Earth

 Invasive alien species, defined as animals and plants that breed and disperse in a landscape beyond their native range, have negative environmental, social, and economic impacts. One example among many is the forage grass genus Brachiaria, originally African and introduced to Brazil to form cattle pasture. It has become a major threat to the survival of native species and biodiversity at several spatial scales. 

Complete eradication of invasive species is often impracticable. Attempts to do so have had undesirable consequences and even been damaging because merely withdrawing an invasive species does not restore the original environment, as in the areas of Cerrado (Brazilian savanna) invaded by pines. Instead of eradication, therefore, the goal should be continuous management, according to many experts. This is the line taken by researchers from Brazil, Argentina, Chile, and the United Kingdom, who have agreed on a strategic approach focusing on impact mitigation rather than elimination.

They call their project CONTAIN Latam. The name refers to the impossibility of eradicating invasive non-native species and the need for containment of their growth and impacts. 

The project resulted from a 2018 call for proposals issued under the aegis of a cooperation agreement involving FAPESP, the UK Natural Environment Research Council (NERC), UK Research and Innovation (UKRI), the Newton Fund, Argentina’s National Scientific and Technical Research Council (CONICET), Chile’s National Commission for Scientific and Technological Research (CONICYT), and Peru’s National Council for Science, Technology and Technological Innovation (CONCYTEC).

The initiative aims at developing management tools to optimize the control of invasive species in the medium to long term. The Brazilian members of the group are affiliated with São Paulo State University (UNESP) and coordinated by Alessandra Fidelis, a professor in UNESP’s Rio Claro Institute of Biosciences.

A study by the CONTAIN group is the subject of an article published recently in the journal BioScience. The study was supported by FAPESP via a research project for which Fidelis is principal investigator in Brazil.

“Our study set out not just to analyze invasive species but also to put forward guidelines for interaction with managers with the aim of containing proliferation of these species and mitigating their impacts,” Fidelis told Agência FAPESP.

The full definition stated early on in the article is that invasive species “successfully transition the three initial invasion stages (transport, introduction, and establishment) and subsequently establish multiple self-sustaining populations composed of individuals that breed, survive and disperse in a landscape beyond their native range”, and that a “subset” of invasive species produces an array of “negative environmental, social, and economic impacts at various spatial scales”. 

In this vast subset, the project focuses on the following: in Brazil, Brachiaria spp., Urochloa spp. and other grasses of African origin introduced as forage crops for cattle pasture, and pines (Pinus spp.) introduced from the northern hemisphere for reforestation and to produce pulp and resin; in Argentina, American mink (Neovison vison)  introduced for fur production, pines, and privet (Ligustrum spp.), of Asian origin and introduced here as a street tree, hedge or ornamental plant; in Chile, pines, mink, and the Yellowjacket or German wasp (Vespula germanica) whose origin is hitherto unknown.

“We propose six criteria for planning to mitigate their impacts. The first three comprise a detailed survey of the situation: mapping their presence and spatial distribution, finding out how long each invasive species has been present and compiling the available data on their impacts,” Fidelis said. “The next three relate to the recommended responses to the situation: the kinds of intervention that are technically, socially, and economically feasible, the potential negative consequences of these interventions, and a cost-benefit analysis of the interventions and their consequences.”

The COVID-19 pandemic has shone a bright light on the risks of degrading the natural environment and the urgent need to implement science-based policies for controlling and mitigating these risks. “In the case of the species on which our study focused, there’s a very strong additional reason for implementing such policies, as mink have been found to be transmitters of the novel coronavirus,” Fidelis said.

All this will evidently be ineffectual unless the knowledge produced by universities and research institutions can cross over from academia to society in general, and especially to those responsible for managing public and private affairs.

A new study from Boston Children's Hospital and the Massachusetts Department of Health compared one of the latest rapid antigen tests for COVID-19 -- the Abbott BinaxNOW -- with a highly accurate PCR test in a high-volume, drive-thru testing environment. They found that the rapid test detected almost all adults who tested positive by PCR if they had had symptoms lasting seven days or less. In symptomatic children with less than seven days of symptoms, the test picked up about 85 percent of true positive cases.

But no matter the age, if the patient had high amounts of virus in their nose, the test caught it 99 percent of the time. It was also able to rule out COVID-19 in almost all people who were not infected, including adults and children with and without symptoms.

"What this means is that if the BinaxNOW antigen test comes back with a positive result, that is a reliable true result," says Nira Pollock, MD, PhD, associate medical director of the Infectious Diseases Diagnostic Laboratory at Boston Children's Hospital, who co-led the study along with Dr. Sandra Smole, director of the Massachusetts State Laboratory. "For a negative test result, we need to think more carefully about exactly who we are testing and why."

Evaluation in a real testing environment

The Abbott BinaxNOW test is a nasal swab test that will be distributed widely throughout Massachusetts for rapid, on-site testing through funding provided by the Massachusetts Department of Public Health (DPH).

The study included 1,380 adults and 928 children who came for testing at a large drive-through community testing program run by DPH and Lawrence General Hospital in an area with a high rate of COVID-19. Each person received an anterior nasal swab -- one that swabs only the inside of each nostril, not farther back -- for BinaxNOW and another for PCR. The BinaxNOW test was performed on-site by trained operators, and the other swab was sent to the Broad Institute for PCR testing.

Viral load may explain the difference in testing results

In adults who had symptoms lasting seven days or less, the BinaxNOW test detected 96.5 percent of COVID-19 cases detected by PCR. In children, the number was 84.6 percent of cases, about a 12 percent difference.

But when the PCR tests were evaluated, they found that symptomatic adults and children had different viral loads, or amounts of virus in their nasal swabs.

Symptomatic adults tended to have high viral loads so they were almost all detected by the BinaxNOW test. But, the symptomatic children had a larger spread of viral burden in that first week of symptoms, which meant about 15 percent of them were missed. This likely means that the difference in detecting symptomatic adults and children -- 96.5 percent versus 84.6 percent -- was due to a difference in the viral load distribution between the two groups, not a problem with the rapid test itself.

Children may have more variable amounts of virus

"Researchers, including me, have found similar hints in other studies that children don't always have as much virus as adults -- but we need to collect more data in children to confirm these findings, since the number of symptomatic children in this study was relatively small," says Pollock. "I think it's possible that kids as a group don't produce the same reliably high viral loads as adults early after COVID-19 infection, but they certainly can. In this study, there were plenty of children that had tons of virus but as a group there were a few more of them that didn't. Therefore, the ability of the BinaxNOW test to detect a positive result was lower than it was in adults."

