Culture

The number of alien (non-native) species, particularly insects, arthropods and birds, is expected to increase globally by 36% by the middle of this century, compared to 2005, finds new research by an international team involving UCL.

Published in Global Change Biology, the study also predicts the arrival of around 2,500 new alien species in Europe, which translates to an increase of 64% for the continent over the 45-year period.

The research team led by the German Senckenberg Biodiversity and Climate Research Centre hope it should be possible to reduce this number with stricter biosecurity regulations.

Alien species are those that humans have moved around the world to places where they do not naturally occur. More than 35,000 such species had been recorded by 2005 (the date of the most recent comprehensive global catalogue). Some of these aliens can go on to become invasive, with damaging impacts to ecosystems and economies. Alien species are one of the main drivers of extinctions of animals and plants.

Co-author Professor Tim Blackburn (UCL Centre for Biodiversity & Environment Research and the Institute of Zoology, ZSL) said: "Our study predicts that alien species will continue to be added to ecosystems at high rates through the next few decades, which is concerning as this could contribute to harmful biodiversity change and extinction.

"But we are not helpless bystanders: with a concerted global effort to combat this, it should be possible to slow down or reverse this trend."

For the study, the research team developed a mathematical model to calculate for the first time how many more aliens would be expected by 2050, based on estimated sizes of source pools (the species that could end up becoming invasive) and dynamics of historical invasions, under a 'business-as-usual' scenario that assumes a continuation of current trends.

The model predicts a 36% increase in the number of alien plant and animal species worldwide by 2050, compared to 2005 levels.

The study identifies high levels of variation between regions. The largest increase is expected in Europe, where the number of alien species will increase by 64% by the middle of the century. Additional alien hotspots are predicted to include temperate latitudes of Asia, North America, and South America. The lowest relative increase in alien species is expected in Australia.

Europe will also see the largest increase in absolute numbers of alien species, with around 2,500 new aliens predicted.

Lead author Dr Hanno Seebens (Senckenberg Biodiversity and Climate Research Centre, Germany) said: "These will primarily include rather inconspicuous new arrivals such as insects, molluscs, and crustaceans. In contrast, there will be very few new alien mammal species such as the well-known raccoon."

Co-author Dr Franz Essl (University of Vienna) added: "Increases are expected to be particularly large for insects and other arthropods, such as arachnids and crustaceans. We predict the number of aliens from these groups to increase in every region of the world by the middle of the century - by almost 120% in the temperate latitudes of Asia."

The study also predicts that the rate of arrival of alien species will continue to increase, at least in some animal groups. Globally, by 2050, alien arthropod and bird species in particular will arrive faster than before, compared to the period 1960 - 2005. In Europe, the rate of new alien arrivals is expected to increase for all plant and animal groups except mammals.

Neither a reversal nor even a slowdown in the spread of alien species is in sight, as global trade and transport are expected to increase in the coming decades, allowing many species to infiltrate new habitats as stowaways.

Dr Seebens said: "We will not be able to entirely prevent the introduction of alien species, as this would mean severe restrictions in international trade.

"However, stricter regulations and their rigorous enforcement could greatly slow the flow of new species. The benefits of such measures have been shown in some parts of the world. Regulations are still comparatively lax in Europe, and so there is great potential here for new measures to curtail the arrival of new aliens."

Precariously balanced rocks (PBRs) are formations found throughout the world where a slender boulder is balanced precariously on a pedestal boulder. They form as blocks preserved on cliffs, or when softer rocks erode and leave the harder rocks behind. They can also form when landslides or retreating glaciers deposit them in strange positions.

Despite their delicate balancing act, many PBRs - like the Brimham Rocks in Yorkshire, or Chiricahua National Monument in Arizona - have survived earthquake shaking over thousands of years. They can therefore tell us the upper limit of earthquake shaking that has occurred since they were first formed - shaking that, were it strong enough, would have caused them to topple.

By tapping into ancient geological data locked within Californian PBRs, Imperial College London researchers have broken ground on a new technique to boost the precision of hazard estimates for large earthquakes by up to 49 per cent.

Earthquake hazard models estimate the likelihood of future earthquakes in a given location. They help engineers decide where bridges, dams, and buildings should be built and how robust they should be - as well as informing earthquake insurance prices in high-risk areas.

The findings are published today in AGU Advances.

Lead author Anna Rood, from Imperial's Department of Civil and Environmental Engineering, said: "This new approach could help us work out which areas are most likely to experience a major earthquake. PBRs act like inverse seismometers by capturing regional seismic history that we weren't around to see, and tell us the upper limit of past earthquake shakes simply by not toppling. By tapping into this, we provide uniquely valuable data on the rates of rare, large-magnitude earthquakes."

Current earthquake hazard estimates rely largely on observations like proximity to fault lines and how seismically active a region has been in the past. However, estimates for rarer earthquakes that have occurred over periods of 10,000 to 1,000,000 years are extremely uncertain due to the lack of seismic data spanning those timescales and subsequent reliance on rocky assumptions.

By counting rare cosmic ray-generated atoms in PBRs and digitally modelling PBR-earthquake interactions, Imperial researchers have created a new method of earthquake hazard validation that could be built into existing models to finetune their precision.

Rock clocks

To tap into the seismology of the past, the researchers set out to determine the fragility (likelihood of toppling due to ground shaking) and age of PBRs at a site near to the Diablo Canyon Nuclear Power Plant in coastal California.

They used a technique called cosmogenic surface exposure dating - counting the number of rare beryllium atoms formed within rocks by long-term exposure to cosmic rays - to determine how long PBRs had existed in their current formation.

They then used 3D modelling software to digitally recreate the PBRs and calculate how much earthquake ground shaking they could withstand before toppling.

Both the age and fragility of the PBRs were then compared with current hazard estimates to help boost their certainty.

