New software marketplace expands licensing opportunities

Business Announcement

DOE/IDAHO NATIONAL LABORATORY

 

IMAGE: MALCOM IS ONE OF MANY SOFTWARE AVAILABLE THROUGH INL’S NEW SOFTWARE MARKETPLACE WEBSITE. view more 

CREDIT: IDAHO NATIONAL LABORATORY

Idaho National Laboratory’s software marketplace is officially open for business.   

The marketplace is a new website developed to widely distribute INL’s innovative software. Its goal: to accelerate industry adoption and fuel innovation in other research organizations. Ultimately, the marketplace is designed to help fulfill the lab’s vision to change the world’s energy future and secure our nation’s critical infrastructure.  

“At INL, technology transfer into the marketplace is important to our mission as it puts our innovations to use and makes actual impact in our community,” said INL Technology Deployment Director Jason Stolworthy. “The website gives us another outlet to distribute and license our software to achieve our mission.” 

The marketplace provides access to software codes and data sets developed at INL through various forms of licenses, including open-source and proprietary options. The site will expand as more software is developed and becomes available.  

View the site at inlsoftware.inl.gov. Questions about licensing or available software can be emailed to td@inl.gov.   

About Idaho National Laboratory
Battelle Energy Alliance manages INL for the U.S. Department of Energy’s Office of Nuclear Energy. INL is the nation’s center for nuclear energy research and development, and also performs research in each of DOE’s strategic goal areas: energy, national security, science and the environment. For more information, visit www.inl.gov. Follow us on social media: Twitter, Facebook, Instagram and LinkedIn.

INL’s Software Marketplace website provides access to a variety of software, like MARMOT, to fuel innovation.

INL’s Software Marketplace offers a variety of software codes and data sets for a multitude of topics, including hydropower.

CREDIT

Idaho National Laboratory

How to make better consistency and availability trade-offs in networks

New theorem benefits distributed system design

Peer-Reviewed Publication

INTELLIGENT COMPUTING

Imagine you want to withdraw some cash from an ATM. You expect it to show your account balance correctly and process your request quickly. However, network delays make it hard for the system to meet both of these simple expectations at the same time. If an ATM system tries to achieve high “consistency,” meaning that it displays the latest account balance by checking a remote database, it could make you wait or even prevent you from accessing your accounts during busy times. On the other hand, if an ATM system favors “availability,” it could let you access your accounts fast, but risk showing inaccurate information. To avoid undesired results, designing ATM systems and other distributed systems requires making smart trade-offs.

Seeking to help system designers make those trade-offs, a group of researchers from the University of California, Berkeley and the Technical University of Dresden discovered a simple algebraic relationship between consistency, availability and network latency. This research was published Feb.15 in Intelligent Computing, a Science Partner Journal.

The researchers call this algebraic relationship the consistency-availability-apparent latency theorem; it quantifies consistency, availability and apparent latency as time intervals. The CAL theorem builds on Eric Brewer’s well-known consistency-availability-network partitioning theorem. Unlike the CAP theorem, which makes system designers choose upfront to sacrifice consistency, availability or both when a network lapse occurs, the CAL theorem allows system designers to adjust their choices depending on the situation — a method that enables “rigorous design with clearly stated assumptions.”

Rigorous design is essential for distributed systems that control complex networks of connected devices such as factory robots, medical devices and security systems, which have varying latencies at different nodes and are prone to network failures. Using the CAL theorem and Lingua Franca coordination language, a powerful tool that lets programmers specify how different nodes should interact with each other, system designers can model complex networks and use the results to customize distributed systems for reliability and efficiency.

The researchers demonstrated the effectiveness of their approach using a simple ATM network for tracking balances and processing transactions. They used the CAL theorem to model a network of ATMs and derive bounds on the network’s latency based on minimum consistency and availability requirements specified using the LF coordination language. Keeping within these bounds, they were able to optimize the design of the network by making decisions about software placement and trade-offs between consistency and availability. In the real world, such optimization may be necessary for the achievement of business goals.

The researchers also showed how to detect and handle violations of network latency requirements after deploying such a system. With built-in fault handlers provided by the LF coordination language, system designers can choose to sacrifice consistency or availability and “handle such failures gracefully.”

