COVID OUT clinical trial suggests metformin effective at reducing odds of serious outcomes for COVID-19 patients seeking early treatment

Trial compared effect of ivermectin, fluvoxamine, and metformin in randomized double-blinded placebo- controlled trial

Peer-Reviewed Publication

UNIVERSITY OF MINNESOTA MEDICAL SCHOOL

 

VIDEO: DR. CAROLYN BRAMANTE FROM THE UNIVERSITY OF MINNESOTA ANSWERS QUESTIONS ABOUT COVID OUT. view more 

CREDIT: UNIVERSITY OF MINNESOTA MEDICAL SCHOOL

Published in the New England Journal of Medicine, researchers — led by the University of Minnesota Medical School and School of Public Health — have found that metformin, a commonly prescribed diabetes medication, lowers the odds of emergency department visits, hospitalizations, or death due to COVID-19 by over 40 percent; and over 50 percent if prescribed early in onset of symptoms. The study also found no positive effect from treatment with either ivermectin or low-dose fluvoxamine.

“We are pleased to contribute to the body of knowledge around COVID-19 therapies in general, with treatments that are widely available,” said Carolyn Bramante, MD, principal investigator of the study and an assistant professor of internal medicine and pediatrics at the U of M Medical School. “Our trial suggests that metformin may reduce the likelihood of needing to go to the emergency room or be hospitalized for COVID-19.”

Bramante noted that this was a secondary outcome of the trial; the primary outcome included whether someone had low oxygen on a home oxygen monitor, and none of the medications in the trial prevented the primary outcome.

The COVID-OUT trial was the nation’s first to study whether metformin, a medication for type 2 diabetes; low-dose fluvoxamine, an antidepressant; and ivermectin, an antiparasitic, or their combinations could serve as possible treatments to prevent ER visits or hospitalization, as well as Long-COVID.

The study design was simple — patients were randomly assigned to receive one of the three drugs individually, placebo, or a combination of metformin and fluvoxamine or metformin and ivermectin. Although the study was placebo-controlled with exact-matching placebo pills, Dr. Bramante says 83% of volunteers received medications supported by existing data because of the six-arm design. Each participant received 2 types of pills to keep their treatment assignment masked, for 3 to 14 days of treatment. Each volunteer tracked their symptoms, and after 14 days, they completed a survey.

The 1323 participants in the trial were limited to adults with a body mass index greater than or equal to 25 kg/m2, which qualifies as overweight – for instance, someone who was at least five feet and six inches tall and weighed more than 155 pounds. To qualify for the study, volunteers enrolled within three days after receiving a positive COVID-19 test. It was among the first randomized clinical trials for COVID-19 to include pregnant women.

The study included those who were vaccinated and those who were not. This is the first published trial where the majority of participants were vaccinated. 

“Although we know COVID-19 vaccines are highly effective, we know that some new strains of the virus may evade immunity and vaccines may not be available worldwide. So we felt we should study safe, available and inexpensive outpatient treatment options as soon as possible,” said Bramante. “Understanding whether outpatient treatments could ensure more people survive the illness if they contract it and have fewer long-term symptoms is an important piece of the pandemic response.”

The clinical trial launched in January 2021 after U of M Medical School researchers identified, through computer modeling and observational studies, that outpatient metformin use appeared to decrease the likelihood of mortality from, or being hospitalized for COVID-19. Their research, in partnership with UnitedHealth Group, was published in the Journal of Medical Virology and in The Lancet Healthy Longevity. Test-tube studies also found that metformin inhibited the Covid-19 virus in lab settings. These findings, along with additional prospective studies supporting the use of higher-dose fluvoxamine and ivermectin, provided the evidence to include all three medications as well as combination arms.

“Observational studies and in vitro experiments cannot be conclusive but do contribute to bodies of evidence,” said Bramante, who is also an internist and pediatrician with M Health Fairview. “To complete this study, we enrolled volunteers nationwide through six institutions in the U.S., including in Minneapolis.”

Participating clinical trial sites included M Health Fairview and Hennepin Healthcare in Minneapolis, Northwestern University in Chicago, Olive View – UCLA Education & Research Institute in Los Angeles, Optum in Colorado and Indiana, and University of Colorado Denver. Co-investigators on the study include Jared Huling, PhD; Thomas Murray, PhD; Hrishikesh Belani, MD; Michelle Biros, MD; David Boulware, MD; David Leibovitz, MD; Jacinda Nicklas, MD; David Odde, PhD; Matt Pullen, MD; Mike Puskarich, MD; John Buse, MD, PhD; Jennifer Thompson, MD; and Christopher Tignanelli, MD.