They found that combining their calculations with existing models reduced the uncertainty of earthquake hazard estimates at the site by 49 per cent, and, by removing the 'worst-case-scenario' estimates, reduced the average size of earthquakes estimated to happen once every 10,000 years by 27 per cent. They also found that PBRs can be preserved in the landscape for twice as long as previously thought.

They conclude that this new method reduces the amount of assumptions, and therefore the uncertainty, used in estimating and extrapolating historic earthquake data for estimates of future risk.

Study co-author Dr Dylan Rood, of Imperial's Department of Earth Science and Engineering, said: "We're teetering on the edge of a breakthrough in the science of earthquake forecasting. Our 'rock clock' techniques have the potential to save huge costs in seismic engineering, and we see them being used broadly to test and update site-specific hazard estimates for earthquake-prone areas - specifically in coastal regions where the controlling seismic sources are offshore faults whose movements are inherently more difficult to investigate."

The team are now using their techniques to validate hazard estimates for southern California - one of the most hazardous and densely populated regions of the United States.

Anna said: "We're now looking at PBRs near major earthquake faults like the San Andreas fault near Los Angeles. We're also looking at how to pinpoint which data - whether it be fault slip rates or choice of ground shaking equations - are skewing the results in the original hazard models. This way we can improve scientists' understanding of big earthquakes even more."

The Arctic is warming two or three times faster than the rest of the planet. This amplified warming is due to several factors, but the relative importance of each one remains still unclear. "We do know, however, that clouds could play an important role," says Julia Schmale, an EPFL professor who heads the Extreme Environments Research Laboratory and holds the Ingvar Kamprad Chair. "By reflecting the sun's rays back into space or trapping heat close to the Earth's surface like a blanket, clouds help either cool off or warm up the planet."

Schmale - along with scientists from the Paul Scherrer Institute's Laboratory of Atmospheric Chemistry and Stockholm University's Department of Environmental Science and Bolin Centre for Climate Research - spent several weeks collecting data near the North pole in August and September 2018, as part of the US-Swedish expedition Arctic Ocean 2018 on board the Swedish icebreaker Oden. The scientists measured the chemical and physical properties of atmospheric molecules and aerosol particles to better understand the conditions leading to cloud formation.

How aerosols are formed in the Arctic

"One of our objectives was to investigate how new aerosol particles could form in the Arctic atmosphere," says Andrea Baccarini, a PhD student at the Paul Scherrer Institute and now scientific collaborator in the extreme Environments research Laboratory. "Under the right conditions, gas molecules condense together into small clusters that can grow, eventually forming aerosols." If these aerosols grow even just a small amount larger, they can function as cloud condensation nuclei, which are essential for cloud formation.

In the Arctic summer and fall, the concentration of aerosols is extremely low. "The contribution of newly formed aerosols can be extremely important and even a small change in aerosol concentration in the high Arctic could have a major impact on cloud formation or alter clouds' radiative properties," says Baccarini. It is also still not clear how important local aerosol processes are to cloud formation in comparison to regional or long-range transport, for example. "With this expedition, we could investigate the exact sources of aerosol particles that are needed to form clouds" adds Paul Zieger, an assistant professor at Stockholm University who led the research project on aerosol-cloud processes of the 2018 expedition.

Iodic acid appears in early fall

The research team found that iodic acid, a chemical compound which had not previously been observed in the region, triggers the formation of new aerosols between late summer and early fall. "There is less ice in the Arctic at the end of the summer, a lot of open water and the concentration of iodic acid is very low at that point," says Schmale. "Towards the end of August the temperature drops and the water starts refreezing, marking the beginning of the so called freeze-up period. This is when the iodic acid concentration sharply increases leading to frequent new aerosol particle formation events''.

The team developed a simple model to explain the variability of iodic acid in the atmosphere, which largely depends on local meteorological conditions. They were also able to describe the full chain of events that leads all the way from new particle formation to clouds, from the gas molecule that initially creates a particle to the formation of cloud condensation nuclei. "Observing and describing this process under real-world conditions was an extremely rare opportunity", says Schmale.

Memphis, Tenn. (September 30, 2020) - Researchers at the University of Tennessee Health Science Center working with colleagues at MD Anderson Cancer Center in Houston have found that some antibodies to SARS-CoV-2, the virus that causes COVID-19, are more protective than others, when it comes to reinfection.

This information, discovered from the joint study and published online in the Journal of Clinical Investigation's JCI Insight, has implications for the overall understanding of the virus and whether infection actually does trigger immunity, according to Michael Whitt, PhD, associate dean of the Office of Medical Education in the UTHSC College of Medicine, chair of the Department of Medical Education, and a professor and former chair of the Department of Microbiology, Immunology, and Biochemistry. Dr. Whitt is one of the principal investigators on the antibody study, which is ongoing at UTHSC.

Dr. Whitt and his laboratory team, which includes three fourth-year medical students and two Master of Medical Laboratory Science students, used an assay or test procedure developed in his lab roughly 25 years ago to study the infection mechanism of Ebolavirus. They applied that assay to study infection of and immunity generated against SARS-CoV-2. Dr. Whitt was contacted by researchers at MD Anderson to use his assay to test for the presence of neutralizing antibodies in samples from 134 hospitalized COVID patients and 464 healthy individuals obtained between June 2017 and June 2020.

"We ended up running samples for them (MD Anderson), and those data are presented in the paper," Dr. Whitt said. "Companies have developed assays to show whether people have SARS-CoV-2 antibodies, but these assays only provide a yes or no answer. So why is our work important? We can determine the amount of neutralizing antibody present in the blood, and neutralizing antibodies are the ones that can prevent the individual from becoming infected. If you have an antibody to an internal component of the virus, then that means you have been infected, but those antibodies won't prevent infection.