Additionally, the researchers implemented two coordination extensions based on the CAL theorem — one centralized and one decentralized — that support flexible trade-offs between consistency and availability as network latency changes. The centralized coordination mechanism prioritizes consistency, while the decentralized one prioritizes availability. A system employing these mechanisms can be customized according to the needs of the context.

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JOURNAL

Intelligent Computing

DOI

10.34133/icomputing.0013 

ARTICLE TITLE

Trading Off Consistency and Availability in Tiered Heterogeneous Distributed Systems

MSU to refurbish world’s first superconducting cyclotron for chip testing

MSU’s decades-long tradition of heavy-ion accelerator expertise tapped to help meet current national shortfall of testing capacity for advanced microelectronics, including for space-based applications

Business Announcement

MICHIGAN STATE UNIVERSITY FACILITY FOR RARE ISOTOPE BEAMS

 

IMAGE: MICHIGAN STATE UNIVERSITY WILL ESTABLISH AT THE FACILITY FOR RARE ISOTOPE BEAMS A NEW CHIP-TESTING FACILITY FOR NEXT-GENERATION SEMICONDUCTOR DEVICES, SUPPORTED BY THE DEPARTMENT OF DEFENSE THROUGH A $14.2 MILLION CONTRACT AWARDED BY THE MISSILE DEFENSE AGENCY WITH FUNDING FROM THE TEST RESOURCE MANAGEMENT CENTER. view more 

CREDIT: FACILITY FOR RARE ISOTOPE BEAMS

Michigan State University (MSU) will build on its 60-year track record in accelerator-based nuclear physics leadership by refurbishing the history-making K500 cyclotron and installing it as the heart of a new chip-testing facility for next-generation semiconductor devices. The facility establishment, supported by a $14.2 million contract funded by the U.S. Department of Defense Test Resource Management Center (TRMC) and awarded through the U.S. Department of Defense Missile Defense Agency (MDA), will be based at the Facility for Rare Isotope Beams (FRIB). The facility will help meet the current national shortfall of testing capacity for advanced microelectronics, including those used for commercial spaceflight, 5/6G wireless technology and autonomous vehicles.

The new East Lansing facility will be what amounts to the third act for the K500, which burst onto the nuclear science scene 40 years ago, making history as the world’s first superconducting cyclotron.             

“This new FRIB-adjacent facility at MSU will provide the United States several thousand additional hours of capacity for chip testing annually,” said MSU Interim President Teresa K. Woodruff, Ph.D. “We are ready to leverage a six-decade-long investment by the National Science Foundation in basic nuclear science at MSU for a new purpose that is so central to this critical industry, to U.S. competitiveness, and to national security.”

Among the most immediate goals is the testing of electronic components for use in space, where levels of ionizing radiation are much higher than at the Earth’s surface and where devices must operate for years or even decades with little if any maintenance. The MSU proposal for funding was in direct response to the 2018 National Academies report, “Testing at the Speed of Light,” which outlined a critical national shortfall of testing capacity of space-bound electronic components.

New chapter, same story

The K500’s newest chapter – one relevant to daily headlines that cut across the domains of geopolitics, business and technology – is set to continue a long MSU story of fueling disruptive innovation to create novel physics hardware, which is then leveraged to create sustained and broad-based benefits to support the nation. Perhaps the most prominent example of this pattern: a near copy of the K500 operates today at Texas A&M University where it’s used for nuclear physics research.

“MSU has been purposeful in leveraging its accelerator assets for new applications over the course of its nearly 60-year history in accelerator-based nuclear science leadership,” explained Thomas Glasmacher, FRIB Laboratory director. “This award enables us to continue that tradition at FRIB while delivering on our mission of addressing societal problems by providing this additional resource to advance current U.S. interests.”

The K500’s first act ushered in the superconducting cyclotron era for research with heavy ions. It was built on a shoestring budget, as is typical for the one-of-a-kind nature of devices in accelerator physics, and was often quite unreliable in its early days. Act two followed a hiatus and refurbishment in the late 1990s for coupling with the more powerful K1200 cyclotron. Initially approved by the NSF in 1996, the Coupled Cyclotron Facility (CCF) began operations in 2001 and was used more or less continually until November 2020. It enabled research with fast rare isotope beams at the National Superconducting Cyclotron Laboratory (NSCL), supported by the NSF. Among other things, the lab was known for its efficiency and uptime, eventually surpassing 90 percent, which is noteworthy given the complexity of the equipment.

