Scientists uncover prophage defense mechanisms against phage attacks in mycobacteria

Experimental approach reveals Butters prophage uses a two-component system to block entry of some phages, but not others, from attacking a strain of mycobacteria related to infection-causing strains; important for advancing phage therapies

LEHIGH UNIVERSITY

Research News

 

IMAGE: VASSIE WARE IS A PROFESSOR IN LEHIGH UNIVERSITY'S DEPARTMENT OF BIOLOGICAL SCIENCES AND IS CO-DIRECTOR OF LEHIGH'S HOWARD HUGHES MEDICAL INSTITUTION (HHMI) BIOSCIENCE PROGRAM AND DISTANCE EDUCATION PROGRAM... view more 

CREDIT: LEHIGH UNIVERSITY

A phage is a virus that invades a bacterial cell. While harmless to human cells, phages are potentially deadly to bacteria since many phages enter a cell in order to hijack its machinery in order to reproduce itself, thus destroying the cell.

While this is bad news for bacteria, it may be good news for humans. There is a growing need to develop new treatments that effectively attack deadly strains of bacteria that have become resistant to other medicines. Already used with success in some parts of the world, phage therapy is gaining traction as a more widespread way to fight antibiotic-resistant bacterial infections and even, at some point, some viral infections including, according to a recent article, possibly COVID-19.

Among the challenges: a virus type known as a prophage. A phage enters a bacterial cell and, instead of destroying it, takes up residence. Called a "prophage," it fights off other viruses' attempts to invade. According to Vassie Ware, a professor in Lehigh University's Department of Biological Sciences, many bacterial strains contain prophages. These prophages, she says, may provide defense systems that would make therapeutic uses of phages more challenging. In order to eradicate a pathogen, phages may need to overcome an already-in-residence prophage's defense systems.

Ware and her team (former PhD student Catherine Mageeney, current PhD student Hamidu Mohammed and former undergraduate student Netta Cudkevich), collaborating with former Lehigh Chemical and Biomolecular Engineering and Bioengineering faculty member Javier Buceta and his team (former postdoctoral associate Marta Dies, recent PhD students Samira Anbari and Yanyan Chen), recently conducted a study that focused on a phage called Butters (discovered by Lena Ma in Lehigh's SEA-PHAGES Program in 2012) that attacks a bacterial strain related to mycobacteria that cause tuberculosis or other human infections.

The group uncovered a two-component system of Butters prophage genes that encode proteins that "collaborate" to block entry and subsequent infection of some phages, but not others. While the Butters prophage cannot protect the bacterial cell against all phage attacks, they discovered that more than one defense system is present in the Butters prophage defense repertoire. These weapons, they discovered, are specific for different types of phages. These findings were published in an article earlier this month in mSystems, a journal of the American Society for Microbiology.

"Previous findings by several members of our research team working with other collaborators showed that prophages express genes that defend their bacterial host from infection by some specific groups of phages. For Butters, no genes involved in defense against specific phages had been previously identified," says Ware. "With our experimental approach, we expected to identify genes involved in defense against infection by several phages, but were not expecting to uncover interactions between the two proteins that affected how one of the proteins functions in defense."

The Ware/Buceta team used a multidisciplinary approach to identify the genes and interactions. They utilized bioinformatics tools to predict structural features of proteins encoded by genes expressed by the Butters prophage and to probe databases for the presence of Butters genes within known bacterial strains. Molecular biology techniques were used to engineer mycobacterial strains to express phage genes from the prophage. Microbiology experiments included immunity plating efficiency assays for each engineered bacterial strain to determine if the gene in question would protect the engineered bacterial strain from infection by a particular phage type.

This strategy, says Ware, allowed identification of specific genes as part of the defense mechanism against specific viral attack.

They also conducted microscopy experiments for live-cell imaging to visualize the cellular location of phage proteins within engineered bacterial cells and to show a functional interaction between the phage proteins in question. Biochemical experiments determined that the phage proteins likely interact physically as part of the defense mechanism.

"Collectively, these approaches provided data that allowed the team to construct a model for how the Butters prophage two-component system may function in defense against specific viral attack," says Ware.

Adds Ware: "The diversity of defense systems that exists demonstrates that efforts to establish generic sets of phage cocktails for phage therapy to kill pathogenic bacteria will likely be more challenging."

In addition to advancing phage therapy development, the team's discovery may also be important for engineering phage-resistant bacteria that could be used in the food industry and in some biotechnology applications.