The trial received monetary support from the Parsemus Foundation, Rainwater Charitable Foundation, Fast Grants, and UnitedHealth Group.

In addition, this research was supported by the National Institutes of Health’s National Center for Advancing Translational Sciences, grants UL1TR002494 and KL2TR002492, and the National Institute of Digestive, Diabetes, and Kidney diseases K23 DK124654. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health’s National Center for Advancing Translational Sciences.

 

---

JOURNAL

New England Journal of Medicine

DOI

10.1056/NEJMoa2201662 

METHOD OF RESEARCH

Randomized controlled/clinical trial

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Randomized trial of metformin, ivermectin, and fluvoxamine for Covid-19

Metformin drastically reduces COVID hospitalization, study shows

Widely available drug reduced emergency room visits, hospitalization, and death by COVID-19 by more than half if started within 4 days of symptoms

Peer-Reviewed Publication

PARSEMUS FOUNDATION

The widely available diabetes drug metformin reduced serious outcomes by more than half if started within 4 days of COVID symptoms in a large, randomized, double blind controlled trial, the University of Minnesota announced today. The results were published Aug. 18 in the New England Journal of Medicine.

The study was primarily funded by three philanthropic foundations: Parsemus Foundation, Rainwater Charitable Foundation, and Fast Grants.

“This was really intriguing to us early on when we learned that people who take metformin were catching COVID less and being hospitalized less,” said Elaine Lissner, founder and trustee of small California nonprofit Parsemus Foundation, which works on low-cost solutions neglected by the pharmaceutical industry. “But you don’t know whether it’s just coincidence until you start at the beginning, with a rigorous randomized trial.”

“When we learned that researchers at the University of Minnesota were already trying to raise funds to test it, we jumped at the opportunity.”

A little-known past

Metformin, also known as Glucophage, has an added benefit: a little-known past in the 1950s as an anti-viral called “Fluamine.” In more recent research, it also seems to affect mTOR inflammation pathways. Since COVID involves viral inflammation, lead researcher Dr. Carolyn Bramante and team thought the combination of anti-inflammatory plus antiviral action was intriguing enough to put to the test.

The study almost didn’t happen, though. At the time, most government and pharmaceutical funds were going to vaccine research, or the search for profitable new drugs.

“We took a chance and gave what we could, enough to get the first few study sites started and generate preliminary data to strengthen the case for other funders,” said Linda Brent, executive director of the Parsemus Foundation. “But the study never would have made it if it weren’t for the dedicated larger funders who believed in it right away and came on board with critical support.”

Three medications studied

For added rigor, the large University of Minnesota study compared three medications that were considered promising at the time—fluvoxamine, an antidepressant that had shown strong results in previous studies; ivermectin, the object of much interest and passion; and metformin — and provided valuable answers, even about the drugs that were not the clear winner.

“You can argue about details, but in the end, this was kind of ‘three strikes and you’re out’ for ivermectin,” said Lissner. “But ivermectin deserved this kind of careful study, head-to-head with other medications, to finally get solid answers. You have to give everything a fair test.”

“And I think a lot of us were pretty disappointed that the fluvoxamine results were not conclusive. We did learn that the dose the study used, which was a third to half as much as used in previous studies in an attempt to avoid side effects, was not enough to make a significant difference. I don’t think the door is closed on fluvoxamine at higher doses, though.”

“But in the end,” added Lissner, “you have to accept what the science tells you, no matter which you were rooting for. And it’s probably better this way. Metformin is an incredibly common drug, taken by millions of people all over the world. There’s no stigma like with an antidepressant, and it’s a lot easier to take than the other two.”

In 2019, metformin was the fourth-most commonly prescribed medication in the United States, with more than 85 million prescriptions written for over 17 million patients. FDA guidelines indicate that it should not be taken by people with advanced kidney disease, and should be taken with food, or in extended-release formulation, to avoid stomach upset. Side effects are minor and include loose stools. Metformin is also considered safe for use in pregnant women.

The study included 1323 participants most at risk of serious outcomes—adults over 30 and with BMI over 25 kg/m2—to get lifesaving results more quickly. Future studies could include lower-risk participants. However, studies of metformin for other indications, such as the national TAME trial by the American Federation for Aging Research, remain unfunded.

“I think there are lessons for all of us in making sure our global clinical trial systems are more robust and ready to jump in on globally critical studies like this in the future,” emphasized Lissner. “It shouldn’t be little foundations like us funding studies of global importance. In the meantime, I hope all the hard work and late nights pay off, and clinicians around the world take notice: metformin, an exceedingly inexpensive drug they prescribe every day, if given to high-risk people with COVID right away, can reduce serious outcomes by more than half.”