This track record loomed large in MSU’s successful bid for FRIB, which the FRIB Project team built ahead of schedule and on budget. FRIB experiments are underway using what will be the world’s most powerful heavy-ion linear accelerator (linac).

The new linac might have finally spelled the end of the lower energy K500. However, in a pattern that has recurred in the history of innovation, the older technology instead has found new and, given the more than $500 billion semiconductor market and strategic importance of the chip industry, perhaps even wider relevance.

“The laboratory has always had an emphasis on building instruments that advanced the options available for solving basic and applied research problems in nuclear science,” said Andreas Stolz, MSU professor and FRIB rare isotope operations department manager. "We are excited to apply our operational expertise and the K500 cyclotron to a new purpose, especially one so relevant to the national interest.” Stolz is the principal investigator on the MDA contract.

Creating an ‘unparalleled ecosystem’

The new facility will complement a host of related work and initiatives at MSU and furthers university leadership in nuclear science, microelectronics and semiconductors. FRIB’s Single Event Effects (FSEE) facility is already operational, offering a menu of beams and ion cocktails for use in research. Another example: MSU’s new Space Electronics Center, a collaboration with Texas Instruments, was announced this fall and leverages FRIB to provide a range of services to industry, including research projects, workforce development, technical workshops and forums for small corporate delegations to have a presence on MSU’s campus. MSU’s nuclear physics graduate program has been ranked No. 1 since 2010 by U.S. News and World Report.

“MSU, FRIB and the College of Engineering, through the Space Electronics Center, are creating an unparalleled ecosystem that will include strong industry and government participation to advance the state-of-the-art in radiation-hardened components and space electronics, and above all, to develop the necessary talent that will support this technology discipline for years to come and solidify the U.S. position as a leader in this field,” said John Papapolymerou, MSU Research Foundation Professor and chair of the MSU Electrical and Computer Engineering Department.

Use of the new MSU facility will extend far beyond defense and aerospace applications since today more than ever, the semiconductor industry is marked by the creation of ever smaller, denser and more complex custom circuitry. Following the broad outlines of Moore’s Law, the industry has delivered a steady march of faster, cheaper and more power-efficient computing technologies for decades. Advanced semiconductor devices, with nanometer-scale features and often purpose-built with stacked interconnected chips to further increase capability, are increasingly susceptible to ionizing radiation.

Usually such effects – bit-flips of memory elements in a chip – don’t permanently damage the device. However, there are examples of real-world problems, from the trivial (impacting the outcome of a 2013 Super Mario game contest) to the more serious (causing injuries on a 2008 Qantas flight, which plunged downward when the onboard computer malfunctioned.) Risks only increase as more of daily life becomes dependent on applications ultimately mediated by computer hardware and software.

“Space electronics applications can act as a catalyst to attract a brand-new generation of engineers and scientists needed to fill the more than 50,000 positions in the general area of semiconductors over the next five years or so, said Papapolymerou. “MSU will play a central and pivotal role in this talent pipeline development.”

Experts, experience will guide the next transition

FRIB will draw on a deep well of institutional and operational expertise to transition the K500 cyclotron into its third act.

"Downtime to tune the equipment or fix problems is expensive, not only in dollars but also in lost opportunities for discovery and education, so we've long been incentivized to be efficient and meet the needs of our experimenters," says Sam Austin, University Distinguished Professor Emeritus in nuclear physics and former NSCL Director. "We're proud of our culture and approach, which is to do what it takes to make our users successful.”

NSF investment in accelerator-related research at MSU dates back to 1961 and resulted in many important advances in basic and applied rare isotope research, many of which are outlined in Austin’s 2016 book “Up from Nothing.” These advances include dozens of examples of experimental apparatus and techniques, from spectrographs to superconducting solenoids to stopping fast beams.        

“This is really about the value of sustained vision and concomitant actions over decades,” said Glasmacher. “Part of building resiliency in U.S. science and technology, whether in nuclear science or semiconductors, is not to forget work that’s come before, but rather to leverage assets for future discoveries.” 

Michigan State University will establish at the Facility for Rare Isotope Beams a new chip-testing facility for next-generation semiconductor devices, supported by the Department of Defense through a $14.2 million contract awarded by the Missile Defense Agency with funding from the Test Resource Management Center.

