, "they wanted, for example, those who did not wear masks or evaded restrictions to be punished, even though they themselves were more likely to make riskier choices".

According to Lupiáñez, "very difficult choices were made without taking into account the social cost involved. They only took into account a single, short-term perspective. And now we know that four out of ten people were at risk of suffering a mental health-related illness as a result of the shock produced by this pandemic. All this will have implications in the medium term".

Another of the effects identified by the authors of this paper is that, under the shock of the pandemic, people tended to want immediate benefits and made on-the-spot decisions, some of them momentous, such as deciding to move from the city to a rural setting. "These were decisions in which the cost-benefit assessment was highly conditioned by the pandemic. It seemed as if the world was coming to an end and people preferred to benefit today, immediately, without thinking about tomorrow," said Lupiáñez.

According to the authors, their conclusions have important implications in terms of public health. The current pandemic and the various mitigation strategies, such as lockdowns, have had significant detrimental consequences in terms of occupational and health impacts. It is important, they say, that these be taken into account in "designing better responses and communication campaigns for future pandemics".

Astronomers have discovered new hints of a giant, scorching-hot planet orbiting Vega, one of the brightest stars in the night sky.

The research, published this month in The Astronomical Journal, was led by University of Colorado Boulder student Spencer Hurt, an undergraduate in the Department of Astrophysical and Planetary Sciences.

It focuses on an iconic and relatively young star, Vega, which is part of the constellation Lyra and has a mass twice that of our own sun. This celestial body sits just 25 light-years, or about 150 trillion miles, from Earth--pretty close, astronomically speaking.

Scientists can also see Vega with telescopes even when it's light out, which makes it a prime candidate for research, said study coauthor Samuel Quinn.

"It's bright enough that you can observe it at twilight when other stars are getting washed out by sunlight," said Quinn, an astronomer at the Harvard and Smithsonian Center for Astrophysics (CfA).

Despite the star's fame, researchers have yet to find a single planet in orbit around Vega. That might be about to change: Drawing on a decade of observations from the ground, Hurt, Quinn and their colleagues unearthed a curious signal that could be the star's first-known world.

If the team's findings bear out, the alien planet would orbit so close to Vega that its years would last less than two-and-a-half Earth days. (Mercury, in contrast, takes 88 days to circle the sun). This candidate planet could also rank as the second hottest world known to science--with surface temperatures averaging a searing 5,390 degrees Fahrenheit.

Hurt said the group's research also helps to narrow down where other, exotic worlds might be hiding in Vega's neighborhood.

"This is a massive system, much larger than our own solar system," Hurt said. "There could be other planets throughout that system. It's just a matter of whether we can detect them."

Youthful energy

Quinn would like to try. Scientists have discovered more than 4,000 exoplanets, or planets beyond Earth's solar system, to date. Few of those, however, circle stars that are as bright or as close to Earth as Vega. That means that, if there are planets around the star, scientists could get a really detailed look at them.

"It would be really exciting to find a planet around Vega because it offers possibilities for future characterization in ways that planets around fainter stars wouldn't," Quinn said.

There's just one catch: Vega is what scientists call an A-type star, the name for objects that tend to be bigger, younger and much faster-spinning than our own sun. Vega, for example, rotates around its axis once every 16 hours--much faster than the sun with a rotational period that clocks in at 27 Earth days. Such a lightning-fast pace, Quinn said, can make it difficult for scientists to collect precise data on the star's motion and, by extension, any planets in orbit around it.

To take on that game of celestial hide-and-seek, he and colleagues pored through roughly 10 years of data on Vega collected by the Fred Lawrence Whipple Observatory in Arizona. In particular, the team was looking for a tell-tale signal of an alien planet--a slight jiggle in the star's velocity.

"If you have a planet around a star, it can tug on the star, causing it to wobble back and forth," Quinn said.

Hot and puffy

The search may have paid off, said Hurt, who began the study as a summer research fellow working for Quinn at the CfA. The team discovered a signal that indicates that Vega might host what astronomers call a "hot Neptune" or maybe a "hot Jupiter."

"It would be at least the size of Neptune, potentially as big as Jupiter and would be closer to Vega than Mercury is to the sun," Hurt said.

That close to Vega, he added, the candidate world might puff up like a balloon, and even iron would melt into gas in its atmosphere.

The researchers have a lot more work to do before they can definitively say that they've discovered this sizzling planet. Hurt noted that the easiest way to look for it might be to scan the stellar system directly to look for light emitted from the hot, bright planet.

For now, the student is excited to see his hard work reflected in the constellations: "Whenever I get to go outside and look at the night sky and see Vega, I say 'Hey, I know that star."

FAYETTEVILLE, Ark. - Moral outrage is an attractive behavior, particularly to people seeking long-term relationships, according to a new paper by researchers including a University of Arkansas psychologist.

The work indicates that people who displayed moral outrage were considered more benevolent and trustworthy than a control person not displaying outrage, and therefore more likely to possess other prosocial behaviors that would benefit a long-term relationship. There was a catch, however: Researchers found that people had to take action to address the moral wrong in question and not just talk about it to be more attractive to the opposite sex.

"I've done previous work where I've looked at how prosocial behavior actually makes individuals be seen as better long-term prospects," said Mitch Brown, psychology instructor and first author of the study published in the journal Emotion. "But I was interested in understanding how emotional displays could do the same thing, actually."

Brown and his colleagues conducted four studies with a total of 870 participants designed to investigate how displays of moral outrage were perceived in the context of mating. Participants were asked to rate the attractiveness of fictional dating profiles of people of the same and opposite sexes. The study focused on heterosexuals, and the same-sex questions were used to gauge perceptions of how moral outrage influenced perceptions of an individual as interest in mating. "This latter test has important implications for identifying likely sources of intrasexual competition that could interfere with one's own mating goals," the researchers wrote.

