Tech

Researchers at Aalto University and the Niilo Mäki Institute have used neuroimaging to pinpoint where the brain activates - or doesn't activate - among children identified as having a high risk of dyslexia. Magnetoencephalography (MEG) has rarely been used to study the reading disorder in children.

The brain study was carried out at Aalto University by measuring brain activity with MEG, which measures the weak magnetic fields arising from electrical activity in the brain, over a period of two days. Earlier studies have shown that difficulties in processing sounds may be partly responsible for dyslexia, and that these challenges may relate to the left auditory cortex which processes language.

During the study, the children listened to nonsensical four-syllable words from a loudspeaker and were asked to repeat them. The researchers then asked the children if they had heard the word before.

'The words were nonsense words that really don't mean anything. We wanted to see how the kids learned to create memories of new words. We noticed that children at a high risk of dyslexia also have deficiencies in learning new words based on hearing them. Their memories of new words were not very precise, and they weren't capable of differentiating the made-up words from each other. This is an indication of a broader difficulty in processing words in the brain, which makes learning to read more difficult as well', says Dr Anni Nora, a postdoctoral researcher who developed the MEG measurement test together with Professor Riitta Salmelin and Assistant Professor Hanna Renvall at Aalto University.

Neural activation in the right cerebral hemisphere of the children at a high risk of dyslexia was comparable to that of children in the control group. Problems in processing the sound content of speech, and in learning new words was focused in activity of the left-hemisphere auditory cortex -- the area of the brain that specialises in processing language and speech, and where word memory support is located.

'Considerably less brain activation was found in the left cerebral hemisphere among children at risk of dyslexia. Particularly in children, the processing of language and speech can also be seen in the right hemisphere, but over time the emphasis moves to the left side - each side focuses on more specific tasks as kids grow older. It would be interesting to know if problems with reading and writing are caused by how the cerebral hemispheres specialise,' Nora adds.

Study participants were in their first and second years of school and had been identified, with the help of a teacher, as high risk. The research team performed neuropsychological examinations, tested reading and writing skills and cognitive abilities, and measured brain functions. The children were also asked about their motivation, including their beliefs about their own reading skills.

Support from tips and feedback

Anomalous brain activity at age 7 or 8 did not completely predict later development of reading; other factors seem to be involved, including a child's belief in their own ability to learn. The Niilo Mäki Institute studied this further, using tools and tests including a game called GraphoLearn (in Finnish Ekapeli), which is used to teach reading skills to Finnish children.

'Children were asked to read out both words and meaningless pseudowords that they could not guess. The study also included a part that tested how GraphoLearn affected difficulties in reading and writing. Generally, playing this learning game did not have a significant effect. But children who were confident about their reading skills got additional benefit from playing the game, and they made better progress in their reading skills than those in the control group. It might be a good idea to develop tools for special education teachers to help them support children's self-efficacy', says postdoctoral researcher Miia Ronimus of the Niilo Mäki Institute.

GraphoLearn is a mobile learning game developed at the University of Jyväskylä and the Niilo Mäki Institute. The players connect letters to the sounds of speech and the game adapts to the child's skill level. Children with the weakest reading and writing skills were selected for the six-week GraphoLearn period. Supervision of the exercise was left to the teachers and parents. Based on the study, features such as tips and verbal feedback were added to the game.

'The learning game now offers tips on how to improve performance. If a child reacts very quickly, for example, the game might instruct the child to take it easy and slow down,' Ronimus says.

At the start of Neurodiversity Celebration Week, new research from Cranfield University demonstrates the importance of organisations becoming more inclusive employers when it comes to neurodiversity.

It has been estimated that one in seven of the population of the UK is neurodiverse. However, according to research by the Institute of Leadership and Management, only half of managers would employ a neurodiverse person.

Last week, in an interview with The Times, The Second Sea Lord Vice Admiral Nick Hine, revealed that ten years ago he was diagnosed with autism.

Speaking to The Times, the Vice Admiral, said: ""The world is made for neuro-typical people by neuro-typical people, and therefore it's not surprising that people who are not neuro-typical have a series of challenges or a series of difficulties both in interacting with that world, but also in the world interacting with them.

"If you want to transform, if you want a different way of doing business, you can't keep asking the same question of the same people and expect a different answer."

Although the original use of the term, neurodiversity, is rooted in research related to Asperger's syndrome, it has since been expanded to include dyslexia, dyspraxia, dyscalculia, Autism Spectrum Disorder (ASD), Tourette syndrome and Attention Deficit Hyperactivity Disorder (ADHD).

Research published in the journal, Employee Relations by Cranfield University reveals that:

Stereotype Threat comes before actual occurrence of a stereotype and that the discovery process starts before individuals join an organisation - those who are neurodiverse fear joining an organisation based on an assumption of what the organisation will be like.

The neurodiverse react to discrimination in similar ways to those with a visible difference-the neurodiverse can be put off from applying for jobs or revealing their difference when they are employed because of potential threat of stereotyping.

Dr Robby Allen from Cranfield University, said: "Increasingly, enlightened companies including NASA, Willis Towers Watson, Microsoft and Ford have reviewed their recruitment processes to take on more neurodiverse people.

"In such a competitive global economy, it is surprising that more companies are not embracing the unique specialist skills that those who diverge from the 'norm' can bring to an organisation.

"Internationally, the neurodiverse represent an untapped source of unique skills that can be of great advantage to organisations. However, this research reveals a potential paradox where an organisation cannot identify those that would bring greater benefit to the workforce if the neurodiverse within that workforce is reluctant to reveal themselves because of the stigma of stereotyping."

As part of the research two studies were conducted. One study, employed three exercises consisting of brochures, learning sets and posters to test organisational cues, notions of intelligence and situational cues. It collected data from 53 participants to establish whether stereotype threat observed in visible difference such as race, gender and intelligence is equally relevant to neurodiversity. The second study consisted of interviews with 44 participants to establish stereotype threat source, reaction and effect on declaration of invisible difference.

Low plasma levels of protein TGFB1 and polymorphisms in gene TGFB1 act as biomarkers for the prognosis of gastric adenocarcinoma, according to a study led by the University Complutense of Madrid (UCM).

In particular, these variants are 12% more frequent in patients with metastatic tumors, "which indicates their importance in the clinical progression of this disease", stated José Manuel Martín Villa, Professor of Immunology and researcher at the Department of Immunology, Ophthalmology and Otolaryngology of the UCM.

In addition to identifying patients with poorer progression and high mortality, these markers also identify individuals at risk of developing this stomach tumor.

The finding, published in the Journal of Cellular and Molecular Medicine, "helps establish newer and more appropriate therapeutic regimens", according to Martín Villa.