The new facility will increase by thousands of hours annually the nation’s chip-testing capacity for next-generation semiconductor devices, including those used in applications such as commercial spaceflight, 5/6G wireless technology and autonomous vehicles.

Michigan State University will refurbish its history-making K500 cyclotron and install it as the heart of a new chip-testing facility for next-generation semiconductor devices at the Facility for Rare Isotope Beams. The new facility will be what amounts to the third act for the K500, which made history on the nuclear science scene 40 years ago as the world’s first superconducting cyclotron.

Sam Austin, University Distinguished Professor Emeritus in nuclear physics and former National Superconducting Cyclotron Laboratory Director, penned the 2016 book “Up from Nothing,” detailing accelerator-related research at MSU dating back to 1961.

CREDIT

Facility for Rare Isotope Beams

Michigan State University has been advancing the common good with uncommon will for more than 165 years. One of the world's leading research universities, MSU pushes the boundaries of discovery to make a better, safer, healthier world for all while providing life-changing opportunities to a diverse and inclusive academic community through more than 400 programs of study in 17 degree-granting colleges.

SPYWARE

AI-equipped eyeglasses read silent speech

Reports and Proceedings

CORNELL UNIVERSITY

ITHACA, N.Y. – Cornell University researchers have developed a silent-speech recognition interface that uses acoustic-sensing and artificial intelligence to continuously recognize up to 31 unvocalized commands, based on lip and mouth movements.

The low-power, wearable interface – called EchoSpeech – requires just a few minutes of user training data before it will recognize commands and can be run on a smartphone.

Ruidong Zhang, doctoral student of information science, is the lead author of “EchoSpeech: Continuous Silent Speech Recognition on Minimally-obtrusive Eyewear Powered by Acoustic Sensing,” which will be presented at the Association for Computing Machinery Conference on Human Factors in Computing Systems (CHI) this month in Hamburg, Germany.

“For people who cannot vocalize sound, this silent speech technology could be an excellent input for a voice synthesizer. It could give patients their voices back,” Zhang said of the technology’s potential use with further development.

In its present form, EchoSpeech could be used to communicate with others via smartphone in places where speech is inconvenient or inappropriate, like a noisy restaurant or quiet library. The silent speech interface can also be paired with a stylus and used with design software like CAD, all but eliminating the need for a keyboard and a mouse.

Outfitted with a pair of microphones and speakers smaller than pencil erasers, the EchoSpeech glasses become a wearable AI-powered sonar system, sending and receiving soundwaves across the face and sensing mouth movements. A deep learning algorithm then analyzes these echo profiles in real time, with about 95% accuracy.

“We’re moving sonar onto the body,” said Cheng Zhang, assistant professor of information science and director of Cornell’s Smart Computer Interfaces for Future Interactions (SciFi) Lab.

“We’re very excited about this system,” he said, “because it really pushes the field forward on performance and privacy. It’s small, low-power and privacy-sensitive, which are all important features for deploying new, wearable technologies in the real world.”

Most technology in silent-speech recognition is limited to a select set of predetermined commands and requires the user to face or wear a camera, which is neither practical nor feasible, Cheng Zhang said. There also are major privacy concerns involving wearable cameras – for both the user and those with whom the user interacts, he said.

Acoustic-sensing technology like EchoSpeech removes the need for wearable video cameras. And because audio data is much smaller than image or video data, it requires less bandwidth to process and can be relayed to a smartphone via Bluetooth in real time, said François Guimbretière, professor in information science.

“And because the data is processed locally on your smartphone instead of uploaded to the cloud,” he said, “privacy-sensitive information never leaves your control.”

For additional information, see this Cornell Chronicle story.

Media note: Pictures of EchoSpeech can be viewed and downloaded here: https://cornell.box.com/v/EchoSpeechGlasses. A video can be found here: https://youtu.be/ZjucAwFqVqQ.

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DOI

10.1145/3544548.3580801 

Researchers create embryo-like structures from monkey embryonic stem cells for the first time

Peer-Reviewed Publication

CELL PRESS

 

IMAGE: CYNOMOLGUS MONKEY EMBRYO MODEL CAPTURES GASTRULATION AND EARLY PREGNANCY view more 

CREDIT: CELL STEM CELL/LI ET AL.

