The Lancet Global Health Commission report details for the first time how future investment in strengthening medical oxygen systems could have a huge impact by saving millions of lives and improving pandemic preparedness.

Almost 400 million children and adults require medical oxygen every year. More than five billion people, 60 per cent of the world’s population, don’t have access to safe and affordable medical oxygen services.

The Commission, co-chaired by Makerere University in Uganda, the International Centre for Diarrheal Disease Research (icddr,b) in Bangladesh, Murdoch Children’s Research Institute (MCRI) in Australia, Karolinska Institute in Sweden and the Every Breath Counts Coalition in the US was launched in 2022 against the backdrop of the COVID-19 pandemic. The Commission was tasked with submitting actionable recommendations for governments, industry, global health agencies, donors and the healthcare workforce.

MCRI Dr Hamish Graham said the COVID-19 pandemic had put a spotlight on the longstanding global inequities in accessing medical oxygen.

“Oxygen is required at every level of the healthcare system for children and adults with a wide range of acute and chronic conditions,” he said. Previous efforts, including the major investments in response to the COVID-19 pandemic, largely focused on the delivery of equipment to produce more oxygen, neglecting the supporting systems and people required to ensure it was distributed, maintained, and used safely and effectively.”

Dr Graham said channelling investments into national oxygen plans and bolstering health systems, including wider use of pulse oximeters (a small device that measures how much oxygen is in the blood), would help solve the medical oxygen crisis.

“We urgently need to make high-quality, pulse oximeters more affordable and widely accessible,” he said. Pulse oximeters are available in 54 per cent of general and 83 per cent of tertiary hospitals in low- and middle-income countries, with frequent shortages and equipment breakdowns.

“Concerningly, in these countries the devices are performed for only 20 per cent of patients presenting to general hospitals and almost never for those at primary healthcare facilities. We see the greatest inequities in small and rural government health facilities and across Sub-Saharan Africa.”

Dr Graham said the importance of medical oxygen must also be recognised and integrated into broader national strategies and pandemic preparedness and response planning.

“Governments should bring together public and private sector partners with a stake in medical oxygen delivery, including health, education, industry, energy and transport to design a system and set up a governance structure that supports the new Global Oxygen Alliance (GO₂AL) and replenishing The Global Fund with a strong oxygen access mandate,” he said.

Key findings from the report published in The Lancet Global Health include:

• The global need for medical oxygen is high. Every year, 374 million children and adults need medical oxygen, including 364 million patients with acute medical and surgical conditions and nine million patients with long-term oxygen needs due to chronic obstructive pulmonary disease.
• Global access to oxygen is highly inequitable with huge gaps in coverage despite pandemic-related investments. Less than one in three people in low- and middle-income countries who need oxygen for acute medical or surgical conditions receives it.

• Costs to fill the oxygen gap are large but represent a highly cost-effective investment that will have wide reaching impacts. Closing the large acute medical and surgical oxygen access gap in low- and middle-income countries requires an additional $US6.8 billion annually.

• National Medical Oxygen Plans are essential to facilitate investment and effectively coordinate service delivery. Less than 30 countries have developed National Oxygen Plans to date but all governments are encouraged to have one by 2030.

• Oxygen systems must be designed to suit the context, include operational costs, and be affordable to all patients. There is no one-size-fits-all national medical oxygen system. Governments should define priorities and optimise their systems to suit local conditions.

• Pulse oximetry is the gateway to safe, quality, affordable oxygen care and needs to be integrated in clinical guidelines, education and all levels of the healthcare system. Pulse oximetry measures should be routinely assessed in patients at all levels of health care.

• A need for closer collaboration between the medical oxygen industry, national governments and global health agencies. Companies should adopt specific oxygen access targets and publish progress while global health agencies should regularly assess oxygen industry progress similar to how the pharmaceutical industry operates.