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Biodiversity monitoring programmes need a culture of collaboration

Integration of contributors promotes the quantity and quality of data

GERMAN CENTRE FOR INTEGRATIVE BIODIVERSITY RESEARCH (IDIV) HALLE-JENA-LEIPZIG

Research News

 

IMAGE: THE PARTICIPATION OF EXPERT VOLUNTEERS IN CITIZEN SCIENCE PROJECTS (HERE AT THE BUTTERFLY MONITORING GERMANY, A PROJECT OF THE UFZ) IS A FUNDAMENTAL PILLAR OF BIODIVERSITY MONITORINGS IN GERMANY, ESPECIALLY... view more 

CREDIT: ANDRÉ KÜNZELMANN/UFZ

Ecological monitoring is the recording of biological diversity and its spatial and temporal changes. The lack of monitoring programmes which cover a broad range of species often means that, in many countries, no clear assessments can be made about the status of biodiversity. As a result, factors which may lead to declines cannot be identified and remedied.

The necessary information, and the various stakeholders such as public authorities, scientists, specialist organisations, nature conservation associations and certain professional groups from the private sector would definitely be available in many places. However, they cannot always work in a coordinated way, as they often operate within very different institutional frameworks. Valuable knowledge and data are therefore not pooled, and gaps in the collection of data not filled. "This is why we have to create a culture of integration involving all those who are active in biodiversity monitoring," says the first author of the study, Dr Hjalmar Kühl, ecologist at iDiv and the Max Planck Institute for Evolutionary Anthropology (MPI EVA).

Framework of trust

This can be achieved by bringing the various stakeholder groups together. "What's needed is a framework within which decisions are not always made centrally, but in which the various groups network, trust each other and decide together what needs to be done," says Kühl. "This self-organisation can increase the participants' motivation and thus ensure greater acceptance on the part of the respective interest groups and anchor the topic of biodiversity more firmly in the public consciousness."

To achieve this, workshops and symposia could bring relevant stakeholders together to collaborate in developing appropriate incentives and the necessary technical requirements for the exchange of data, results and analyses. "New approaches for the analysis of a wide range of monitoring data show how the information provided by a monitoring network can be interlinked with that from others," says co-author Dr Diana Bowler, ecologist at the Helmholtz Centre for Environmental Research (UFZ) and iDiv. This allows the activities of various interest groups and individuals to be easily integrated.

In Europe, between 80 and 90 percent of biodiversity data is collected by volunteers

The assistance and involvement of volunteers, participants in Citizen Science programmes and species experts from professional associations is indispensable in many cases. For example, it was only through a study by the Krefeld Entomological Association which, in 2017, revealed the severe decline in flying insects that insect protection became a topic for the political agenda in Germany. Particularly, in the case of species groups such as beetles, hoverflies and cicadas, for whose identification the authorities rely on taxonomic expertise, volunteer participation is important for long-term surveys.

"There's a long history of volunteer natural scientists who are fascinated by biological diversity and work for its preservation," says last author Prof Aletta Bonn, research group leader at the UFZ, iDiv and the Friedrich Schiller University Jena. "This citizen science data can be integrated with other monitoring data to identify trends and information gaps. A cultural change regarding cooperation in science is required - towards integrated monitoring for sustainable biodiversity protection."

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This study was funded by, among others, the Deutsche Forschungsgemeinschaft (DFG; FZT 118, 202548816) as part of "sMon - Biodiversity Trends in Germany", a synthesis project of the German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, in cooperation with public authorities, specialist organisations and associations.

 

Surprisingly mature galaxies in the early Universe

CNRS

Research News

 

IMAGE: ARTIST'S ILLUSTRATION OF A DUSTY, ROTATING DISTANT GALAXY, IN THE EARLY UNIVERSE. IN THIS IMAGE, THE RED COLOR REPRESENTS GAS, AND BLUE/BROWN REPRESENTS DUST AS SEEN IN RADIO WAVES WITH... view more 

CREDIT: © B. SAXTON NRAO/AUI/NSF, ESO, NASA/STSCI; NAOJ/SUBARU

When the Universe was only a tenth of its current age its galaxies experienced a growth spurt. It was this period that the scientists in the ALPINE project (1) focused on when they used ESO's ALMA (2) telescope to carry out the first ever large survey of distant galaxies. To their surprise, these galaxies observed in the early stages of their life were far more mature than expected. Their work is the subject of a series of articles published on 27 October 2020 in the journal Astronomy & Astrophysics, signed among others by members of the CNRS and Aix-Marseille Université (3).

Galaxies began to form very early in the history of the Universe. To study their infancy, it is therefore necessary to go back to the dawn of time, by observing very distant galaxies. The ALPINE project focused on a period between 1 and 1.5 billion years after the Big Bang, when the first galaxies experienced a phase of rapid growth. Although such distant galaxies have already been observed, this is the first time that so many of them have been studied systematically. Images of 118 massive (4) galaxies, obtained with the Hubble (visible light) and Spitzer (near infrared) space telescopes, as well as spectra acquired using the ground-based VLT and Keck telescopes, were supplemented by 70 hours of observation with ALMA at submillimetre wavelengths (between the infrared and radio waves).