Human embryo development and early organ formation remain largely unexplored due to ethical issues surrounding the use of embryos for research as well as limited availability of materials to study. In a paper published April 6 in the journal Cell Stem Cell, a team of investigators from China report for the first time the creation of embryo-like structures from monkey embryonic stem cells. The investigators also transferred these embryo-like structures into the uteruses of female monkeys and determined that the structures were able to implant and elicit a hormonal response similar to pregnancy.

“The molecular mechanisms of human embryogenesis and organogenesis are largely unclear,” says co-corresponding author Zhen Liu of the Chinese Academy of Sciences (CAS) in Shanghai. “Because monkeys are closely related to humans evolutionarily, we hope the study of these models will deepen our understanding of human embryonic development, including shedding light on some of the causes of early miscarriages.”

“This research has created an embryo-like system that can be induced and cultured indefinitely,” says co-corresponding author Qiang Sun, also of CAS. “It provides new tools and perspectives for the subsequent exploration of primate embryos and reproductive medical health.”

The investigators started with macaque embryonic stem cells, which they exposed to a number of growth factors in cell culture. These factors induced the stem cells to form embryo-like structures for the first time using non-human primate cells.

When studied under a microscope, the embryo-like structures, also called blastoids, were found to have similar morphology to natural blastocysts. As they further developed in vitro, they formed arrangements that looked like the amnion and yolk sac. The blastoids also started to form the types of cells that eventually make up the three germ layers of the body. Single-cell RNA sequencing revealed that the different types of cells found within the structures had similar gene expression patterns to cells found in natural blastocysts or post-implantation embryos.

The blastoids were then transferred into the uteruses of 8 female monkeys; in 3 of the 8, the structures implanted. This implantation resulted in the release of progesterone and chorionic gonadotropin, hormones normally associated with pregnancy. The blastoids also formed early gestation sacs, fluid-filled structures that develop early in pregnancy to enclose an embryo and amniotic fluid. However, they did not form fetuses and the structures disappeared after about a week.

In future work, the investigators plan to focus on further developing the system of culturing embryo-like structures from monkey cells. “This will provide us with a useful model for future study,” says co-corresponding author Fan Zhou of Tsinghua University. “Further application of monkey blastoids can help to dissect the molecular mechanisms of primate embryonic development.”

The researchers acknowledge the ethical concerns surrounding this type of research but emphasize that there are still many differences between these embryo-like structures and natural blastocysts. Importantly, the embryo-like structures do not have full developmental potential. They note that for this field to advance it’s important to have discussions between the scientific community and the public.

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This work was supported the National Key Research and Development Program of China, Shanghai Municipal Science and Technology Major Project, the Strategic Priority Research Program of the Chinese Academy of Sciences, the Basic Frontier Scientific Research Program of CAS, the Haihe Laboratory of Cell Ecosystem Innovation Fund, Tsinghua-Peking Center for Life Sciences, the Startup Fund, and the Dushi Special Fund at School of Life Sciences, Tsinghua University.

Cell Stem Cell, Liu et al. “Cynomolgus monkey embryo model captures gastrulation and early pregnancy” https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00080-2

Cell Stem Cell (@CellStemCell), published by Cell Press, is a monthly journal that publishes research reports describing novel results of unusual significance in all areas of stem cell research. Each issue also contains a wide variety of review and analysis articles covering topics relevant to stem cell research ranging from basic biological advances to ethical, policy, and funding issues. Visit: http://www.cell.com/cell-stem-cell. To receive Cell Press media alerts, contact press@cell.com.

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JOURNAL

Cell Stem Cell

DOI

10.1016/j.stem.2023.03.009 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Cynomolgus monkey embryo model captures gastrulation and early pregnancy

Life-threatening childbirth complications among Medicaid enrollees vary widely by state and race-ethnicity

Threefold difference between lowest rate of severe maternal morbidity in Utah compared to highest in D.C.; causes differ

Peer-Reviewed Publication

MICHIGAN MEDICINE - UNIVERSITY OF MICHIGAN

The risk of life-threatening maternal complications from childbirth may be higher depending on where you live, a new study finds.

For Medicaid enrollees in Utah, the rate of “near miss” instances that could have led to the death of a birthing person during pregnancy or delivery was the lowest in the U.S., occurring among 80 per 10,000 live births.