In addition to the UCM, the study counted on the participation of the Department of Gastrointestinal Surgery of University Hospital Príncipe de Asturias (Alcala de Henares, Community of Madrid, Spain) and the Gregorio Marañón Healthcare Research Institute (Madrid, Spain).

Possibility of extrapolating the data

Regarding the detected serological marker, Martín Villa explains that, "the role of the TGFB1 protein in the progression of cancer, modulating the immune response, is controversial. However, these data indicate that this cytokine has a direct effect on the disease, because its absence causes these tumors to become malignant and more invasive, aggravating the patients' condition".

To reach these conclusions, the researchers obtained genetic material from a Spanish population and determined the variants using molecular biology techniques.

The patients were stratified according to internationally established criteria for disease stages (I to IV). Statistical approaches were employed to determine the association between these genetic markers and the development and progression of the disease.

"This study was conducted over the course of 5 years, which has enabled us to associate these genetic variants with patient survival in the medium term", added Martín Villa who also leaves the door open to the possibility that the identified genetic and serological markers are also involved in other tumors such as colorectal cancer.

SAN ANTONIO -- March 18, 2021 -- Working with a team led by French astronomers, Southwest Research Institute scientists helped identify incredibly powerful winds in Jupiter's middle atmosphere for the first time. The team measured molecules exhumed by the 1994 impact of comet Shoemaker-Levy 9 to trace winds in excess of 900 miles per hour near Jupiter's poles.

Jupiter's distinctive red and white bands of swirling clouds allow scientists to track winds in the planet's lower atmosphere, and the SwRI team members have particular expertise in the vivid Jovian aurora, associated with strong winds in the gas giant's upper atmosphere. Until now, wind patterns in the cloudless stratosphere, between the two atmospheric layers, have eluded observation.

"The team of astronomers led by Laboratoire d'Astrophysique de Bordeaux (LAB) in France had to get creative," said SwRI's Dr. Vincent Hue, co-author of an Astronomy & Astrophysics paper describing this research. "They followed fallout from that long-ago comet impact to track molecular evidence, specifically hydrogen cyanide, to measure stratospheric 'jets' -- like Earth's jet streams -- on Jupiter."

The Atacama Large Millimeter/submillimeter Array (ALMA) radio telescope facility allowed scientists to measure stratospheric winds in what they refer to as a unique meteorological beast in our solar system for the first time.

"The most spectacular result is the presence of strong jets, with speeds up to 400 meters per second (900 miles per hour), which are located under the auroras at the poles," said LAB's Thibault Cavalié, lead author of the paper.

"The stratospheric jets could behave like a giant vortex with a diameter up to four times that of Earth," said co-author Bilal Benmahi, also of LAB.

Previous studies predicted that upper-atmosphere winds would decrease in velocity and disappear well before reaching as deep as the stratosphere. The new ALMA data beg to differ, finding surprisingly strong stratospheric winds near Jupiter's pole. SwRI scientists study the Jovian aurora using the SwRI-led Ultraviolet Spectrograph (UVS) aboard NASA's Juno spacecraft, providing their expertise in interpreting these measurements.

Using 42 of ALMA's 66 high-precision antennas, the team measured the Doppler shift of hydrogen cyanide molecules -- tiny changes in the frequency of radiation emitted by the molecules -- caused by the winds in this region of the planet.

"By measuring this shift, we were able to deduce the speed of the winds much like one could deduce the speed of a passing train by the change in the frequency of the train whistle," Hue said.

In addition to the surprising polar winds, the team also used ALMA to confirm the existence of strong stratospheric winds around the planet's equator. The jets spotted in this part of the planet have average speeds of about 370 mph.

"These findings also set the stage for similar yet more extensive measurements to be made by the JUICE mission and its Submillimetre Wave Instrument," said SwRI's Dr. Thomas Greathouse, another co-author, referring to the European Space Agency's JUpiter ICy moons Explorer. JUICE is expected to launch into space next year, carrying the next generation of SwRI's Ultraviolet Spectrograph instrument.

- It is as if China is two completely different countries, if we look at how they appear in two such different cases as Africa and the Arctic, says Christer Henrik Pursiainen. He is a professor at the Department of Technology and Security at UiT The Arctic University of Norway.

According to Pursiainen, it is not just the temperature difference that separates Africa from the Arctic. It also provides a good opportunity to take a closer look at how China adapts to two completely different situations and how they use widely differing methods to gain influence.

Together with professors Rasmus Gjedssø Bertelsen from UiT and Chris Alden from the London School of Economics, he has published the article "The Arctic and Africa in China's Foreign Policy: How Different Are They and What Does This Tell Us?" in the journal Arctic Review on Law and Politics.

Economic growth provides calm

China will soon be the world's largest economy and many of the country's 1.4 billion inhabitants are experiencing a real increase when it comes to standard of living. The country's elite want to keep the Communist Party in power and to ensure inner peace and stability, they must ensure continuous economic growth.

- This is much of the reason why China is increasing its global presence. To ensure the legitimacy of the Communist Party, economic growth must be maintained. China's worst nightmare is that what happened in the Soviet Union will also happen there, says Pursiainen.

To ensure economic growth, China is completely dependent on international trade. They are the world's largest importer of raw materials and energy and are the world's largest trading nation. The vast majority of this trade goes by sea, and therefore it is absolutely crucial to secure and strengthen the transport of goods and services.

China therefore, in 2013, started what has gradually become known as the Belt and Road Initiative. As a modern silk road, trade, and the road to becoming the world's largest superpower, will be increased through a massive investment in the development of trade routes and infrastructure across large parts of the world.

- China knows very well that they will slowly but surely become the leading superpower for the next 100 years. It can only be delayed by the United States, but I think the chance of this is small. The United States has had its century, says Pursiainen.

He points out that China is not in a hurry, and that they may have a different perception of time than politicians in most Western countries.

- Chinese leaders are elected for life. And the Chinese look 50-100 years ahead in time and thousands of years back. They know they have been a great power - and will be again, he says.

A learning state

China gradually began its presence in Africa as early as the mid-1950s. At first modestly, but today China is Africa's largest trading partner, measured at $ 204 billion in 2018.
Weak governance and little international control has given China great flexibility in how to position itself in Africa.

- China is a learning state and they began their relations with Africa a long time ago. They gradually started investing, and today Africa is a major borrower. China has become a power factor throughout Africa and Chinese companies and migrants have established themselves across the continent in telecommunications, ports, car factories, small farms and shops, says Pursiainen.

He believes that one of the reasons why China has gained so much influence and acceptance in the various African countries is that they are open about the intention not to export communism and that they do not in principle interfere in national politics. This has made it easier for heads of state to let them into their countries.