ALMA can quantify dust, a sign of maturity in galaxies, and cold gas, which provides information about their rate of growth and the number of stars they can form, as well as the motion of this gas, thus revealing the dynamics of galaxies. And this turned up some surprising data. For a start, the observed galaxies proved to be very rich not only in cold gas, which fuels star formation, but also in dust, which is thought to be a by-product of stars at the end of their lives. So despite their young age, these galaxies had apparently seen the formation and death of a first generation of stars! The galaxies surveyed also exhibit an astonishing diversity of shapes: some are disordered, others already have a rotating disc that may end up as a spiral structure like the Milky Way, while yet others have been spotted in the process of merging. Another surprising observation is that certain galaxies appear to be ejecting gas, forming mysterious haloes around them. The survey thus raises a number of new questions about the early evolution of galaxies.

CAPTION

Mosaic showing some of the galaxies observed by ALMA. The bright yellow regions are those where the most stars are forming (the ionised carbon (C+) line makes it possible to see the formation of stars obscured by dust). The second image from the left in the top row shows a triple merger.

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To find out more, read NRAO's news release:
https://public.nrao.edu/news/galaxies-in-the-infant-universe-were-surprisingly-mature/

Notes:

(1) Acronym for the ALMA Large Program to INvestigate C+ at Early times
(2) ALMA (Atacama Large Millimeter/submillimeter Array) is a telescope designed for the study of radiation from the coldest objects in the Universe, and consists of 66 antennas located in the Atacama desert in the Chilean Andes.
(3) from the Laboratoire d'Astrophysique de Marseille (CNRS/Aix-Marseille Université/CNES) and the Institut de Recherche en Astrophysique et Planétologie (CNRS/Université Toulouse III - Paul Sabatier/ CNES).
(4) They have already reached a mass similar to that of the Milky Way today.

Galaxies in the infant universe were surprisingly mature

ALMA telescope conducts largest survey yet of distant galaxies in the early universe

NATIONAL RADIO ASTRONOMY OBSERVATORY

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VIDEO: BRIEF VIDEO EXPLAINING THIS RESEARCH RESULT. view more 

CREDIT: B. SAXTON NRAO/AUI/NSF

Massive galaxies were already much more mature in the early universe than previously expected. This was shown by an international team of astronomers who studied 118 distant galaxies with the Atacama Large Millimeter/submillimeter Array (ALMA).

Most galaxies formed when the universe was still very young. Our own galaxy, for example, likely started forming 13.6 billion years ago, in our 13.8 billion-year-old universe. When the universe was only ten percent of its current age (1-1.5 billion years after the Big Bang), most of the galaxies experienced a "growth spurt". During this time, they built up most of their stellar mass and other properties, such as dust, heavy element content, and spiral-disk shapes, that we see in today's galaxies. Therefore, if we want to learn how galaxies like our Milky Way formed, it is important to study this epoch.

In a survey called ALPINE (the ALMA Large Program to Investigate C+ at Early Times), an international team of astronomers studied 118 galaxies experiencing such a "growth spurt" in the early universe. "To our surprise, many of them were much more mature than we had expected," said Andreas Faisst of the Infrared Processing and Analysis Center (IPAC) at the California Institute of Technology (Caltech).

Galaxies are considered more "mature" than "primordial" when they contain a significant amount of dust and heavy elements. "We didn't expect to see so much dust and heavy elements in these distant galaxies," said Faisst. Dust and heavy elements (defined by astronomers as all elements heavier than hydrogen and helium) are considered to be a by-product of dying stars. But galaxies in the early universe have not had much time to build stars yet, so astronomers don't expect to see much dust or heavy elements there either.

"From previous studies, we understood that such young galaxies are dust-poor," said Daniel Schaerer of the University of Geneva in Switzerland. "However, we find around 20 percent of the galaxies that assembled during this early epoch are already very dusty and a significant fraction of the ultraviolet light from newborn stars is already hidden by this dust," he added.

Many of the galaxies were also considered to be relatively grown-up because they showed a diversity in their structures, including the first signs of rotationally supported disks - which may later lead to galaxies with a spiral structure as is observed in galaxies such as our Milky Way. Astronomers generally expect that galaxies in the early universe look like train wrecks because they often collide. "We see many galaxies that are colliding, but we also see a number of them rotating in an orderly fashion with no signs of collisions," said John Silverman of the Kavli Institute for the Physics and Mathematics of the Universe in Japan.