"Neutralizing antibodies are directed to the spike (S) protein, which is responsible for the binding of the virus to receptors on a host cell and for entry of the virus into the cell," Dr. Whitt explained. "However, not all antibodies to the S protein have neutralizing activity, so it is only a subset of antibodies to the S protein that can prevent infection. One of the questions we wanted to address is, do all people who have had the disease, COVID-19, generate neutralizing antibodies? That answer is clearly, no. The other question is, for those who do produce neutralizing antibodies, how much do they make?"

Further research will help answer questions about immunity. This is vital to plans for reopening the community.

"What we don't know is how much neutralizing antibody is needed to prevent infection or reinfection," Dr. Whitt said. "Just because you have detectable antibodies doesn't mean that you're protected from infection."

As a medical educator, Dr. Whitt said he is proud that the research in his lab has included students. "I think that speaks to the academic and training opportunities here at UTHSC," he said.

Along with Dr. Whitt, researchers in the Department of Microbiology, Immunology, and Biochemistry at UTHSC are working on ways to test the general population in Memphis for the SARS-CoV-2 antibody. Professor Maria Gomes-Solecki, DVM, and her team have developed and are vetting a prototype ELISA (enzyme-linked immunosorbent assay), a blood test that could be used to mass-test antibodies in the community that would signal individual exposure.

Colleen Jonsson, PhD, professor and the Van Vleet Chair of Excellence in Virology and director of the Regional Biocontainment Laboratory at UTHSC, is leading the efforts with live SARS-CoV-2 to identify neutralizing antibodies and therapeutics to treat COVID-19. Dr. Jonsson is the lead investigator on a protocol to perform testing of the general population in Memphis for the SARS-CoV-2 antibodies.

As many as 800 million children have dangerously high lead values in their blood. The neurotoxin can cause permanent brain damage.

The huge international numbers come from a new report from Pure Earth and UNICEF. Pure Earth works to solve pollution problems that can be harmful to humans.

"A child's earliest years of life are characterized by rapid growth and brain development. This makes children particularly vulnerable to harmful substances in the environment," says Kam Sripada, a postdoc at the Norwegian University of Science and Technology (NTNU) who has contributed to the report.

Sripada collaborates with international organizations to research social health inequalities, especially among children.

"Exposure to lead during pregnancy and early in life can lead to a child never reaching his or her potential," she says.

Sripada works at NTNU's Center for Global Health Inequalities Research (CHAIN) in collaboration with the Norwegian Institute of Public Health and UNICEF.

Lead is an element, but also a powerful neurotoxin that can cause damage at a level as low as five micrograms of lead per decilitre of blood. Lead poisoning can be acute, and can cause everything from stomach pain to brain damage, coma and death.

But lead poisoning can also come on slowly, because it accumulates in the body over a long period of time. The most common symptom is lethargy due to anaemia. High lead levels can attack blood and bone marrow, the nervous system and the kidneys.

Lead poisoning can also contribute to a lower IQ and behavioural problems that can last a lifetime.

"Lead is a health threat to children in every single country in the world. However, children in low- or middle-income countries are the most vulnerable, especially in South Asia and among marginalized groups in general. There are major social differences when it comes to lead exposure and other environmental toxins that we need to address," says Sripada.

A lot of the lead comes from lead-acid batteries that are not responsibly recycled. The number of motor vehicles has tripled in low- and middle-income countries in the last 20 years, which in turn has led to a sharp increase in lead-containing batteries. About half of the batteries are not properly recycled or recovered.

Water pipes, industry, paint and a number of household products such as canned foods, contaminated spices, make-up and toys also contribute. Lead that was previously used in gasoline is still found in the soil to this day.

Indirectly, countries can suffer enormous income losses as the children grow up with these sources of lead exposure. As adults, they often are not able to contribute optimally to the societal economy.

"This is a report with global significance," says NTNU Professor Terje Andreas Eikemo, who heads CHAIN.

Both the World Health Organization (WHO) and the Centers for Disease Control and Prevention in the United States believe that the situation requires international measures, such as more information and strengthening of the health care system in several countries.

"This report shines the spotlight on lead as an important global environmental and health problem that is especially tied to children's health and development," says Heidi Aase, who heads the NeuroTox study at the Norwegian Institute of Public Health.

The NeuroTox study examines relationships between environmental toxins in the mother's womb, including lead, and various measures of brain development. ADHD, autism and cognitive functions are considered in a large sample of Norwegian children. Environmental toxins found in the mother's body during pregnancy can affect the baby's development.

CHAIN will use the NeuroTox study to study relationships between socio-economic factors, such as income, education and living conditions, and levels of lead and other environmental toxins in pregnant women and their children.

"The UNICEF report and other studies show that poverty is associated with higher lead levels and an increased risk of harmful effects on health. We'll investigate whether this picture applies to pregnant women and children in Norway as well," says Aase.

The research results from NeuroTox and CHAIN can also be used in different ways internationally, such as to prevent social inequality in health including the harmful effects of environmental toxins.

The average blood levels of lead in children from low- and middle-income countries in the UNICEF report are far higher than in Norwegian children. Nevertheless, the report has calculated that many Norwegian children may have lead levels above the limit that we know has harmful effects on brain development.

"This is concerning," says NeuroTox researcher Gro Dehli Villanger.

Studies show that damage to the brain and nervous system can occur at far lower lead levels than the limit used in the report.

"As of today, no value limit has been established that is considered safe and therefore the number of children affected could be much higher both in Norway and in other countries," says Villanger.

Source: The toxic truth. Children's exposure to lead pollution undermines a generation of future potential. https://www.unicef.org/reports/toxic-truth-childrens-exposure-to-lead-pollution-2020

SAN FRANCISCO, CA--September 30, 2020--Unlike most T cells, which launch immune responses against foreign molecules, regulatory T cells are the peacekeepers of the human immune system, damping down inflammatory reactions when they're not needed. Now, researchers at Gladstone Institutes, in collaboration with scientists at UC San Francisco (UCSF) and the Technical University of Munich (TUM), have mapped out the networks of genes that help differentiate regulatory T cells from other T cells. Their findings could lead to immune therapies that strengthen or weaken the function of regulatory T cells.

