Culture

ATLANTA -- New research at ACR Convergence, the American College of Rheumatology's annual meeting, reveals that people of color with rheumatic disease have worse health outcomes from COVID-19 infection, are more likely to be hospitalized to treat their coronavirus infection, and are more likely to require invasive ventilator treatment (ABSTRACT #0006).

COVID-19 is the disease caused by the novel SARS-CoV-2 coronavirus. As part of the response to the global pandemic, the rheumatology community launched the COVID-19 Global Rheumatology Alliance physician registry, an international collection of data on patients with rheumatic diseases who have been diagnosed with COVID-19. These data have been used for a number of studies that clarify how people with rheumatic diseases, many of whom take immunosuppressant drugs to control their conditions, are affected by COVID-19.

People with rheumatic disease, particularly those on immunosuppressants, are may be at higher risk for severe infections. What doctors and their patients do not know is why.. This new study used the data collected in the registry to determine if patients are more likely to experience more severe outcomes from COVID-19, and to learn if COVID-19 health outcomes vary by race and ethnicity for patients in the United States (U.S.).

"At the time we were examining data from the registry, there was growing attention on the disproportionate impact of COVID-19 among racial/ethnic minorities in the U.S.," says study co-author Milena Gianfrancesco, PhD, MPH, Assistant Adjunct Professor at the University of California, San Francisco School of Medicine. "We know that racial/ethnic minority rheumatic disease patients experience higher risk and disease severity in general. We were interested in examining whether the inordinate burden of COVID-19 also affected this susceptible population. Understanding disparities in COVID-19 outcomes can help us identify vulnerable populations and ensure that patients at high risk are adequately tested and treated."

The study included 694 U.S. patients who were defined as white, Black, Latinx or other race/ethnicity from the global rheumatology registry from March 24 to May 22, 2020. The researchers examined COVID-19 outcomes, including whether patients were hospitalized, required ventilation support such as supplementary oxygen and/or invasive ventilation, and if they died or survived their coronavirus infection. They controlled the data for age, sex, smoking status and rheumatic disease diagnoses (including rheumatoid arthritis, lupus, psoriatic arthritis, ankylosing spondylitis and others). They also controlled data for other common health problems that affect people with rheumatic diseases, such as cardiovascular disease, hypertension, lung disease, diabetes, and chronic renal insufficiency or end-stage renal disease. They also looked at arthritis medications that patients used, including immunosuppressants. The study's data also included each patient's level of rheumatic disease activity, or if their inflammatory arthritis was in remission, low, moderate or high.

According to the study's findings, people with rheumatic disease who are of racial or ethnic minorities were more likely to experience poor health outcomes from COVID-19 infection, including hospitalization and necessary ventilation support, compared to white patients. Black and Latinx patients had 2.7 and 1.98 higher odds, respectively, of needing hospitalization for COVID-19 compared to whites. Black and Latinx patients had threefold increased odds of needing ventilation support compared to whites. The study found no differences in mortality rates based on race or ethnicity.

"Bringing these results to light will hopefully lead to actionable changes within the rheumatology community and beyond," says Dr. Gianfrancesco. "We need to be sure that patients who are at high risk of severe COVID-19 outcomes have access to testing, treatment and a vaccine when one is eventually available. I would also add that rheumatology providers can be advocates and trusted allies for their patients. They can ensure that patients are aware of disease risks by providing materials in multiple languages."

A short online game in which players are recruited as a "Chief Disinformation Officer", using tactics such as trolling to sabotage elections in a peaceful town, has been shown to reduce susceptibility to political misinformation in its users.

The free-to-play Harmony Square is released to the public today, along with a study on its effectiveness published in the Harvard Misinformation Review.

It has been created by University of Cambridge psychologists with support from the US Department of State's Global Engagement Center and Department of Homeland Security Cybersecurity and Infrastructure Security Agency (CISA).

The gameplay is based on "inoculation theory": that exposing people to a weak "dose" of common techniques used to spread fake news allows them to better identify and disregard misinformation when they encounter it in future.

In this case, by understanding how to incite political division in the game using everything from bots and conspiracies to fake experts, players get a form of "psychological vaccine" against the product of these techniques in the real world.

"Trying to debunk misinformation after it has spread is like shutting the barn door after the horse has bolted. By pre-bunking, we aim to stop the spread of fake news in the first place," said Dr Sander van der Linden, Director of the Cambridge Social Decision-Making lab and senior author of the new study.

Twitter has started using a "pre-bunk" approach: highlighting types of fake news likely to be encountered in feeds during the US election. However, researchers argue that familiarising people with techniques behind misinformation builds a "general inoculation", reducing the need to rebut each individual conspiracy.

In the 10-minute game Harmony Square, a small town neighbourhood "obsessed with democracy" comes under fire as players bait the square's "living statute", spread falsehoods about its candidate for "bear controller", and set up a disreputable online news site to attack the local TV anchor.

"The game itself is quick, easy and tongue-in-cheek, but the experiential learning that underpins it means that people are more likely to spot misinformation, and less likely to share it, next time they log on to Facebook or YouTube," said Dr Jon Roozenbeek, a Cambridge psychologist and lead author of the study.

Over the course of four short levels, users learn about five manipulation techniques: trolling to provoke outrage; exploiting emotional language to create anger and fear; artificially amplifying reach through bots and fake followers; creating and spreading conspiracy theories; polarizing audiences.

In a randomized controlled trial, researchers took 681 people and asked them to rate the reliability of a series of news and social media posts: some real, some misinformation, and even some faked misinformation created for the study, in case participants had already come across real-world examples.

They gave roughly half the sample Harmony Square to play, while the other half played Tetris, and then asked them to rate another series of news posts.