ALMA has spotted very distant galaxies before, such as MAMBO-9 (a very dusty galaxy) and the Wolfe Disk (a galaxy with a rotating disk). But it was hard to say whether these discoveries were unique, or whether there were more galaxies like them out there. ALPINE is the first survey that enabled astronomers to study a significant number of galaxies in the early universe, and it shows that they might evolve faster than expected. But the scientists don't yet understand how these galaxies grew up so fast, and why some of them already have rotating disks.

Observations from ALMA were crucial for this research because the radio telescope can see the star formation that is hidden by dust and trace the motion of gas emitted from star-forming regions. Surveys of galaxies in the early universe commonly use optical and infrared telescopes. These allow the measurement of the unobscured star formation and stellar masses. However, these telescopes have difficulties measuring dust obscured regions, where stars form, or the motions of gas in these galaxies. And sometimes they don't see a galaxy at all. "With ALMA we discovered a few distant galaxies for the first time. We call these Hubble-dark as they could not be detected even with the Hubble telescope," said Lin Yan of Caltech.

To learn more about distant galaxies, the astronomers want to point ALMA at individual galaxies for a longer time. "We want to see exactly where the dust is and how the gas moves around. We also want to compare the dusty galaxies to others at the same distance and figure out if there might be something special about their environments," added Paolo Cassata of the University of Padua in Italy, formerly at the Universidad de Valparaíso in Chile.

ALPINE is the first and largest multi-wavelength survey of galaxies in the early universe. For a large sample of galaxies the team collected measurements in the optical (including Subaru, VISTA, Hubble, Keck and VLT), infrared (Spitzer), and radio (ALMA). Multi-wavelength studies are needed to get the full picture of how galaxies are built up. "Such a large and complex survey is only possible thanks to the collaboration between multiple institutes across the globe," said Matthieu Béthermin of the Laboratoire d'Astrophysique de Marseille in France.

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The National Radio Astronomy Observatory is a facility of the National Science Foundation, operated under cooperative agreement by Associated Universities, Inc.

Media contact:

Iris Nijman
NRAO News and Public Information Manager
inijman@nrao.edu

A list of ALPINE publications to date can be found here: http://alpine.ipac.caltech.edu/#publications

All ALPINE papers are dedicated to the memory of Olivier Le Fèvre, Principal Investigator of ALPINE.

Co-Principal Investigators of ALPINE are:

- Andreas Faisst, Caltech/IPAC, USA

- Lin Yan, Caltech, USA

- Peter Capak, Caltech/IPAC, USA

- John Silverman, Kavli Institute for the Physics and Mathematics of the Universe, Japan

- Matthieu Béthermin, Laboratoire d'Astrophysique de Marseille, France

- Paolo Cassata, University of Padua, Italy

- Daniel Schaerer, University of Geneva, Switzerland

The Atacama Large Millimeter/submillimeter Array (ALMA), an international astronomy facility, is a partnership of the European Organisation for Astronomical Research in the Southern Hemisphere (ESO), the U.S. National Science Foundation (NSF) and the National Institutes of Natural Sciences (NINS) of Japan in cooperation with the Republic of Chile. ALMA is funded by ESO on behalf of its Member States, by NSF in cooperation with the National Research Council of Canada (NRC) and the Ministry of Science and Technology (MOST) and by NINS in cooperation with the Academia Sinica (AS) in Taiwan and the Korea Astronomy and Space Science Institute (KASI).

ALMA construction and operations are led by ESO on behalf of its Member States; by the National Radio Astronomy Observatory (NRAO), managed by Associated Universities, Inc. (AUI), on behalf of North America; and by the National Astronomical Observatory of Japan (NAOJ) on behalf of East Asia. The Joint ALMA Observatory (JAO) provides the unified leadership and management of the construction, commissioning and operation of ALMA.

 

Antarctica yields oldest fossils of giant birds with 21-foot wingspans

Two fossils from a group of extinct seabirds represent the largest individuals ever found

UNIVERSITY OF CALIFORNIA - BERKELEY

Research News

 

IMAGE: AN ARTIST'S DEPICTION OF ANCIENT ALBATROSSES HARASSING A PELAGORNITHID -- WITH ITS FEARSOME TOOTHED BEAK -- AS PENGUINS FROLIC IN THE OCEANS AROUND ANTARCTICA 50 MILLION YEARS AGO. view more 

CREDIT: COPYRIGHT BRIAN CHOO

Fossils recovered from Antarctica in the 1980s represent the oldest giant members of an extinct group of birds that patrolled the southern oceans with wingspans of up to 21 feet that would dwarf the 11½-foot wingspan of today's largest bird, the wandering albatross.

Called pelagornithids, the birds filled a niche much like that of today's albatrosses and traveled widely over Earth's oceans for at least 60 million years. Though a much smaller pelagornithid fossil dates from 62 million years ago, one of the newly described fossils -- a 50 million-year-old portion of a bird's foot -- shows that the larger pelagornithids arose just after life rebounded from the mass extinction 65 million years ago, when the relatives of birds, the dinosaurs, went extinct. A second pelagornithid fossil, part of a jaw bone, dates from about 40 million years ago.