"Piecing together the genetic networks that control the biology of regulatory T cells is a first step toward finding drug targets that change the function of these cells to treat cancer and autoimmune diseases," says Director of the Gladstone-UCSF Institute of Genomic Immunology Alex Marson, MD, PhD, a senior author of the study.

All T cells, named because they develop in the thymus gland, have similar receptors on their surfaces and play a role in the immune responses that destroy viruses, bacteria, and some cancer cells. But regulatory T cells have a distinct function, acting as a brake to suppress other T cells so that immune reactions don't go overboard. Studies in mice have suggested that increasing the number of regulatory T cells--and therefore putting stronger "brakes" on the immune system--might help subdue symptoms of autoimmune diseases. On the other hand, blocking regulatory T cells, or lifting these molecular brakes, is suspected to help the immune system better fight cancer.

Therapies that boost populations of regulatory T cells--by removing the cells from patients' bodies, expanding them, and infusing them back in--are already being tested in people with autoimmune disease, including type 1 diabetes, and organ transplant recipients. So far, however, such treatments generally haven't involved actually altering the function of the immune cells.

"Most of our previous knowledge about regulatory T cells is from mouse models," says Kathrin Schumann, a co-first and co-corresponding author of the paper and former UCSF postdoctoral fellow, now an assistant professor at the Technical University of Munich. "We wanted to genetically dissect human regulatory T cells to better understand how they're wired and how we can manipulate them. Once we understand the functions of each gene, we can precisely edit cells to treat disease."

In the new study, published in the journal Nature Immunology, Marson, Schumann, and their collaborators used CRISPR-based gene-editing technology to alter regulatory T cells, selectively removing any of 40 different transcription factors. The 40 transcription factors--master genes that control the activation of many other genes--were chosen because previously published data had already hinted that they might perform specific functions in the regulatory cells compared to other T cells.

The researchers then focused on the 10 transcription factors that had the strongest effect in this initial screen, and looked across tens of thousands of genes to see which ones were turned on or off in the altered cells. In all, they performed this analysis on 54,424 individual regulatory T cells.

By analyzing the subsets of genes activated or silenced by these 10 original transcription factors, the team put together vast networks of genetic programs involved in the biology of regulatory T cells. Among the most surprising results, the study revealed that the little-studied transcription factor HIVEP2 has a strong effect on regulatory T cell function. In follow-up studies in mice, the scientists found that removing the HIVEP2 gene reduced the ability of the regulatory T cells to quell inflammation.

"This was a significant hit," said Sid Raju, a co-first author of the paper and former UCSF computational biologist who is now a graduate student at the Broad Institute of MIT and Harvard. "This gene had really never been implicated in regulatory T cell biology before."

The team also says their study acts as a proof-of-principle for how powerful the combination of CRISPR gene editing and the analysis of individually edited cells can be in studying the genetics of human biology and human disease.

"Now, we can theoretically take any specialized cell from the body and start removing individual genes and study the consequences on the cells in much finer detail than ever before," says Marson. "This really opens up human cells removed from the body as a tractable experimental system."

The cathedral in Odense, Denmark, has for nine centuries held the relics of the Danish King St. Canute the Holy and his brother Benedikt. They were both murdered here in AD 1086, and just a few years later, in AD 1100, King Canute was sanctified.

The history of the relics has been that of turmoil at times, varying from initial worship of the Catholic believers to being walled up and hidden after the protestant reformation in AD 1536.

Since the 19th century the brothers' wooden shrines have been on display in the cathedral as heritage objects of national importance.

Now, researchers have examined some of the textiles in the two shrines. They conclude that King Canute's shrine no longer holds the precious silk textiles placed in it at his enshrinement.

In stead it is likely that the textiles from his brother's shrine at some point have been moved to King Canute's shrine.

The shrines of Canute and Benedikt have long been a puzzle in Danish history. They both contain several well-preserved textiles of silk and linen and the question is: How old are the textiles and what is their historical context?

According to historical sources, both brothers were covered in valuable textiles when enshrined. Sources have described how Canute's shrine in AD 1536 was lined with beautiful and rare silk.

Decades later, both shrines were walled up in the cathedral, placed vertically so that the bones and textiles lay in a heap at the bottom of each shrine, and hereafter there are no reportings of the precious textiles in King Canute's shrine when it was re-examined in AD 1694 and AD 1833.

- It is tempting to suggest that the king's precious textiles have been stolen at some point after AD 1582, says professor and an expert in archaeometry, Kaare Lund Rasmussen from University of Southern Denmark.

When the two shrines were removed from their walled up hiding places and prepared to be put on display in 1874, researchers at the time were puzzled by the absence of valuable textiles in King Canute's shrine - his brother Benedikt had the more valuable textiles - and they declared themselves unable to judge in which of the shrines the found fabrics belonged.

They decided to move the best textiles from Benedikt's shrine to King Canute's shrine, so that he could be presented with the most beautiful, most precious textiles when on display under a glass lid.
Professor Kaare Lund Rasmussen and colleagues have performed chemical analysis of the textiles in both shrines and conclude that they are of the same age, and that their age fit with AD 1086, when the two brothers were enshrined.

- Put together with historical sources this convinces us that today, King Canute lies in his shrine with what is actually his brother's burial textiles, says professor Kaare Lund Rasmussen.

Among the textiles, intended for Benedikt but later placed with Canute, are a pillow with birds and a textile called the Eagle Silk.

- They are exquisite and beautiful, but King Canute's textiles must have been even more exquisite, says Kaare Lund Rasmussen.

According to senior researchers at the Danish National Museum, Ulla Kjær and Poul Grinder-Hansen, the luxurious silks may have been sent from South Italy to the shrines in Denmark by King Canute's widow, Edel, possibly brought home by Canute's half-brother, King Erik 1. Ejegod.