Over time, large Chinese investments have led to a relationship of dependence.

- It has turned into a relationship where many African countries have become dependent on Chinese support - and more specifically Chinese companies and people, says Pursiainen.

Must secure own investments

To ensure stability in the areas of Africa in which they operate, and to ensure trade flows and investments, China is choosing a proven method.

- They use the same tactics as the United States, with the establishment of military bases, they contribute with peacekeeping forces to the UN and the African Union (AU) and they have a number of "private" security companies, which are subordinate to the Communist Party, says Pursiainen.

In 2015, the Chinese established their first, and so far only, military base in Djibouti on the Horn of Africa. The base has about 10,000 soldiers and is closely linked to a major port project nearby. Although they claim this is primarily a logistics base and for defense against piracy in the area, it gives the Chinese authorities a significant military presence and a full overview of all ship traffic through the Red Sea and the Gulf of Aden.

- They claim they are there to help and ensure stability, but this is a way for China to become a global superpower, says Pursiainen.

In addition, China has several agreements with various African countries when it comes to arms sales, military exercises and other forms of cooperation.

The Arctic

As China has gained a stronger voice in international politics in recent years, they have also turned their attention and interest to the Arctic and the opportunities that exist there.

The motivation is the same - to ensure economic growth and influence. But the approach China chooses is completely different. While they have been able to gain a foothold due to weak states and a poorly developed system of government in Africa, the situation is quite different in the north. The Arctic is surrounded by developed countries with established laws and regulations and is an area that has far greater international attention.

This means that China must seek influence by other means.

- Chinese foreign policy is very adaptable and flexible. They are very good at this. China has defined itself as a near-Arctic country. Of course they are not, but still they claim that right. And what we observe is that while China follows existing rules in the Arctic, they are actively working to influence and change them to their advantage, says Pursiainen.

China is doing this by engaging broadly in global organizations where they already have an important seat. This applies, for example, to the UN, where they are trying to influence the future use of the Arctic through both the Convention on the Law of the Sea and the International Maritime Organization (IMO).

The same applies to the Arctic Council. After gaining an ad-hoc role as an observer in 2007, China worked purposefully to gain a more permanent role in the Council. Despite the fact that this was first met with skepticism from Canada, Russia and the USA, they eventually gained a permanent place as an observer in 2013. Although this does not give China an active role in the decisions made, they get to legitimately participate in the debate on the future of the Arctic.

Important with laws and regulations

Although China claims that through increased presence in the Arctic, they can achieve win-win situations for everyone involved, those who are researching this are divided. Some push the alarm button, some are moderate, while others predict a more positive effect of China's entry into the Arctic.

While Chinese investment has to some extent been welcomed by the countries around the Arctic, many are concerned about the economic and political influence that may accompany such investments.

- If we are to learn from such a comparison between two continents as different as Africa and the Arctic, then that must be that it is important to secure and maintain strong regional and national institutions, based on laws and regulations. This will counteract any negative aspects of increased Chinese involvement, says Pursiainen.

He points out that it is crucial to ensure that China does not use its economic muscles to enter into agreements with countries in a vulnerable situation. This will create a dependency relationship, as seen in some African countries, where China gains too much power.

- What we are trying to say is that one should be happy that China is investing, also in the Arctic. But, we must be vigilant and not let them establish their own rules, says Pursiainen.

Researchers are developing new autonomous technologies that can help people check that isolated elderly family members are okay.

We are living in a world where elderly parents are increasingly distant from their relatives, as many relocate for work opportunities.

There are now more than 4 million people aged 65 and older who are living alone in the UK.

The series of national lockdowns during the coronavirus pandemic has made it even harder for people to check that those elderly loved ones are safe and well.

Families want peace of mind that their elderly relatives are living well, and are maintaining a relatively active lifestyle. Although we can call them to check in on them, it is often not enough.

Dr Rebecca Killick, Principle Investigator of the study from Lancaster University, said: "We can call them using phones, or video conferencing tools, but often we can find that many elderly people will say they are fine, and we aren't convinced. You try to probe further but it is hard when you don't have all the social clues that can confirm your suspicions."

To help overcome these problems, the researchers, from Lancaster University, working with technology company Howz have devised a new way of interpreting statistical data from smart home sensors.

These sensors, which work much like household security sensors, record movement and other activities such as the opening and closing of doors and the use of appliances.

The researchers novel statistical analysis methods includes representing the visualisation of data in a circular graph that can be layered, rather than in a linear form. Traditional statistical methods struggle with the periodic nature of people's daily routines - with active times, when making meals or drinks, and less active times, when sleeping, reading or watching TV.

The new method overcomes these previous limitations in identifying changes, using what statisticians call 'changepoint analysis'.

The system of sensors from Howz, combined with the insights gained from the researchers' new statistical approach, were deployed in the homes of four study participants for 56 days.

The results show that the system was able to identify broad patterns in a day, such as hours in the day participants were awake and asleep, as well as times they were doing activities like preparing meals.

In addition, the new statistical method meant they were able to more easily and more accurately track and compare the routines of the participants over multiple days. This is important as this lays the foundation for systems that can quickly identify subtle changes in behaviour that could indicate a deterioration in health.

Dr Killick said: "This research allows us to identify an individual's daily, or weekly, pattern of changing behaviour and spot unexpected deviations. This can then be used as a nudge for family members, or carers, to have a conversation."

"Our novel approach has reformulated the problem of identifying patterns of behaviour so that the data can be compounded day after day, and over time more subtle changes can be found. This is crucial as we can now detect changes in behaviour earlier or catch changes that would have been missed previously."

The researchers believe that their new statistical approach to changepoints could also be useful in other research areas, including the environment, official statistics and business.

(Boston)-- Uncontrolled diabetes increases maternal and fetal risks during pregnancy. As a result, the American Diabetes Association (ADA) recommends that family planning should be discussed and effective contraception should be available to the more than three percent of (more than one million) reproductive-age women in the United States with diabetes. Yet a new study has found that women with diabetes are less likely to use contraception after their diabetes diagnosis.

"Efforts are needed to ensure that women with diabetes receive the counseling and clinical services needed to carefully plan their pregnancies," said corresponding author Mara Murray Horwitz, MD, assistant professor medicine at Boston University School of Medicine.

Using claims data from a large national insurance provider to identify reproductive-age women, the researchers divided them into two groups: those who received a new diabetes diagnosis and those who did not receive a diabetes diagnosis. They then matched individuals in each group on important other variables to make the groups more similar. Using medical diagnosis, pharmacy fill and procedure codes, they measured contraception use in the two groups during the year before the diagnosis and during the year after the diagnosis. Finally, they compared the change in contraception use from the year before the diagnosis to the year after the diagnosis, in the diagnosed group versus in the undiagnosed group.