The perceived reliability of misinformation dropped an average of 16% in those who completed Harmony Square compared to their assessment prior to playing. The game also reduced willingness to share fake news with others by 11%. Importantly, the players' own politics - whether they leaned left or right - made no difference.

Having the "control group" who played Tetris allowed the scientists to determine an "effect size" of 0.54 for the study, said Van der Linden.

"The effect size suggests that if the population was split equally like the study sample, 63% of the half that played the game would go on to find misinformation significantly less reliable, compared to just 37% of the half left to navigate online information without the inoculation of Harmony Square," he said.

The project follows other playful attempts by CISA to illustrate how "foreign influencers" use disinformation to target "hot button" issues. A previous demonstration took the example of whether pineapple belongs on pizza.

However, Harmony Square is based on the findings of a number of studies from the Cambridge team showing how similar gamified approaches to digital literacy significantly reduce susceptibility to fake news and online conspiracies.

The team behind the game, which includes the Dutch media agency DROG and designers Gusmanson, have recently worked with the UK Cabinet Office on Go Viral!, an intervention that specifically tackles conspiracies around COVID-19.

Harmony Square is geared towards the politically charged misinformation that has plagued many democracies over the last decade. "The aftermath of this week's election day is likely to see an explosion of dangerous online falsehoods as tensions reach fever pitch," said Van der Linden.

"Fake news and online conspiracies will continue to chip away at the democratic process until we take seriously the need to improve digital media literacy across populations. The effectiveness of interventions such as Harmony Square are a promising start," he said.

The combined environmental threat of plastic pollution and ocean acidification are having significant impacts on species living in our oceans, according to new research.

An international team of scientists found that after three weeks of being submerged in the ocean, the bacterial diversity on plastic bottles was twice as great as on samples collected from the surrounding seawater.

However, in areas of elevated carbon dioxide, a large number of taxonomic groups - including bacteria that play an important role in carbon cycling - were negatively impacted.

Conversely, other species - including those have previously been shown to thrive in areas of high ocean plastics and to potentially cause disease on coral reefs - were enriched by it.

The research also showed that while many groups of bacteria were shared between plastic, free-living and particle-associated samples, almost 350 were found uniquely on plastics.

Writing in the journal Marine Pollution Bulletin, researchers say the study adds to growing evidence that the increasing presence of plastic marine debris is providing a novel habitat for bacteria.

However, their results highlight that environmental conditions and local ecological processes will play an important role in determining its broader impact over the coming decades.

The study was led by the University of Tsukuba (Japan) and the University of Plymouth (UK), in collaboration with Keimyung University (Korea), Kyungpook National University (Korea) and Nanjing University (China).

Scientists submerged a number of plastic bottles in seas off the Japanese Island of Shikine, a region renowned for its CO2 seeps where the escaping gas dissolves into the sea water and creates conditions similar to that expected to occur worldwide in coming years.

They then used a combination of DNA sequencing and statistical techniques to analyse how bacteria colonise the plastic in comparison to the surrounding natural environment, and whether the increased CO2 levels would cause changes in the bacteria's distribution.

Lead author Dr Ben Harvey, Assistant Professor at the University of Tsukuba's Shimoda Marine Research Center and a graduate of the BSc (Hons) Ocean Science programme in Plymouth, said: "Discarded plastic drinking bottles have become a common sight in our oceans and we were expecting to see them being colonised by different types of bacteria. We also predicted that raised CO2 levels would cause significant changes in the bacterial colonies, but it was still surprising to see the extent of that change and how the raised levels affected species differently. To see beneficial species dwindling while harmful species thrive is an obvious present and future cause for concern."

Researchers from Tsukuba, Plymouth and other collaborators have published several studies over the past decade showing the threats posed by ocean acidification in terms of habitat degradation and a loss of biodiversity.

It is also the latest research by the University of Plymouth into plastics, with it being awarded a Queen's Anniversary Prize for Higher and Further Education in 2020 for its ground-breaking research and policy impact on microplastics pollution in the oceans.

Jason Hall-Spencer, Professor of Marine Biology at the University of Plymouth and senior author on the study, added: "Up to 13 million tons of plastics from land end up in the oceans each year and they have been shown to affect all types and sizes of marine species. Combine that with rising CO2 levels and the threat posed to the global ocean is stark. It reinforces the importance of taking steps to meet the standards demanded by international climate treaties so as to reduce the impact of ocean acidification and warming. It is also within our power to change cultures so that litter created on land does not become an environmental hazard in our oceans, both now and for future generations."

Researchers from Illinois State University, North Carolina State University, University of South Carolina, and University of Maryland published a new paper in the Journal of Marketing that examines the impact of moving nutrition labels, typically placed on the back of product packages, to the front.

The study, forthcoming in the Journal of Marketing, is titled "Competitive Effects of Front-of-Package Nutrition Labeling Adoption on Nutritional Quality: Evidence from Facts Up Front Style Labels" and is authored by Joon Ho Lim, Rishika Rishika, Ramkumar Janakiraman, and P.K. Kannan.

Can changing food packaging improve product nutrition quality? While this change may be simple, there's a lot at stake.

Diet-related chronic diseases impose a growing burden on the United States economy by increasing costs of health care and widening diet-related health disparities. Since the 1970s, the American diet has shifted considerably towards foods higher in calories and lower in nutritional quality. According to the Centers for Disease Control and Prevention estimates, more than one-third of American adults are obese. Childhood and adolescent obesity rates have also skyrocketed in the last 30 years with one in five school-aged children considered obese. To combat this disconcerting trend, public policy makers, food manufacturers, and grocery retailers have made efforts over time to design nutrition labels that can educate consumers about the nutritional value of the foods they purchase and help consumers make healthier choices. The World Health Organization (WHO) also considers nutrition labeling to be a key policy option for promoting healthier diets.