• Accurate and timely data on oxygen systems is essential for effective decision making and oxygen service access. New toolssuch as the 10 Oxygen Coverage Indicators and a national Access to Medical Oxygen Scorecard (ATMO₂S) would help governments to both plan their national oxygen systems and report progress implementing the WHO Oxygen Resolution.

The report comes after it was announced MCRI would partner with 12 countries in the Pacific and Southeast Asia under a $10 million initiative to improve child and adolescent health across the region.

The Australian Government has awarded MCRI a strategic grant as part of its Partnerships for a Healthy Region Initiative.

The three-year funding will be used to establish the ReALiSE program — the Regional Alliance for Learning in Systems for Equitable Child and Adolescent Health — which will strengthen resilience in public health systems and engage with youth leaders and local communities to improve the health of all young people.

While taste receptors are traditionally associated with the tongue and our ability to perceive flavors, recent studies have shown that these receptors exist in other parts of the body, where they likely play different roles. This new study is the first to identify specific “sweet taste” receptors, known as TAS1R2 and TAS1R3, on the surface of heart muscle cells. The work will be presented at the 69th Biophysical Society Annual Meeting, to be held February 15 — 19, 2025 in Los Angeles.

The new research found that these receptors are not just present on heart muscle, but also functional. When the researchers stimulated these receptors in both human and mouse heart cells using aspartame, a common artificial sweetener, they observed a significant increase in the force of heart muscle contraction and accelerated calcium handling — key processes for a healthy heartbeat.

“After you eat a meal, it’s been shown that your heart rate and blood pressure actually are increasing,” said Micah Yoder, a graduate student in the lab of Jonathan Kirk at Loyola University Chicago. “Previously, this was thought to be a neural axis that’s being signaled. But we’re proposing a more direct consequence, where we have a spike in our blood sugar after eating a meal, and that’s binding to these sweet taste receptors on the heart muscle cells, causing a difference in the heartbeat,” he added.

Intriguingly, the researchers also found that these receptors are more abundant in the hearts of patients with heart failure, suggesting a possible link to disease. Further investigation revealed that stimulating the receptors triggers a cascade of molecular events within the heart cells, involving key proteins that control calcium flow and muscle contraction.

“During heart failure, the heart is changing its energetic landscape and prioritizing glucose uptake and glucose usage. So, it’s possible that during this energetic change, the heart might need to change its nutrient sensing abilities to accommodate this switch,” Yoder explained.

Additionally, their research may explain why high consumption of artificially sweetened beverages is linked to arrhythmogenesis, or an irregular heartbeat. Not only are these sweet taste receptors particularly stimulated by artificial sweeteners like aspartame, Yoder noted, he found that overstimulation of these sweet taste receptors lead to a an increase in arrhythmic like behavior in the heart cells.

But further research is needed to fully understand the long-term effects of stimulating these receptors in the heart as well as how these receptors might be targeted to strengthen the heart in the case of heart failure.

Bearing sharp teeth and powerful jaw muscles, suggesting a strong bite, the newly-identified ‘Bastetodon’ was a leopard-sized “fearsome” mammal. It would have been at the top of all carnivores and the food chain when our own monkey-like ancestors were evolving.

Findings, published in the peer-reviewed Journal of Vertebrate Paleontology, detail how this ferocious creature would have likely preyed on primates, early hippos, early elephants, and hyraxes in the lush forest of Fayum, Egypt, which is now home to a desert.

Describing the discovery, palaeontologist and lead author Shorouq Al-Ashqar, from Mansoura University and the American University in Cairo, says: “For days, the team meticulously excavated layers of rock dating back around 30 million years.

“Just as we were about to conclude our work, a team member spotted something remarkable — a set of large teeth sticking out of the ground. His excited shout brought the team together, marking the beginning of an extraordinary discovery: a nearly complete skull of an ancient apex carnivore, a dream for any vertebrate paleontologist.”

Bastetodon belongs to a species in an extinct group of carnivorous mammals called hyaenodonts. Hyaenodonts evolved long before modern-day carnivores such as cats, dogs, and hyenas. These predators with hyena-like teeth hunted in African ecosystems after the extinction of the dinosaurs.