They found that both sexes viewed moral outrage as desirable for a long-term mate, but women were much more attracted than men possibly due to the prosocial attitudes of trustworthiness and benevolence it conveyed that could be seen as more valuable to women. "Women incur a substantially larger minimal cost in reproduction (e.g., nine-month gestation, lactation) compared with men (e.g., single instance of sperm provision), which necessitates employment of stringent mate selection criteria to offset these costs," the authors wrote.

They also found that the expression of moral outrage alone did not increase attractiveness, possibly because outrage without action could heighten perceptions of undesirable traits such as neuroticism and disagreeableness.

Key Takeaways:

Machine learning offers more accurate targeting in mobile advertising.

Behavioral targeting is more effective than contextual targeting.

There is a possibility for self-regulation because too much behavioral targeting can reduce competition and hurt ad networks' revenues.

CATONSVILLE, MD, March 8, 2021 - It's a common assumption among marketers that if you can customize any form of marketing, particularly mobile advertising, you'll get better results. With this in mind, mobile marketing relies significantly on user tracking data as a cornerstone advertising strategy.

New research has looked into the value of user tracking data for targeting purposes and offered some insights about the privacy outcomes of such activities in a multisided mobile advertising market. This not only represents new thinking on marketing strategy, but could help mitigate certain societal concerns over privacy issues and the use of certain tracking data in mobile advertising.

The research study, "Targeting and Privacy in Mobile Advertising," is to be published in the March issue of the INFORMS journal Marketing Science. It is authored by Omid Rafieian of Cornell University and Hema Yoganarasimhan of the University of Washington.

The study found that a machine learning-based targeting approach improves the average click-through rate by more than 66.8% compared to simpler targeting models.

"The difference mainly stems from behavioral information as opposed to contextual information," said Rafieian. "What this means is that the machine-learning approach is able to learn user preferences from their past behavioral data, such as the ads they have seen and clicked on. Unlike traditional approaches, machine-learning methods do not put restrictive assumption on user behavior, and in turn, are able to identify more complex patterns in user preference."

"Once we established the effectiveness of our machine-learning approach, we turned to the privacy question: can we expect any stop on behavioral targeting and user tracking in this market?," said Yoganarasimhan. "What we found was that although behavioral targeting helps advertisers find better match with impressions, the ad network may want to protect consumer privacy and not allow very granular behavioral targeting for economic reasons. This is because too much targeting can result in softer competition between advertisers, where each advertiser cherry-picks narrow segments, thereby leading to lower revenues for ad networks."

The research used large-scale data from a leading in-app network of a country in Asia. Study authors created a machine-learning framework for targeting that uses both contextual and behavioral information.

They conducted a comprehensive comparison between the value of contextual and behavioral targeting from different players' viewpoints. The key insight from the paper was a misalignment between what ad networks and advertisers want: while advertisers demand more privacy-invasive targeting tools, ad networks have natural economic incentives to limit behavioral targeting to increase competition between advertisers. This hints at a future where the market can self-regulate and protect consumers' privacy.

Oncotarget published "Chemotherapy sensitivity testing on ovarian cancer cells isolated from malignant ascites" which reported that the authors aim is to determine the feasibility of cell proliferation assays of tumor cells isolated from malignant ascites to predict in vitro chemotherapy sensitivity, and to correlate these results with clinical outcome.

Cell samples were enriched for tumor cells and EOC origin was confirmed by intracellular staining of CK7, surface staining of CA125 and EpCAM, and HE4 gene expression.

In vitro sensitivity to chemotherapy was determined in cell proliferation assays using intracellular ATP content as an indirect measure of cell number.

In twelve of the fourteen remaining cases in vitro drug sensitivity and clinical outcome corresponded, while in two samples there was no correspondence.

Larger observational studies are required to confirm the correlation between the in vitro sensitivity and clinical outcome.

Dr. Anne M. van Altena from The Radboud University Medical Center said, "Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy worldwide."

Standard first-line treatment for advanced EOC consists of a combination of a debulking surgery and chemotherapy, with paclitaxel and a platinum-based compound administered either intravenously or intraperitoneally.

There is a need for more tools and assays to predict the clinical response to chemotherapy in EOC patients.

Konecny and co-workers reported a significant decrease in progression-free and overall survival of patients tested to be resistant in vitro using ATP tumor chemosensitivity assays performed on tumor cells isolated from biopsies.

A more personalized, tumor-specific treatment for EOC patients would be of great value to improve therapeutic decision-making and clinical outcome.

The aim of this Oncotarget study is to determine whether tumor cells isolated from ascites of EOC patients can be used to determine chemotherapy sensitivity by using in vitro proliferation assays.

The aim of this Oncotarget study is to determine whether tumor cells isolated from ascites of EOC patients can be used to determine chemotherapy sensitivity by using in vitro proliferation assays.

The van Altena Research Team concluded in their Oncotarget Research Paper, "our study shows the feasibility of assessing in vitro chemotherapy sensitivity on tumor cells isolated from ascites. A larger, prospective study, which takes into account the insights that were gained in this pilot study, is ongoing and will be reported in due course."