"Our fossil discovery, with its estimate of a 5-to-6-meter wingspan -- nearly 20 feet -- shows that birds evolved to a truly gigantic size relatively quickly after the extinction of the dinosaurs and ruled over the oceans for millions of years," said Peter Kloess, a graduate student at the University of California, Berkeley.

The last known pelagornithid is from 2.5 million years ago, a time of changing climate as Earth cooled, and the ice ages began.

Kloess is the lead author of a paper describing the fossil that appears this week in the open access journal Scientific Reports. His co-authors are Ashley Poust of the San Diego Natural History Museum and Thomas Stidham of the Institute of Vertebrate Paleontology and Paleoanthropology at the Chinese Academy of Sciences in Beijing. Both Poust and Stidham received their Ph.Ds from UC Berkeley.

CAPTION

This five-inch segment of fossilized jaw, which was discovered in Antarctica in the 1980s, dates from 40 million years ago. The skull of the bird would have been about two feet long, while the pseudoteeth, which were originally covered with horny keratin, would have been up to an inch long. At this scale, the bird's wingspan would have been 5 to 6 meters, or some 20 feet.

Birds with pseudoteeth

Pelagornithids are known as 'bony-toothed' birds because of the bony projections, or struts, on their jaws that resemble sharp-pointed teeth, though they are not true teeth, like those of humans and other mammals. The bony protrusions were covered by a horny material, keratin, which is like our fingernails. Called pseudoteeth, the struts helped the birds snag squid and fish from the sea as they soared for perhaps weeks at a time over much of Earth's oceans.

Large flying animals have periodically appeared on Earth, starting with the pterosaurs that flapped their leathery wings during the dinosaur era and reached wingspans of 33 feet. The pelagornithids came along to claim the wingspan record in the Cenozoic, after the mass extinction, and lived until about 2.5 million years ago. Around that same time, teratorns, now extinct, ruled the skies.

The birds, related to vultures, "evolved wingspans close to what we see in these bony-toothed birds (pelagornithids)," said Poust. "However, in terms of time, teratorns come in second place with their giant size, having evolved 40 million years after these pelagornithids lived. The extreme, giant size of these extinct birds is unsurpassed in ocean habitats,""

The fossils that the paleontologists describe are among many collected in the mid-1980s from Seymour Island, off the northernmost tip of the Antarctic Peninsula, by teams led by UC Riverside paleontologists. These finds were subsequently moved to the UC Museum of Paleontology at UC Berkeley.

Kloess stumbled across the specimens while poking around the collections as a newly arrived graduate student in 2015. He had obtained his master's degree from Cal State-Fullerton with a thesis on coastal marine birds of the Miocene era, between 17 million and 5 million years ago, that was based on specimens he found in museum collections, including those in the UCMP.

"I love going to collections and just finding treasures there," he said. "Somebody has called me a museum rat, and I take that as a badge of honor. I love scurrying around, finding things that people overlook."

Reviewing the original notes by former UC Riverside student Judd Case, now a professor at Eastern Washington University near Spokane, Kloess realized that the fossil foot bone -- a so-called tarsometatarsus -- came from an older geological formation than originally thought. That meant that the fossil was about 50 million years old instead of 40 million years old. It is the largest specimen known for the entire extinct group of pelagornithids.

The other rediscovered fossil, the middle portion of the lower jaw, has parts of its pseudoteeth preserved; they would have been up to 3 cm (1 inch) tall when the bird was alive. The approximately 12-cm (5-inch-) long preserved section of jaw came from a very large skull that would have been up to 60 cm (2 feet) long. Using measurements of the size and spacing of those teeth and analytical comparisons to other fossils of pelagornithids, the authors are able to show that this fragment came from an individual bird as big, if not bigger, than the largest known skeletons of the bony-toothed bird group.

A warm Antarctica was a bird playground

Fifty million years ago, Antarctica had a much warmer climate during the time known as the Eocene and was not the forbidding, icy continent we know today, Stidham noted. Alongside extinct land mammals, like marsupials and distant relatives of sloths and anteaters, a diversity of Antarctic birds occupied the land, sea and air.

The southern oceans were the playground for early penguin species, as well as extinct relatives of living ducks, ostriches, petrels and other bird groups, many of which lived on the islands of the Antarctic Peninsula. The new research documents that these extinct, predatory, large- and giant-sized bony-toothed birds were part of the Antarctic ecosystem for over 10 million years, flying side-by-side over the heads of swimming penguins.