The team — who go under the title ‘Sallam Lab’ — named the specimenafter the cat-headed ancient Egyptian goddess Bastet, who symbolized protection, pleasure, and good health. The name acknowledges the region where the specimen was found, famous for its fossils and Ancient Egyptian artifacts. The name is also a nod to the short, cat-like snout and teeth of this fearsome, leopard-sized carnivore (“-odon” means “tooth”).

Its skull was unearthed on Sallam Lab’s expedition to the Fayum Depression, an area where digs reveal an important time window into about 15 million years of evolutionary history of mammals in Africa. This timespan not only captures the transition from the Eocene’s global warming to the Oligocene’s global cooling, but also reveals how these climate shifts played a crucial role in shaping ecosystems that we still see today.

Beyond just a new ancient creature discovery, the finding of Bastetodon has already allowed the research team to reevaluate a group of lion-sized hyaenodonts that was discovered in the rocks of the Fayum over 120 years ago. In their paper the team also construct the genus Sekhmetops to describe this century-old material and to honor Sekhmet, the lion-headed goddess of wrath and war in ancient Egyptian mythology (“-ops” means “face”). In 1904, Sekhmetops was placed within a European group of hyaenodonts. The team demonstrated Bastetodon and Sekhmetops both belonged to a group of hyaenodonts that actually originated in Africa. In ancient Egypt, Bastet was often associated with Sekhmet, making the two genera scientifically and symbolically connected.

The study demonstrates the relatives of Bastetodon and Sekhmetops spread from Africa in multiple waves, eventually making it to Asia, Europe, India, and North America. By 18 million years ago, some relatives of these hyaenodonts were among the largest mammalian meat-eaters to ever walk the planet.

However, cataclysmic changes in global climate and tectonic changes in Africa opened the continent to the relatives of modern cats, dogs, and hyenas. As environments and prey changed, the specialized, carnivorous hyaenodonts diminished in diversity, finally going extinct and leaving our primate relatives to face a new set of antagonists.

“The discovery of Bastetodon is a significant achievement in understanding the diversity and evolution of hyaenodonts and their global distribution,” Shorouq adds.

“We are eager to continue our research to unravel the intricate relationships between these ancient predators and their environments over time and across continents.”

Concluding, co-author Dr. Matt Borths, Curator of Fossils at the Duke Lemur Center Museum of Natural History at Duke University in Durham, North Carolina, says: “The Fayum is one of the most important fossil areas in Africa. Without it, we would know very little about the origins of African ecosystems and the evolution of African mammals like elephants, primates, and hyaenodonts. Paleontologists have been working in the Fayum for over a century, but the Sallam Lab demonstrated there is more to discover in this remarkable region.”

The model, which upends the decades-old “hard steps” theory that intelligent life was an incredibly improbable event, suggests that maybe it wasn’t all that hard or improbable. A team of researchers at Penn State, who led the work, said the new interpretation of humanity’s origin increases the probability of intelligent life elsewhere in the universe.

“This is a significant shift in how we think about the history of life,” said Jennifer Macalady, professor of geosciences at Penn State and co-author on the paper, which published today (Feb. 14) in the journal Science Advances. “It suggests that the evolution of complex life may be less about luck and more about the interplay between life and its environment, opening up exciting new avenues of research in our quest to understand our origins and our place in the universe.”

Initially developed by theoretical physicist Brandon Carter in 1983, the “hard steps” model argues that our evolutionary origin was highly unlikely due to the time it took for humans to evolve on Earth relative to the total lifespan of the sun — and therefore the likelihood of human-like beings beyond Earth is extremely low.

In the new study, a team of researchers that included astrophysicists and geobiologists argued that Earth’s environment was initially inhospitable to many forms of life, and that key evolutionary steps only became possible when the global environment reached a “permissive” state.