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DOI - https://doi.org/10.18632/oncotarget.27827

Full text - https://www.oncotarget.com/article/27827/text/

Correspondence to - Anne M. van Altena - Anne.vanAltena@radboudumc.nl

Keywords -
ovarian cancer,
chemotherapy sensitivity,
prediction,
ascites,
proliferation assays

About Oncotarget

Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:

SoundCloud - https://soundcloud.com/oncotarget
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Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls

Journal

Oncotarget

DOI

10.18632/oncotarget.27827

Oncotarget published "High-fat diet-fed ovariectomized mice are susceptible to accelerated subcutaneous tumor growth potentially through adipose tissue inflammation, local insulin-like growth factor release, and tumor associated macrophages" which reported that the association between obesity and colorectal cancer (CRC) risk has been well established. This relationship appears to be more significant in men than in women, which may be attributable to sex hormones - controlled animal studies to substantiate these claims and the mechanisms involved are lacking. MC38 murine colon adenocarcinoma cells were injected subcutaneously into high-fat diet fed male, female and ovariectomized female C57BL/6 mice.

HFD OVX mice exhibited the most significant tumor growth compared to HFD male and female mice and this was associated with increased subcutaneous adipose tissue.

Further, the subcutaneous adipose tissue depots within HFD OVX mice exhibited more severe macrophage associated inflammation compared to female, but not male mice.

Conditioned media from subcutaneous adipose tissue of HFD OVX contained higher IGF-1 levels compared to male, but not female mice.

Finally, HFD OVX mice had increased M2-like gene expression in their tumor-associated macrophages compared to female mice.

Dr. Angela Murphy from The University of South Carolina said, "There is convincing evidence that excess body weight is associated with increased risk for late onset (> 50 years of age) colorectal cancer (CRC)."

There is convincing evidence that excess body weight is associated with increased risk for late onset (> 50 years of age) colorectal cancer (CRC)

Taken together, the current literature suggests that:

sex disparities are evident in obesity-enhanced CRC, and
hormonal status likely plays a role in CRC risk in women

These perturbations have been associated with CRC risk and are likely biological factors that link obesity to CRC risk.

For instance, the homeostasis model of risk assessment-insulin resistance has been reported to be associated with risk for CRC.

As hormone status is an influential risk factor for both obesity and CRC, the Oncotarget authors also sought to examine the effect of ovarian hormone deficiency on obesity-enhanced CRC.

Overall, this study provides insight into the contributions of hormonal status, fat distribution, and local versus systemic effects of obesity on CRC risk.

The Murphy Research Team concluded in their Oncotarget Research Paper, "our study confirms that established obesity following 20–21 weeks of high-fat-diet feedings enhanced the growth of subcutaneously implanted MC38 tumors, but this appears to be largely due to the increase in tumorigenesis in the OVX mice. We established that diet induced obesity and associated insulin resistance manifest differently in male, female, and OVX mice. Although we were unable to completely replicate epidemiological data, we report that obese OVX mice are most vulnerable to accelerated subcutaneous tumor growth in the MC38 model. Our data suggest several potential mechanisms including increased local adiposity, increased local inflammation and IGF-1, and polarization of macrophages to an M2 phenotype, providing insight into this obesity enhanced tumor growth in OVX mice."

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DOI - https://doi.org/10.18632/oncotarget.27832

Full text - https://www.oncotarget.com/article/27832/text/

Correspondence to - Angela Murphy - Angela.Murphy@uscmed.sc.edu

Keywords -
colorectal cancer,
obesity,
metabolism,
macrophage,
inflammation

About Oncotarget

Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:

SoundCloud - https://soundcloud.com/oncotarget
Facebook - https://www.facebook.com/Oncotarget/
Twitter - https://twitter.com/oncotarget
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/

Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls

Journal

Oncotarget

DOI

10.18632/oncotarget.27832

Personalised 3D printed models created from cardiac imaging data, mainly from cardiac CT images have been increasingly used in cardiovascular disease, primarily in the preoperative planning and simulation of complex surgical procedures, as well as medical education. 3D printed models are proved to be highly accurate in replicating normal anatomy and cardiac pathology with reported differences less than 0.5 mm between 3D printed models and original sources images. Further to these applications, a new research direction of utilising 3D printed models is to study the optimal CT scanning protocols in cardiovascular disease with the aim of reducing radiation dose while preserving diagnostic image quality. To achieve this goal, an appropriate printing material is essential to ensure that the printed models possess elasticity and flexibility similar to normal tissue properties.

Zhonghua Sun, a John Curtin Distinguished Professor and medical imaging researcher from Curtin University, Australia has been in search of suitable 3D printing materials to print realistic models, and more importantly, to print cardiovascular models with similar tissue properties to replicate heart and aortic arteries. Prof. Sun's research interests lie in 3D image visualization and diagnosis; 3D printing, virtual reality and artificial intelligence in medical applications, specifically in the cardiovascular disease. In his recent work, published in Current Medical Imaging, Prof. Sun and his team presents research findings for printing the aorta models with printing materials having similar CT attenuation to that of normal aortic wall on both pre- and post-contrast CT scans. This study further advances the current applications of 3D printing in cardiovascular disease to another level by presenting evidence that 3D printed personalised aorta models can be used to study optimal CT protocols, in addition to the value that 3D printed aorta models serve as a useful tool for pre-surgical planning and simulation of endovascular repair of aortic disease.

In his latest article, Prof Sun and his team reported findings on how the identified materials can be used to print realistic aorta models. They first created a 25-mm long type B aortic dissection model from CT images, then printed 4 models with use of two materials, namely Agilus from Stratasys and Visijet CE-NT from 3D Systems. These materials are soft and can be mixed with another material such as photopolymer resin to create a range of products with different elastic properties. These 4 aortic models consisted of two Agilus models printed with A40 and A50, representing two different degrees of hardness, another two Visijet models printed with Visijet CE-NT with different hardness, A30 and A70. The Visijet CE-NT A30 has a tensile strength between 0.2 and 0.4 which is close to the aging arteries, while Agilus A40 and A50 have a tensile strength of 0.5 to 1.5. The 4 aorta models were scanned on a 192-slice CT scanner with the standard aorta CTA protocol, and the scans were performed with and without use of contrast medium to measure CT attenuation at true lumen, false lumen, intimal flap and two junction areas between the true and false lumens. Results showed that Agilus models had higher CT attenuation than Visijet CE-NT models on non-contrast CT images, with Agilus A50 having an average CT attenuation similar to that of original CT images. On contrast images, only Visijet CE-NT A30 produced CT attenuation similar to that of original images, while the remaining models printed with other materials resulted in significantly higher CT attenuation than that of original images. This study shows that Visijet CE-NT A30 is considered an appropriate material to print aortic dissection model due to its similar elasticity to the normal aorta.