At the time of Canute's canonization and enshrinement, silk weaving in Europe was not yet established outside the boundaries of the Byzantine Empire and silk was both a precious and much-coveted import article.

HARTWELL, Georgia--A new survey among vascular access (VA) and emergency department (ED) clinicians has revealed significant levels of variation in ultrasound-guided peripheral IV (UGPIV) practices and supply use across hospitals and alternate care settings. Published in the September issue of the Journal of the Association for Vascular Access, the findings carry critical implications for patient safety.

A total of 1,475 VA and ED practitioners responded to the survey, which was designed to gain better insight into clinicians' current practices regarding UGPIV insertion. The survey also identified inconsistencies in supply use across hospital departments. The survey was conducted by Nancy Moureau, RN, PhD, an internationally recognized expert and consultant in vascular access and CEO of PICC Excellence.

"Identifying gaps and variations in clinical practice forms the basis of quality initiatives intended to improve patient safety. This survey revealed clinically meaningful differences in all variables for UGPIV procedures and supplies," said Dr. Moureau. "Aseptic technique is essential for minimizing contamination, but its effectiveness is diminished if it's not done in a consistent manner. Often inconsistencies in supply usage point to variation in policy application and the potential for substandard practices. The survey results suggest a need for clinical education on the application of UGPIV guidelines, and for greater scrutiny over supplies and techniques in order to promote standardization."

The lack of consistency revealed by the survey is apparent in respondents' varied use of transducer protection and gel. To minimize contamination during UGPIV insertions, current guidelines -- such as those from the American College of Emergency Physicians and the American Institute of Ultrasound in Medicine -- recommend use of a transducer cover and single-use gel packets (sterile or non-sterile). According to the survey, however, just 59 percent of VA clinicians and 11 percent of ED clinicians always use a sterile probe cover during UGPIV procedures, and only 64 percent of VA personnel and 13 percent of ED personnel use sterile gel. In addition, more than 22 percent of respondents stated that they vary between multi-use gel bottles and single-use gel packets, both sterile and non-sterile.

The survey results also highlight issues resulting from the presence of gel in the area of the sterile insertion site. Among the respondents, 41 percent of VA clinicians and 51 percent of ED clinicians reported instances of inadequate gel removal, which results in securement and dressing adherence issues. Poor adherence of dressings can lead to catheter failure and accidental dislodgement. Over half of all VA personnel (52 percent) said they felt that aseptic technique is often compromised by post-procedure gel clean-up.

PIV insertion is the most commonly performed invasive medical procedure among hospitalized patients. Over 70 percent of acute care patients require IV access at some point during their stay. According to Dr. Moureau, up to 60 percent of those patients may be considered to have difficult vascular access (DiVA). These patients frequently require ultrasound guidance in order to successfully achieve peripheral access and receive necessary treatments.

"This study confirms that the lack of consistent, evidence-based guidelines regarding ultrasound-guidance for PIV insertions has led to a great deal of fragmentation, and shows that clinicians are confused over when and how to use this technology in a way that protects patient safety," said emergency vascular access expert Jon Bell, RN, MSN, VA-BC. "There needs to be an objective standard for identifying difficult access patients, as well as a multi-disciplinary effort to conduct research to determine the best practices that will minimize harm to the patient."

The use of ultrasound may increase the risk of contamination during PIV insertions if certain guidelines are not followed to maintain a sterile insertion site and use the appropriate supplies (gel and transducer protection). According to Dr. Moureau, a specialty gel-free insertion dressing that separates the transducer and gel from the insertion site (UltraDrape, Parker Labs) may address and even mitigate many of these issues while reducing the cost of performing UGPIV insertions. In this study, 9 percent of survey respondents reported use of this gel separation safety dressing.

The survey results align with recent concerns from the healthcare quality and safety organization, ECRI (Plymouth Meeting, PA). The nonprofit technology assessment group addressed the issue of standardization in its list of top patient safety concerns for 2020, writing that "policies and education must align across care settings to ensure patient safety."

ECRI also included the use of point-of-care ultrasound in its briefing on 2020 Top 10 Health Technology Hazards, and noted that the rapid adoption of this technology across various care settings has left many organizations struggling to keep up with appropriate safety measures.

Kanazawa, Japan - Bone infections caused by implants are difficult to treat and usually require a prolonged course of antibiotic treatment. In a new study, researchers from Kanazawa University discovered that implant-related bone infections can be effectively treated with a combinational treatment consisting of antibiotics and antibiotic-laden stem cells.

Bone fractures often require implants for stabilization and effective healing of the broken bone. However, implants can cause serious bone infections, such as osteomyelitis, that can only be managed with a prolonged antibiotic treatment. This in turn bears the risk of contributing to the development of antibiotic-resistant bacteria. While major efforts are currently underway to develop new antibiotics that cover these antibiotic-resistant bacteria, a different path has been to study the antibiotic effects of stem cells. One type is the so-called mesenchymal stem cells that naturally reside in the bone marrow and adipose tissue, among others, and that have been shown to possess antimicrobial properties.

"Adipose-derived stem cells, or ADSCs, have the distinct advantage of being abundant in subcutaneous adipose tissues and can thus be easily harvested," says the corresponding author of the study Tamon Kabata. "The goal of our study was to investigate the therapeutic effects of ADSCs in combination with the antibiotic ciprofloxacin in an animal model of implant-related bone infection."

To achieve their goal, the researchers first focused on the effects of ciprofloxacin on ADSCs and found an efficient, time-dependent loading of ADSCs with the antibiotic in the first 24 hours with no adverse effects of ciprofloxacin on the function or viability of the stem cells. The researchers then tested the antimicrobial activity of the antibiotic-loaded ADSCs in vitro (in a tube) and found that they effectively decreased the growth of the bacterium S. aureus, which is also the main microbe causing bone implant-related infections.