For example, complex animal life requires a certain level of oxygen in the atmosphere, so the oxygenation of Earth’s atmosphere through photosynthesizing microbes and bacteria was a natural evolutionary step for the planet, which created a window of opportunity for more recent life forms to develop, explained Dan Mills, postdoctoral researcher at The University of Munich and lead author on the paper.

“We’re arguing that intelligent life may not require a series of lucky breaks to exist,” said Mills, who worked in Macalady’s astrobiology lab at Penn State as an undergraduate researcher. “Humans didn’t evolve ‘early’ or ‘late’ in Earth’s history, but ‘on time,’ when the conditions were in place. Perhaps it’s only a matter of time, and maybe other planets are able to achieve these conditions more rapidly than Earth did, while other planets might take even longer.”

The central prediction of the “hard steps” theory states that very few, if any, other civilizations exist throughout the universe, because steps such as the origin of life, the development of complex cells and the emergence of human intelligence are improbable based on Carter’s interpretation of the sun’s total lifespan being 10 billion years, and the Earth’s age of around 5 billion years.

In the new study, the researchers proposed that the timing of human origins can be explained by the sequential opening of “windows of habitability” over Earth’s history, driven by changes in nutrient availability, sea surface temperature, ocean salinity levels and the amount of oxygen in the atmosphere. Given all the interplaying factors, they said, the Earth has only recently become hospitable to humanity — it’s simply the natural result of those conditions at work.

“We’re taking the view that rather than base our predictions on the lifespan of the sun, we should use a geological time scale, because that’s how long it takes for the atmosphere and landscape to change,” said Jason Wright, professor of astronomy and astrophysics at Penn State and co-author on the paper. “These are normal timescales on the Earth. If life evolves with the planet, then it will evolve on a planetary time scale at a planetary pace.”

Wright explained that part of the reason that the “hard steps” model has prevailed for so long is that it originated from his own discipline of astrophysics, which is the default field used to understand the formation of planets and celestial systems. The team’s paper is a collaboration between physicists and geobiologists, each learning from each other’s fields to develop a nuanced picture of how life evolves on a planet like Earth.

“This paper is the most generous act of interdisciplinary work,” said Macalady, who also directs Penn State’s Astrobiology Research Center. “Our fields were far apart, and we put them on the same page to get at this question of how we got here and are we alone? There was a gulf, and we built a bridge.”

The researchers said they plan to test their alternative model, including questioning the unique status of the proposed evolutionary “hard steps.” The recommended research projects are outlined in the current paper and include such work as searching the atmospheres of planets outside our solar system for biosignatures, like the presence of oxygen. The team also proposed testing the requirements for proposed “hard steps” to determine how hard they actually are by studying uni- and multicellular forms of life under specific environmental conditions such as lower oxygen and temperature levels.

Beyond the proposed projects, the team suggested the research community should investigate whether innovations — such as the origin of life, oxygenic photosynthesis, eukaryotic cells, animal multicellularity and Homo sapiens — are truly singular events in Earth’s history. Could similar innovations have evolved independently in the past, but evidence that they happened was lost due to extinction or other factors?

“This new perspective suggests that the emergence of intelligent life might not be such a long shot after all,” Wright said. “Instead of a series of improbable events, evolution may be more of a predictable process, unfolding as global conditions allow. Our framework applies not only to Earth, but also other planets, increasing the possibility that life similar to ours could exist elsewhere.”

The other co-author on the paper is Adam Frank of the University of Rochester. Penn State’s Astrobiology Research Center, the Penn State Center for Exoplanets and Habitable Worlds, the Penn State Extraterrestrial Intelligence Center, the NASA Exobiology program and the German Research Foundation supported this work.

Scientists at the Okinawa Institute of Science and Technology (OIST) and their international collaborators have discovered that anemonefish have evolved to maintain very low levels of sialic acid in their skin mucus to avoid triggering the release of nematocysts (stinging cells) in their sea anemone hosts. The researchers found that sea anemones also lack these sugar compounds in their own mucus, likely to avoid stinging themselves. Their findings, published in the journal BMC Biology, suggest anemonefish might be using a similar protective strategy to their hosts.