Meanwhile, on the other side of the country in Washington D.C., the rate of such cases was nearly three times higher – 210 per 10,000 deliveries.

The drivers for these unexpected maternal outcomes, referred to as severe maternal morbidity, also varied by race and ethnicity, according to the research in Obstetrics & Gynecology, or The Green Journal.

“Our findings suggest wide variation in rates and potential causes of severe maternal morbidity by state, and by race and ethnicity across and within states,” said lead author Lindsay Admon, M.D., M.Sc., an assistant professor of obstetrics and gynecology at the University of Michigan Medical School and obstetrician-gynecologist at U-M Health Von Voigtlander Women’s Hospital.

“This data highlights states that have the greatest burden of severe maternal complications and may help guide and tailor interventions aimed at reducing morbidity among those at highest risk.”

Researchers analyzed national data from 4.8 million live births among Medicaid enrollees (average age of 27) between 2016 and 2018, tracking unanticipated outcomes resulting in significant short- or long-term health consequences within six weeks of delivery.

Overall, 146 out of every 10,000 live births among Medicaid enrollees in the U.S. involved serious complications, according to the study.

Differences in maternal morbidity rates across states and by race and ethnicity

The new findings come on the heels of alarming data from the Centers for Disease Control and Prevention finding a sharp rise in maternal deaths during the pandemic.

Medicaid finances slightly more than two in five births in the U.S. and a disproportionate number of births to individuals with the greatest risk of experiencing severe maternal complications and death, including Black and Indigenous populations, rural residents, and those living in lower income ZIP codes.

More than two thirds of individuals with live births in the study were eligible for Medicaid for income while a smaller proportion qualified due to pregnancy. 

“Medicaid enrollees are at the highest risk of maternal morbidity and mortality,” Admon said.

“Many states are pursuing clinical interventions and health policies designed to address maternal health inequities through Medicaid programs. But until now, we haven’t had a big picture view of health outcomes on a geographic and demographic level to inform these decisions.”

The five states with the highest rates of severe maternal morbidity included D.C., California, Nevada, New Jersey, and New York. Meanwhile, rates for Utah, Maryland, Rhode Island, Nebraska, and New Hampshire fell in the bottom tenth percentile.

But state-by-state outcomes differed depending on a person’s racial or ethnic group.  Among deliveries to non-Hispanic Black individuals, the three states with the highest rates of severe maternal morbidity were Alaska, New York, and New Jersey while states with the lowest rates were in New Mexico, North Dakota, and Utah.

For white individuals, California, West Virginia, and South Carolina ranked highest for severe adverse maternal health outcomes while the lowest rates were found in Utah, North Dakota and Maine.

Drivers of maternal morbidity

The leading factor linked with severe maternal morbidity among all Medicaid enrollees was eclampsia, a rare but life-threatening complication from high blood pressure during pregnancy that can cause seizures. But conditions varied across states and by race and ethnicity within states.

In Texas, for example, eclampsia was the top driver of potentially fatal maternal outcomes overall among people covered by Medicaid. However, non-Hispanic Black Texans experienced acute heart failure as the leading driver, and white Texans experienced sepsis as the leading driver of maternal health outcomes.

“Previous research suggests that pre-existing chronic conditions like obesity, diabetes, and mental health conditions are linked to greater risk for adverse maternal health outcomes,” Admon said.

“We need to focus on interventions that improve the overall health of our reproductive-aged population and identify clinical, societal, and structural barriers that may prevent individuals from achieving optimal health before pregnancy.”

Since maternal mortality is a relatively rare event, Admon adds, studying severe maternal morbidity to understand “near miss” events that could have resulted in an in-hospital maternal death may help efforts to mitigate the most adverse maternal health outcomes.

“When we look at maternal health across populations within states, we can see that some communities are performing much better than others with respect to life-threatening labor and delivery outcomes,” Admon said.

“This added nuance will be helpful to clinicians, policymakers and advocacy groups who are committed to strategies to improve maternal health across the country.”