But could this novel approach also mitigate implant-related infection in a living organism? The researchers tested this on rats, who received bone implants using screws coated with S. aureus bacteria. The rats developed osteomyelitis 7 days after surgery. Then, the researchers administered one of the following to the animals: ADSCs loaded with ciprofloxacin, ADSCs alone, ciprofloxacin alone, or no treatment at all. Because osteomyelitis can lead to soft tissue swelling and abscess formation at the site of the infection, the researchers quantified the extent of the disease in the animals and found that only ADSCs loaded with ciprofloxacin presented as an effective treatment. Using the imaging modality micro-computed tomography to visualize the affected bones, the researchers further found that ADSC-loaded ciprofloxacin decreased the appearance of osteolysis, or bone degradation, which is not only important for bone health, but also for the stability of the implant.

"These are striking results that show how ADSCs can efficiently be loaded with antibiotics to exert a strong antimicrobial effect. Our findings suggest a potential novel therapy for implant-associated osteomyelitis, for which conventional treatment with only antibiotics is usually insufficient," says Kabata.

As the level of understanding about climate change has increased, the term "climate security" has been increasingly used in the rapidly growing literature on this subject. Although Japan has officially acknowledged the importance of tackling climate change, discussion of climate security has been almost nonexistent among Japanese governmental officials, politicians, and academics. Our aim was to trace discourses related to climate security in Japan to determine why so little exists in Japan and whether or not such discourse could suggest new areas for consideration to more comprehensively respond to the climate change problem.

Because of different interpretations and uses of the term "climate security" in the existing literature, we first categorized existing approaches to climate security into four types and used this categorization to examine Japan's discourse from these perspectives (Table 1). Two of the approaches, namely "long-term irreversible planetary changes" and "short-term abrupt risks to individuals", had been considered in Japan previously but without specific reference to the term climate security. The other two, "cause of conflict and violence" and "impacts to military and defense organizations", however, had not been used and need to be included in discussions of climate change in Japan.

Some of the topics not discussed in Japan include indirect economic losses of Japanese industries via supply chains, loss of Japan's exclusive economic zone due to sea-level rise, and the potential inflow of refugees resulting from extreme weather patterns outside of Japan.

Breast cancer is one of the most common cancers among women in the U.S. It's also the most costly cancer to treat. Now, Jefferson researchers have shown that although the use of an effective and less expensive treatment is on the rise, some patients, specifically Black women and those without private insurance are offered the beneficial therapy less often. The findings pave the way for reducing healthcare costs and increasing patient satisfaction.

"We have identified patient populations at risk of not receiving a beneficial and more cost-effective therapy," says Dr. Alliric Willis, a surgical oncologist and associate professor of surgery at Sidney Kimmel Medical College (SKMC) - Jefferson Health, who led the study along with his research team from SKMC and the College of Population Health at Thomas Jefferson University.

"This research really illustrates that not all patients are being treated equally," says Dr. Willis, who published the results online September 12, 2020 in the International Journal of Radiation Oncology Biology Physics, also known as the Red Journal.

Standard breast-conserving cancer treatment involves surgery followed by radiation therapy, which helps to lower the risk of cancer recurring in the treated breast. Traditionally, patients receive 25 to 30 daily radiation treatments over five to six weeks. In recent years, however, doctors have begun using an alternative radiation treatment plan known as hypofractionated whole breast radiation (HR).

HR uses a higher radiation dose per treatment than the traditional regimen. The higher dose means patients require about half as many treatment sessions -15 to 16 treatments over three to four weeks - to achieve the same total dose. Compared with traditional radiation therapy, the approach is just as effective at reducing the risk of the cancer returning, more cost-effective and offers patients fewer side effects and better breast restoration outcomes following treatment.

"Despite the fact that both patients and practitioners say they prefer hypofractionated radiation because of its efficacy and better cosmetic outcomes, HR use in the U.S., while increasing, has lagged for particular groups," Dr. Willis says.

To better understand who is at risk of missing out on the valuable therapy, Dr. Willis and colleagues turned to the National Cancer Database. The researchers examined data from nearly 260,000 early-stage breast cancer patients over 40 years old who were diagnosed between 2012 and 2016. All patients studied had received radiation treatment following breast conserving surgery. The researchers looked at demographics, tumor attributes and treatment facility characteristics between patients who received either HR or traditional radiation.

The investigation revealed that HR use increased over the four-year study period, from about a quarter of eligible patients in 2012 to more than two-thirds in 2016. Despite the upward trend, the analysis uncovered marked disparities among those who received HR therapy. Patients who identified as white were most likely to receive HR, whereas HR use was lowest for African Americans, for example.

"When we took all other factors into account, African American women were 15% less likely to be treated with HR than white women," Dr. Willis says. "This demonstrates that even though treatment guidelines do not take race into account, race is a factor in breast cancer treatment."

Socioeconomic status also affected those who received HR therapy. Patients with private insurance were more likely to receive HR than uninsured patients or those on Medicaid, according to the study. In addition, patients who lived in zip codes with the highest income levels were 25% more likely to undergo HR than patients from zip codes in the lowest income category.

Where patients sought care made a difference in their treatment, too. Treatment facilities associated with academic medical centers were twice as likely to use HR as community cancer or integrated network cancer facilities.

"This tells us that there is a need to actively communicate information to healthcare providers about the spectrum of treatment options across all treatment facility types," Dr. Willis says.

Dr. Willis hopes that this research will shine light on treatment inconsistencies and motivate physicians to expand their treatment repertoire.

"Patients should have access to all treatment options no matter their race, socioeconomic background or where they seek care," he says. "Hopefully, our research will help to address gaps in provider education and extend this favorable treatment to all patients."

In many patients with Crohn's disease abdominal fat migrates to the wall of the inflamed small intestines. What prompts the fat tissue to "creep" through the abdomen and wrap around the intestines of many patients with this inflammatory bowel disease (IBD) has been an enduring mystery.