The packaged food industry has voluntarily taken steps to inform consumers about the nutritional value of food products so that consumers can make better choices. One such initiative undertaken by is the Front-of-Package (FOP) nutrition label. FOP nutrition labels are voluntarily adopted by food manufacturers and provide nutrient information on the front of food packaging in a clear, simple, and easy-to-read format. The FOP labels present the key information listed on the Nutrition Facts Panel (NFP; displayed on the back or side of food packages) more concisely and often include calorie content and the amounts of key nutrients to limit (e.g., saturated fat, sugar, and sodium per serving). In an innovative study, our research team assessed the effect of the introduction of a FOP nutrition label in a product category on the nutritional quality of food products in the category.

The study reports four sets of findings. First, the adoption of FOP nutrition labeling in a product category results in a significant improvement in the nutritional quality of food products in that category. Second, the effect of FOP is stronger for premium (high-priced) brands and brands with a narrower product line breadth. Third, the FOP adoption effect is stronger for unhealthy categories and categories with a higher competitive intensity. Fourth, manufacturers increase the nutritional quality of products by reducing the calorie content and limiting nutrients such as sugar, sodium, and saturated fat.

Lim explains that "This implies that policy makers, in partnership with food manufacturers and retailers, should encourage adoption of voluntary, standardized, and transparent labeling programs and consider options for broadening the information presented in FOP labels. We believe that policy makers should also invest in educational campaigns that inform consumers about the value of FOP labels and that would further incentivize food manufacturers to offer nutritionally better products."

For food manufacturers, the results suggest that they must devote significant resources to product innovation to stay competitive. Specifically, manufacturers in unhealthy and more competitive categories can be more strategic and invest in innovation so they are ready to provide better products following FOP adoption. Rishika adds that "Food retailers should partner with manufacturers and give them incentives to adopt FOP because this can lead to better-quality products for their consumers and help build a positive brand image. Retailers can also promote products with FOP labels, especially in more competitive and unhealthy product categories, which can spur manufacturers toward more innovation and lead to an increase in the nutritional quality of foods over time." The researchers encourage retailers to invest in measures that help monitor and track sales of products with FOP labels and provide this feedback to their manufacturers regularly to speed up the competitive effect of FOP labels. For consumers, the study finds that the brands that adopted FOP labeling offer nutritionally superior products than those that did not adopt the labeling. This result is particularly helpful for time-starved consumers looking to purchase relatively healthier products.

What The Study Did: Clinicians in the U.S. were interviewed and described their experiences of planning and providing care for patients in settings of limited resources during the COVID-19 pandemic.

Authors: Catherine R. Butler, M.D., M.A., of the University of Washington in Seattle, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2020.27315)

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

What The Study Did: Researchers assessed changes in birth rates by income level among commercially insured women before and after the elimination of cost sharing for contraception under the Patient Protection and Affordable Care Act.

Authors: Vanessa K. Dalton, M.D., of the University of Michigan in Ann Arbor, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2020.24398)

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

Neuroscientists at UCL have used laser beams to "switch on" neurons in mice, providing new insight into the hidden workings of memory and showing how memories underpin the brain's inner GPS system.

The study, published in the journal Cell, explains how researchers harnessed an 'all-optical' approach using twin lasers to simultaneously read and write the activity of 'place cells' (a type of neuron) in mice, as they navigated a virtual reality environment.

Remarkably, by stimulating the place cells, scientists were able to reactivate (or retrieve) the memory of a location where the mice obtained a reward, which in turn "mentally teleported" the mice, causing them to act as if they were in the rewarded place.

This new research builds on the groundbreaking work of Professor John O'Keefe (UCL Cell & Developmental Biology), who won the Nobel Prize in 2014 for discovering place cells. These cells are found in a brain region called the hippocampus, and only become active when an animal enters a specific location in the environment.

Place cells are thought to represent a cognitive map of the environment - like an inner GPS - and retain location memory. The new UCL study is the first to show directly that place cell activity underlies the brain's ability to navigate.

The results provide a deeper understanding of how memories are stored, and the UCL scientists believe the findings could eventually help us develop new therapies for conditions such as dementia and Alzheimer's disease, which affect memory.

First author Dr Nick Robinson (UCL Wolfson Institute for Biomedical Research) said: "These results provide direct causal evidence that mice use the information represented by place cell activity to guide their behaviour. In other words, place cells really do tell the mouse where it is, and mice actually 'listen' to their place cells when they make decisions. This provides new insights about how memories are stored in the brain, as well as new tools for manipulating these memories to influence behaviour."

He added: "Disorders of memory - such as in dementia and Alzheimer's - represent a huge cost to society. This work may eventually lead to a better understanding of these diseases, as well as new targets for therapeutic intervention."

Senior author Professor Michael Hausser (UCL Wolfson Institute for Biomedical Research) said: "This study is a game-changer as it shows that we can use optical reading and writing of activity in specific neurons to manipulate memories, allowing us to better understand - and potentially improve - how neural circuit activity helps us to make decisions."

The experimental study explained

Researchers at UCL Wolfson Institute for Biomedical Research leveraged a powerful approach which combines two revolutionary technologies for using light to read and write electrical activity in the brain.

First, they engineered neurons to express genetically encoded calcium sensors, which allow cells to light up when they are active. Second, they expressed light-sensitive 'optogenetic' proteins in the same neurons, allowing them to activate specific cells with beams of laser light, targeted using digital holography (the same technology as used in a laser light show).

By combining these two techniques, the team could both record and manipulate activity in the same neurons in the brain of a mouse navigating in virtual reality.

The UCL scientists used this approach to perform targeted activation of place cells in the hippocampus in mice navigating to a specific location within the virtual world to collect a sugar water reward. They first optically recorded the activity of large numbers of hippocampal place cells, identifying those which were active specifically at the rewarded location and which could therefore form the basis of the memory for that location. They then used holographically targeted laser beams to activate these specific place cells in a different location in the virtual world.