 

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JOURNAL

Obstetrics and Gynecology

NIH-funded study finds doxycycline reduces sexually transmitted infections by two-thirds

Peer-Reviewed Publication

NIH/NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

 

IMAGE: SCANNED ELECTRON MICROGRAPH IMAGE OF NEISSERIA GONORRHOEAE BACTERIA, WHICH CAN CAUSE GONORRHEA. view more 

CREDIT: NIAID

The oral antibiotic doxycycline prevented the acquisition of sexually transmitted infections (STIs) when tested among men who have sex with men (MSM) and transgender women who took the medication within 72 hours of having condomless sex, according to findings published today in the New England Journal of Medicine. Specifically, the post-exposure approach, termed doxy-PEP, resulted in a two-thirds reduction in the incidence of syphilis, gonorrhea, and chlamydia among the study participants, all of whom reported having an STI within the previous year. However, the research also revealed a slight increase in antibacterial resistance that requires further exploration, the authors found. The research was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. 

“Effective methods for preventing sexually transmitted infections are badly needed,” said Hugh Auchincloss, M.D., NIAID acting director. “This is an encouraging finding that could help reduce the number of sexually transmitted infections in populations most at-risk.” 

STI incidence has been increasing in the United States over the past few years with a disproportionate impact among MSM and transgender women. An estimated 2.5 million cases of syphilis, gonorrhea, and chlamydia occurred in 2021 up from 2.4 million cases in 2020, according to the Centers for Disease Control and Prevention. If left untreated, STIs can lead to serious health consequences, including brain and nerve problems, blindness, infertility and increased risk of HIV acquisition. Antimicrobial resistance among STIs is an emerging public health threat, particularly with Neisseria gonorrhoeae, and threatens available treatment options.

The study was led by researchers at the University of California at San Francisco (UCSF) and the University of Washington, Seattle. It enrolled 501 adults at four clinic sites in San Francisco and Seattle who were at least 18 years of age; assigned male sex at birth; reported sexual activity with a man in the previous year; diagnosed with HIV or taking or planning to take pre-exposure prophylaxis (PrEP) medication to prevent HIV acquisition; and diagnosed with gonorrhea, chlamydia or early syphilis in the prior year. Of those enrolled, 327 participants were taking HIV PrEP medications, and 174 participants were people living with HIV. 

Participants were randomly assigned to receive either doxy-PEP or standard of care. Those in the doxy-PEP arm were instructed to take one 200 milligram (mg) doxycycline-delayed release tablet, ideally within 24 hours but no later than 72 hours after condomless sex. Doxycycline is a broad-spectrum antibiotic in a family called tetracyclines. Participants were assessed by study staff every three months for adherence and side effects to the medication regimen and tested for STIs. Participant acceptability of the medication was assessed at six-and-12-month clinic visits. An independent data and safety monitoring board reviewed study progress and safety and effectiveness data every six months. 

Among participants on HIV PrEP, at least one or more STIs were diagnosed in 10.7% of quarterly clinic visits in the doxy-PEP study arm compared to 31.9% of visits in the standard of care arm. Among study participants living with HIV, one or more STIs were diagnosed in 11.8% of quarterly visits in the doxy-PEP arm versus 30.5% in the standard of care arm. Gonorrhea was the most frequently diagnosed STI in the study. Participants reported good adherence to the medication regimen with 86.2% reporting taking doxy-PEP consistently within 72 hours of condomless sex, and 71.3% reported never missing a dose. No safety or acceptability issues were identified in the study.

“Given its demonstrated efficacy in several trials, doxy-PEP should be considered as part of a sexual health package for men who have sex with men and transwomen if they have an increased risk of STIs,” according to Annie Luetkemeyer, M.D., professor of infectious diseases at Zuckerberg San Francisco General Hospital at UCSF, and co-principal investigator of the study. “It will be important to monitor the impact of doxy-PEP on antimicrobial resistance patterns over time and weigh this against the demonstrated benefit of reduced STIs and associated decreased antibiotic use for STI treatment in men at elevated risk for recurrent STIs.” 

In examining the potential for antimicrobial resistance during doxy-PEP use, the researchers discovered tetracycline resistance in a greater number of incident gonorrhea strains among those in the doxy-PEP arm than among those in the standard of care group (38.5% versus 12.5%, respectively). This suggests that doxy-PEP may offer less protection against gonorrhea strains that are already tetracycline-resistant and that wider population-based surveillance for this type of resistance is important. Additionally, the researchers found that doxy-PEP reduced Staphylococcus aureus—a bacteria commonly found on the skin “colonization”—by 50% after a year. However, in those who still had Staphylococcus aureus colonization at month 12, a modestly higher proportion of those in the doxy-PEP group had doxycycline resistance (16% vs 8%). This is important because doxycycline may be used to treat methicillin-resistant Staphylococcus aureus skin and soft tissue infections. Additional research and longer follow-up periods are needed to examine the potential antimicrobial resistance effect of intermittent doxy-PEP use. Doxy-PEP use in other populations disproportionately impacted by STIs, including women with HIV and those taking HIV PrEP, deserves further exploration as well. 