They found that being diagnosed with diabetes does not make a person more likely to use effective contraception and in fact may lead to a drop in the use of certain types of effective contraception, namely short-acting hormonal methods such as pills and injections.

The ADA states that "women with diabetes have the same contraception options and recommendations as those without diabetes," and that, "the risk of an unplanned pregnancy outweighs the risk of any given contraception option." "Nonetheless, many patients and clinicians report concerns about the need for and safety of contraception in the setting of diabetes. It is conceivable that--as our study suggests--a diabetes diagnosis leads to less, instead of more, contraception counseling, prescribing, and use," added Murray Horwitz, a physician at Boston Medical Center.

The researchers hope that this study leads to more comprehensive care, including family planning with the full range of safe and effective contraceptive options, for persons with diabetes who may become pregnant. "Ultimately we want everyone to be able to choose when and if they become pregnant and to have the information, tools and support as needed to optimize their pregnancy outcomes," she said.

These findings appear online in the journal Primary Care Diabetes.

MADISON, Wis. -- Scientists at the University of Wisconsin-Madison have developed a way to use a cell's own recycling machinery to destroy disease-causing proteins, a technology that could produce entirely new kinds of drugs.

Some cancers, for instance, are associated with abnormal proteins or an excess of normally harmless proteins. By eliminating them, researchers believe they can treat the underlying cause of disease and restore a healthy balance in cells.

The new technique builds on an earlier strategy by researchers and pharmaceutical companies to remove proteins residing inside of a cell, and expands on this system to include proteins outside or on the surface of liver cells.

"In the past, to develop a new drug, we often needed to find a molecule that bound to the protein of interest and also changed the function of the protein. But there are many potential proteins associated with diseases whose function you cannot block easily," says Weiping Tang, a professor of pharmacy and chemistry at the University of Wisconsin-Madison who led the new research. "With the targeted protein degradation strategy, we can go after many of those proteins."

Tang, with colleagues in the UW-Madison School of Pharmacy, demonstrated the new method in proof-of-concept experiments on lab-grown liver cells. They were able to neutralize multiple extracellular proteins, including EGFR, a cancer-associated protein. The scientists published their findings March 4 in the journal ACS Central Science.

The technology works much like a city's trash-collection system. Antibodies attach tags for destruction to specific proteins, marking them as unwanted. A shuttle protein on the liver cell, serving as a kind of garbage truck, recognizes these markers, engulfs the protein, and ferries it to the protein-digesting compartment of the cell, which breaks down the protein into reusable parts.

Many researchers over the past several years, including the Tang group, have developed tools to selectively target for destruction certain cellular proteins found on the inside of cells, named PROTACs. Multiple PROTAC-based drugs are now in clinical trials to treat several cancers.

The Tang lab is now expanding the scope of targets to additional proteins found outside of or on the surface of the liver cell. They have turned to the lysosome, a compartment of the cell that digests and destroys all kinds of materials, including what the cell engulfs from outside. Since the liver is the primary organ that breaks down proteins in the body, it is an ideal tissue to selectively degrade undesired proteins.

To gain access to the lysosome, the researchers relied on a lysosome shuttle named ASGPR. The shuttle is primarily found on the surface of liver cells. It recognizes certain sugars on proteins and delivers the proteins to the lysosome for digestion.

To help encourage ASGPR to recognize and help destroy disease-causing proteins, researchers in earlier studies learned they could attach three specific sugars to the proteins. But first they had to figure out how to go about attaching them to the proteins they wanted to eliminate.

Tang's group focused on antibodies, which are ideal candidates since they recognize and bind to specific proteins. The team attached the sugary tag that would activate ASGPR to an antibody that would track down the specific proteins they hoped to destroy. In this way, the scientists could shuttle the protein to the lysosome of liver cells with this highly targeted trash-collection system.

They tested their technology against several proteins, including EGFR, which tumors produce in excess. By attaching the sugary tag to an EGFR antibody, the scientists were able to deplete a significant amount of the protein that otherwise accumulated outside of cancerous liver cells grown in the lab.

Tang's lab is now working to refine the ASGPR method by making it more effective, and to expand the strategy to destroy proteins on the surface of other types of cells. They are also interested in collaborating with other researchers to help them test the removal of a wider array of disease-associated proteins.

"I believe there's a great future ahead of us, but we need to invest our resources and time to investigate the protein degradation strategy further," says Tang.

The ongoing COVID-19 pandemic changed the higher education experience for students across the United States, with more than 90 percent of institutions reporting a shift in education delivery with the arrival of COVID-19.

The rapid transition to remote study came with its own learning curve for students and faculty alike. But for many students with disabilities, the shift offered new educational modalities as well as challenges - and the hope that some changes will continue after the threat of the virus subsides.

"This was a really unique, historical moment," says Nicholas Gelbar '06 (ED), '07 MEd, '13 Ph.D., an associate research professor with the Neag School of Education. "Remote learning, online learning, had been percolating for a while, and then there's this moment where everything went online. For the group that we research - college students with disabilities - this is an especially unique time, because most of the services they receive at the college level are set up for in-person learning. This shift made us wonder, how do these services and these supports, these accommodations that they receive, how do they translate to this online world?"

Gelbar is a co-author of a new study, recently published in the Journal of Postsecondary Education and Disability, that examined the impact of the rapid transition to online learning during the spring 2020 academic semester on college students with disabilities. The researchers conducted a national survey of more than 340 students in both two and four-year programs to measure the perceptions of college students with disabilities about their experiences. The online survey was conducted in August and September 2020.

Overall, the researchers found that, despite certain drawbacks, the students surveyed felt supported by their institutions, faculty, and disability services offices.

"What we found is that the students said there were things that were kind of advantageous and there were things that were harder in the online environment," Gelbar says. "They found the learning management systems accessible. They were able to change how they took notes, because they were able to watch an online lecture and then watch it over again, so they could take notes multiple ways. They said their instructors were really helpful about communicating any changes to assignments or projects that happened."

Gelbar continued, "The drawback was that they reported having family demands that impacted their learning. They talked about how home isn't always the best place to do their studying - there's distractions. They said they felt less connected to other students and to their instructors."

A major, positive change reported by the students was the shift to online communication with disability service providers at their universities, who typically help students access the accommodations they need to conduct their studies, things like extended deadlines on assignments, more time for test taking, and assistance with taking notes.