Remarkably, place cell stimulation was sufficient to retrieve the memory of the rewarded location, leading the mouse to seek the reward at the new location. In other words, the stimulation of the neurons with light "mentally teleports" the animal, causing them to act as if they were in the rewarded place. This is the first demonstration of how the activation of place cells enables us to retrieve memories of our environment and helps us to navigate.

ATLANTA -- Results from a large, international survey shows that only a small fraction of children with rheumatic diseases reported contracting COVID-19. Those who did become infected with COVID-19 all had benign outcomes and did not develop significant complications, despite the fact that most children were taking immunosuppressive medications. The research was presented at ACR Convergence, the American College of Rheumatology's annual meeting (ABSTRACT #1685).

The most common pediatric rheumatic disease is juvenile idiopathic arthritis (JIA), which is a group of chronic conditions that cause arthritis (joint swelling and inflammation) affecting children and teenagers. JIA may involve one or many joints, may also affect the eyes, and cause other symptoms, such as fevers or rash.

As the COVID-19 pandemic surged worldwide in early 2020, the risk of COVID-19 and serious complications or death was unknown for children with rheumatic diseases. Many of these patients are treated with immunosuppressive medications that leave them more susceptible to infections.

"At the time, parents and physicians did not know whether to continue a child's immunosuppressive medications to prevent COVID-19 and related complications," says the study's co-author, Jonathan S. Hausmann, MD, Instructor in Medicine at Harvard Medical School and a pediatric rheumatologist at Boston Children's Hospital.

To learn more about the impact of COVID-19 on children with rheumatic diseases, Dr. Hausmann and his fellow researchers analyzed data from the international COVID-19 Global Rheumatology Alliance Patient Experience Survey, a global patient registry. They sent surveys to parents of children with rheumatic diseases through patient support organizations and social media. Parents provided information on their child's rheumatic disease diagnosis, medications, whether or not the child ever developed COVID-19 and any outcomes they experienced if they were infected.

The study collected data from April 3 to May 8, 2020 and includes 427 children under age 18. Most of the children in the study lived in the Americas, and were white, female and between 5 and 14 years old. Most had JIA, and they were taking either conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). Both classes of drugs suppress the immune system and help to control the arthritis, while also making children at increased risk of infection. The survey also included children with other pediatric rheumatic diseases such as lupus, dermatomyositis, and autoinflammatory diseases.

Among the 427 children in the study, only five, or 1.2%, were diagnosed with COVID-19, none of whom required hospitalization or had severe outcomes. Because the study is based on self-reported responses from parents who were engaged in social media or who were willing to fill out a survey, it may not fully represent all children with pediatric rheumatic diseases, and it may be more likely to include a healthier population, the researchers say.

"These findings are important as policymakers and educators contemplate reopening schools with the pandemic still ongoing, and with parents and physicians struggling to make decisions of whether to send their children back to school," says Dr. Hausmann. "Our study suggests that children with rheumatic disease should continue their immunosuppressive drugs during the pandemic, as it does not appear to place them at increased risk of COVID-19 related complications. Our findings support the recent ACR guidelines for managing immunosuppression during the pandemic."

Next, this research group plans to develop a prospective, international registry of people with rheumatic disease of all ages to assess long-term outcomes of the COVID-19 pandemic, explore the willingness to receive and assess the efficacy of a vaccine, assess the impact of the environment on COVID-19, and track the effects of the pandemic on the physical and mental health of participants over time, he adds.

ATLANTA -- New research presented at ACR Convergence, the American College of Rheumatology's annual meeting, shows that tuberculosis (TB) screening and ongoing clinical care is needed for people on methotrexate who live in areas where the highly infectious illness is common. Methotrexate users who also take corticosteroids or other immunosuppressant therapies are at particular risk and need adequate TB screening (ABSTRACT #0223).

Methotrexate is one of the most effective and commonly used medications in the treatment of rheumatoid arthritis and other forms of inflammatory arthritis in both adults and children. Methotrexate is part of a group of arthritis treatments called disease-modifying antirheumatic drugs (DMARDs).

Methotrexate effectively control rheumatic diseases and more people around the world are being prescribed this treatment. In many areas, TB is endemic and a serious health risk for local populations. Since methotrexate suppresses a person's immune system, the researchers wanted to know if they are at increased risk of TB infection. Current guidelines for the management of rheumatic diseases do not address TB risk for people who take methotrexate. To learn more, researchers in Canada conducted a systematic review of published literature on TB rates among people who take less than 30 milligrams of methotrexate per week.

"Methotrexate is the foundation medication for treatment of many rheumatic diseases, especially rheumatoid arthritis (RA). Our concern is that methotrexate can affect cell-mediated immunity, which may increase susceptibility to infections, including tuberculosis," says the study's co-author, Carol Hitchon, MD, Associate Professor of Medicine at the University of Manitoba. "TB is endemic across Africa and other parts of the world. Existing guidelines do not address the possible increased risk of TB in these areas. As one step in developing recommendations for the use of methotrexate intended for these areas, we wanted to review the literature on methotrexate use, and the incidence and new diagnosis of TB in people taking methotrexate."

The researchers reviewed published studies from January 1990 to May 2018 that contained the words methotrexate and tuberculosis, as well as citations from review articles. They identified titles, abstracts or full manuscripts from 4,707 different reports, which were then independently screened to pull out studies on TB in patients taking methotrexate. They collected data on TB incidence, or new TB diagnosis versus reactivation of latent TB infection; TB outcomes, such as pulmonary symptoms, dissemination and death; and the safety of isoniazid, the antibiotic used to treat TB. After removing duplicates and studies with insufficient information, 31 moderate-quality studies were used for the review. Only 27% reported data from low to moderate human development index countries.