"In a lifestyle likely similar to living albatrosses, the giant extinct pelagornithids, with their very long-pointed wings, would have flown widely over the ancient open seas, which had yet to be dominated by whales and seals, in search of squid, fish and other seafood to catch with their beaks lined with sharp pseudoteeth," said Stidham. "The big ones are nearly twice the size of albatrosses, and these bony-toothed birds would have been formidable predators that evolved to be at the top of their ecosystem."

Museum collections like those in the UCMP, and the people like Kloess, Poust and Stidham to mine them, are key to reconstructing these ancient habitats.

"Collections are vastly important, so making discoveries like this pelagornithid wouldn't have happened if we didn't have these specimens in the public trust, whether at UC Riverside or now at Berkeley," Kloess said. "The fact that they exist for researchers to look at and study has incredible value."

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Black Hispanic individuals hardest hit by COVID-19

Higher death, hospitalization rates compared to non-white Hispanic individuals, variable by race

BOSTON MEDICAL CENTER

Research News

 

Boston - Results from a new study led by Boston Medical Center (BMC) demonstrate the disproportionate impact of COVID-19 on Hispanic groups within the US, with the most severe outcomes, including death and intensive care, among Hispanic Black individuals. Analyzing data from the Centers for Disease Control and Prevention, researchers found differences between Hispanic groups, with higher rates of hospitalization and increased risk of death for Hispanic Black compared to Hispanic multiracial individuals. Published online in the Journal of Immigrant and Minority Health, the results highlight that Hispanic populations as a whole have worse COVID-19 outcomes compared to the Hispanic white population, demonstrating the need for more accurate demographic data collection efforts in order to better address the disparities among Hispanic individuals impacted by COVID-19.

Results from previous COVID-19 research have shown that Latinx populations, as a whole, have worse outcomes compared to other ethnic groups. This study, the first to use a nationally representative COVID-19 database, delves further into the data to investigate the differential impact of COVID-19 on different racial groups within the Hispanic community.

For this study, researchers analyzed data reported to the Centers for Disease Control and Prevention between April 5 and May 18, 2020, with a cohort of 78,323 individuals. They compared hospitalization, intensive care unit admission, need for breathing support, and death rates among Hispanic white, Hispanic Black, and Hispanic multiracial/other groups. Next, they compared these results with the data on the above criteria for non-Hispanic white individuals.

Hispanic Black individuals in the cohort had the highest rate of comorbidities, at 51 percent, as well as hospitalizations, which were 45 percent. Hispanic/multiracial individuals were more frequently admitted to the intensive care unit (10 percent), had the highest incidence of requiring breathing support through mechanical ventilation (10 percent) and more frequent rates of death due to COVID-19 (16.1 percent). Overall, Hispanic groups fared worse than non-Hispanic white individuals. The relative risk of death was 1.36, 1.72 and 1.68 times higher for Hispanic white, Hispanic Black and Hispanic multiracial compared to non-Hispanic white individuals.

"Our results clearly show that Hispanic individuals are more likely to be hospitalized and die from COVID-19 infection than non-Hispanic individuals, with the worst outcomes among Hispanic Black individuals," said Sarah Kimball, MD, co-director of BMC's Immigrant & Refugee Health Center and the study's corresponding author. One of the challenges, the authors note, is the incomplete information on race and ethnicity included in the reported data given variations among how the information is collected and reported. At this time, there are no universal standards or processes in place at health care institutions related to how racial or ethnic information is collected from patients.

"The dilemma is that we know these disparities among racial groups aren't biological, and reflect the systemic impacts of racism and inequality. Yet, we need better data collection on racial and ethnic groups, in order to develop interventions tailored to address the COVID-19 disparities among specific patient populations," added Kimball, who is also an assistant professor of medicine at Boston University School of Medicine. "The better data we have access to, the more targeted we can be in our public health and treatment approaches to dismantle the effects of racism and the disparities that we see among different groups within the Hispanic community, which can help decrease COVID-19-specific disparities in these individuals."

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This study was funded in part by the National Institutes of Health.

About Boston Medical Center
Boston Medical Center (BMC) is a private, not-for-profit, 514-bed, academic medical center that is the primary teaching affiliate of Boston University School of Medicine. It is the largest and busiest provider of trauma and emergency services in New England. BMC offers specialized care for complex health problems and is a leading research institution, receiving more than $166 million in sponsored research funding in fiscal year 2019. It is the 13th largest funding recipient in the U.S. from the National Institutes of Health among independent hospitals. In 1997, BMC founded Boston Medical Center Health Plan, Inc., now one of the top ranked Medicaid MCOs in the country, as a non-profit managed care organization. Boston Medical Center and Boston University School of Medicine are partners in Boston HealthNet - 12 community health centers focused on providing exceptional health care to residents of Boston. For more information, please visit http://www.bmc.org.