In asymptomatic adults, the test picked up about 70 percent of cases compared with 65.4 percent in asymptomatic children, which Pollock says is also likely to reflect the distribution of viral loads in people without symptoms -- since they don't have symptoms, they might end up getting tested early or late in their illness when the amount of virus present may be variable.

The researchers also learned that interpreting the BinaxNOW test did not vary depending on who performed the test -- two independent readers got the same answer every time. "That suggests to me that you do not need more than one person to do the test," says Pollock. "That's good to know in cases where this test may be used in a school nurse's office or another site where there is only one person available to do the testing."

What comes next

"Given the difference we saw between symptomatic adults and children, we need to think carefully about what to do in children who have a negative rapid test, and whether it might sometimes be necessary to supplement that rapid test with PCR testing," says Pollock. The same is true for potential use in asymptomatic adults and children where the detection rates are even lower. "Public health officials need to thoughtfully consider the prevalence of COVID-19 in a community and the specific goals of a community's testing program when deciding how to use this rapid test," she says.

Pollock expects that her DPH colleagues will consider use of the BinaxNOW test in adults and children with symptoms of seven days or less without recommending a PCR confirmatory test. The team thinks that given the current high rates of COVID-19 transmission in many communities, positive BinaxNOW results in anyone should be trustworthy; any positive test with BinaxNOW does not routinely need a PCR test to confirm it. DPH generally updates its testing guidance as new information becomes available for new tests. In any case, the BinaxNOW test is not recommended for use in adults or children with symptoms lasting longer than seven days.

March 1, 2021 - Benign bone tumors may be present in nearly 20 percent of healthy children, based on a review of historical radiographs in The Journal of Bone & Joint Surgery. The journal is published in the Lippincott portfolio in partnership with Wolters Kluwer.

Although that may sound frightening, non-ossifying fibromas and other common benign bone tumors in symptom-free children are harmless and may resolve over time, reports the new study by Christopher D. Collier, MD, of Indiana University School of Medicine and colleagues. "These findings provide unique evidence to answer many commonly encountered questions when counseling patients and their families on benign bone tumors," the researchers write.

Study offers reassurance that benign bone tumors in healthy children are harmless
Benign bone tumors are commonly detected in children incidentally on radiographs made for other reasons. Although some benign childhood bone tumors are classified as active or aggressive, these are usually discovered when they cause discomfort or pathologic fracture (caused by underlying disease).

When latent benign bone tumors are discovered incidentally in an asymptomatic child, the child is usually evaluated by a specialist, such as a pediatric orthopaedic surgeon or orthopaedic oncologist. For some specialists, children with benign tumors account for more than half of new patients.

"Understandably, these tumors cause a lot of anxiety for patients and families as they await confirmation that the tumor is benign," Dr. Collier says. "They need reassurance and often ask how common these tumors are, when did they first appear, and whether they will resolve over time? We don't have much evidence to date to address these questions."

The researchers analyzed a unique collection of radiographs from a study called the Brush Inquiry, in which a series of healthy, "normal" children in Cleveland, Ohio, underwent annual radiographs from 1926 to 1942. Although the Brush Inquiry provided valuable information on skeletal growth and development in children, such a study couldn't be performed today for ethical reasons, now that the risks of radiation exposure are recognized.

Close to a century later, the Brush Inquiry radiographs provide a unique opportunity to identify benign bone tumors and their outcomes over several years of follow-up. Dr. Collier and colleagues analyzed a total of 25,555 digitized radiographs in 262 children, followed from infancy to adolescence.

The results confirmed the high prevalence of benign bone tumors. A total of 35 benign bone tumors were found in 33 children - an overall rate of 18.9 percent when considering that only the left side of the children was radiographed.

More than half of the tumors were a type called non-ossifying fibromas, which are masses of connective tissue that have not hardened into bone. These fibromas tended to appear around age five, with another peak around the time of skeletal maturation, possibly related to changing growth rates. Of 19 non-ossifying fibromas detected, seven disappeared over time. Others may have resolved in the years after the children stopped undergoing annual radiographs.

Less-common benign bone tumors included enostoses, sometimes called "bone islands"; and osteochondromas or enchondromas, representing areas of abnormal but harmless cartilage growth. These tumors persisted through the last-available radiographs in all patients who had them.

The findings are generally consistent with previous studies of the rates of benign bone tumors in healthy adults. It is one of the first studies of benign bone tumors in children, and the only one to provide longitudinal follow-up, including the age at first appearance. Dr. Collier adds: "Despite the inherent limitations of our historical study, it may provide the best available evidence regarding the natural history of asymptomatic benign childhood bone tumors."

Click here to read "The Natural History of Benign Bone Tumors of the Extremities in Asymptomatic Children: A Longitudinal Radiographic Study."
DOI: 10.2106/JBJS.20.00999

Early exposure to tough conditions--particularly warmer waters and nightly swings of low oxygen--could leave lasting scars on oysters' ability to grow meaty tissue. A team of biologists at the Smithsonian Environmental Research Center (SERC) reported the discovery in a new study, published online Feb. 26 in the journal Ecological Applications.

Eastern oysters in Chesapeake Bay live mostly in shallow tributaries. It's a rough environment for shellfish that can't move. During hotter months, oxygen levels can swing drastically, from perfectly healthy levels in the day to near zero at night. To save energy, some oysters react by focusing more on shell growth than tissue growth. That could pose a problem for anyone involved in the seafood industry.

"What we all of course want to eat at the raw bar is the oyster tissue," said Sarah Donelan, a SERC postdoctoral fellow and lead author of the new report. "Customers and restaurants might be less pleased if there's less tissue in what looks to be a large oyster."

Total oyster growth suffered most when oysters experienced low oxygen alone. But early exposure left marks that were far easier to miss. There, researchers discovered a sharp drop in how fast oysters grow tissue versus shell. Oysters invested more in growing their shells--and less in the succulent, slurpable tissue inside--when exposed to the double punch of low oxygen and warmer waters both early and later in life.

Scars That Lie Dormant

For this study, Donelan teamed up with SERC senior scientists Matt Ogburn and Denise Breitburg. Ogburn studies conservation of oysters and other fishery species in Chesapeake Bay. Breitburg specializes in how fish and shellfish cope with the many environmental dangers that can coexist in the Chesapeake.