Details about the study results were published online August 18 in the New England Journal of Medicine and can be found in the University of Minnesota’s COVID-OUT study press release.

About the Parsemus Foundation (San Francisco): The Parsemus Foundation works to create meaningful improvements in human and animal health and welfare by advancing innovative and neglected medical research. The foundation’s focus is on supporting proof-of-concept studies and then pursuing press coverage of the results, so that the advances change treatment practice rather than disappearing into the scientific literature. As a small, agile nonprofit organization, the Parsemus Foundation was able to pivot from its regularly funded programs to a new focus on COVID-19 treatment during the pandemic. More information on the Parsemus Foundation and the work presented here can be found at: https://www.parsemus.org/humanhealth/covid-19/

 

---

JOURNAL

New England Journal of Medicine

METHOD OF RESEARCH

Randomized controlled/clinical trial

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19

Durable coating kills COVID virus, other germs in minutes

Polyurethane locks in the antimicrobial power of tea tree and cinnamon oils. The new technology could start making public spaces safer within a year

Peer-Reviewed Publication

UNIVERSITY OF MICHIGAN

Images

There may soon be a new weapon in our centuries-old battle against germs: the first durable coating that can quickly kill bacteria and viruses and keep on killing them for months at a time. 

Developed by a team of University of Michigan engineers and immunologists, it proved deadly to SARS-CoV-2 (the virus that causes COVID-19), E. coli, MRSA and a variety of other pathogens. It killed 99.9% of microbes even after months of repeated cleaning, abrasion and other punishment on real-world surfaces like keyboards, cell phone screens and chicken-slathered cutting boards.

The coating could be a game changer in traditionally germ-laden public spaces like airports and hospitals, according to Anish Tuteja, a professor of material science and engineering at U-M and co-corresponding author of the paper published in Matter.

"We’ve never had a good way to keep constantly-touched surfaces like airport touch screens clean," he said. "Disinfectant cleaners can kill germs in only a minute or two but they dissipate quickly and leave surfaces vulnerable to reinfection. We do have long-lasting antibacterial surfaces based on metals like copper and zinc, but they take hours to kill bacteria. This coating offers the best of both worlds."

The coating, which is clear and can be brushed or sprayed on, gets its durability and germ-killing power by combining tried-and-true ingredients in a new way. It uses antimicrobial molecules derived from tea tree oil and cinnamon oil, both used for centuries as safe and effective germ killers that work in under two minutes. The coating’s durability comes from polyurethane, a tough, varnish-like sealer that’s commonly used on surfaces like floors and furniture.

"The antimicrobials we tested are classified as 'generally regarded as safe' by the FDA, and some have even been approved as food additives," Tuteja said. "Polyurethane is a safe and very commonly used coating. But we did do toxicity testing just to be sure, and we found that our particular combination of ingredients is even safer than many of today’s antimicrobials."

The results of the study’s durability tests suggest that the coating could keep killing germs for six months or longer before its oil begins to evaporate and reduce its disinfectant power. But even then, Tuteja says it can be recharged by wiping it with fresh oil; the new oil is reabsorbed by the surface, starting the cycle again.

Tuteja estimates that the technology could be commercially available within a year; it has been licensed to Hygratek, a spinoff company that Tuteja founded with assistance from U-M Innovation Partnerships.

The key challenge was to combine the oil and polyurethane in a way that let the oil molecules do their germ-killing work while preventing them from evaporating quickly.
The research team—including associate professor of materials science and engineering and biomedical engineering Geeta Mehta, a co-corresponding author; and materials science and engineering PhD students Abhishek Dhyani and Taylor Repetto, co-first authors—found a possible solution in cross-linking, a well-known process that uses heating to link materials together at the molecular level. The smaller oil molecules readily combined with the cross-linking polymer molecules, forming a stable matrix.

But to kill germs, the oil molecules need to penetrate their cell walls, which they can’t do if they’re tightly tethered into the matrix. Eventually, they found a middle ground by partially cross-linking the materials—enough to keep some of the oil molecules free to do their work, but keeping others bound tightly to the polyurethane.

"There was some trial and error, but we eventually found that cross-linking only some of the oil did what we needed," Tuteja said. "The free oil tends to stay with the oil that’s cross-linked into the matrix, helping the coating last longer."

Once the basic recipe was set, the researchers set about finding a combination of active ingredients that would kill a wide variety of the germs that trouble humans most. To identify a representative sample of microbes, they worked with co-corresponding authors Christiane E. Wobus, an associate professor of microbiology and immunology, and J. Scott VanEpps, an associate professor of emergency medicine, both at the U-M Medical School. Ultimately, they found a precise balance of antimicrobial molecules that were effective, safe and inexpensive.