Aorta CT angiography (CTA) is currently the reference method in preoperative assessment of aortic aneurysm and dissection. Further, CTA is commonly used to follow-up patients treated with endovascular stent grafts. Therefore, regular CTA follow-ups of these patients at 3, 6 and 12 months, yearly thereafter contribute to cumulative radiation dose, which raises serious concerns due to radiation-induced malignancy. Dose optimization is clinically important to these patients receiving multiple CT scans. "3D printed aortic models with Visijet CE-NT material give the appearance of translucent light yellow allowing its use for education purpose, in addition to its reported value in guiding complex aortic surgery or endovascular aortic repair," says Prof. Sun. He also added "printing aortic dissection models is very challenging compared to other cardiovascular models due to very thin membranous structure of the intimal flap." The CTA images used in this study represented nice anatomical structures including intimal flap which were segmented and printed without any difficulty. This confirms the importance of quality of source images to guarantee printing high-quality models.

Prof. Sun's team is continuing to work on printing more anatomical structures including ribs, thoracic vertebrae, soft tissues, lungs and heart which allows for simulation of more realistic environment. "The phantom should be improved to mimic the in vivo circumstance and this allows for investigation of optimal aorta CT scanning protocols for detection of aortic dissection," says Prof. Sun.

The perils of machine learning - using computers to identify and analyze data patterns, such as in facial recognition software - have made headlines lately. Yet the technology also holds promise to help enforce federal regulations, including those related to the environment, in a fair, transparent way, according to a new study by Stanford researchers.

The analysis, published this week in the proceedings of the Association of Computing Machinery Conference on Fairness, Accountability and Transparency(link is external), evaluates machine learning techniques designed to support a U.S. Environmental Protection Agency (EPA) initiative to reduce severe violations of the Clean Water Act. It reveals how two key elements of so-called algorithmic design influence which communities are targeted for compliance efforts and, consequently, who bears the burden of pollution violations. The analysis - funded through the Stanford Woods Institute for the Environment's Realizing Environmental Innovation Program - is timely given recent executive actions(link is external) calling for renewed focus on environmental justice.

"Machine learning is being used to help manage an overwhelming number of things that federal agencies are tasked to do - as a way to help increase efficiency," said study co-principal investigator Daniel Ho, the William Benjamin Scott and Luna M. Scott Professor of Law at Stanford Law School. "Yet what we also show is that simply designing a machine learning-based system can have an additional benefit."

Pervasive noncompliance

The Clean Water Act aims to limit pollution from entities that discharge directly into waterways, but in any given year, nearly 30 percent of such facilities self-report persistent or severe violations of their permits. In an effort to halve this type of noncompliance by 2022, EPA has been exploring the use of machine learning to target compliance resources.

To test this approach, EPA reached out to the academic community. Among its chosen partners: Stanford's Regulation, Evaluation and Governance Lab (RegLab), an interdisciplinary team of legal experts, data scientists, social scientists and engineers that Ho heads. The group has done ongoing work with federal and state agencies to aid environmental compliance.

In the new study, RegLab researchers examined how permits with similar functions, such as wastewater treatment plants, were classified by each state in ways that would affect their inclusion in the EPA national compliance initiative. Using machine learning models, they also sifted through hundreds of millions of observations - an impossible task with conventional approaches - from EPA databases on historical discharge volumes, compliance history and permit-level variables to predict the likelihood of future severe violations and the amount of pollution each facility would likely generate. They then evaluated demographic data, such as household income and minority population, for the areas where each model indicated the riskiest facilities were located.

Devil in the details

The team's algorithmic process helped surface two key ways that the design of the EPA compliance initiative could influence who receives resources. These differences centered on which types of permits were included or excluded, as well as how the goal itself was articulated.

In the process of figuring out how to achieve the compliance goal, the researchers first had to translate the overall objective into a series of concrete instructions - an algorithm - needed to fulfill it. As they were assessing which facilities to run predictions on, they noticed an important embedded decision. While the EPA initiative expands covered permits by at least sevenfold relative to prior efforts, it limits its scope to "individual permits," which cover a specific discharging entity, such as a single wastewater treatment plant. Left out are "general permits," intended to cover multiple dischargers engaged in similar activities and with similar types of effluent. A related complication: Most permitting and monitoring authority is vested in state environmental agencies. As a result, functionally similar facilities may be included or excluded from the federal initiative based on how states implement their pollution permitting process.

"The impact of this environmental federalism makes partnership with states critical to achieving these larger goals in an equitable way," said co-author Reid Whitaker, a RegLab affiliate and 2020 graduate of Stanford Law School now pursuing a PhD in the Jurisprudence and Social Policy Program at the University of California, Berkeley.

Second, the current EPA initiative focuses on reducing rates of noncompliance. While there are good reasons for this policy goal, the researchers' algorithmic design process made clear that favoring this over pollution discharges that exceed the permitted limit would have a powerful unintended effect. Namely, it would shift enforcement resources away from the most severe violators, which are more likely to be in densely populated minority communities, and toward smaller facilities in more rural, predominantly white communities, according to the researchers.