"Low oxygen and warming waters are a real double whammy for marine organisms," Breitburg said. "Warmer water holds less oxygen and causes oxygen to decline faster. At the same time, cold-blooded animals like oysters and finfish require more oxygen at warmer temperatures."

Donelan, an evolutionary biologist, wanted to find out if exposure to threats when very young could shape oysters later in life. Nightly swings of low oxygen put a special brand of pressure on the shellfish.

"If it's always bad, they can evolve over time to cope with those poor conditions," Donelan said. "But especially for [immobile] organisms like oysters, these fluctuations can be very stressful."

Donelan ran her experiment in a small lab SERC scientists affectionately call "The Room of DOOM" (the acronym stands for "Dissolved Oxygen Oyster Mortality"). It is a cramped, dark room filled with aquaria where biologists mimic conditions in shallow Chesapeake waters. Donelan took 3,600 young oysters, each about 3 months old, and exposed them to four possible scenarios. Some oysters experienced hotter water temps, some experienced nightly swings of low oxygen, some received both, and some got neither. After 18 days, Donelan gave the oysters a rest.

At first the oysters did not look any worse for wear. All oysters were roughly the same size regardless of whether they had been in hot water, oxygen-starved water or perfectly normal water. When Donelan estimated each oyster's shell and tissue size, she did not find any significant differences either.

But the effects of stress may simply have lain dormant. After a two-month break, Donelan put half the oysters back into experimental tanks. When faced with the same rough conditions again, oysters that had suffered from both low oxygen and hotter waters in Phase One started showing signs of strain.

The oysters managed to grow to a respectable size. But Donelan noticed something odd: Compared to more pampered oysters, oysters that suffered both stressors twice grew their shells more than their tissue. Their tissue-versus-shell growth ratio was merely half that of oysters that escaped the early double exposure.

It was a troubling find, because for oysters and oyster farmers alike, the meaty tissue is what really matters.

Ensuring A Safe Start

This raised a question for the biologists: Why would early exposure not toughen up the oysters instead? Donelan has spent her career watching animals adapt, and she's seen it work both ways. In this case, she suspects the combination of warming and low oxygen leaves a scar that does not easily heal.

"I think that there's likely a physiological change that's irreversible," Donelan said.

Perhaps a critical gene turned off--or turned on. Perhaps something in the oyster's microbiome shifted, making them less efficient at processing oxygen. Whatever went on behind the scenes, it pushed the oysters to grow their shells more than the tissue they need to survive and spawn more oysters.

Fortunately, oyster farmers have some options for protecting their stock. This could involve tracking oxygen levels in the water, to see which areas are vulnerable to low-oxygen swings. It could mean bubbling extra oxygen into oxygen-starved zones. For farmers with indoor systems, keeping young oysters in tanks and out of the field longer could offer more protection.

"Of course it's more of a time investment to have to move oysters around or look at dissolved oxygen profiles on your farm, but it could be worth it," Donelan said.

The key, she said, is to protect oysters while they are still young. Oysters that were not exposed to the warm water-low oxygen combo early in life fared much better when they faced the same combo later.

Meanwhile, oysters are not the only creatures that suffer these "carryover effects" from stress. They contain a telling message for conservationists: What other dangers could be headed off by protecting organisms while they are young?

In the middle of the Indian Ocean lies some of the last coral reef wilderness on Earth. The Chagos Archipelago, a collection of atolls, including Earth's largest - the Great Chagos Bank- is home to reefs that have been largely undisturbed by humans for the last 50 years. Some estimates indicate the Chagos Archipelago may contain more than half of the healthy coral reefs remaining in the entire Indian Ocean. These reefs are protected both by their remote location, and in one of the world's largest no-take marine reserves--the British Indian Ocean Territory (BIOT) marine protected area.

In 2015, scientists at the Khaled bin Sultan Living Oceans Foundation (KSLOF) came to the Chagos Archipelago to assess the status of the reefs. Over the course of two months at sea, an international team of scientists conducted thousands of surveys of the benthic and reef fish communities at over 100 locations across the archipelago. This research was conducted as part of the Foundation's Global Reef Expedition (GRE), a 5-year research mission that circumnavigated the globe to assess the health and resiliency of coral reefs.

"The Global Reef Expedition was designed to evaluate the status of the benthic and reef fish communities and assess the impact of anthropogenic and natural disturbances on coral reef ecosystems," said Alexandra Dempsey, the Director of Science Management at KSLOF and one of the report's authors. "One priority for us was to study reefs with minimal human disturbance, and there was no better place on Earth to do that than the Chagos Archipelago."

Their findings are detailed in a new report, the Global Reef Expedition: Chagos Archipelago Final Report, which contains detailed information on the diversity and abundance of corals and reef fish species along with valuable baseline data on the state of the reefs at a point in time.

What they found during the research mission were reefs with a stunning diversity of coral and an abundance of fish. Of all of the reefs surveyed on the Global Reef Expedition--the largest coral reef survey and mapping expedition in history--the reefs of the Chagos Archipelago were some of the most diverse and had some of the highest coral cover and fish biomass. They also had more fish per square meter than in any country studied on the GRE.

"When we first arrived in the Chagos Archipelago, the reefs were stunning," said Renée Carlton, Marine Ecologist at KSLOF and lead author on the report. "We saw reefs covered in a diverse assemblage of live coral, and surrounded by an astounding abundance of fish. It was refreshing to see such thriving reefs."

However, even here in what may be the most remote and well-protected reefs on Earth, there were signs of human impacts. Towards the end of the research mission, KSLOF scientists witnessed the beginning of what would become a catastrophic and global mass coral bleaching event, illustrating the expanse of the coral reef crisis. The data contained in the report released today are the last data collected in the Chagos Archipelago before this disastrous bleaching event caused mass coral mortality on the reefs.

"Of all the reefs visited on the Global Reef Expedition, those of the Chagos Archipelago were surely the most remote and the most undisturbed," said Sam Purkis, KSLOF's Chief Scientist as well as Professor and Chair of the Department of Marine Geosciences at the University of Miami's Rosenstiel School of Marine and Atmospheric Science. "To witness a coral bleaching event develop during our research mission was heart-wrenching, but there's compelling evidence that reefs which are spared direct human pressures such as overfishing and coastal development, have amplified resilience, so there was hope that the archipelago would bounce back to health relatively quickly."