Based on the case control studies, the review showed that there is a modest increased risk of TB for patients on methotrexate, and that rates of TB in people with rheumatic disease who are treated with either methotrexate or biologic drugs are generally higher than the general population. Two cohort studies reported TB incidence in Moldova and China, where the disease is endemic. They showed 12 TB cases in 44 patients in Moldova and nine cases in 114 patients in China. Based on other studies on TB infection rates in countries like Spain, South Africa and Canada, the researchers found that infection rates were higher if patients were prescribed methotrexate along with corticosteroids or other immunosuppressants. They also found that methotrexate users had higher rates of TB that was extra-pulmonary, or disease that spreads beyond a patient's lungs, compared to the general population.

Five studies from China, the U.S., Japan and Belgium all evaluated the safety of using methotrexate and isoniazid together. Based on this data, the researchers found that isoniazid-related liver toxicity and neutropenia, or low white blood cell count, were more common when people took the antibiotic along with methotrexate, but these effects were usually reversible.

"This work has important implications for physicians using methotrexate in areas of the world with high rates of TB and for travelers returning from regions with high TB rates," says Dr. Hitchon. "TB reactivation should be considered for anyone with possible prior TB exposure. This is especially true for patients who are also on steroids. Overlapping toxicity profiles, such as liver toxicity, for methotrexate with TB treatments indicate a need for close monitoring."

3D printing has seen great advancements in various aspects over the past few decades, and many industries have seen innovative breakthroughs in their respective fields. Amongst them, the water treatment industry has also reaped benefits off the prospects of 3D printing. High performance spacers and membranes can be fabricated by 3D printing, and they help increase permeate production while minimising energy consumption in purification processes.

Researchers from Nanyang Technological University (NTU) and the Singapore University of Technology and Design (SUTD) reviewed the recent efforts, shortcomings as well as the conflicting reports of 3D printing in membrane-based water treatment (refer to figure). Their research paper entitled 'A review on spacers and membranes: Conventional or hybrid additive manufacturing?' has been published in Water Research.

In the paper, they showed the potential of 3D printed spacers. The great freedom of design in 3D printing enables the fabrication of complex and innovative spacers, which was previously impossible with conventional heat extrusion methods. These spacers were able to reduce the number of dead zones within the flow channel, and help mitigate detrimental membrane fouling problems. Some spacer designs such as the helical spacer, turbospacer, and column spacer were even able to reduce energy consumption.

An interesting perspective was also presented in the paper regarding the feasibility of 3D printed membranes. Microfiltration membranes (MF) with pore sizes

In an attempt to resolve this confusion, the paper critically analyses these 3D printed membranes, especially on 3D printing's role in the overall fabrication process. Hybrid additive manufacturing, a process where 3D printing is used in conjunction with other established fabrication methods, is also introduced in the paper. It shows how 3D printing can still be a powerful tool in the fabrication of membranes when used together with other established processes despite its inadequate printing resolution.

"3D printing is gradually evolving from a single-standalone process to a multi-integrated process. The application continues to grow in the water treatment industry, especially the membrane-based technologies. Future focus is expected to shift from lab scale prototyping to large scale manufacturing," said principal investigator Associate Professor Chong Tzyy Haur from NTU.

"It will not be an easy challenge to overcome upscaling and material limitations, but consistent research efforts are already evident today. Potentially, 4D printing can even be a possibility in the future to fabricate smart spacers and membranes that adapt to its surrounding environment," explained co-author Professor Chua Chee Kai from SUTD.

An international team of scientists has used ancient DNA samples to elucidate the population history of dogs. The results show that dogs had already diverged into at least five distinct lineages by about 11,000 years ago and that their early population history only partially reflects that of human groups.
Dogs were the first species to be successfully domesticated by humans, and they have been our close companions for at least 15,000 years. In spite of the long and intimate relationship between the two species, little is known about how dog populations diversified and dispersed around the world - or to what extent these developments were linked to human migrations. A large-scale international collaboration now sheds new light on these issues. "With the aid of genetic and statistical analyses, we were able to reconstruct the population history of prehistoric dogs, and investigate its relationship to that of humans," says Laurent Frantz. Frantz (formerly at Queen Mary University of London) was recently appointed Professor of the Paleogenomics of Domesticated Animals at Ludwig-Maximilians-Universitaet (LMU) in Munich and is one of the lead authors of the new study. "Our results revealed that the migration patterns of humans and dogs did not always coincide," he adds.

Frantz and his colleagues sequenced a total of 27 ancient dog genomes from Europe, the Near East and Siberia, the oldest of which dates to 10,900 years ago. Their results demonstrate that dogs had already diversified into distinct populations prior to that time. Five separate lineages can be distinguished in the data: Arctic, American, Near Eastern/African, Asiatic and European. The European lineage, to which the great majority of today's most popular breeds belong, is the result of hybridization between the Arctic and Near Eastern/African lines.
"One of the biggest surprises for me was that we detected only a minor amount of gene flow from wolves to dogs," Frantz says. "In contrast to the case with many other domesticated pets, the genetic contribution of the wild ancestors of dogs left very little sign in their genomes following their initial domestication. He speculates that this might reflect strong selection on the part of humans against wolf hybrids - which were perhaps more aggressive.