"Breaking down the big idea of the compliance initiative into smaller chunks that a computer could understand forced a conversation about making implicit decisions explicit," said study lead author Elinor Benami, a faculty affiliate at the RegLab and assistant professor of agricultural and applied economics at Virginia Tech. "Careful algorithmic design can help regulators transparently identify how objectives translate to implementation while using these techniques to address persistent capacity constraints."

GAINESVILLE, Fla. --- Evolutionary arms races between marine animals overhauled ocean ecosystems on scales similar to the mass extinctions triggered by global disasters, a new study shows.

Scientists at Umeå University in Sweden and the Florida Museum of Natural History used paleontological databases to build a multilayered computer model of the history of marine life over the last 500 million years. Their analysis of the fossil record closely echoed a seminal 1981 study by paleontologist J. John Sepkoski - with one key difference.

Sepkoski's ground-breaking statistical work showed abrupt ocean-wide changes in biodiversity about 490 and 250 million years ago, corresponding to two mass extinction events. These events divided marine life into what he called "three great evolutionary faunas," each dominated by a unique set of animals.

But the new model reveals a fourth.

The fierce fight for survival that played out between predatory marine animals and their prey about 250 to 66 million years ago may have been an equally powerful force, reshaping ocean diversity into what we see today. This third grand transition was much more gradual than its predecessors and driven by organisms, rather than external processes.

"What we learned is that not all major shifts in animal life have been related to mass extinction events," said study lead author Alexis Rojas, who earned his Ph.D. at the University of Florida. Rojas is now a postdoctoral researcher at the Integrated Science Lab, a hub dedicated to interdisciplinary research at Umeå University.

Many scientists have long held the view that external factors such as volcanic activity, asteroid impacts or changes in climate are the primary drivers of major shifts in the Earth's biosphere, said study co-author Michal Kowalewski, Rojas' doctoral adviser and the Florida Museum Thompson Chair of Invertebrate Paleontology.

"The fossil record tells us that some of the key transitions in the history of life were rapid changes triggered by abrupt external factors. But this study shows that some of those major transitions were more gradual and may have been driven by biological interactions between organisms," he said.

One reason Sepkoski's work was so revolutionary was that he took a mathematical approach to a practical problem: The fossil record is too big and complex for one person to be able to discern life's underlying patterns by looking at specimens alone.

"When its components are examined individually or in small groups, the complexity of their form, function, interaction, and history often seems overwhelming, and almost infinite," he wrote in the introduction to his 1981 study.

Organizing these components into a hierarchy of systems, he argued, presented a more complete view. Sepkoski's modelling divided 500 million years of ocean life into three great dynasties, each separated by a mass extinction that cleared the way for new groups to flourish and dominate. After the reign of trilobites, clamlike animals known as brachiopods and certain ancient corals and ammonites rose to prominence. After the cataclysmic end-Permian extinction, sometimes known as the "Great Dying," they were in turn replaced by snails, clams, crustaceans, modern corals and various kinds of bony fishes.

Sepkoski's hypothesis fundamentally changed how scientists thought about the history of life, Kowalewski said. It offered an organized way of understanding the history of marine ecosystems - the overarching storyline and plot twists.

But as our knowledge of the fossil record grows, so does Sepkoski's dilemma of how to analyze such vast and complex information, said Kowalewski.

"With millions of fossil specimens now documented, there is simply no feasible way for our brains to process such massive archives of paleontological data," he said. "Fortunately, analytical methods continue to improve, giving us better ways to extract and examine information hidden inside these immensely complex data."

Rojas took on this challenge by using the latest advancements in data modelling. Specifically, he was interested in using complex network tools to create a better representation of the fossil record. Unlike other approaches in paleobiology, complex networks use a linked structure of nodes representing physical and abstract variables to uncover underlying patterns in a given system. Network approaches can be applied to social phenomena - for example, showing a Facebook user's patterns of interactions with friends on the platform - but they can also be applied to complex natural systems. Like Sepkoski, Rojas is a classically trained paleontologist looking for a fresh perspective on the fossil record.

"There are many processes happening at the same time at multiple scales: in your neighborhood, your country and across the entire planet. Now imagine the processes that occur in one day, one year or 500 years. What we are doing is trying to understand all these things across time," he said.

A simple network might consist of a single layer - all records of animal life and where they lived. But Rojas and his colleagues' network incorporates different intervals of time as individual layers, a feature lacking in previous research on macroevolution. The result is what Rojas described as a new, abstracted fossil record, a complement to the physical fossil record represented by the specimens in museum collections.

"It's important because the questions we are asking, the processes we are studying, occur at different scales in time and space," Rojas said. "We've taken some steps back so we can look at the entire fossil record. By doing that, we can explore all sorts of questions."

Think of it like navigating a Google Earth that represents the oceans over the last 500 million years. When and where would you go?

"Our interactive map of marine life shows smaller groups of animals and their interactions within each evolutionary fauna," Rojas said. "At the most basic levels, this map shows ocean regions with particular animals. The building blocks of our study are the individual animals themselves."

This complex network shows what Sepkoski's model could not capture: a gradual transition in ocean life coincident with the Mesozoic Marine Revolution, which started about 150 million years ago during the Mesozoic Era. First hypothesized in the 1970s, this revolution was caused by the rapid increase of marine predators such as bony fish, crustaceans and snails, which have dominated oceans ever since. Their proliferation drove prey to become more mobile, hide beneath the ocean floor or enhance their defenses by thickening their armor, developing spines or improving their ability to regenerate body parts.

Sepkoski knew about the Mesozoic Marine Revolution, but his model, limited by the methods and data available at the time, was unable to delineate the ocean ecosystems preceding and following this gradual transition. The study by Rojas and his colleagues demonstrates that both physical and biological processes play key roles in shaping ocean life at the highest levels.