During the first signs of bleaching, corals in the Chagos Archipelago turned cotton-candy colored shades of pink, blue, and yellow before turning white, as the corals tried to protect themselves from the sun's harmful rays after losing their symbiotic algae. As the warm waters persisted, the extent of the bleaching was readily apparent and impacted the vast majority of the shallow-water corals. A study shortly after the bleaching event found live coral fell dramatically from the relatively healthy 31-52% observed on the Global Reef Expedition, to only 5-15%. Since then, there have been promising signs the reefs are recovering, however, it is unlikely the reefs have returned to the same state they were in prior to bleaching.

The report released today will provide marine managers with information on what the reefs were like before the devastating bleaching event, so changes to the reef can be tracked over time and monitor how the ecosystem is recovering. The Foundation has shared the report with representatives from the BIOT Marine Protected Area (MPA) as well as scientists and conservation organizations invested in the preservation of these remarkable reefs.

The Global Reef Expedition mission to the Chagos Archipelago gave scientists the chance to study some of the most pristine coral reefs in the Indian Ocean. Their findings illustrate what reefs can be when protected in large no-take MPAs, but they also highlight the perils all reefs face in a changing world.

Tsukuba, Japan - Single-celled algae and animal sperm cells are widely separated in evolution but both swim in the same way, by waving their protruding hairs, called cilia or flagella. Motion is driven by molecular motors, complex assemblies of proteins that exert a force when changing shape. The motor proteins are connected to the cell's internal skeleton of microtubules; the moving force from the motor causes microtubules to slide, moving the flagella and propelling the cell.

Now a team led by Professor Kazuo Inaba of the University of Tsukuba in collaboration with scientists from Osaka University, Tokyo Institute of Technology and Paul Scherrer Institute has described a new protein that is closely associated with one class of motors, called dyneins. They recently published their findings in Science Advances.

The team isolated molecular motor complexes from sperm cells of a marine invertebrate, the sea squirt Ciona intestinalis. Among the components, they discovered a novel protein related to a protein with a blue-light sensing function, called BLUF. They named the new protein "DYBLUP" for dynein-associated BLUF protein. Comparing gene sequences, they found DYBLUP has been conserved during evolution across a wide range of organisms, from some fungi and algae to animals (but is not found in arthropods or higher plants).

Working with the single-celled alga Chlamydomonas, the team used powerful electron microscopy techniques to show that DYBLUP is part of the molecular tether linking the motor protein to the microtubules.

They then showed that DYBLUP is also involved in regulating the motor in response to light. Chlamydomonas cells normally swim towards dim blue light but away from bright blue light, which damages the cells. Mutant cells of the algae that lacked DYBLUP behaved like normal cells in dim blue light. Initially they avoided strong blue light, but over time they became accustomed to and were then strongly attracted towards it.

"We have discovered a new feature of molecular motors", says Professor Inaba, corresponding author. "Not only is DYBLUP conserved widely across different species, it's also involved in responses to light. In mutant Chlamydomonas cells without DYBLUP protein, it seems the linkage between the motor and the cell skeleton is partly broken, leading to uncontrolled beating of the flagella and altered cell behavior in blue light."

"Both the function and evolution of DYBLUP are fascinating," Professor Inaba continues. "Greater understanding of this protein might also open the way for new technologies to manipulate molecular motors, perhaps using light as a trigger."

Tokyo, Japan - Researchers from Tokyo Metropolitan University have revealed how liquid foams collapse by observing individual collapse "events" with high-speed video microscopy. They found that cracks in films led to a receding liquid front which sweeps up the original film border, inverts its shape, and releases a droplet which hits and breaks other films. Their observations and physical model provide key insights into how to make foams more or less resistant to collapse.

Understanding how foams collapse is serious business. Whether it's ensuring fire extinguishing foams stay long enough to put out flames, cleaning up toxic foams in seas and rivers, or simply getting the perfect rise on a cake, getting to grips with how foam materials collapse is vital to tailoring their properties, both to keep foams around longer or help them disappear quicker.

That's why a team led by Prof. Rei Kurita of Tokyo Metropolitan University have been carrying out high-speed video microscopy experiments on liquid foams. By generating foams sandwiched between two thin, transparent plates, they have direct access to the whole range of complex phenomena that occur when they begin to collapse. In previous work, they showed that a key way in which foams collapse is via the generation of droplets when individual films rupture. These droplets fly off at high speeds and break other surrounding films, leading to a cascade of breakages that cause the foam to break down. Yet, it was not yet known how exactly the droplets were formed. Importantly, it was not clear when droplets were formed, and when they weren't.

Now, the team has begun to unravel the complex mechanism behind how these droplets are made. When an initial crack forms in a film, the film recedes and leaves a wobbling line of liquid where the original film border was, named as the Released Vertical Plateau Border (RVPB). While it wobbles, there is an accumulation of liquid in the center of the RVPB. When a further crack is created in the remaining film, a receding line of liquid is created which sweeps up the RVPB (see Figure). Interestingly, videos showed that this front has a tendency to invert in shape as it travels. The team found that this is largely due to an inertial effect, as the heavier central part moves less under a constant force. Importantly, it is this inversion that ultimately causes a droplet to be released, initiating a cascade of film breakage events. Their work stands in contrast to previous investigations that looked at standing individual films; the accumulation of liquid in the middle of RVPBs is only possible inside foams, where liquid can be supplied by surrounding films and borders. The physical model they developed to describe the dynamics was shown to give reliable predictions of front velocity and relevant time scales.

Finally, the team replaced lab reagents with a household detergent and repeated the experiment, creating a much more long-lasting foam. When a bubble is burst at the side, they found a similar accumulation of liquid in the center of RVPBs, though significantly less than before. The enhanced elasticity of the film also meant it was extremely unlikely for two cracks to form in the same film; that meant no droplets were formed i.e. no collective bubble collapse: in light of the mechanism found above, this shows conclusively that both less transport within RVPBs and fewer cracks contributed directly to foam stability. Insights like these are vital for guiding the design of new foam materials with enhanced properties; the team hopes that their work may inspire state-of-the-art insulation materials, detergents, food products and cosmetics.