Tuteja emphasizes that they’re not locked into one specific formula; the team’s understanding of individual ingredients’ properties enables them to tweak the formula for specific applications or rebalance the antimicrobial agents to kill specific germs.

"It’s never our goal just to develop a one-off coating, but instead to develop a library of underlying material properties to draw from," Tuteja said. "If we can understand those properties, then we can develop coatings to meet the needs of specific applications."

The study was funded by the Office of Naval Research, with additional support from the University of Michigan, Marie Skłodowska-Curie Actions, the National Institutes of Health and the Department of Defense, with raw materials provided by Covestro.

The University of Michigan has applied for a patent based on this technology. Tuteja and the University of Michigan have a financial interest in Hygratek.

Study: Surfaces with instant and persistent antimicrobial efficacy against bacteria
and SARS-CoV-2 (DOI: 10.1016/j.matt.2022.08.018)

JOURNAL

Matter

DOI

10.1016/j.matt.2022.08.018 

Hospital superbugs use thin stretchy fibers to attach to surfaces and cause infections

Peer-Reviewed Publication

UNIVERSITY OF TURKU

The antibiotic-resistant Acinetobacter baumannii bacterium is one of the most globally harmful bacteria that causes hospital-acquired infections. Researchers at the University of Turku have discovered that the bacterium spreads by attaching to surfaces using ultrathin stretchy fibers. The researchers also revealed how these fibers are formed on the bacterial surface and suggested new approaches to prevent bacterial infections. The new findings have been published in Nature, one of the leading scientific journals in the World.

Infections related to hospitals and medical devices form major healthcare problems worldwide. These infections are associated with the ability of pathogens to colonize both biotic and abiotic surfaces.

“The pan-antibiotic resistant Acinetobacter baumannii is one of the most troublesome pathogens for healthcare institutions globally and currently tops the World Health Organization’s priority pathogens list for the development of new antibiotics,” says the Head of the Joint Biotechnology Laboratory Anton Zavialov from the MediCity Research Center at the Faculty of Medicine, University of Turku, Finland.

Zavialov’s research group, consisting of the Doctoral Researcher Henri Malmi and Senior Researchers Natalia Pakharukova, Minna Tuittila, and Sari Paavilainen discovered unique surface structures that enables Acinetobacter baumannii and related pathogenic bacteria to colonize medical devices and infect patients.

“This discovery may help fighting many bacterial infections, because the same surface attachment mechanism is used by many important bacterial pathogens, including Pseudomonas aeruginosa, the second top priority pathogen on the WHO list,” says Zavialov.

Bacterium attaches to surfaces using ultrathin stretchy fibers

Acinetobacter baumannii is capable of colonizing medical devices by means of archaic chaperone-usher (ACU) pili. ACU pili are hair-like protein fibers found on the surface of many pathogenic bacteria.

Using cryo-electron microscopy, the researchers found that the pili have a unique ultrathin zigzag architecture. The fibers firmly attach the bacterium to various biotic and abiotic surfaces with tiny sticky finger-like structures at their ends. Once the sticky fingers grip the surface, the fiber is difficult to detach because it can stretch by changing its conformation from the zigzag to linear shape.

“This phenomenon is well known to sailors. It is now common to use stretchable elements in mooring lines to dock boats safely in relatively rough water. If you imagine a bacterium the same size as a human, then the attachment fibers of this giant bacterium will still be 100 times thinner than human hands. The ability to stretch is critical for such thin fibers to withstand high shear forces which bacteria experience in their environment,” Zavialov explains.

“Our results suggest that the unique zigzag structure of the fibers also plays an important role in their secretion to the bacterial surface. Fibers are secreted from the inside of the bacterium through its outer membrane in the extended linear conformation. On the surface, they change their conformation to the zigzag shape, which prevents them from slipping back into the bacterium. Theoretically, we can develop drugs preventing this conformational change. Such drugs would block fiber biogenesis, abolishing bacterial attachment,” Henri Malmi concludes.