"We are integrating the two hypotheses - the Mesozoic Marine Revolution and the three great evolutionary faunas into a single story," Rojas said. "Instead of three phases of life, the model shows four."

DALLAS - March 8, 2021 - A study led by UT Southwestern and Children's Health researchers defines parameters for the number of white blood cells that must be present in children's urine at different concentrations to suggest a urinary tract infection (UTI). The findings, published recently in Pediatrics, could help speed treatment of this common condition and prevent potentially lifelong complications.

UTIs account for up to 7 percent of fevers in children up to 24 months old and are a common driver of hospital emergency room visits. However, says study leader Shahid Nadeem, M.D., assistant professor of pediatrics at UTSW as well as an emergency department physician and pediatric nephrologist at Children's Medical Center Dallas, these bacterial infections in infants and toddlers can be difficult to diagnose because their symptoms are similar to other fever-causing conditions.

If a diagnosis is delayed, he explains, a UTI can develop into a serious infection that can cause lasting consequences. For example, UTI-related kidney scarring has been linked with hypertension and chronic kidney disease later in life.

To diagnose a UTI, doctors must culture a urine sample and wait for it to grow telltale bacteria in a petri dish containing nutrients. However, says Nadeem, this process can take up to two days, delaying treatment. Consequently, he and other doctors typically rely on testing urine for a white blood cell-linked protein known as leukocyte esterase (LE), then confirm the presence of white blood cells - a sign of immune activity - by looking for them in urine under a microscope.

In children, he adds, the number of white blood cells can be highly variable, with some of this variation potentially due to varying urine concentration. As such, it's been unknown what white blood cell number threshold should be used to begin treating a suspected UTI based on urine concentration.

To determine these parameters, Nadeem and his colleagues searched medical records of children younger than 24 months old who were brought to the emergency department at Children's Medical Center between January 2012 and December 2017 with a suspected UTI and had both a urinalysis - in which their urine concentration and the presence of LE and white blood cells were assessed - and a urine culture. The search turned up 24,171 patients, 2,003 of whom were diagnosed with a UTI based on urine culture.

Using their urine's specific gravity - the density of urine compared with water, a measurement that serves as a surrogate for concentration - and the number of white blood cells present in the field of a high-power microscope, the researchers came up with cutoff points for three urine concentration groups: For low urine concentrations, children needed only three white blood cells to suspect UTI; for moderate concentrations, that number was six; and for high concentrations, it was eight.

For each of these concentration groups, leukocyte esterase remained constant, says Nadeem - suggesting that it's a good trigger for analyzing urine for the presence of white blood cells.

Knowing how many white blood cells tend to be present in urine samples at different concentrations in children with UTIs could help physicians start treating these infections before they receive urine culture results, he adds, giving relief to patients and their parents and preventing complications.

"The earlier we can start treatment, the better it is for these young patients," Nadeem says. "Our results add more information to physicians' toolboxes to make this decision."

Traumatic brain injury (TBI) is a major cause of disability and a risk factor for early-onset dementia. The injury is characterized by a physical insult followed acutely by complement driven neuroinflammation. Complement, a part of the innate immune system that functions both in the brain and throughout the body, enhances the body's ability to fight pathogens, promote inflammation and clear damaged cells. Complement plays a role in the brain, regardless of infection or injury, as it influences brain development and synapse formation. In TBI, complement- induced inflammation partially determines the outcome in the weeks immediately following injury. However, more research is needed to define a role for the complement system in neurodegeneration following head injury, specifically in the long-term, chronic phase of TBI. Furthermore, therapeutic management of TBI patients is limited to the acute phase following injury, as little is known about the link between the initial insult and the chronic neurodegeneration and cognitive decline in the months and years that follow.

Researchers at the Medical University of South Carolina (MUSC), the Ralph H. Johnson VA Medical Center and elsewhere have reported a link between the complement system and the chronic phase of TBI. Their results, published online on Jan. 12 in the Journal of Neuroscience, showed that inhibition of complement at two months after TBI disrupts neurodegeneration and improves cognitive function.

"TBI is associated with cognitive decline and dementia, and there are zero pharmacological treatments to prevent that cognitive decline," said Stephen Tomlinson, Ph.D., a professor and interim chairman of the Department of Microbiology and Immunology, who studies brain injury and the complement system.

"The vast majority of studies that have been done investigating different therapeutics in TBI have all been done with acute treatments, within hours of the initial insult. Our study is significant because we are starting treatments out to two months after TBI."

To understand more fully the timing of complement and chronic TBI, the Tomlinson Lab first looked at the body's response to the damaged area. They showed that certain brain cells, called microglia, destroy neuronal synapses that have been marked by complement for degradation. This process reduces the overall number and density of synapses in the brain. Further, they reported ongoing complement activation up to three months after one initial TBI insult, with expanding neuroinflammation across brain regions. This inflammatory response promotes degeneration of synapses and was predictive of progressive cognitive decline.

The researchers then explored the therapeutic effects of blocking complement. They used a complement inhibitor that specifically targets sites of complement activation and brain cell injury. Inhibiting complement interrupted the decline in brain cell function and reversed mental losses on tasks that evaluate spatial learning and memory, even when delivery of the inhibitor was delayed until two months after the injury.

"One big advantage of our approach is that we do not systemically inhibit complement," said Tomlinson.

"With acute treatments, it is not that big of an issue but chronically treating someone with a complement inhibitor systemically is not optimal because complement does other important things, ranging from host defense to controlling homeostatic and regenerative mechanisms."

Thus far, therapeutic investigations in preclinical models have focused almost entirely on acute treatments for TBI. With this new insight into TBI pathology, the Tomlinson team suggests that all phases of injury, including chronic time points, may be responsive to therapeutic treatments, specifically those involving complement inhibition.