In order to trace the relationships between the population histories of dogs and humans, the team compared the ancient dog genomes with genetic datasets for humans, obtained from DNA samples that were of comparable age, geographical origin and cultural context to those of the canine samples. This comparison revealed that certain aspects of the population history of the dog could indeed be correlated with that of their human contemporaries. For instance, the first farmers, who migrated to Europe and Africa from the Levant during the Neolithic period, were apparently accompanied by their dogs. These then interbred with dogs domesticated by the hunter-gatherer cultures that they encountered in their new homes. However, the resulting diversification of prehistoric dogs has left hardly any traces in the genomes of their modern European descendants. "A process of homogenization subsequently set in, the causes of which remain unknown. In fact, we found that the genome of a dog found at a 5000-year-old site in Southern Sweden can explain practically all of the genetic heritage of modern European dogs. This means that a single population with ancestry similar to that of this individual replaced all other populations on the continent," Frantz explains.

In other cases, however, the migratory patterns of humans and their hounds do not run in parallel with each other. For instance, the migration of peoples from the Eastern steppe zones during the Bronze Age not only led to a dramatic cultural transition, it also left a clear imprint on the genomes of the European populations of that era - but not on those of their dogs. In other words, the arrival of migrants from the steppes did not lead to large-scale and long-term shifts in the genetic heritage of European dogs. The researchers suspect that factors such as trading patterns, preferences for particular types of dog, variations in susceptibility to infectious diseases, or the adoption of local breeds by the incoming population could account for this striking finding.
When, where and how often wolves were domesticated by humans are issues that remain controversial. The fact that dogs had already diversified into several different lineages prior to 11,000 years ago points to a long prehistory during the Paleolithic period. "Our data support the idea that dogs were domesticated only once, and subsequently dispersed across the globe together with humans," says Frantz. In his view, the question of where the initial domestication took place is still an open one, which requires further investigation.

Ludwig-Maximilians-Universitaet (LMU) in Munich researchers have developed photoresponsive derivatives of the anticancer drug Taxol®, which allow light-based control of cytoskeleton dynamics in neurons. The agents can optically pattern cell division and may elucidate how Taxol acts.
The cells of higher organisms rely on three dynamically reconfigurable systems of protein filaments (collectively referred to as the cytoskeleton), which play crucial roles in all fundamental cellular processes involving motion and directionality. One of these systems consists of massive hollow polymer tubes called microtubules, which are in turn made up of globular subunits called tubulins. Microtubules serve as highways for intracellular transport of mitochondria, neurotransmitters and other biochemical cargos - and coordinated microtubule assemblies form the spindle apparatus that is responsible for the ordered segregation of chromosomes to the daughter cells during cell division (mitosis). Hence, compounds that bind specifically to microtubules and stabilize or destabilize them, provide vital tools for research on cellular cargo trafficking, regulation of mitosis and patterning of embryonic development. Such compounds also find application as powerful anticancer drugs that inhibit tumor-cell proliferation - and drugs such as paclitaxel (Taxol), vinca alkaloids, epothilones, auristatins and dolastatins have been used to treat millions of cancer patients worldwide.

"The problem with using these drugs as research tools is that they are not precise enough to tell us what we need to know," says Oliver Thorn-Seshold, who is in LMU's Department of Pharmacy. Biology is regulated at the subcellular level and with extreme temporal accuracy, but these drugs act on all the cells they reach, and it has not been possible to modulate their dynamics over time. Now, he and his colleagues have solved this problem. In cooperation with Dirk Trauner (New York University) and Anna Akhmanova (Utrecht University), he has developed light-responsive analogs of these drugs, which can be locally activated at specific times. This allows one to control their interactions with microtubules far more precisely. "These light-responsive reagents give us access to a range of powerful, high-precision biology studies," explains Thorn-Seshold. The researchers have used their light-responsive compounds to optically control cell division, cell survival, cytoskeleton structure and remodelling rates down to the level of individual cells, and even to subcellular regions in neurons.

By developing light-responsive analogs of one of the most powerful and clinically important anticancer drugs - paclitaxel, a taxane class drug that stabilizes microtubules - the team hopes also to impact applied research. These high-precision photoresponsive taxanes may be useful for decoding how the clinical drugs exert both their desirable antitumour activity, and their undesirable side-effects, which are primarily caused by damage to neurons. "Since our photoresponsive analogues are also powerfully active in neurons, but can uniquely be applied to selected neurons within a given sample for tightly controlled studies, we believe that our compounds will give us a better understanding of how these side-effects arise," Thorn-Seshold says.

The new compounds are the latest in a set of high-precision, light-responsive cytoskeleton research reagents developed by Dr. Thorn-Seshold and Prof. Trauner since 2013. Taxol is a difficult molecule to work on, because only a few modifications can be made easily. Most modifications could require months or years of effort to synthesize, before even a single compound can be tested. "Taxanes are also very water-insoluble compounds, which makes them tricky to apply reliably to cells or animals; we struggled to tune our compounds' polarity and solubility, and still cannot explain the patterns we observed," Thorn-Seshold explains. However, the researchers are confident that this new reagent approach brings significant benefits. "There are important differences in both the biological and therapeutic effects of microtubule destabilisers, such as those we previously developed, compared to the stabilisers we have now created." By bringing microtubule stabilisation under high-precision control, Thorn-Seshold and his colleagues are convinced that these new reagents will open up entirely new perspectives for cell biology research on topics where temporally or subcellularly specific roles of microtubules determine downstream biological effects, such as in cargo transport, cell migration, mitotic progression, and especially in neurobiology during neuron development or axonal regeneration.

Researchers at the University of São Paulo (USP) in Brazil have shown for the first time that stimulating expression of a protein naturally produced by the human body can be a strategy to combat loss of skeletal muscle mass, which happens normally with aging but can intensify in cases of neurodegenerative or inflammatory disease, or in patients who spend long periods in intensive care units (ICUs).

Ten days in an ICU are estimated to result in the loss of up to 20% of muscle mass in the legs and in important respiratory muscles such as the diaphragm. There are no drugs that can effectively treat these cases without severe side-effects. Only physiotherapy, breathing exercises, and electrostimulation can safely reverse ICU-acquired muscle atrophy.