Comparing symbiotic and non-symbiotic species

The study combined multiple approaches, including glycobiology (the study of sugars) and transcriptomics — the study of all RNA molecules produced by an organism’s genome to understand gene expression and regulation. The researchers measured and analyzed mucus samples from both anemonefish and non-symbiotic damselfish species, using advanced techniques to separate and analyze the components of a mixture (liquid chromatography).

Sialic acids are important sugar molecules naturally present in most living organisms that play important roles in cellular processes such as cell-cell interactions and protein communication. Previous studies have shown that these molecules can trigger the release of sea anemone stinging cells. Very interestingly, scientists found that while anemonefish maintain certain levels of sialic acid in their internal organs like the brain and gut, they have specifically evolved to have very low levels in their protective mucus layer compared to non-symbiotic damselfish.

They also studied a unique case of the domino damselfish, which can live with anemones as juveniles. They found that these fish also show reduced sialic acid levels in their mucus during their juvenile stage, suggesting that different species have evolved similar adaptations for achieving symbiosis with sea anemones.

A particularly interesting finding was the correlation between sialic acid levels and the developmental stages of anemonefish. Young larvae, which are not yet ready to live with sea anemones, have normal sialic acid levels and get stung if they approach an anemone. However, when they metamorphose and develop their characteristic white stripes and bright orange coloring, their sialic acid levels drop, allowing them to safely enter the anemone.

“Our findings represent a major advancement because it’s one of the first studies to combine glycobiology with transcriptomic analysis to investigate this mechanism,” Dr. Natacha Roux, a researcher at Centre de Recherches Insulaires et Observatoire de l’Environnement (CRIOBE) and former researcher in OIST’s Computational Neuroethology Unit, elaborated.

Adapting for co-existence

The research team has two main hypotheses about how anemonefish maintain low sialic acid levels: either their mucus-producing cells express high levels of enzymes that cut sialic acid, or bacteria in their mucus microbiome are responsible for breaking it down. The second hypothesis is supported by previous observations that when anemonefish and sea anemones live together, their bacterial flora converge over time.

Prof. Vincent Laudet, head of OIST’s Marine Eco-Evo-Devo Unit emphasized that this is likely just one part of a complex symbiotic relationship. “Other factors might include the thickness of fish scales, the exchange of nutrients between species, and possible adjustments by the anemones themselves. The relationship is mutually beneficial, with anemonefish receiving protection from predators while helping to defend the anemone and providing nutritional benefits,” he said.

Future research aims to provide ultimate proof of this mechanism by attempting to manipulate the system — making anemonefish sensitive to anemone stings and non-symbiotic fish resistant. However, this is technically challenging and remains a work in progress. The study is also significant because it represents the first major paper from a new international research laboratory collaboration between France’s National Centre for Scientific Research (CNRS) and OIST.

Most cases are caused by a genetic mutation; Dravet syndrome in particular is most often caused by variants in the sodium channel gene SCN1A.

Recent research from Michigan Medicine takes aim at another variant in SCN1B, which causes an even more severe form of DEE.

Mice without the SCN1B gene experience seizures and 100 percent mortality just three weeks after birth.

Using mouse models, the investigative team, led by Chunling Chen, M.D., and Yukun Yuan, M.D., Ph.D., in the lab of Lori Isom, Ph.D., of the Department of Pharmacology at the Medical School, tested a gene therapy to replace SCN1B to increase the expression of beta-1 protein, which is necessary for the regulation of sodium channels in the brain.

Administering the therapy to newborn mice increased their survival, reduced the severity of their seizures and restored brain neuron excitability.

The team notes that different forms of SCN1B gene expression may result in different outcomes for the therapy.

However, the proof-of-concept is the first step toward a gene replacement therapy for SCN1B-linked developmental and epileptic encephalopathy.