Now, investigators have identified a critical clue. In a study published in the journal CELL this week, researchers from Cedars-Sinai show that the peculiar creeping activity of the fat appears to initially be protective but then ends up doing more harm than good.

"Creeping fat is often a landmark for surgeons performing resections on an IBD patient's bowels because they know when they see it, that's likely where the lesions are located," said Suzanne Devkota, PhD, principal investigator and lead author of the study. "But we don't know whether the presence of the fat is making the disease worse or trying to protect the intestines from something."

Devkota and a team of investigators performed in-depth molecular examinations of small intestine and fat tissue samples from 11 Crohn's patients who had undergone surgery. Adipose tissue - commonly known as fat -- is more than an energy storehouse. It is a dynamic endocrine tissue full of immune cells that appear to be triggered in certain cases of inflammatory bowel disease.

"We found that the adipose tissue is actually responding to bacteria that have migrated out of the patient's damaged intestines and directly into the fat. We believe the 'creeping' migration of the fat around the intestines is intended to try and plug leaks in the diseased organ to prevent the gut bacteria from getting into the bloodstream," Devkota said.

But the response that begins as protective apparently has no "off" switch. If the bacteria remains in the fat it will continue to migrate to a possible source of the gut bug. But the presence of the fat may be contributing to the development of severe intestinal scarring, or fibrosis, which occurs in 40% of Crohn's patients. Surgical removal of parts of the small bowel is the only option for many of them and it comes with life-changing consequences. Patients with ulcerative colitis, the other most common IBD, do not develop creeping fat.

The data led researchers to a specific microbe responsible for prompting the fat to travel to the small intestine and protectively encase the organ, imperiling its function.

"We identified a pathogen found in the digestive system, Clostridium innocuum, as the microbial invader that triggers the fat to creep over to the small bowel. Also, the structure of this particular infectious agent makes it well-suited for a lipid-rich environment," said David Underhill, PhD, co-investigator on the study and chair of Biomedical Sciences and the Janis and William Wetsman Family Chair in Inflammatory Bowel Disease at Cedars-Sinai.

This research could point the way to new therapeutics, Cedars-Sinai experts say.

"Improving the lives of our IBD patients is the goal of our research. We've identified a specific infectious agent that can trigger a process that makes Crohn's worse. This is a critical step toward the development of therapies that target C. innocuum, allowing us to prevent or minimize the damaging effect of creeping fat," said Stephan R. Targan, MD, director of the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute at Cedars-Sinai.

A study from the University of Pittsburgh School of Medicine and Cedars-Sinai addresses a mystery first raised in March: Why do some people with COVID-19 develop severe inflammation? The research shows how the molecular structure and sequence of the SARS-CoV-2 spike protein-part of the virus that causes COVID-19-could be behind the inflammatory syndrome cropping up in infected patients.

The study, published this week in the Proceedings of the National Academy of Sciences, uses computational modeling to zero in on a part of the SARS-CoV-2 spike protein that may act as a "superantigen," kicking the immune system into overdrive as in toxic shock syndrome-a rare, life-threatening complication of bacterial infections.

Symptoms of a newly identified condition in pediatric COVID-19 patients, known as Multisystem Inflammatory Syndrome in Children (MIS-C), include persistent fever and severe inflammation that can affect a host of bodily systems. While rare, the syndrome can be serious or even fatal.

The first reports of this condition coming out of Europe caught the attention of study co-senior author Moshe Arditi, M.D., director of the Pediatric Infectious Diseases and Immunology Division at Cedars-Sinai and an expert on another pediatric inflammatory disease-Kawasaki disease.

Arditi contacted his long-time collaborator, Ivet Bahar, Ph.D., distinguished professor and John K. Vries Chair of computational and systems biology at Pitt School of Medicine, and the two started searching for features of the SARS-CoV-2 virus that might be responsible for MIS-C.

Bahar and her team created a computer model of the interaction between the SARS-CoV-2 viral spike protein and the receptors on human T cells, the foot soldiers of the immune system. Under normal circumstances, T cells help the body fight off infection, but when these cells are activated in abnormally large quantities, as is the case with superantigens, they produce massive amounts of inflammatory cytokines-small proteins involved in immune system signaling--in what's known as a "cytokine storm."

Using this computer model, the team was able to see that a specific region on the spike protein with superantigenic features interacts with T cells. Then, they compared this region to a bacterial protein that causes toxic shock syndrome and found striking similarities in both sequence and structure. Importantly, the proposed SARS-CoV-2 superantigen showed a high affinity for binding T cell receptors-the first step toward touching off a runaway immune response.

"Everything came one after another, each time a huge surprise. The pieces of the puzzle ended up fitting extremely well," said Bahar, co-senior author on the study.

By finding protein-level similarities between SARS-CoV-2 and the bacterial structure that causes toxic shock syndrome, the researchers said they may have opened up new avenues for treating not only MIS-C patients, but also adults with COVID-19 infection experiencing cytokine storm.

The researchers also collaborated with scientists studying adult COVID-19 patients in Germany and found that those who experienced severe symptoms had a T cell response similar to what is seen in people exposed to superantigens and very different from the T cell response in patients who had only mild symptoms.

"Our research finally begins to unravel the potential mechanisms involved and raises the possibility that therapeutic options for toxic shock syndrome, such as intravenous immunoglobulin and steroids, may be effective for managing and treating MIS-C in children and hyperinflammation in adult coronavirus patients," said Arditi, professor of pediatrics and biomedical sciences at Cedars-Sinai.

Arditi's and Bahar's labs are now using the ideas generated by this study to search for and test antibodies specific to the SARS-CoV-2 superantigen, with the goal of developing therapies that specifically address MIS-C and cytokine storm in COVID-19 patients.