“We were able to demonstrate that overexpression of protein kinase A [PKA] significantly improved muscle resistance to fatigue in mice. This is because PKA both suppresses FoxO proteins, which activate genes associated with atrophy and increases the formation of muscle fibers with augmented oxidative potential [respiratory capacity], thereby promoting hypertrophy and greater resistance to fatigue in specific muscles,” said Luiz Carlos Navegantes, a professor in the Physiology Department of the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP) and a co-author of the article on the research published in the journal FASEB J.

The study was supported by FAPESP and offers a new direction for the search for drugs that protect muscles from atrophy without severe adverse side-effects such as cardiac hypertrophy, tachycardia, heart attack, and even death.

“The beneficial role of PKA in muscles, which consists of stimulating anabolism and strength, is unique to all known proteins, making it a strategic target and object of study for the treatment of neuromuscular disease and pathological conditions that lead to weakness and muscle atrophy,” Navegantes told Agência FAPESP.

Metabolic relationship

The FMRP-USP research group, which is led by Professor Isis do Carmo Kettelhut, discovered 23 years ago that the hormone adrenalin not only breaks down energy sources such as lipids and carbohydrate but also inhibits degradation of the proteins in muscle fibers. “That was a paradigm shift,” Navegantes said. “Adrenalin had always been considered a hormone that mobilized energy, not one that prevented excessive breaking down of proteins, which would be catastrophic, especially if they maintain muscle contraction.”

Since they discovered that adrenalin protects muscles, the group has investigated the therapeutic potential of drugs similar to the hormone (sympathomimetics) but without managing to avoid adverse side-effects. “Everyone wants to preserve muscle proteins, from athletes who aim to increase muscle mass to patients who need their diaphragm to continue breathing normally,” Navegantes said. “However, these drugs can have effects that damage the organism and may even be deadly because of cardiac hypertrophy.”

The main problem with using synthetic adrenalin and sympathomimetics, he added, is that they have systemic effects and cannot be targeted to specific muscles. This was evidenced in another study conducted by the group in which the sympathomimetic formoterol was tested for chronic treatment of muscle mass loss and fatigue. In an article published in Cachexia, Sarcopenia and Muscle, the researchers described the effects of this drug, which is widely prescribed for asthma, and showed that it can also promote muscle growth and the strengthening of skeletal muscle.

“Muscles grew owing basically to two mechanisms: direct action of the drug inhibiting protein degradation, and increased secretion of insulin, a well-known anabolic hormone,” Navegantes said. “However, although sympathomimetics are extremely interesting to combat atrophy and have already been adopted in clinical practice, they can have adverse side-effects, especially cardiac hypertrophy, and chronic use of these drugs is therefore dangerous.”

Targeted action

The group decided to study PKA as a potential solution to the problem by means of selective gene transfer, targeting a specific muscle. “PKA was known to be activated by adrenalin and hence associated with lipid and carbohydrate breakdown for energy. However, PKA is located inside muscle cells and adrenalin is a circulating hormone. This difference enabled us to target the effect of PKA on a specific muscle in mice.”

In order for adrenalin to inhibit muscle degradation while also breaking down lipids and carbohydrates, PKA must be activated, Navegantes continued. The adrenalin attaches to a cell membrane receptor and sends a signal that leads to stimulation of PKA in the cytosol (intracellular fluid). Suppression of the genes associated with muscle atrophy is one of the final effects mediated by PKA in cell nuclei.

The researchers used electroporation to activate genes associated with PKA production not in all cells but in a single muscle. By this method, a plasmid was inserted in vivo by electric pulse into the muscle, where it modified the DNA of the muscle fiber. PhD candidate Dawit Albieiro Pinheiro Gonçalves learned the method during an internship in Italy with FAPESP’s support.

“It’s a technique used to prove hypotheses in live animals,” Navegantes explained. “You apply a pulse to the muscle you’re studying and introduce a plasmid that modifies the muscle’s genes [by genetic editing] so as to produce a protein of interest, in this case, PKA. In this manner, you can intervene selectively in a specific skeletal muscle without altering the animal’s other tissues.”

The intervention resulted in overexpression of PKA catalytic subunits (PKAcat) and growing oxidative fiber conversion, substantially improving resistance to muscle fatigue. “When we did the opposite, introducing a molecule called PKI that inhibited endogenous PKA, we observed activation of genes associated with atrophy and a reduction in muscle fiber area,” he said.

The discovery that PKA protects muscle fibers could lead to drug development. “We proved using electroporation that endogenous PKA inhibits loss of muscle mass. Next, we plan to study drugs that activate PKA, and to work with partners to conduct studies in clinical and experimental models, analyzing how it acts in aging and neurodegenerative diseases,” Navegantes said.

Solving the equations of general relativity for colliding black holes is no simple matter.

Physicists began using supercomputers to obtain solutions to this famously hard problem back in the 1960s. In 2000, with no solutions in sight, Kip Thorne, 2018 Nobel Laureate and one of the designers of LIGO, famously bet that there would be an observation of gravitational waves before a numerical solution was reached.

He lost that bet when, in 2005, Carlos Lousto, then at The University of Texas at Brownsville, and his team generated a solution using the Lonestar supercomputer at the Texas Advanced Computing Center. (Concurrently, groups at NASA and Caltech derived independent solutions.)

In 2015, when the Laser Interferometer Gravitational-Wave Observatory (LIGO) first observed such waves, Lousto was in shock.

"It took us two weeks to realize this was really from nature and not from inputting our simulation as a test," said Lousto, now a professor of mathematics at Rochester Institute of Technology (RIT). "The comparison with our simulations was so obvious. You could see with your bare eyes that it was the merger of two black holes."