These findings are critical, as rehabilitative interventions are the only available management strategy for TBI to improve cognitive and motor functions. Additionally, cumulative evidence shows that rehabilitation is likely to speed up recovery but not change long-term outcomes.

"It gives us a new way of perceiving TBI management. Really, the only therapy at the moment is rehabilitation therapy, which clinically has very little benefit. We have found that rehabilitation and complement inhibition have additive effects," said Tomlinson.

Looking forward, Tomlinson wants to take the translational approach of complement inhibition in the chronic phase of TBI out further, past that two-month window, and is investigating whether the treatment will still work in mice if it is begun six months to a year out from the initial TBI. Additionally, Tomlinson is developing models of repetitive TBI and plans to investigate anxiety and depressive behaviors in addition to early onset dementia, a significant concern in regard to veterans, soldiers and athletes.

Currently, multiple complement inhibitors are in various stages of clinical development, including those that are targeted specifically to sites of injury and disease. Tomlinson himself is a co-founder of a company that is investigating targeted complement inhibition, leading to the potential of incorporating complement inhibition into the clinic. Thus, studies undertaken in the Tomlinson lab could have deep and lasting impacts at the clinical level, where complement inhibition could eventually help the thousands of patients that suffer from TBI each year.

BOSTON - The higher rates of obesity in Black, Indigenous and People of Color (BIPOC) compared with other groups in the United States can be attributed in large part to systemic racism, according to a new perspective article published in the Journal of Internal Medicine. The authors offer a 10-point strategy to study and solve the public health issues responsible for this disparity.

"First, it is important to recognize that the interplay of obesity and racism is real. Once persons recognize this, they can begin to appropriately address and treat obesity in BIPOC communities," says co-author Fatima Cody Stanford, MD, MPH, MPA, an obesity medicine physician-scientist, educator, and policy maker at Massachusetts General Hospital and Harvard Medical School.

"In writing this article, we wanted to bring attention to the systemic racism in the obesity epidemic and the direct harms to people of color from bearing a serious disease that is socially caused," adds co-author Daniel Aaron, JD, MD, an attorney at the U.S. Food and Drug Administration,* Harvard Law School fellow, and member of The Justice Initiative, a collaboration between Harvard Law School and Howard University School of Law aimed at furthering racial justice.

Stanford and Aaron note that BIPOC suffer chronic stress from experiencing racism in their environments, which can increase the severity of obesity. Also, BIPOC who want help losing weight have a harder time accessing health care, and when they do, they face real and perceived systemic racism within medicine. Furthermore, marginalized BIPOC are more likely to live in areas with an abundance of stores that sell unhealthy food and a lack of stores offering affordable, nutritious options. Even with access to supermarkets, processed food is usually cheaper than fruits or vegetables, and processed food companies engage in disproportionate marketing towards BIPOC.

"Too many people are unaware of how racist structures, institutions and people may be contributing to the direct harm of BIPOC, leading to obesity," says Aaron. "Society has failed to provide essential public health services and comprehensive and equitable medical care to Americans who are not white. Nor have we held accountable the institutions that profit from obesity among BIPOC and propagate systemic racism. Many voices have raised alarms for years, yet they have often gone unheard."

The perspective article stresses that addressing obesity's disproportionate harm to BIPOC will involve changes to public health organizations, medical and research institutions, governments and corporations. "Rather than push for educational campaigns and attempts to 'enlighten' minorities, we should instead look to increased liability and scrutiny of those who aggressively market unhealthy food to BIPOC and concentrate their establishments in BIPOC communities. And we must aim to provide BIPOC access to the same rights: to money, healthy food, medical care, housing, education and freedom from discrimination," says Aaron.

Aaron and Stanford aim to stir more thoughtful and transformative policy approaches that place the onus on powerful parties that benefit from existing arrangements and on people and institutions that are hesitant to change--not on the victims of systemic racism. They offer a 10-point strategy towards this goal.

"The implications could have far-reaching effects on well-being, as obesity is associated with more than 200 chronic diseases, many of which disproportionately affect BIPOC, and it's a risk factor for contracting and dying from COVID-19," says Stanford. "The immense costs--to lives, health, and wealth--of not preventing and treating obesity are exacerbated for BIPOC, and we urgently need to study and solve the core issues at the intersection of obesity and systemic racism."

Here is a link to a free Altmetric Report on this Research Output

Aging-US published "Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial" which reported that the aim of the current study was to evaluate whether hyperbaric oxygen therapy (HBOT) affects telomere length (TL) and senescent cell concentrations in a normal, non-pathological, aging adult population.

Thirty-five healthy independently living adults, aged 64 and older, were enrolled to receive 60 daily HBOT exposures.

Whole blood samples were collected at baseline, at the 30th and 60th session, and 1-2 weeks following the last HBOT session.

Telomeres length of T helper, T cytotoxic, natural killer and B cells increased significantly by over 20% following HBOT.

In this Aging-US study, the most significant change was noticed in B cells which increased at the 30th session, 60th session and post HBOT by 25.68%±40.42 , 29.39%±23.39 and 37.63%±52.73, respectively.

Dr. Amir Hadanny and Dr. Shai Efrati said, "Aging can be characterized by the progressive loss of physiological integrity, resulting in impaired functions and susceptibility for diseases and death."

At the cellular level, there are two key hallmarks of the aging process: shortening of telomere length and cellular senescence.

Shortened TLs can be a direct inherited trait, but several environmental factors have also been associated with shortening TL including stress, lack of physical endurance activity, excess body mass index, smoking, chronic inflammation, vitamins deficiency and oxidative stress.