 

Low cost, customized prosthesis using 3D printing

SUTD, together with Tan Tock Seng Hospital, developed a novel 3D printed non-metallic self-locking prosthetic arm for a patient with a forequarter amputation - it is more comfortable, flexible and 20% cheaper than a conventional prosthesis.

SINGAPORE UNIVERSITY OF TECHNOLOGY AND DESIGN

Research News

 

IMAGE: THE SCHEMATIC REPRESENTATION OF THE VARIOUS STAGES INVOLVED IN THE USER-CENTERED, ITERATIVE PROCESS OF PROSTHESIS DESIGN. view more 

CREDIT: SUTD

Upper limb forequarter amputations which involve the removal of the entire arm and scapula require highly customized prosthetic devices that are expensive but yet, usually underutilized due to their high maintenance and low comfort levels. At the same time, while cosmetic prostheses - artificial limbs which provide patients the appearance of a pre-amputated body part - have a higher rate of continuous use, they have limitations in functional use.

Combining both technical and clinical expertise, the Singapore University of Technology and Design's (SUTD) Medical Engineering and Design Laboratory collaborated with Tan Tock Seng Hospital's (TTSH) Foot Care and Limb Design Centre, the largest provider of prosthetic services in Singapore, on a patient-specific upper limb prosthesis. This cosmetic prosthesis with a self-locking function was found to be more comfortable and around 20 percent cheaper compared to similar prostheses available in the industry.

To reduce the underutilization and delivery time, while taking improved fit, function and comfort into consideration, the research team turned to 3D printing due to its versatility and ability to cater to the device's geometrical and functional complexity.

The team also adopted a user-centered design approach, involving the patient throughout the customized design and development process. They then meticulously captured and documented the design process so that it can serve as a blueprint for other device applications or be replicated for other patients with limb amputations, thus reducing the over reliance on a prosthetist's judgement, skills and experience for an optimal fit.

Based on regular consultations with the patient and prosthetist at TTSH, including the shadowing of the patient to better understand his daily activities and functional needs, it was concluded that the new prosthesis needed to be lightweight, capable of dissipating heat, locking at 90° of flexion, comfortable to wear and void of metal components that would be detectable by airport scanners.

The research team used a digital scanner to capture residuum and contralateral arm geometries to replicate the patient's arm with high precision. They then designed different parts of the prosthesis from the captured geometries, 3D printed and verified these for fit, comfort, and function (refer to image). Their research paper was published in the Prosthetics and Orthotics International Journal.

The patient's satisfaction for the 3D printed prosthesis over his conventionally made prosthesis rated higher for its overall effectiveness, accurate size, symmetrical appearance and ease of use. Even though the new prosthesis weighed 100 grams more than the current prosthesis, the patient preferred it due to its improved suspension contributing to the feel of a lighter arm during use. However, the prosthesis was perceived to be less durable due to the patient's unfamiliarity with the quality of 3D printing, his concerns of the elbow locking mechanism breaking, and the appearance of the mesh structure compared to his current prosthesis.

"Digitalization and 3D printing have been transforming the design and manufacture of complex medical devices, surgery planning, medical education, and care delivery. Even though 3D printing technology has been around for more than three decades since the early 90's, it wasn't until recently that people really began to appreciate and trust it for end-use fabrication. In this work, 3D printing freed us from the manufacturing constraints and enabled us to optimize the design to suit the patient's needs. More importantly, this work sets the groundwork for future patient-specific end-use 3D printed parts for prosthetic needs," said principal investigator, Assistant Professor Subburaj Karupppasamy from SUTD's Engineering Product Development pillar.

Trevor Binedell, Principal Prosthetist at the Foot Care and Limb Design Centre, TTSH, and PhD student from SUTD, added, "The collaboration between TTSH and SUTD has led to a great outcome for this patient. User-design and the digitalization techniques have elevated the levels of patient-specific care to create individual designs that truly meet the needs of the user. This process has the potential to improve unique designs for many of our patients and enhance their quality of lives."

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Irregular appearances of glacial and interglacial climate states

A clearer picture of the sequence of glacial and interglacial periods

ALFRED WEGENER INSTITUTE, HELMHOLTZ CENTRE FOR POLAR AND MARINE RESEARCH

Research News

 

During the last 2.6 million years of Earth's climate has altered between glacial and interglacial states. As such, there have been times in which the transition between the two climate states appeared with either regular or irregular periodicity. AWI researcher Peter Köhler has now discovered that the irregular appearance of interglacials has been more frequent than previously thought. His study makes a significant contribution to our understanding of Earth's fundamental climate changes.