Whether flu or coronavirus, it can take several days for the body to ramp up an effective response to a viral infection. New research appearing in the journal Nature Immunology describes how different cells in the immune system work together, communicate, and - in the case of cells called neutrophils - bring about their own death to help fight off infections. The findings could have important implications for the development of vaccines and anti-viral therapies.

"The immune system consists of several different types of cells, all acting in coordination," said Minsoo Kim, Ph.D., a professor of Microbiology and Immunology at the University of Rochester Medical Center (URMC) and senior author of the study. "These findings show that cells called neutrophils play an important altruistic role that benefits other immune cells by providing key resources for their survival and, in the process, enhancing the body's immune response against a virus."

Neutrophils are a key component of the innate immune system, the part of the body's defenses that is always switched on and alert for bacterial and viral invaders. The vast majority of white cells circulating in blood are neutrophils and, as a result, these cells are the first on the scene to respond to an infection.

However, neutrophils are not fully equipped to eliminate a viral threat by themselves. Instead, when the respiratory tract is infected with a virus like influenza or COVID-19, a large number of neutrophils rush to the infection site and release chemical signals. This triggers the production of specialized T cells, which are part of the body's adaptive immune system, which is activated to produce a more direct response to specific infections. Once mobilized in sufficient quantities, a process that typically takes several days, these T cells target and ultimately destroy the infected cells.

The new study, which was conducted in mice infected with the flu virus, shows that in addition to jump-starting the adaptive immune response, neutrophils have one more important mission that requires that they sacrifice themselves. As T cells arrive at the infection site, the neutrophils initiate a process called apoptosis, or controlled death, which releases large quantities of a molecule called epidermal growth factor (EGF). EGF provides T cells with the extra boost in energy necessary to finish the job.

"This study represents an important paradigm shift and shows that the adaptive immune system doesn't generate a successful response without instruction and help from the innate immune system," said Kim. "The findings reveal, for the first time, how different immune cells work together, and even sacrifice themselves, to accomplish the same goal of protecting the host from the viral infection."

Kim and his colleagues point out that this new understanding of how the immune system functions opens the door to potential new methods to intervene and optimize the collaboration between different immune cells during viral infection. These efforts could ultimately lead to more effective vaccines and anti-viral therapies for respiratory infections like the flu and coronavirus.

Is it time to reframe the assisted dying debate?

Several articles published by The BMJ today explore the debate around assisted dying, in which, subject to safeguards, terminally ill people who are near to death, suffering, and of sound mind, could ask for drugs that they would take to end their lives.

The views expressed are the authors' own and do not reflect the position of any organisation that they are associated with.

Lucy Thomas is a consultant in public health who also works closely with patients with life-limiting illnesses and their families. This experience has led her to question why assisted dying is framed as a medical solution to a medical problem and to propose radically de-medicalising the debate.

She points to studies showing that physical symptoms are not predictive, or only weakly predictive, of the desire to hasten death, whereas depression, hopelessness, and perception of being a burden are the strongest predictors.

She argues that responding to a patient's expressed desire to end life in a fundamentally different way depending on whether or not they have a serious illness or disability institutionalises discriminatory attitudes about the relative value of different lives.

She states that "with medical criteria for what constitutes an acceptable reason for ending life, and with doctors as the arbiters and administrators, medically-assisted dying extends medical authority rather than enhancing patient autonomy, with deeply damaging unintended consequences".

So what happens if we challenge this profoundly medicalised perspective, she asks?

She believes that moving outside the medical frame "brings the fundamental ethical and practical dilemmas into focus, facilitating serious discussion about how society should respond to those with mental capacity and a consistent desire to end life prematurely."

Discussions should include philosophical issues such as what constitutes a rational decision to end one's life, as well as more practical questions such as how could we judge whether an individual's desire to end life is a response to circumstances that should be challenged rather than accepted, how could we predict that someone's desire to end life could never be reversed and, if society were to legalise assistance to end life, who would be best placed to provide it?

As with any issue as complex as this, there are no easy answers or simple solutions, concludes Thomas. "Acknowledging this profound complexity may be the first step towards a more constructive debate."

In a second article, Paul Cosford, Emeritus Medical Director at Public Health England explains how incurable lung cancer has prompted him to consider again his personal views on assisted dying.

"I never wanted to be a supporter of changing the law in favour of assisted dying," he writes. "I have always thought that the law is too blunt an instrument to deal well with the complexities of such difficult moral and ethical issues."

He points to the dangers - that assisted dying becomes an expectation, not just an option in certain clearly defined circumstances, and that the lives of people who are seriously ill, who live with disability, or are just different from the norm might be devalued.

These are genuine concerns, he says, but he is convinced that it is time to look at this again. "We need to set aside entrenched positions on each side of the debate and look openly at the problems faced by people at the end of their lives," he writes.

"We need to understand why rational, law abiding people sometimes feel compelled to travel to Switzerland for such care, often not telling their families why they are going. And we need to understand why their loved ones are sometimes prosecuted afterwards for helping them."

"Surely this tells us that our current arrangements are inhumane," he concludes. "I, among others, would be happy to help with such a review."

More open-minded and constructive conversations about end-of-life choice is also something that general practitioner Dr Zoe Norris calls for in a linked opinion article.

She acknowledges that doctors have expertise to offer on this important topic, but says "we must ensure the full breadth of opinion is represented, and we should not allow our contributions to the debate to drown out others' especially not those of our patients."

Regardless of our own personal views, "we cannot ignore the voices of those who have witnessed first-hand the horrific things that can happen when we deny people choice and control over their death," she writes. "I believe as doctors it is our duty to listen to them."

"The BMJ supports the legalisation of assisted dying," says Dr Fiona Godlee, Editor in chief. "The great majority of the British public are in favour and there is now good evidence that it works well in other parts of the world, as a continuation of care for patients who request it and are in sound mind.

"We believe that this should be a decision for Society and Parliament, and that medical organisations should adopt at least a neutral position to allow an open and informed public debate."