Lousto is back again with a new numerical relativity milestone, this time simulating merging black holes where the ratio of the mass of the larger black hole to the smaller one is 128 to 1 -- a scientific problem at the very limit of what is computational possible. His secret weapon: the Frontera supercomputer at TACC, the eighth most powerful supercomputer in the world and the fastest at any university.

His research with collaborator James Healy, supported by the National Science Foundation (NSF), was published in Physical Review Letters [https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.125.191102] this week. It may require decades to confirm the results experimentally, but nonetheless it serves as a computational achievement that will help drive the field of astrophysics forward.

"Modeling pairs of black holes with very different masses is very computational demanding because of the need to maintain accuracy in a wide range of grid resolutions," said Pedro Marronetti, program director for gravitational physics at NSF. "The RIT group has performed the world's most advanced simulations in this area, and each of them takes us closer to understanding observations that gravitational-wave detectors will provide in the near future."

LIGO is only able to detect gravitational waves caused by small and intermediate mass black holes of roughly equal size. It will take observatories 100 times more sensitive to detect the type of mergers Lousto and Healy have modeled. Their findings show not only what the gravitational waves caused by a 128:1 merger would look like to an observer on Earth, but also characteristics of the ultimate merged black hole including its final mass, spin, and recoil velocity. These led to some surprises.

"These merged black holes can have speeds much larger than previously known," Lousto said. "They can travel at 5,000 kilometers per second. They kick out from a galaxy and wander around the universe. That's another interesting prediction."

The researchers also computed the gravitational waveforms -- the signal that would be perceived near Earth -- for such mergers, including their peak frequency, amplitude, and luminosity. Comparing those values with predictions from existing scientific models, their simulations were within 2 percent of the expected results.

Previously, the largest mass ratio that had ever been solved with high-precision was 16 to 1 -- eight times less extreme than Lousto's simulation. The challenge of simulating larger mass ratios is that it requires resolving the dynamics of the interacting systems at additional scales.

Like computer models in many fields, Lousto uses a method called adaptive mesh refinement to get precise models of the dynamics of the interacting black holes. It involves putting the black holes, the space between them, and the distant observer (us) on a grid or mesh, and refining the areas of the mesh with greater detail where it is needed.

Lousto's team approached the problem with a methodology that he compares to Zeno's first paradox. By halving and halving the mass ratio while adding internal grid refinement levels, they were able to go from 32:1 black hole mass ratios to 128:1 binary systems that undergo 13 orbits before merger. On Frontera, it required seven months of constant computation.

"Frontera was the perfect tool for the job," Lousto said. "Our problem requires high performance processors, communication, and memory, and Frontera has all three."

The simulation isn't the end of the road. Black holes can have a variety of spins and configurations, which impact the amplitude and frequency of the gravitational waves their merger produces. Lousto would like to solve the equations 11 more times to get a good first range of possible "templates" to compare with future detections.

The results will help the designers of future Earth- and space-based gravitational wave detectors plan their instruments. These include advanced, third generation ground based gravitational wave detectors and the Laser Interferometer Space Antenna (LISA), which is targeted for launch in the mid-2030s.

The research may also help answer fundamental mysteries about black holes, such as how some can grow so big -- millions of times the mass of the Sun.

"Supercomputers help us answer these questions," Lousto said. "And the problems inspire new research and pass the torch to the next generation of students."

The incidence of dementia in patients with rheumatoid arthritis is lower in patients receiving biologic or targeted synthetic disease modifying antirheumatic drugs (DMARDs) than in patients who receive conventional synthetic DMARDs, according to a new study. The study was presented at the virtual annual meeting of the American College of Rheumatology.

"Being on a biologic or targeted synthetic DMARD actually decreased your risk of incidence of dementia by 17% compared to patients who were on a conventional synthetic DMARD only," said lead study author Sebastian Sattui, MD, MS, a rheumatology fellow at Hospital for Special Surgery (HSS) in New York City. The study was done in collaboration with investigators from Weill Cornell Medicine and the University of Alabama at Birmingham.

Dr. Sattui said that the treatment in patients with rheumatoid arthritis has become more complex based on the understanding that rheumatoid arthritis has an impact well beyond what are thought of as the classical manifestations. Previous studies have suggested that inflammatory diseases such as rheumatoid arthritis can increase the risk for dementia and that TNF agents may have a role in preventing the incidence of dementia.

In the new study, researchers identified a cohort of patients with rheumatoid arthritis in Medicare claims data from 2006 to 2017. To be eligible, patients had to have continuous enrollment of at least 12 months in Medicare Part A, B and D, be at least 40 years of age and have no prior diagnosis of dementia.

In the sample of 141,326 eligible patients with rheumatoid arthritis, the crude incident rate of dementia was 2.0 per 100 person-years for patients on conventional synthetic DMARDs and 1.3 for patients on any biological DMARD. After adjusting for factors such as age, sex and other comorbidities, patients on biologic or targeted synthetic DMARDs had an adjusted 17% lower risk for dementia than patients on conventional synthetic DMARDs. No significant differences were observed between the different classes of biologic or targeted synthetic DMARDs, suggesting that decreased risk is possibly explained by the overall decrease in inflammation rather than a specific mechanism of action.

The researchers say clinicians should factor this new information into treatment decisions, but prospective studies are needed. "Our work shows yet another dimension in which treatment of rheumatoid arthritis can impact the overall health and quality of life of our patients," said Dr. Sattui. "Rheumatoid arthritis is a systemic disease and it can have cognitive implications. However, these complications seem to share similar pathways to those of articular disease, and the medications that we use to treat rheumatoid arthritis could be effective in the prevention of dementia in patients with rheumatoid arthritis. Future studies need to assess the impact of the interventions, such as the treat-to-target strategy, on the incidence of dementia in patients with rheumatoid arthritis."