In order to understand human beings' role in the development of our current climate, we have to look back a long way, since there has always been climate change - albeit over vastly different timescales than the anthropogenic climate change, which is mainly due to the use of fossil fuels over the past 200 years. Without humans, for millions of years, climate altered between glacial and interglacial states over periods of many thousands of years, mainly because of the Earth's tilt which changes by a few degrees with a periodicity of 41,000 years. This in turn changes the angle at which the sun's rays strike Earth - and as such the energy that reaches the planet, especially at high latitudes in summer. However, there is strong evidence that during the course of the last 2.6 million years, interglacials have repeatedly been 'skipped'. The Northern Hemisphere - particularly North America - remained frozen for long periods, despite the angle of the axial tilt changing to such an extent that more solar energy once again reached Earth during the summer, which should have melted the inland ice masses. This means Earth's tilt can't be the sole reason for Earth's climate to alter between glacial and interglacial states.

In order to solve the puzzle, climate researchers are investigating more closely at what points in Earth's history irregularities occurred. Together with colleagues at Utrecht University, physicist Peter Köhler from the Alfred Wegener Institute (AWI) has now made a significant contribution towards providing a clearer picture of the sequence of glacial and interglacial periods over the last 2.6 million years. Until now, experts thought that, especially over the past 1.0 million years, glacial and interglacial periods deviated from their 41,000- year cycle, and that interglacial periods were skipped, as a result of which some glacial periods lasted for 80,0000 or even 120,000 years. "For the period between 2.6 and 1.0 million years ago, it was assumed that the rhythm was 41,000 years," says Peter Köhler. But as his study, which has now been published in the scientific journal Nature Communications, shows, there were also repeated irregularities during the period between 2.6 and 1.0 million years ago.

Köhler's study is particularly interesting because he re-evaluated a well-known dataset that researchers have been using for several years - the LR04 climate dataset - yet arrived at completely different conclusions. This dataset consists of a global evaluation of core samples from deep-sea sediments that are millions of years old, and includes measurements from the ancient shells of microscopic, single-celled marine organisms - foraminifera - that were deposited on the ocean floor. Foraminifera incorporate oxygen from the seawater into their calcium shells. But over millennia, the level of specific oxygen isotopes - oxygen atoms that have differing numbers of neutrons and therefore different masses - varies in seawater.

18O reveals what the world was like in the past

The LR04 dataset contains measurements of the ratio of the heavy oxygen isotope 18O to the lighter 16O. The ratio of 18O/16O stored in the foraminifera's shells depends on the water temperature. But there is also another effect that leads to relatively large amounts of 18O being found in the foraminifera's shells in glacial periods: when, during the course of a glacial period, there is heavy snowfall on land, which leads to the formation of thick ice sheets, the sea level falls - in the period studied, by as much as 120 m. Since 18O is heavier than 16O, water molecules containing this heavy isotope evaporate less readily than molecules containing the lighter isotope. As such, comparatively more 18O remains in the ocean and the 18O content of the foraminifera shells increases. "If you take the LR04 dataset at face value, it means you blur two effects - the influence of ocean temperature and that of land ice, or rather that of sea level change," says Peter Köhler. "This makes statements regarding the alternation of the glacial periods uncertain." And there is an additional factor: climate researchers mainly determine the sequence of glacial periods on the basis of glaciation in the Northern Hemisphere. But using 18O values doesn't allow us to say whether prehistoric glaciation chiefly occurred in the Northern Hemisphere or in Antarctica.

Computer model separates the influencing parameters

In an attempt to solve this problem, Köhler and his team evaluated the LR04 dataset in a completely different way. The data was fed into a computer model that simulates the growth and melting of the large continental ice sheets. What sets it apart: the model is capable of separating the influence of temperature and that of sea level change on the 18O concentration. Furthermore, it can accurately analyse where and when snow falls and the ice increases - more in the Northern Hemisphere or in Antarctica. "Mathematicians call this separation a deconvolution," Köhler explains, "which our model is capable of delivering." The results show that the sequence of glacials and interglacials was irregular even in the period 2.6 to 1.0 million years ago - a finding that could be crucial in the coming years. As part of the ongoing major EU project 'BE-OIC (Beyond EPICA Oldest Ice Core)', researchers are drilling deeper than ever before into the Antarctic ice. With the oldest ice core recovered to date, 'EPICA', they have 'only' travelled back roughly 800,000 years into the past. The ancient ice provides, among other things, information on how much carbon dioxide Earth's atmosphere contained at that time. With 'Beyond EPICA' they will delve circa 1.5 million years into the past. By combining the carbon dioxide measurements with Köhler's analyses, valuable insights can be gained into the relation between these two factors - the fluctuations in the sequence of glacials and the carbon dioxide content of the atmosphere. And this can help us understand the fundamental relationship between greenhouse gases and climate changes in Earth's glacial history.

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