"There were lots of universities that responded by saying, 'well, you aren't on campus anymore, so how do we get you changes to your accommodations?'" says study co-author Michael Faggella-Luby, a professor of special education at Texas Christian University, director of the Alice Neeley Special Education Research and Service (ANSERS) Institute, and a former associate professor at the Neag School of Education. "We can't do it the old way, where, you come in and meet with us, we write you a letter, you take the letter to your professor, they sign it. We can't do this anymore, so some universities responded by moving the whole process online. Well, now everybody wins. It's much easier to do those things."

It's also more private, Faggella-Luby says - allowing students to discuss their need for accommodations with their professors outside of an open classroom environment.

"We know only half the college kids who have disabilities when they get to college file the paperwork to get the services that they have an entitlement to," says Faggella-Luby. "Why? Well, at least for some, they don't want to be one of those kids who has to stay behind at the end of the first class with a piece of paper in their hand, basically saying, 'Hi, I'm a kid with a disability.' What this did was expedite, but also destigmatize - create an opportunity for folks to be able to communicate in a private way about something that is very private, and yet still maintain a high level of services. That to me was essential."

"Some students with chronic health issues talked about how even going to meet with the disability service staff was a challenge because of the health issues - just getting across campus - but being able to check in virtually made all the difference," says Joseph Madaus, professor of educational psychology with the Neag School of Education; director of UConn's Collaborative on Postsecondary Education and Disability, or CPED; and principal investigator for the study.

Communication, the researchers said, was at the heart of the responses they received, which they said were highly bimodal - respondents had either very positive or very negative feelings about how things went at their university.

"When the students talked about what worked well and what was important, it was clear, consistent, early, proactive communication and flexibility," says Madaus. "And then when students talked about what didn't go well, it was that the communication wasn't clear and it wasn't proactive and things were just not stable anymore."

"We were concerned that maybe kids lost access to their accommodations, and then just got railroaded and totally forgotten about," Faggella-Luby says. "In fact, that wasn't what they were telling us. Instead, there were these positive ways of communicating. People were seeing if they needed additional accommodations. The professors going online and making the video pause-able, which they've never done before, now allowed them to have completely different, enhanced access, without having to ask for it."

The students also noted the benefits of changes - like the availability of closed captioning and transcripts for recorded lectures, and flexibility on assignments and due dates - which Madaus noted are also principles of Universal Design for Learning, a framework for teaching faculty to incorporate methods that support multiple ways of learning while maintaining quality educational standards.

"The students didn't voice this, but what they said fell into categories of Universal Design, where faculty are presenting material in multiple ways," Madaus said, "and that benefits not only the students with disabilities, but it will benefit a wide range of learners within the environment."

The researchers noted their sample included mostly women, that most participants were from the eastern portion of the country, and that the study represented only a snapshot in time - focusing on period when the pandemic was new.

"We've wondered if maybe the students had a higher tolerance, because they sort of appreciated that this shift that happened was unprecedented and that everyone was basically doing the best that they could," Gelbar says.

The research team is currently crafting a second survey to look at how students with disabilities perceived their educational experiences into 2020-2021 academic year, when the pandemic had been ongoing for months and faculty would have presumably had more time to prepare for a completely remote experience. They also intend to ask additional questions about the impact of quarantine on learning as well as the pandemic's overall impact on student mental health.

But what the study did show, the researchers said, is that, for disability service providers, offering some form of remote services is beneficial, as is proactively providing course offerings in different modalities that can make course materials more accessible to all students.

"In the online format, we can make things more accessible to students," Gelbar says, "and the more that we do that proactively, it's not only benefiting students with disabilities, but all students."

"The benefits of high-quality training for university faculty and these Universal Design practices help every single discipline," says Faggella-Luby, "and what comes out of it is better content-area learning, And it's not one more thing to do, it's the right thing to do, and kids learn better. Your degree means more, their mastery is better. It's a horrible situation that we had to go through, but I hope that's something that lives from this."

Millions of children weighing less than 15kg are currently denied access to Ivermectin treatment due to insufficient safety data being available to support a change to the current label indication. The WorldWide Antimalarial Resistance Network (WWARN)'s new meta-analysis published today provides evidence that supports removing this barrier and improving treatment equity.

A systematic review and an individual patient data meta-analysis of Ivermectin use in children weighing less than fifteen kilograms: Is it time to reconsider the current contraindication? shows that concerns regarding the potential for neurotoxicity of Ivermectin in infancy are misplaced. The data provide limited but encouraging evidence that the Ivermectin tolerability and safety profile in children weighing less than 15kg is similar to that in heavier, older individuals.

Ivermectin is a safe, broad-spectrum anthelminthic drug registered for the treatment of several neglected tropical diseases (NTDs) including onchocerciasis, lymphatic filariasis, scabies, and strongyloidiasis. These frequently afflict young children but Ivermectin use is restricted because of a lack of evidence for the safety of these drugs - alternative treatments to ivermectin are frequently less effective or potentially even toxic.

Available data suggest that adult-based dosing is not appropriate for children and that a standard dose may not reach effective levels in small children for all NTDs. The ideal dose of Ivermectin for different indications in small children is not known and further investigation through well-designed clinical trials to optimise this and characterise the safety profile is needed. A randomised, placebo-controlled, double-blind, dose escalation trial, called the Ivermectin Safety in Small Children trial, is underway to assess the safety, tolerability, pharmacokinetics, and scabies efficacy of escalating doses of ivermectin in children weighing less than 15 kg in Bangladesh, Brazil, Kenya and Mozambique.

WWARN's review of the literature conducted an individual-level participant data (IPD) meta-analysis across all clinical trials, case series, case reports, and database entries for reports on the use of Ivermectin in children weighing less than 15kg published between 1 January 1980 to 25 October 2019. 1,088 children weighing less than 15kg were administered oral Ivermectin and overall 1.4% experienced 18 adverse events all of which were mild and self-limiting - no serious adverse events were reported.

Dr Kevin Kobylinski from the WWARN Ivermectin Exposure in Small Children Study Group said: "Our systematic review suggests that Ivermectin is as safe and well tolerated in children weighing less than 15kg as it is persons weighing more than15 kg. Hopefully, this work encourages future, well-designed clinical trials and review by regulatory authorities so that the contraindication of Ivermectin use in children weighing less than 15kg can be removed allowing equitable access to ivermectin use in small children."

To continue developments in this field, greater clarity is needed when reporting Ivermectin use in children to include the weight of any child below 15kg and report any associated adverse events (AEs). An IPD call for Ivermectin safety in children weighing less than 15kg has been organised by WWARN and data from future publications, or clarifications to the publications cited, can be contributed by contacting the study authors. The evidence in this review has been compiled into an IPD database, held at WWARN, and is available on request via info@wwarn.org

The impact on populations affected by NTDs

During mass drug administration (MDA) campaigns for operational reasons and to expedite delivery, dosing is usually based on height, not weight. Only people taller than 90cm are eligible to receive Ivermectin. Many children at 90 cm weigh between 11-15kg and millions weighing less than 15kg have taken Ivermectin for onchocerciasis and lymphatic filariasis in Africa but this was not documented. Over 400 million people were treated with Ivermectin during MDAs in 2019 alone, primarily in Africa, with over four billion treatments administered via MDA to date, supporting the case that Ivermectin is a safe drug.