Treatments for beating tumours are mainly based on CD8 T lymphocytes, which specialise in detecting and eliminating intracellular infections and in killing cancer cells. A large proportion of patients, however, do not respond to these treatments. This prompted a research team from the Swiss Cancer Centre Léman (SCCL, Switzerland) to bring together the universities of Geneva (UNIGE) and Lausanne (UNIL), the Ludwig Institute for Cancer Research (LICR), EPFL and CHUV to investigate CD4 T lymphocytes. While these play a supporting role with CD8 T cells, their ability to eliminate tumour cells directly has been a matter of controversy. Using innovative nanoimaging technologies designed at the EPFL laboratory, the scientists found that when the CD4 T lymphocytes were directly put in close contact to the cancer cells, up to a third of them could also kill them. This discovery, the subject of an article in Science Advances, is significant and broadens the therapeutic perspectives based on administering CD4 T lymphocytes to patients who are resistant to conventional therapies.

When cancer cells proliferate in our bodies, our immune system kicks in. The first line of fighters capable of destroying tumour cells are CD8 T lymphocytes known as cytotoxic T cells, backed up by CD4 T lymphocytes. The latter secrete factors that help the former in many ways. "That's why lots of cancer treatments are based on CD8 T lymphocytes," begins Camilla Jandus, last author of the study and a professor in the Department of Pathology and Immunology in UNIGE's Faculty of Medicine and adjunct scientist at LICR. "Unfortunately, some patients don't respond to these treatments, and so we have to find new ones."

The SCCL team turned their focus to CD4 T lymphocytes, which offer invaluable support to our immune system, as Pedro Romero, a professor in the Department of Fundamental Oncology in UNIL's Faculty of Medicine and Biology, explains: "These have a much wider spectrum of functional specialisations than CD8 T lymphocytes, and for a long time we didn't know for sure whether they had the capacity to differentiate into killer lymphocytes."

20,000 individual "boxing rings"

To address this question, the scientists examined CD4 T lymphocytes from around twenty patients with melanoma who were being treated at CHUV. "Although melanoma isn't the most common skin cancer, it is the deadliest, and it's particularly sensitive to immunotherapies," spells out Professor Jandus. The researchers isolated the CD4 T lymphocytes from both the blood and fragments of the tumours with the idea of comparing them directly. Dissociated tumour cells and CD4 T cells were co-incubated to observe their behaviour individually. Observation tools were then required to provide highly-advanced resolution down to the single cell level. "We created chips of over 20,000 mini-wells of 65 picolitres (1 picolitre = 10-12 litre) that can accommodate a CD4 T cell and a tumour cell in each of them, and function like boxing rings," says Hatice Altug, a professor in EPFL's Bionanophotonic Systems Laboratory. The researchers then photographed all these thousands wells simultaneously every five minutes for 24 hours in order to observe the interactions occurring between the two cells from a large set of pairs. "We know that it takes about two and a half hours for a CD8 to kill a tumour cell, and we decided to observe these boxing rings for 24 hours without knowing how, and if, the CD4s would react," continues Professor Altug.

A third of the CD4s emerged victorious

To the great satisfaction of the scientists, the high-throughput integration of dynamic imaging data showed that up to a third of the CD4 T lymphocytes succeeded in killing the tumour cell to which they were closely linked within five hours. As Professor Romero stresses: "These direct observations at the level of individual lymphocytes, which were revealed for the first time at such a level of sensitivity, definitively confirm the existence of CD4 T lymphocytes capable of killing tumour cells. And this happens while the tumour cells sometimes manage to divert them from their function of providing protective support to make allies of them."

By analysing the killer variety of CD4 T lymphocytes in detail, the scientists found that they expressed the SLAMF7 molecule, which promoted their tumor killer activity. "That's why we're now going to isolate and cultivate in vitro the best killer variety of CD4 T lymphocytes so we can turn them into a veritable army of trillions of cells, which we can then inject into patients on whom CD8-based treatments don't work," says Dr Jandus. The human body naturally has only a small number of CD4 T lymphocytes directed against tumours, and not enough to defeat them. "The ability to visualise this close combat with our picowell chip paves the way for expanding the arsenal in the fight against cancer, which we now need to develop," concludes Professor Altug.

The ocean floor is vast and varied, making up more than 70% of the Earth's surface. Scientists have long used information from sediments at the bottom of the ocean -- layers of rock and microbial muck -- to reconstruct the conditions in oceans of the past.

These reconstructions are important for understanding how and when oxygen became available in Earth's atmosphere and ultimately increased to the levels that support life as we know it today.

Yet reconstructions that rely on signals from sedimentary rocks but ignore the impact of local sedimentary processes do so at their own peril, according to geoscientists including David Fike in Arts & Sciences at Washington University in St. Louis.

Their new study published Feb. 26 in Science Advances is based on analyses of a mineral called pyrite (FeS2) that is formed in the presence of bacteria. With its chemical-reduced iron (Fe) and sulphur (S), the burial of pyrite in marine sediments is one of the key controls on oxygen levels in Earth's atmosphere and oceans.

The researchers compared pyrite in sediments collected in a borehole drilled in the shelf just off the eastern coast of New Zealand with sediments drilled from the same ocean basin but hundreds of kilometers out into the Pacific.

"We were able to get a gradient of shallow to deep sediments and compare the differences between those isotopic compositions in pyrite between those sections," said Fike, professor of Earth and planetary sciences and director of environmental studies at Washington University.

"We demonstrate that, for this one basin in the open ocean, you get very different signals between shallow and deep water, which is prima facie evidence to argue that these signals aren't the global fingerprint of oxygen in the atmosphere," said Fike, who also serves as director of Washington University's International Center for Energy, Environment and Sustainability (InCEES).

Instead of pointing directly to oxygen, the same signals from pyrite could be reinterpreted as they relate to other important factors, Fike said, such as sea level change and plate tectonics.

Fike and first author Virgil Pasquier, a postdoctoral fellow at the Weizmann Institute of Sciences in Israel, first questioned the way that pyrite has been used as a proxy in a study published in PNAS in 2017 using Mediterranean Sea sediments. For his postdoctoral research, Pasquier has been working with professor Itay Halevy at the Weizmann Institute to understand the various controls on the isotopic composition of pyrite. Their results raise concerns about the common use of pyrite sulfur isotopes to reconstruct Earth's evolving oxidation state.

"Strictly speaking, we are investigating the coupled cycles of carbon, oxygen and sulfur, and the controls on the oxidation state of the atmosphere," Pasquier said.