---

JOURNAL

Nature

DOI

10.1038/s41586-022-05095-0 

ARTICLE TITLE

Archaic chaperone-usher pili self-secrete into superelastic zigzag springs

THE GREAT BICYCLE RACE

La Vuelta air not always healthy

Utrecht researchers map air quality of all stages of La Vuelta

Reports and Proceedings

UTRECHT UNIVERSITY

 

IMAGE: MAP DEPICTING THE AIR QUALITY OF THE VUELTA STAGE IN UTRECHT. CREDIT: UTRECHT UNIVERSITY view more 

CREDIT: UTRECHT UNIVERSITY

The Netherlands is preparing for La Vuelta Holanda which starts on Friday 19 August. How clean is the air in the places that the peloton is visiting? Researchers from Utrecht University have mapped the annual average air quality of each stage of La Vuelta and demonstrate that the air is most polluted at the start (Utrecht) and finish (Madrid). They also conclude that for many stretches the air quality does not meet World Health Organization (WHO) guidelines. Nevertheless, the health benefits of cycling generally outweigh the risks.

It’s often said that "cycling is healthy" when we set off in all kinds of weather. But how clean is the air you breathe if you cycle the same route as the La Vuelta peloton on a normal day? This was the question researchers Roel Vermeulen and Jules Kerckhoffs asked themselves. Using satellite images, traffic information and air quality data about nitrogen dioxide, particulate matter and ozone, they made a stage map booklet [insert link] showing the air quality for each stage of La Vuelta.

The conclusion is clear: the most polluted stages are those in the Netherlands and the Spanish stage from La Rozas to Madrid. Particularly in the urban areas, the air quality does not meet WHO guidelines. On top of that, there are a few places where the European limit value is exceeded. It is generally accepted that places with poor air quality can cause adverse health effects. In the Netherlands, researchers estimate that approximately five thousand people die prematurely each year due to poor air quality. Worldwide, that is estimated to be around 7 million.

Alternative stage map book
The stage maps created by Utrecht University researchers as part of the Expanse project, illustrate average air pollution over the course of a year. Vermeulen and Kerckhoffs focus on the value recommended by the WHO for nitrogen dioxide in a year: ten micrograms per cubic meter. If you were to cycle the route to work or study every day, this is a critical value. If you cycle the route occasionally the 24-hour guideline of 25 micrograms per cubic meter is more relevant. According to the WHO, exceeding these guidelines results in damage to health. However, the EU limit value that is used in the Netherlands is a lot higher: 40 micrograms per cubic meter. This value is also reflected in the graphs accompanying the maps.

“Much has been done in recent years to improve air quality, but we see that there are still many places where the air is not healthy," said Vermeulen, who studies how environmental factors affect our health. "So improving air quality still requires attention." Vermeulen therefore calls on municipalities to look beyond the EU standard to which they must adhere, and to improve air quality according to WHO guidelines. For example, municipalities could encourage residents to travel by bike instead of by car for short distances and indirectly stimulate this behaviour when designing cities. "The so-called 15-minute cities, where facilities can be reached on foot or by bike within fifteen minutes, are a good example of this."

For the cyclists of the Vuelta, their trip will not directly result in damage to their health; after all, they ride each stage once only and not every day. Furthermore, there is no regular traffic on the road on the day of La Vuelta. This means that the air quality during the stage will be better, as was also previously demonstrated during the Grand Depart of the Tour de France.

CAPTION

Map depicting the air quality of the Vuelta stage in Vitoria. Credit: Utrecht University

CREDIT

Utrecht University

The most polluted routes of La Vuelta
The research shows that the air quality of the first three stages in the Netherlands and of the final stage in and near Madrid, does not come close to the WHO advisory value for nitrogen dioxide (10 micrograms per cubic meter).

During a part of the third stage (Breda - Breda), the concentration of nitrogen dioxide is higher than the 24-hour WHO guidelines for nitrogen dioxide, and a small part is even higher than the EU limit (about 40 kilometers). The average pollution of the total ride is 21 micrograms per cubic meter. The other stages in the Netherlands are also on average substantially more polluted than those in Spain, both for nitrogen dioxide and particulate matter. The prologue in Utrecht even has an average concentration of 32 micrograms per cubic meter. Because this stage is only 23.3 kilometers long, stages two (Den Bosch - Utrecht) and three (Breda - Breda) are worse for health. This is because you inhale more polluted air and therefore have a higher average over a 24 hours period.

If we look at the average concentration of nitrogen dioxide of the last stage (Las Rozas - Madrid), we see that it is even higher than the stages in the Netherlands. 35 kilometers of this stage exceed the EU limit of 40 micrograms of nitrogen dioxide per cubic meter. As in Utrecht, this is because a large part of the stage is cycled in the inner city of Madrid.

Vitoria-Gasteiz - Laguardia: the cleanest stage
By comparing previous stages with that of Vitoria-Gasteiz to Laguardia in Spain, we can see how great the differences are. During stage four the concentration of nitrogen dioxide was below the WHO advisory value for almost the entire stage (142.5 km). The average of this route is 6.5 micrograms per cubic meter. Interestingly the stage is not the cleanest for ozone. Ozone is formed from reactions of nitrogen oxides and volatile organic compounds in warm and sunny weather. Because the temperature is higher in Spain, ozone concentrations are typically higher than those in the Netherlands.