Ivermectin has been proposed as a novel malaria control tool due to its ability to kill Anopheles mosquitoes and Ivermectin MDAs can suppress Plasmodium transmission. Coverage is one of the most critical components of MDA efficacy and excluding children under 15kg excludes roughly 20% of the population in many malaria endemic areas. In Africa, children under five years old are frequently bitten by Anopheles and become an important reservoir of Plasmodium and facilitating its onward transmission.

NTDs cause growth stunting in children, for example infection with soil-transmitted helminths (STHs). This growth stunting means that some children may not reach 90cm until they are older but ironically are denied Ivermectin during MDA campaigns which could eliminate the very parasites causing their stunted growth. Additionally, STH infections at a young age are associated with impairment of cognitive development, and reduced school attendance further justifying the importance of including children under 15 kg in Ivermectin MDAs.

Read the research: A systematic review and an individual patient data meta-analysis of Ivermectin use in children weighing less than fifteen kilograms: is it time to reconsider the current contraindication?

HOUSTON - (March 18, 2021) - If you're looking for one technique to maximize photon output from plasmons, stop. It takes two to wrangle.

Rice University physicists came across a phenomenon that boosts the light from a nanoscale device more than 1,000 times greater than they anticipated.

When looking at light coming from a plasmonic junction, a microscopic gap between two gold nanowires, there are conditions in which applying optical or electrical energy individually prompted only a modest amount of light emission. Applying both together, however, caused a burst of light that far exceeded the output under either individual stimulus.

The researchers led by Rice physicist Douglas Natelson and lead authors Longji Cui and Yunxuan Zhu found the effect while following up experiments that discovered driving current through the gap increased the number of light-emitting "hot carrier" electrons in the electrodes.

Now they know that adding energy from a laser to the same junction makes it even brighter. The effect could be employed to make nanophotonic switches for computer chips and for advanced photocatalysts.

The details appear in the American Chemical Society journal Nano Letters.

"It's been known for a long time that it's possible to get a light emission from these tiny structures," Natelson said. "In our previous work, we showed that plasmons play an important role in generating very hot charge carriers, equivalent to a couple of thousand degrees."

Plasmons are ripples of charge that carry energy, and when triggered, flow across the surface of certain metals, including gold. In the voltage-driven mechanism, electrons tunnel through the gap, exciting plasmons, which leads to hot electrons recombining with electron "holes" and emitting photons in the process.

Even though the effect seemed dramatic at the time, it paled in comparison to the new discovery.

"I like the idea of '1+1=1,000," Natelson said. "You do two things, each of which doesn't give you much light in this energy range, but together, holy cow! There's a lot of light coming out."

The specific mechanisms are worthy of further study, he said. One possibility is that optical and electrical drives combine to enhance the generation of hot electrons. An alternative is that light emission gets a boost via anti-Stokes electronic Raman scattering. In that process, light input prompts already excited hot carriers to relax back to their ground states, releasing more photons.

"Something interesting is going on there, where each of these individual excitations is not enough to give you the amount of light coming out," Natelson said. "But put them together and the effective temperature is much higher. That's one possible explanation: that the light output is an exponential function of the temperature. Reaching that effective temperature takes hundreds of femtoseconds.

"The Raman mechanism is more subtle, where light comes in, grabs energy from the voltage, and even stronger light leaves," he said. "That happens even faster, so a time-dependent experiment could probably help us figure out the dominant mechanism.

"The reason it's neat is that you can, in principle, couple the electrical drive and light coming in to do all kinds of things," Natelson said. "If the hot carrier picture is right, there's the possibility of doing some interesting chemistry."

Co-authors of the paper are Peter Nordlander, the Wiess Chair in Physics and Astronomy and a professor of electrical and computer engineering and of materials science and nanoengineering at Rice, and Massimiliano Di Ventra, a professor of physics at the University of California, San Diego. Cui, a former postdoctoral fellow at Rice, is now an assistant professor of mechanical engineering and materials science and engineering at the University of Colorado Boulder. Zhu is a graduate student at Rice. Natelson is chair and a professor of physics and astronomy and a professor of electrical and computer engineering and of materials science and nanoengineering.

When it comes to recreational crabbing--one of the most iconic pastimes along Maryland's shores--the current estimate of 8% of "total male commercial harvest" runs just a little too low. Biologists, with local community support, found stronger evidence for the underestimate in the first tagging study to estimate the recreational blue crab harvest statewide.

"It's such an important cultural activity here to go out and harvest crabs," said Matt Ogburn, a biologist with the Smithsonian Environmental Research Center (SERC) and co-author of the new report. Once declared a "commercial fishery failure" in 2008 after years of record low numbers, blue crabs have made a somewhat bumpy but steady comeback over the past decade.

To keep that recovery going, fishery managers need a clear idea of how many crabs end up in commercial traps and on the tables of recreational crabbers. Commercial crabbers are required to report how many crabs they catch each season. But recreational crabbers have no such obligation. This leaves managers in the awkward position of having to make their best educated guess.

"The recreational fishery is a bit of an unknown," said Robert Semmler, a doctoral student at Lancaster University and lead author of the new study, published March 15 in The Canadian Journal of Fisheries and Aquatic Sciences. "And a lot of people are concerned about the recreational fishery. Particularly within the commercial sector, fishers are concerned about how big the recreational fishery is and whether that is possibly impinging on their ability to fish themselves."

Tag, Release, Reward

Right now, the Chesapeake Bay Stock Assessment Committee estimates recreational harvest to be 8% of the total male commercial harvest. Since recreational crabbers are not allowed to harvest females--one of the new regulations put in place in 2008 to ensure blue crabs continue to spawn--comparing "total male" harvests in theory offers a better apples-to-apples comparison.

But the 8% figure has its skeptics. To get it, managers relied on surveys and other voluntary self-reports from recreational crabbers conducted in 2001, 2002, 2005 and 2011. Those surveys suggested recreational crabbing amounted to 5-8% of the total commercial harvest. Some of those surveys suggested a higher figure--11.6%--of the total male commercial harvest. For managers, estimating recreational crabbing as "8% of total male commercial harvest" seemed like a happy medium. Even so, some people recall seeing far more recreational crabbing in certain parts of the Chesapeake Bay.