"It's much more sexy for a paper to reconstruct past changes in ocean chemistry than to focus on the burial of rocks or what happened during the burial," he said. "But I find this part even more interesting. Because most microbial life -- especially back when oxygen was initially accumulating in the atmosphere -- occurred in sediments. And if our ultimate goal is to understand oxygenation of the oceans, then we have to understand this."

For this study, the team conducted 185 sulfur isotope analyses of pyrite along the two boreholes. They determined that changes in the signals in pyrite from the nearshore borehole were more controlled by sea level-driven changes in local sedimentation, rather than any other factor.

In contrast, sediments in the deeper borehole were immune to the sea-level changes. Instead, they recorded a signal associated with the long-term reorganization of ocean currents.

"There is a water depth threshold," said Roger Bryant, a co-author and PhD graduate of Fike's laboratory at Washington University, now a postdoctoral fellow at the University of Chicago. "Once you go below that water depth, sulfur isotopes apparently are not sensitive to things like climate and environmental conditions in the surface environment."

Fike added: "The Earth is a complicated place, and we need to remember that when we try to reconstruct how it has changed in the past. There are a number of different processes that impact the kinds of signals that get preserved. As we try to better understand Earth's long-term evolution, we need to have a more nuanced view about how to extract information from those signals."

NARRAGANSETT, R.I. - February 26, 2021 - A team of researchers from the University of Rhode Island's Graduate School of Oceanography and their collaborators have revealed that the abundant microbes living in ancient sediment below the seafloor are sustained primarily by chemicals created by the natural irradiation of water molecules.

The team discovered that the creation of these chemicals is amplified significantly by minerals in marine sediment. In contrast to the conventional view that life in sediment is fueled by products of photosynthesis, an ecosystem fueled by irradiation of water begins just meters below the seafloor in much of the open ocean. This radiation-fueled world is one of Earth's volumetrically largest ecosystems.

The research was published today in the journal Nature Communications.

"This work provides an important new perspective on the availability of resources that subsurface microbial communities can use to sustain themselves. This is fundamental to understand life on Earth and to constrain the habitability of other planetary bodies, such as Mars," said Justine Sauvage, the study's lead author and a postdoctoral fellow at the University of Gothenburg who conducted the research as a doctoral student at URI.

The process driving the research team's findings is radiolysis of water - the splitting of water molecules into hydrogen and oxidants as a result of being exposed to naturally occurring radiation. Steven D'Hondt, URI professor of oceanography and a co-author of the study, said the resulting molecules become the primary source of food and energy for the microbes living in the sediment.

"The marine sediment actually amplifies the production of these usable chemicals," he said. "If you have the same amount of irradiation in pure water and in wet sediment, you get a lot more hydrogen from wet sediment. The sediment makes the production of hydrogen much more effective."

Why the process is amplified in wet sediment is unclear, but D'Hondt speculates that minerals in the sediment may "behave like a semiconductor, making the process more efficient."

The discoveries resulted from a series of laboratory experiments conducted in the Rhode Island Nuclear Science Center. Sauvage irradiated vials of wet sediment from various locations in the Pacific and Atlantic Oceans, collected by the Integrated Ocean Drilling Program and by U.S. research vessels. She compared the production of hydrogen to similarly irradiated vials of seawater and distilled water. The sediment amplified the results by as much as a factor of 30.

"This study is a unique combination of sophisticated laboratory experiments integrated into a global biological context," said co-author Arthur Spivack, URI professor of oceanography.

The implications of the findings are significant.

"If you can support life in subsurface marine sediment and other subsurface environments from natural radioactive splitting of water, then maybe you can support life the same way in other worlds," said D'Hondt. "Some of the same minerals are present on Mars, and as long as you have those wet catalytic minerals, you're going to have this process. If you can catalyze production of radiolytic chemicals at high rates in the wet Martian subsurface, you could potentially sustain life at the same levels that it's sustained in marine sediment."

Sauvage added, "This is especially relevant given that the Perseverance Rover has just landed on Mars, with its mission to collect Martian rocks and to characterize its habitable environments."

D'Hondt said the research team's findings also have implications for the nuclear industry, including for how nuclear waste is stored and how nuclear accidents are managed. "If you store nuclear waste in sediment or rock, it may generate hydrogen and oxidants faster than in pure water. That natural catalysis may make those storage systems more corrosive than is generally realized," he said.

The next steps for the research team will be to explore the effect of hydrogen production through radiolysis in other environments on Earth and beyond, including oceanic crust, continental crust and subsurface Mars. They also will seek to advance the understanding of how subsurface microbial communities live, interact and evolve when their primary energy source is derived from the natural radiolytic splitting of water.

What The Study Did: Researchers in this observational study assess at what age young people ages 12 to 17 start using cigarettes.

Authors: Adriana Pérez, Ph.D., of the University of Texas Health Science Center at Houston in Austin, 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.2021.0218)

Editor's Note: The article includes conflicts 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.

Curcumin is a polyphenol compound produced by plants of the Curcuma longa species and has been reported to have many physiological activities, which include anti-oxidation, anti-inflammatory, anti-cancer, and anti-amyloid properties. However, the mechanism and network of action are not completely clear. Amyloidosis is a group of diseases characterized by abnormal aggregates of proteins, known as amyloid fibrils, and subsequent deposition in various tissues and organs, such as Alzheimer's disease, immunoglobulin light chain amyloidosis.

In previous studies, curcumin has been shown to suppress the aggregation and cytotoxicity of many amyloid proteins in vitro, such as amyloid ß (Aß), α-synuclein, transthyretin, and prion protein, and has also been reported to inhibit the deposition of Aß fibrils in a mouse model of Alzheimer's disease. The group investigated amyloid deposition and molecular changes in a mouse model of amyloid apolipoprotein A-II (AApoAII) amyloidosis, in which mice were fed a curcumin-supplemented diet. In this research, it was found that curcumin intake elevated ApoA-II and HDL-cholesterol concentration in plasma by activating the peroxisome proliferator-activated receptor alpha (PPARα) signaling pathway, resulting in increased AApoAII amyloid deposition and peroxisome proliferation. These findings demonstrate the novel agonistic effect of curcumin on PPARα, which is an important transcription factor for lipid metabolism, and may have far-reaching significance for the treatment of amyloidosis and other metabolic disorders.