Ban the bicycle?
This research shows that nitrogen dioxide concentrations above 25 micrograms per cubic meter (the daily limit according to the WHO) in urban areas are often unavoidable for cyclists. Does this mean you should have to take the bus to work from now on? "No," say Kerckhoffs and Vermeulen. "Even if you compare polluted air and other risks such as accidents to the health benefits of cycling, the risks are smaller than the benefits. Our evaluation is therefore not intended to discourage cycling. What we do want is to raise awareness about air quality in the Netherlands, and show that from a health perspective, there is still work to be done. Part of the solution can be found in the stimulation of active transport (cycling, walking) especially for short distances. We can stimulate this for example, by improving cycling infrastructure and by designing our urban living environment in such a way that all basic daily needs can be found within a 15-minute walk or bike ride from your home (the 15-minute city).

---

METHOD OF RESEARCH

Experimental study

In new study in The Crop Journal, scientists develop cutting edge vascular system image analysis pipeline for crops

This accurate, deep learning pipeline can detect the vascular system of plants with high detail, helping agricultural practices

Peer-Reviewed Publication

CACTUS COMMUNICATIONS

 

IMAGE: A DEEP-LEARNING PIPELINE BATCH-PROCESSES A SERIES OF COMPUTER TOMOGRAPHIC IMAGES OF THE MAIZE STEM TO VISUALIZE AND ANALYZE ITS VASCULAR CHARACTERISTICS. view more 

CREDIT: CHUNJIANG ZHAO VIA THE CROP JOURNAL

A plant’s vascular system is essential for maintaining stem structure, providing mechanical support, and for delivering resources to various plant organs. However, the structure and distribution of these vascular bundles varies greatly across individual plants, and this poses a great challenge in automating the process of their identification and quantification. Therefore, the ability to deliver a rapid and accurate quantitative and functional evaluation of these plant systems is vital to agricultural research.

The histological study of sectioned plant tissue (done under a microscope) is the foundation of plant anatomy and microscopy techniques. Spanning light-based, fluorescence, and electron-based techniques, this is the backbone of inner tissue plant research. However, the physical and chemical treatments during sample preparation for these methods can alter the natural structure of specimens. Micro-computed tomography (micro-CT), however, can deliver high-resolution imagery with minimal preprocessing that is non-destructive to tissue specimens. Unfortunately, some manual adjustments are necessary for CT image reconstruction which results in errors and variation introduced unwittingly by the observer.

In terms of capability, Deep Convolutional Neural Network (CNN) approach, a data-driven feature extraction technique, has only recently achieved state-of-the-art performance in detecting objects in segmented images, allowing it to be routinely used in image-based phenotyping in plant phenomics (i.e., a study of the plant’s phenotype and its evolution). Now, a group of researchers at Beijing Academy of Agriculture and Forestry Sciences (BAAFS), led by Dr. Jianjun Du, has developed a CNN based deep-learning pipeline that can rapidly produce accurate analyses of vascular bundle architecture. “We believe we can break new ground in understanding the relationship between vascular bundle architecture at the single-plant level and the traits involved in water transport,” says Dr. Chunjiang Zhao, corresponding author of a study detailing their methods and findings. The study was published online on 27 May 2022 in The Crop Journal.

The team was particularly interested in studying how plants that express plasticity in the structure of their stems can quickly adapt to their environment. It is this plasticity that allows for changing structure without hindering growth and development. To study it, they grew maize under natural and drought conditions and utilized information extracted from CT images to examine the vascular bundles for different stem internodes (which is the part of the stem between two nodes, or branching areas), evaluate architectural differences in stem structure, and investigate the relationship between flow rates and structural traits. Their pipeline processed images and detected vascular bundles in the plants, identified specific zones (the periphery, the epidermis, and the inner zones) within the bundles, categorized bundles into phenotypes based on specific traits (quality, quantity, size, and shape), and performed a statistical analysis of these traits in different stem internodes. They also conducted sap flow experiments to study the traits of vascular bundles in maize at the single-plant level to gain an insight into the water use efficiency of the different phenotypes.

“We could achieve an image processing time of three seconds, and for the first time we shed light on the thickness of the epidermis (which is the outermost layer) of the maize stem. Our pipeline is incredibly accurate too. During testing, it enumerated vascular bundles across all types of internodes and quantified size-related traits with an R2–which indicates consistency–of over 0.98,” Dr. Du explains the novelty of their study.