"If those methods underestimated the amount of recreational fishing, if we keep doing the same thing, we'll always be underestimating it, and we won't know that," Ogburn said.

So Ogburn, Semmler and SERC's Fisheries Conservation Lab decided it was time to try a new method to see if the 8% figure would hold up. The project was part of Semmler's master's thesis during his time at the University of Maryland.

The biologists used a technique called "mark-recapture." They teamed up with local watermen to mark 6,800 crabs with vinyl tags on their shells. Their tagging effort spanned 15 regions along Maryland's eastern and western shores, including the bay mainstem and several tributaries, giving them a thorough picture of crabbing statewide.

The tags contained the lab's phone number and an offer for a reward. Anyone who captured a tagged crab could call the number, tell the scientists where they caught the crab and if they were a commercial or recreational crabber.

The assist from the local community was critical. Biologist Rob Aguilar, head technician for the Fisheries Conservation Lab, helped the team find crabbers to let scientists on their boats and tag the crabs. But success truly hinged on having enough crabbers willing to call in their catches.

"It's good to have that relationship and to have people in the community know that they can trust the science, because they were involved in it," Semmler said.

From there, it became a simple algebra problem. Once the scientists had three variables--total commercial harvest, number of commercial captures called in and number of recreational captures called in--they could plug them in to find the number they really wanted: total recreational harvest.

Moving Targets

However, the team did not stop there. They took things a step further to account for crabs moving throughout the bay. Blue crabs do not stay in one place. They move back and forth between the saltier bay mainstem--where commercial crabbing prevails--to fresher tributaries, where recreational crabbing is more common. Ignoring crab movement could easily skew the team's estimates.

Once they took that into account, their results changed. Without crab movement, the team calculated recreational harvest at 4.04 million crabs, or roughly 8.4% of "total male" commercial harvest--right in line with the current 8% estimate. But with crab movement in the equation, recreational harvest rose to 5.39 million crabs--or 11.2% of "total male" commercial harvest.

Shifting to an 11.2% estimate, the authors say, would give Maryland a more accurate picture of recreational crabbing throughout the state. This would also bring the assessment close to the average of 11.6% of "total male" commercial harvest estimated from prior recreational crabbing surveys.

By doing tagging surveys in over a dozen regions, the lab also pinned down spots where the recreational take is higher than average. Hot spots of recreational crabbing tended to be in tributaries with clusters of waterfront homes and easy access for recreational boaters.

"Depending on where you live, recreational harvest could range from near zero to more than twice the size of commercial harvest in densely populated places like the Severn River," Ogburn said. "That means you might see high recreational harvest of crabs in your local area, but once you average across the entire state, the level of harvest isn't much higher than expected."

In a study aimed at investigating the mechanism responsible for exacerbating rheumatoid arthritis in smokers, researchers at the Center for Research on Inflammatory Diseases (CRID), linked to the University of São Paulo (USP) in Brazil, discovered a novel path in the inflammatory process associated with the bone damage caused by rheumatoid arthritis. The discovery opens up opportunities for new therapeutic interventions to mitigate the effects of the disease, for which there is no specific treatment at this time.

An article on the study is published in Proceedings of the National Academy of Sciences (PNAS). The researchers identified the action of a molecular mechanism involved in the inflammatory process: release by T-lymphocytes of extracellular vesicles loaded with genetic material (microRNAs). The vesicles reach cells in bone tissue, increasing the formation of osteoclasts, cells that break down bone matrix in joints (a critical function in bone maintenance, repair, and remodeling).

“The study set out to extend our understanding of how cigarette smoke exacerbates the inflammatory process in rheumatoid arthritis. We discovered a path associated with bone damage. This is an important finding since pain and inflammation have been treated with medications, but the bone damage that is a debilitating complication of this disease is practically irreversible,” said Fernando de Queiroz Cunha, principal investigator of CRID, one of the Research, Innovation and Dissemination Centers (RIDCs) supported by FAPESP.

Rheumatoid arthritis is an autoimmune disease in which for an unknown reason the immune system mistakes parts of the patient’s body for an invading pathogen and attacks them. The inflammation triggered by the immune system’s overreaction is known to involve Th17 cells, a T-cell subtype, and to create cascading effects such as the release of cytokines (signaling proteins), including IL-17, as well as other molecules that participate in the disease’s progression.

Smoking is known to be an aggravating factor for rheumatoid arthritis. Previous research by the same CRID group showed that cigarette smoke exacerbates the inflammatory process in arthritis mainly by activating the aryl hydrocarbon receptor (AhR) on Th17 cells. 

“AhR is a pollutant-detecting intracellular sensor that participates in the inflammatory process. When AhR is activated on T-cells by certain ligands, they differentiate to Th17 even more. The increase in Th17 cells exacerbates the inflammatory process. Although smoking doesn’t cause rheumatoid arthritis, it makes the disease worse,” said Paula Donate, a CRID researcher whose postdoctoral research was supported by FAPESP. 

Donate explained that AhR acts mainly as a transcription factor. “If this receptor is activated by an external agent such as cigarette smoke, it enters the cell nucleus together with other proteins and promotes the transcription of various genes, including microRNAs, which are small regulatory RNAs inside the cell,” she said.

Extracellular component

In the study, the researchers wanted to find out which microRNAs in Th17 cells were more expressed owing to AhR activation. Their analysis pointed to miR-132. They analyzed the full set of microRNAs expressed by Th17 cells and correlated the findings with data from a laboratory trial involving mice and human patient samples.

“To our surprise, however, when we treated T-cells with antagonists of the microRNAs, they continued to differentiate normally into Th17 cells, releasing the cytokines characteristic of the inflammatory process in rheumatoid arthritis. If it had no influence on the intracellular process, it was a sign that miR-132 could be released into the extracellular medium,” Donate said.

When the researchers isolated extracellular vesicles released by Th17 and studied them in vitro, they found that the large amounts of miR-132 packaged in extracellular vesicles acted as inflammatory mediators, inducing differentiation of osteoclasts via inhibition of the enzyme cyclooxygenase 2 (COX-2).

“Extracellular vesicles are a key cellular communication mechanism. They’re released by practically all cell types and found in all kinds of body fluid. In the case of Th17 cells, the vesicles released in joints can transport microRNAs to bone tissue, augmenting the quantity of osteoclasts and bone erosion. In sum, this is a previously unknown mechanism that we succeeded in elucidating and that in future could be a basis for novel therapies for joint injury,” Donate said.

Lung cancer is the leading cause of cancer death in the U.S. for both men and women. While risk for this disease can be influenced by environmental and lifestyle factors like smoking, studies estimate that 18% of lung cancer cases are due to inherited genetic variants. New research led by Baylor College of Medicine investigates how genetic variants contribute to increased risk of lung cancer.