It was reported that high-fat diet supplement aggravates a variety of amyloid deposition including Aß in Alzheimer's disease model mice, but a link between lipid metabolism and the development of amyloidosis has not been completely established. These results provide a promising molecular target to understand the molecular mechanism of amyloidogenesis, which the activation state of PPARα pathway may be a bridge to connect the change of lipid metabolism level and the degree of amyloid deposition. In addition, it has been regarded that curcumin, as an agonist of PPARγ, exerts anti-inflammatory, anti-cancer and antioxidant activities in the past. However, this study demonstrates that curcumin is a PPARα/γ dual activator and may affect expression levels of proteins involved in amyloid deposition and other metabolism functions in a complex manner. By focusing on the PPARα pathway, the group hope to provide an opportunity to reconsider the mechanism of the physiological effects of curcumin.

In the next stage, the group would like to clarify how curcumin activates the PPARα signaling pathway in vitro and confirm whether the activation of PPARα can affect amyloid deposition on other types of amyloidosis in vivo (Alzheimer's disease, ATTR amyloidosis etc.). The goal in this research is to elucidate the molecular pathways involved in the pathogenesis of amyloidosis in vivo and to develop effective therapeutic or preventive methods against the development of amyloidosis. As a future study, the group hopes to fully understand the molecular fluctuations of PPARα-activated cells and verify the effectiveness of interventions in these pathways for various metabolic diseases.

Eminent scientists warn that key ecosystems around Australia and Antarctica are collapsing, and propose a three-step framework to combat irreversible global damage.

Their report, authored by 38 Australian, UK and US scientists from universities and government agencies, is published today in the international journal Global Change Biology. Researchers say I heralds a stark warning for ecosystem collapse worldwide, if action if not taken urgently.

Lead author, Dr Dana Bergstrom from the Australian Antarctic Division, said that the project emerged from a conference inspired by her ecological research in polar environments.

"I was seeing unbelievably rapid, widespread dieback in the alpine tundra of World Heritage-listed Macquarie Island and started wondering if this was happening elsewhere," Dr Bergstrom said.

"With my colleagues from the Australian Antarctic Division and the University of Queensland we organised a national conference and workshop on 'Ecological Surprises and Rapid Collapse of Ecosystems in a Changing World', with support from the Australian Academy of Sciences."

The resulting paper and extensive case studies examine the current state and recent trajectories of 19 marine and terrestrial ecosystems across all Australian states, spanning 58° of latitude from coral reefs to Antarctica. Findings include:

Ecosystem collapse (defined as potentially irreversible change to ecosystem structure, composition and function) is occurring now in 19 case studies. This conclusion is supported by empirical evidence, rather than modelled predictions.

No ecosystems have collapsed across their entire range, but for all case studies there is evidence of local collapse.

The 19 ecosystems include the Great Barrier Reef, mangroves in the Gulf of Carpentaria, the Mediterranean forests and woodlands, the arid zone of central Australia, Shark Bay seagrass beds in Western Australia, Great Southern Reef kelp forests, Gondwanan conifer forests of Tasmania, Mountain Ash forest in Victoria, and moss beds of East Antarctica.

Drivers of ecosystem collapse are pressures from global climate change and regional human impacts, categorised as chronic 'presses' (eg. changes in temperature and precipitation, land clearing) or acute 'pulses' (eg. heatwaves, storms, fires and pollution after storms).

Michael Depledge CBE, Emeritus Professor at the University of Exeter and former Chief Scientific Advisor to the Environment Agency of England and Wales, said the research had particular significance following the UK Government commissioned Dasgupta Review , which recently highlighted the catastrophic economic damage associated with biodiversity loss.

Professor Depledge said: "Our paper is a further wake-up call that shows ecosystems are in varying states of collapse from the tropics to Antarctica. These findings from Australia are a stark warning of what is happening everywhere, and will continue without urgent action. The implications for human health and wellbeing are serious. Fortunately, as we show, by raising awareness, and anticipating risks there is still time to take action to address these changes.

"Our paper will hopefully increase awareness that our ecosystems are collapsing around us. We can already observe the damaging consequences for the health and wellbeing of some communities and anticipate threats to others. Taking stronger action now will avoid heaping further misery on a global population that is already bearing the scars of the global pandemic".

The paper recommends a new '3As' framework to guide decision-making about actions to combat irreversible damage:

Awareness of the importance of the ecosystem and the need for its protection;

Anticipation of the risks from current and future pressures

Action on reducing the pressures to avoid or lessen their impacts

Example:

Protecting pencil pines from fire in the Southwest Tasmanian Wilderness World Heritage Area: by mapping vegetation values against fire sensitivity (to identify fire-prone Gondwanan conifer communities), maintaining an area specific awareness of the shifting causation of bushfires (increasing frequency of dry lightning strikes), and developing new action strategies to lessen the pressure of unregulated fire (installing sprinkler systems), conservation managers established and used Awareness and Anticipation to formulate positive Action.

The scientific team concluded that in the near future, even apparently resilient ecosystems are likely to suffer collapse as the intensity and frequency of pressures increase.

"Anticipating and preparing for future change is necessary for most ecosystems, unless we are willing to accept a high risk of loss," Dr Bergstrom said.

"Protecting the iconic ecosystems we have highlighted is not just for the animals and plants that live there. Our economic livelihoods, and therefore ultimately our survival, are intimately connected to the natural world."

Researchers from the Andalusian Centre for Molecular Biology and Regenerative Medicine (CABIMER), in collaboration with the Swiss Institute for Experimental Cancer Research (ISREC) have studied the mechanisms behind the higher tendency of people with Mulibrey syndrome to develop tumours. Their results point to the important role of the TRIM37 protein, whose absence explains the appearance of tumour cells.

Mulibrey syndrome is a so-called rare disease as it occurs in less than 5 out of every 10,000 inhabitants. Some of these diseases usually have a very definite genetic basis. Consequently, studying the molecular functions of the altered genes in patients with these diseases, in addition to contributing to the search for new methods of diagnosis and treatment, helps us to understand the basic mechanisms necessary for the individual's proper development.

The disease is characterised by growth retardation, heart failure problems and liver pathologies. In addition, patients have a greater tendency to develop certain types of tumours. The scientific literature shows that development of this disease is associated with the lack of function of a gene known as TRIM37. However, the molecular role that this protein plays and how its lack of function leads to disease remains unresolved. This research focused specifically on how the gene's lack of function may contribute to tumour development in patients affected by Mulibrey syndrome.