“We need new, effective STI prevention methods and three studies have now demonstrated that doxy-PEP significantly reduces gonorrhea, chlamydia and syphilis. In the next several years during the implementation of doxy-PEP, we need to learn about maximizing equitable access and impact,” said Dr. Connie Celum, Professor of Global Health and Medicine at the University of Washington and co-principal investigator of the DoxyPEP Study. 

Reference: AF Leutkemeyer et al. Doxycycline to prevent bacterial sexually transmitted infections. NEJM DOI: 10.1056/NEJMoa2211934 (2023).

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JOURNAL

New England Journal of Medicine

DOI

10.1056/NEJMoa2211934 

ACCELERATIONISM

Birch reduction simplified to a one-minute mechanochemical process

Peer-Reviewed Publication

HOKKAIDO UNIVERSITY

 

IMAGE: BALL MILLING JAR AND REAGENTS USED IN THE SIMPLIFIED MECHANOCHEMICAL BIRCH REDUCTION. (PHOTO: KOJI KUBOTA) view more 

CREDIT: KOJI KUBOTA

The traditionally cumbersome yet widely-used Birch reduction can now be carried out in a mere minute in air using an optimized mechanochemical approach.

The Birch reduction is a reaction commonly used to make medicines and bioactive compounds, but the laborious process typically requires that chemists handle liquid ammonia, use cryogenic temperatures, and carry out time-consuming steps. Researchers at the Institute for Chemical Reaction Design and Discovery (WPI-ICReDD) in Hokkaido University have developed a simplified method for performing the Birch reduction that avoids the use of ammonia, can be done at room temperature and in ambient air, and is 20-150 times faster than conventional methods.

A number of lithium-based methods for performing the Birch reduction in solution have been previously developed, but since lithium reacts with both air and water, these processes still required complicated reaction setups with an inert atmosphere or dehydrated conditions.  Researchers in this study saw an opportunity to avoid these issues by switching from a solution-based method to a solvent-less method using a ball mill, in which reactants are shaken rapidly in a small metal jar along with a metal ball that smashes the solid reactants together.

“In previous studies, we found that using a ball mill for reactions of metals such as magnesium and calcium with organic compounds improved the reaction rate and greatly simplified the process,” said co-author Associate Professor Koji Kubota. “Based on this, we wondered if we could develop a more straight-forward Birch reduction process by performing reactions of lithium metal with aromatic compounds in a ball mill.”

The key to this strategy is that the mechanical impact from the ball breaks through the surface layer on the lithium that reacted with the air, exposing the pure lithium underneath to the other reactants and enabling the Birch reduction to proceed. This approach can be carried out in ambient air and at room temperature, making for a much easier process.

Researchers demonstrated the versatility of the process, successfully testing it with a wide variety of organic compounds, including pharmaceutical intermediates and other bioactive molecules. In most cases, the Birch reduction was completed in an astonishingly quick one minute.

The process was successfully scaled up to larger gram-scale batches, and the team believes this technique could enable the simplified synthesis of a wide variety of molecules, while also marking an important advance in mechanochemistry.

“The Birch reduction is used extensively in drug discovery and various chemical industries, and our research has made significant advancements, resulting in a much simpler and more eco-friendly Birch reduction process,” commented Professor Hajime Ito, who led the study. “We expect this breakthrough to accelerate drug discovery and various other areas of chemical research.”

Overview of the simplified protocol for the Birch reduction using a ball mill.

 (Yunpeng Gao, Koji Kubota, Hajime Ito. Agewandte Chemie International Edition. March 21, 2023)

JOURNAL

Angewandte Chemie International Edition

DOI

10.1002/anie.202217723 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Mechanochemical Approach for Air-Tolerant and Extremely Fast Lithium-Based Birch Reductions in Minutes