In addition, the sap flow experiments showed that the rate of flow was affected not only by the structure of the vascular bundles, but also by environmental and meteorological conditions.

So why are these findings so important? “We believe we have laid the foundation for deeper studies on identification of genes essential to determining water use efficiency, and development of crop breeds that can ensure national food security. The pipeline certainly allows for future work to establish the relationship between sap flow and the specific traits of vascular bundles,” says Dr. Du with a smile. Their research might lead to improved, more resilient crops in the future!         

 

***

Reference

DOI: https://doi.org/10.1016/j.cj.2022.04.012

Authors: Jianjun Du, Ying Zhang, Xianju Lu, Minggang Zhang, Jinglu Wang, Shengjin Liao, Xinyu Guo, and Chunjiang Zhao

Affiliations:
Beijing Key Lab of Digital Plant, Research Center of Information Technology, Beijing Academy of Agriculture and Forestry Sciences, China

 

About Professor Chunjiang Zhao
Dr, Chunjiang Zhao, a member of the Chinese Academy of Engineering, received his Ph.D from China Agriculture University in 1993. He is currently a professor at the Beijing Academy of Agricultural and Forestry Sciences and develops technology for efficient information acquisition, quantitative analysis, diagnostic decision making, and intelligent equipment control. He has published over 400 articles and founded the International Symposium on Intelligent Information Technology in Agriculture to promote cooperation between scientists and engineers. He holds advisory roles in the Ministry of Agriculture of China, the Natural Science Foundation, and the Ministry of Science and Technology.

 

---

JOURNAL

The Crop Journal

DOI

10.1016/j.cj.2022.04.012 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

A deep learning-integrated phenotyping pipeline for vascular bundle phenotypes and its application in evaluating sap flow in the maize stem

Cameras candidly capture bushmeat mammals to avert crisis

Finding the best indicators for sustainable hunting in the African rainforest

Peer-Reviewed Publication

KYOTO UNIVERSITY

 

IMAGE: USE OF CAMERA TRAPS FOR LOCALLY-BASED WILDLIFE MONITORING view more 

CREDIT: KYOTOU CAAS/YOH IZUMORI

Kyoto, Japan -- Bushmeat is not a vegan term but a commodity in crisis. With the decline of wildlife due to commercial overexploitation in the world's tropical rainforests, the bushmeat crisis is impacting biodiversity and the livelihoods of local populations.

While community participatory-based wildlife monitoring of wildlife by local people can be a solution, the challenge has been in finding indicators -- biostatistical information -- that accurately and easily estimate the total biomass of mammals targeted for bushmeat hunting abundance of bushmeat biomass.

Now, Projet Coméca, consisting of a team of researchers from Kyoto University and Cameroon, has conducted camera trap surveys in the rainforests of southeast Cameroon to predict the total biomass of large rodents and duikers, the local African forest ungulates.

"We're willing to work together empowering the locals to establish a system with the technology to take the initiative to monitor wildlife bushmeat abundance by themselves, leading to sustainable bushmeat wildlife management," says lead author Shun Hongo.

After setting up camera traps at three sites in a local forest to record videos of five target mammals, the team used the random encounter and staying time model, or REST, a statistical model to estimate spatial variation in each species' population density and corresponding the total biomass.

The research team subsequently compared the relationships between the total biomass and six indicators, which had previously been proposed by different bushmeat researchers. Based on that data, six candidate indicators were extracted, enabling the researchers to compare the relationships between the biomass totals and corresponding indicators.

Two of these -- the ratio of red duikers to blue duikers, and the ratio of all duikers to rodents -- were deemed promising as they showed positive linear correlations with total bushmeat biomass.

"Our indicators appear to be important variables tools for sustainable management of bushmeat hunting food resources," the author adds.

"Since forest ungulates and large rodents are widely distributed in rainforests worldwide, other communities in tropical areas may also be able to apply similar indicators for their local wildlife areas management.”