The researchers performed whole exome sequencing on germline (inherited) DNA from eight large-scale datasets, including 1,045 patients with a family history of lung cancer or early-onset cancer. Those groups are more likely to harbor genetic risk variants. The analysis also included 885 control cases.

"We were looking for variants that have a relatively high impact on risk but occur at relatively low frequency," said Dr. Chris Amos, corresponding author of the study, professor of medicine - epidemiology and population sciences and director of the Institute for Clinical and Translational Research (ICTR) at Baylor. "If a variant occurs at low frequency, you have to look at many different large data sources to validate the variant. These results can be replicated in many different European populations."

The researchers identified 25 new rare pathogenic variants associated with lung cancer susceptibility and validated five of those variants. Of those five, two variants involved genes with known connections to lung cancer risk, ATM and MPZL2. Three variants involved novel lung cancer susceptibility genes, POMC, STAU2 and MLNR. According to co-first author of the study, Dr. Yanhong Liu, exome sequencing allowed the researchers to identify more variants that impact proteins and cell function.

Investigating the contribution of insertions or deletions

"Mutations of DNA where sections are either inserted or deleted have been understudied compared to single nucleotide variants, but they are also very important because they can result in truncated proteins," said Liu, assistant professor of medicine - epidemiology and population sciences and member of the Dan L Duncan Comprehensive Cancer Center at Baylor. "Of the 25 candidate variants we identified, two-thirds of them are insertions or deletions."

In order to further understand the effect of these candidate variants on cellular functions, the Baylor researchers applied endogenous DNA damage assays, which test for replications of certain types of mutations in DNA. They hypothesized that lung cancer risk genes lead to an increased level of endogenous DNA damage in cells, leading to genomic instability and ultimately causing cancer.

"Many studies have looked at lung cancer risk genes, but the function of those genes has not been well understood. In our study, we found that dysregulation or mutations in these candidate genes showed increased DNA damage, suggesting that their potential cancer-causing role might be due to genome instability at the DNA level," said Dr. Jun Xia, co-first author of the study and postdoctoral associate in the Department of Molecular and Human Genetics and ICTR at Baylor.

The analysis showed that POMC, MLNR and ATM variants led to increased levels of DNA damage. ATM is known to be a critical first responder to DNA damage, and several ATM variants are linked to increased susceptibility for multiple cancers. According to Amos, understanding which variants cause increased DNA damage could be key to unlocking treatments for these cancers.

"We know from breast cancer that PARP inhibitors, drugs that prevent DNA repair, work in people with inherited BRCA1 and BRCA2 mutations because those cells already have some DNA damage due to the inherited mutation. If you disable PARP, the cancer cells can't repair DNA damage and won't survive," said Amos, member of the Dan L Duncan Comprehensive Cancer Center at Baylor and CPRIT Scholar. "It's possible that people with inherited ATM mutations causing them to develop lung cancer may respond to those PARP inhibitors as well, and that is something that needs to be studied further."

LOS ANGELES (March 18, 2021) -- COVID-19 disproportionately affects men compared with women, raising the possibility that a hormone like progesterone may improve clinical outcomes for certain hospitalized men with the disease. New research from Cedars-Sinai published online in the journal Chest supports this hypothesis.

The pilot clinical trial, involving 40 men, is believed to be the first published study to use progesterone to treat male COVID-19 patients whose lung functions have been compromised by the coronavirus. While the findings are promising, larger clinical trials are needed to establish the potential of this experimental therapy, the investigators said.

The study was prompted by multiple reports that men are at higher risk of mortality and severe illness from COVID-19 than are women, according to Sara Ghandehari, MD, director of Pulmonary Rehabilitation in the Women's Guild Lung Institute at Cedars-Sinai and principal investigator for the trial.

"As an ICU doctor, I was struck by the gender disparity among COVID-19 patients who were very sick, remained in the hospital and needed ventilators," she said. In addition, some published research had indicated that premenopausal women, who generally have higher progesterone levels, had less severe COVID-19 disease than did postmenopausal women, who have lower progesterone levels. While the bodies of both men and women naturally produce progesterone, women produce much more of the hormone during their reproductive years.

Protective Effect from Female Hormones

Ghandehari hypothesized that the gender differences in disease outcomes might be due, in part, to a protective effect from female hormones. In particular, preclinical studies elsewhere had pointed to progesterone as having certain anti-inflammatory properties. This finding suggested progesterone might be useful in dampening a sometimes-fatal immune response, known as a "cytokine storm," that can worsen lung damage and attack other organs in COVID-19 patients.

For the Cedars-Sinai clinical trial, conducted from April through August 2020, 40 male patients who were hospitalized with moderate to severe COVID-19 were randomly assigned to one of two groups. Patients in the control group received the standard medical care at the time for the disease. Patients in the experimental group received standard care plus twice-daily injections of 100 milligrams of progesterone for five days while they were hospitalized. Both groups were assessed daily for 15 days or until they were discharged from the hospital.

Study Results

The study showed that, compared with the control group, patients in the group treated with progesterone scored a median 1.5 points higher on a standard seven-point scale of clinical status after seven days. The scale ranged from a high of 7 ("not hospitalized, no limitations on activities") to 1 ("death"). Although the progesterone group overall also had fewer days of hospitalization and a lower need for supplemental oxygen and mechanical ventilation, the differences between the two groups in those specific categories were not statistically significant.

There were no serious adverse events, including life-threatening events, attributable to progesterone administration. There were two deaths, one in each group, during the15-day study period, neither of which was attributable to progesterone.

"While our findings are encouraging for the potential of using progesterone to treat men with COVID-19, our study had significant limitations," Ghandehari said.

She noted the sample size was relatively small and involved mainly white, Hispanic and obese patients with a moderate burden of comorbidities, which increase the risk for worse outcomes. Further, although the clinical trial was randomized and controlled, it was unblinded--meaning that the investigators, the patients and the treating physicians knew who received the experimental treatment.

"Further research is necessary in larger, more heterogeneous populations, including postmenopausal women and at other treatment centers, to establish the degree of clinical efficacy and to assess any other potential safety concerns of this treatment approach," said Ghandehari, who also is assistant director of the Lung Transplant Program at Cedars-Sinai.

Progesterone is approved by the U.S. Food and Drug Administration (FDA) for use in fertility-related conditions in women but not for the modulation of immunologic-based, inflammatory responses. The FDA allowed this special use for the purpose of the Cedars-Sinai clinical trial under an investigational new drug application.

In addition to multiple Cedars-Sinai investigators, this study involved Donald Stein, PhD, from Emory University in Atlanta, and Heli Ghandehari, an independent biostatistical consultant from San Diego.