Cellular senescence is an arrest of the cell cycle which can be caused by telomere shortening, as well as other aging associated stimuli independent of TL such as non-telomeric DNA damage.

The accumulation of senescent cells with aging reflects either an increase in the generation of these cells and/or a decrease in their clearance, which in turn aggravates the damage and contributes to aging.

On the cellular level, it was demonstrated that HBOT can induce the expression of hypoxia induced factor, vascular endothelial growth factor and sirtuin, stem cell proliferation, mitochondrial biogenesis, angiogenesis and neurogenesis.

The Hadanny/Efrati Research Team concluded in their Aging-US Research Output that hyperbaric oxygen therapy is a well-established treatment modality for non-healing wounds, radiation injuries as well as different hypoxic or ischemic events .

In recent years, a growing evidence from preclinical as well as clinical trials demonstrate the efficacy of HBOT for neurological indications including idiopathic sudden sensorineural hearing loss, post stroke and post traumatic brain injury, central sensitization syndrome such as fibromyalgia syndrome and age related cognitive decline and animal models of Alzheimer's disease.

For the first time, the current study aimed to evaluate the physiological effect on the cellular level in aging humans without any functional limiting disease.

Aging-US published "In search of preventive strategies: novel high-CBD Cannabis sativa extracts modulate ACE2 expression in COVID-19 gateway tissues" which reported that Cannabis sativa, especially those high in the anti-inflammatory cannabinoid cannabidiol, has been found to alter gene expression and inflammation and harbour anti-cancer and anti-inflammatory properties.

Working under a Health Canada research license, the Aging-US authors developed over 800 new C. sativa cultivars and hypothesized that high-CBD C. sativa extracts may be used to down-regulate ACE2 expression in target COVID-19 tissues.

Using artificial 3D human models of oral, airway and intestinal tissues, they identified 13 high-CBD C. sativa extracts that decrease ACE2 protein levels.

Some C. sativa extracts down-regulate serine protease TMPRSS2, another critical protein required for SARS-CoV-2 entry into host cells.

While their most effective extracts require further large-scale validation, their study is important for future analyses of the effects of medical cannabis on COVID-19. The extracts of their most successful novel high-CBD C. sativa lines, pending further investigation, may become a useful and safe addition to the prevention/treatment of COVID-19 as an adjunct therapy.

Dr. Olga Kovalchuk and Dr. Igor Kovalchuk said, "There is a global pandemic of the COVID-19 disease, which is caused by the zoonotic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)."

Similar to other respiratory pathogens, SARS-CoV-2 is transmitted through respiratory droplets from coughing and sneezing. However, aerosol transmission and close-contact transmission cannot be ruled out as means of disease spread.

An in-depth analysis of The Cancer Genome Atlas and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression datasets revealed that ACE2 is expressed in oral mucosa and enriched in the epithelial cells of the tongue.

High levels of ACE2 expression in oral epithelial tissues suggests that the oral cavity could be highly susceptible to SARS-CoV-2 infection and thus an important target for prevention strategies.

Similarly, numerous studies have reported high levels of ACE2 in the lower respiratory tract; higher levels of ACE2 expression, such as those seen in smokers and patients with chronic obstructive pulmonary disease, are associated with higher COVID-19 predisposition and enhanced disease severity.

Using artificial 3D human tissue models, the authors show that high-CBD C. sativa extracts may down-regulate ACE2 expression in target COVID-19 tissues, suggesting an importance of these extracts in COVID-19 prevention.

The Kovalchuk/Kovalchuk Research Team concluded in their Aging-US Research Output, "While our most efficacious extracts require further validation through large-scale analyses, our study is important for future analyses of the effects of medical cannabis on COVID-19. Given the current dire and rapidly developing epidemiological situation, every possible therapeutic opportunity needs to be considered and researched."

Researchers have identified a critical mechanism that allows deadly bacteria to gain resistance to antibiotics.

The findings offer a potential new drug target in the search for effective new antibiotics as we face the growing threat of antimicrobial resistance (AMR) and infections caused by bacterial pathogens.

The study investigated quinolone antibiotics which are used to treat a range of bacterial infections, including TB (tuberculosis). Quinolones work by inhibiting bacterial enzymes, gyrase and topoisomerase IV, thereby preventing DNA replication and RNA synthesis essential to growth.

They are highly-successful antimicrobial agents widely used in current medicine, however bacterial resistance to them and other treatments is a serious problem.

Previous studies had identified one resistance mechanism caused by the production of pentapeptide repeat proteins (PRPs), a family of molecules that also act as DNA gyrase inhibitors.

One of these, called MfpA, confers quinolone resistance to Mycobacterium tuberculosis, the causative agent of TB.

In this study John Innes Centre researchers in the group of Professor Tony Maxwell set out to discover how PRPs such as MfpA, work at the molecular level.

They purified MfpA from Mycobacterium smegmatis, a close relative of M. tuberculosis, and showed that it can inhibit the supercoiling reaction of DNA gyrase, the target of quinolones in TB causing mycobacteria.

Further investigations showed that MfpA can prevent poisoning of gyrase by quinolones, thus protecting the bacterial host cell from the antibiotic.

Using X-ray crystallography, the researchers showed that MfpA binds to the ATPase domain of gyrase, and that this explains its ability to both inhibit the supercoiling reaction and prevent quinolone poisoning.

"We did not expect the exact mechanism of MfpA to be the prevention of DNA binding to the gyrase ATPase domain; this is a unique mode of action," said Professor Tony Maxwell, corresponding author of the study.

"We believe this understanding will help drive new ideas for antibiotic development among academics and researchers in the pharma industry," he added.

Further investigative work will involve molecular modelling based on the MfpA-gyrase structure to design small molecules that could mimic this interaction and offer more insights into how it works.