###

The paper "Predicting bushmeat biomass from species composition captured by camera traps: implications for locally-based wildlife monitoring" appeared on 26 August 2022 in Journal of Applied Ecology, with doi: 10.1111/1365-2664.14257  

About Kyoto University

Kyoto University is one of Japan and Asia's premier research institutions, founded in 1897 and responsible for producing numerous Nobel laureates and winners of other prestigious international prizes. A broad curriculum across the arts and sciences at both undergraduate and graduate levels is complemented by numerous research centers, as well as facilities and offices around Japan and the world. For more information, please see: http://www.kyoto-u.ac.jp/en

---

JOURNAL

Journal of Applied Ecology

DOI

10.1111/1365-2664.14257 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Predicting bushmeat biomass from species composition captured by camera traps: implications for locally -based wildlife monitoring

ARTICLE PUBLICATION DATE

26-Aug-2022

Better wildlife observation with new counting method

Peer-Reviewed Publication

LINKÖPING UNIVERSITY

 

IMAGE: TOM LINDSTRÖM, ASSOCIATE PROFESSOR AT LINKÖPING UNIVERSITY. view more 

CREDIT: MAGNUS JOHANSSON/LINKÖPING UNIVERSITY

Are wildlife populations in Sweden increasing or decreasing? It is difficult to count wild animals, but the amount harvested through hunting gives an indication. Now, these statistics can be made clearer and more useful, thanks to a new model developed by Swedish researchers to count how many wild animals are hunted.

“We believe that this system will make the statistics clearer and more reliable. The idea is that this model is to be used from the autumn forward, for presenting official statistics about how many wild animals are harvested through hunting in Sweden”, says Tom Lindström, associate professor at the Department of Physics, Chemistry and Biology (IFM) at Linköping University, who has done the study in collaboration with Göran Bergqvist at the Swedish Association for Hunting and Wildlife Management.

Hunting is a way of getting an overview of the size of wild populations. For some species, it is the only indicator we have. Knowing how many wild animals are harvested through hunting every year is, therefore, an important part of wildlife monitoring, which needs to be adapted to changes in the ecosystem.

For example, the reporting of hunting of moose and large mammals is required by law, but for most species – everything from jays to wild boars – reporting is optional. The Swedish Association for Hunting and Wildlife Management is responsible for annual statistics around how many of these animals are harvested. Hunting teams report how much they have shot of around fifty species, and across how much land they have hunted. But because reporting is optional, and because reports are lacking for some of Sweden’s hunting grounds, statistical methods are used to calculate how many wild animals are harvested on these blind spots not covered by the hunting teams’ reports. One of the significant weaknesses with the analysis method that has been used until now is that it is very sensitive to low reporting – especially for species the hunting of which varies between hunting teams and are, generally, not so hunted. Tom Lindström gives an example:

“In 2015, the analysis appeared to show that many more beavers had been harvested than in previous years. However, when we analysed the data, it turned out that the big difference was because a single hunting team reported that they had shot a single beaver. Because this analysis method is so sensitive to single reports, it made it look like many thousands of beavers had been shot in that club.”

For this reason, the researchers developed a new analysis model which can give a better estimation as to how many wild animals of each species are harvested each year. The study, published in the journal Ecological Indicators, consists of two parts. In the first part, the researchers analysed various parameters and developed a model that is good at describing data. They then used the model to predict how many wild animals would be hunted on the area for which data were missing.

 Analyses made with the new model can contribute to insights about hunting behaviour in Sweden. In the study, the researchers saw that the hunting teams that had greater areas to hunt in generally shot fewer animals per area. The correlation was similar for all species hunted. There may have been fewer animals in those areas, so a larger area is needed in order to have a chance of catching something – or there may be other explanations. Time is another piece of the puzzle. The researchers have done something called auto-regressive modelling, which means that the analysis of the hunting volume in one area takes account of the volumes from previous years. 

This new statistical framework solves several problems.

“The model presents the uncertainty in these analyses in an honest way, and shows a range, instead of a definite figure. It is also less sensitive for individual hunting reports, and this reduces the uncertainty of the analysis”, says Tom Lindström.

The project was funded by Swedish Association of Hunting and Wildlife Management and The Swedish Environmental Protection Agency. Computation was executed on resources provided by the Swedish National Infrastructure for Computing (SNIC).

 

The article: Estimating harvest when hunting bag data are reported by area rather than individual hunters: A Bayesian autoregressive approach, Tom Lindström, Göran Bergqvist, (2022), Ecological Indicators, published online 19 June 2022, DOI: 10.1016/j.ecolind.2022.108960

For more information, contact:

Tom Lindström, associate professor, tom.lindstrom@liu.se, +4613-28 24 59

Karin Söderlund Leifler, press information officer, karin.soderlund.leifler@liu.se, +46 13 28 13 95

---

DOI

10.1016/j.ecolind.2022.108960 

METHOD OF RESEARCH

Computational simulation/modeling

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Estimating harvest when hunting bag data are reported by area rather than individual hunters: A Bayesian autoregressive approach

ARTICLE PUBLICATION DATE

19-Jun-2022

COI STATEMENT

Tom Lindstrom reports financial support was provided by Swedish Association for Hunting and Wildlife Management.