TRIM37 is a ubiquitin ligase; a protein that is able to modify other target proteins by adding a small third protein called ubiquitin. This modification can have several effects on the target protein: from stabilising and promoting its function to abruptly triggering its degradation. This study, led by Dr. Fernando Romero Balestra (Cabimer/US) in collaboration with a group from the Swiss Institute for Experimental Cancer Research (ISREC), with the participation of other researchers from the Andalusian Centre for Molecular Biology and Regenerative Medicine (Cabimer), including Dr. Pablo Huertas (Cabimer/US), Andrés Domínguez Calvo (Cabimer/US), and CSIC researcher Dr. Rosa M. Ríos (Cabimer/CSIC), has discovered that cells isolated from patients with Mulibrey syndrome are unable to control the number of small cell organelles called centrosomes. Centrosomes are involved in the nucleation and organisation of the microtubules necessary for the formation of the mitotic spindle and the correct segregation of genetic material during cell division. Healthy cells have two centrosomes which, after cell division, are distributed between the two daughter cells, thus inheriting one centrosome each. Each daughter cell, before entering the next mitosis, has to "build" a new centrosome by a complicated and highly regulated molecular process that guarantees the formation of a single new centrosome and ensures the correct segregation of chromosomes in the next mitosis. This present study describes how cells from Mulibrey syndrome patients, by having a higher number of centrosomes, during cell divisions form abnormal mitotic spindles that frequently make mistakes and generate cells with an incorrect number of chromosomes.

Interestingly, this dysregulation of centrosome number and the associated chromosome segregation problems is a feature present in many tumour types. Therefore, the researchers suggest that the role of TRIM37 as a regulator of centrosome number may be key in tumour formation in Mulibrey syndrome patients. But what are the molecular mechanisms connecting TRIM37 with the formation of new centrosomes? To answer this question the study turns to molecular biology and cell biology techniques. To characterise the mechanisms by which these new centrosomes are formed without control in cells lacking TRIM37, the researchers used human cell lines that can be easily grown in the laboratory and, in turn, can be modified with Crispr/Cas9 genomic editing techniques or with RNA interference (RPE-1 and HeLa cells).

The use of these techniques has revealed how the absence of TRIM37 activates centrosome formation through a hitherto undescribed pathway of centrosome formation that depends on the proteins Centrobin, PLK4, HsSAS-6 and PLK1. The lack of TRIM37 induces the formation of Centrobin and PLK4 structures that serve as a platform for uncontrolled centrosome production.

The results of this study contribute to a better understanding of the molecular mechanisms involved in Mulibrey syndrome and open the door to the search for personalised treatments for Mulibrey syndrome patients who develop tumour pathologies. In the future, the authors plan to investigate whether the molecular mechanism involved in extra centrosome formation plays a key role in other tumour types.

MEMPHIS, Tenn. - Extremely low birth weight (ELBW) infants with moderate to large patent ductus arteriosus (PDA) may benefit from transcatheter PDA closure (TCPC) in the first four weeks of life, according to research published by Le Bonheur Cardiologist Ranjit Philip, MD, and Medical Director of Interventional Cardiac Imaging and Interventional Catheterization Laboratory Shyam Sathanandam, MD. Early PDA closure may prevent early onset pulmonary vascular disease, promote growth and facilitate faster weaning off supplemental oxygen and ventilator support.

"The primary objective of this study was to describe changes in hemodynamics, respiratory support and growth associated with TCPC in ELBW infants," said Philip. "We also wanted to describe clinical outcomes in early versus delayed PDA closures to identify factors associated with worse clinical outcomes."

The study followed 100 infants with a hemodynamically significant PDA (hsPDA) who were born at less than 27 weeks gestation, weighed less than 1 kg at birth and were referred for possible TCPC. The infants were separated by age into those who underwent TCPC at less than 4 weeks (group 1), 4-8 weeks (group 2) and greater than 8 weeks of age (group 3).

A hemodynamic assessment was completed as part of the procedure and included baseline pulmonary to system flow ratio, pulmonary artery systolic pressure (PASP), degree of shunting and pulmonary vascular resistance. To assess respiratory outcomes of these infants, a respiratory severity score (RSS) was calculated by a product of the mean airway pressure and the fractional inspired oxygen with a lower score denoting less respiratory support.

"The presence of moderate to large PDA in ELBW preterm infants is associated with poor respiratory outcomes and an increased mortality," said Philip. "Our study aimed to determine if early PDA closure demonstrated a reduction in these adverse outcomes.

While all infants were on mechanical ventilator support at the time of TCPC, baseline RSS was highest for infants in group 3. Although younger and smaller, infants in group 1 were able to extubate sooner compared to group 3 and reach an RSS of less than two (denoting minimal support) significantly faster than those with late PDA closure.

Pulmonary hypertension (PHT) also influenced RSS. Those with PHT were referred for PDA closure later and consequently had a higher pre-procedure RSS. This group took a longer time to return to baseline RSS following TCPC in comparison to infants without PHT.

Finally, age at PDA closure effected weight gain for these infants. Specifically between four and eight weeks, the weight gain for infants in group 1 was much more rapid than those in group 3 who still had the PDA at this age.

"Growth during the four to eight week period is important for the overall outcomes of these ELBW infants," said Philip. "This further supports the notion that earlier PDA closure would be beneficial for ELBW infants."

The study's results raise questions regarding when, how and whether a PDA should be closed in ELBW infants. Based on this study, benefits of early closure in ELBW include rapid improvement of respiratory status and normal weight gain. Delayed PDA closure and PHT are risk factors for worse respiratory outcomes.

In terms of how closure is performed, the study shows that TCPC can be performed with good success with no significant adverse events while also obtaining invaluable information on hemodynamic significance. And finally, this is the first-time published study of PDA closure whose hemodynamics were measured prior to closure.

"When we first started offering this novel procedure, the infants were usually older and more critical. Since January 2016, with our growing experience in TCPC, younger and smaller infants are being referred," said Philip. "As our team has gotten more comfortable with the procedure and post-procedure care, ELBW infants are referred for TCPC between the second and third week of life."

The study concluded that it may be beneficial to close hsPDAs in the first four weeks of life before the onset of elevated pulmonary vascular resistance in ELBW infants with the additional benefits of faster weaning off ventilator and oxygen support and better weight gain. Researchers concluded that additional RCTs are needed to examine the short and long-term benefits for ELBW infants, evaluating no intervention versus TCPC and long-term neurodevelopmental outcomes.