New Zealand drug agency provides model to insulate NICE from impacts of trade deals

UNIVERSITY OF BATH

Research News

UK policymakers preparing trade deals post-Brexit can learn important lessons from New Zealand's 'unique drug agency' the Pharmaceutical Management Agency (PHARMAC), if prices for therapies and access to key drugs are to be protected, say researchers behind a new study.

Over two decades, New Zealand has managed to reduce spending on drugs significantly and consistently despite maintaining access for its population to key treatments. As such, it is an outlier among the world's richest nations: no other OECD country has managed to achieve this.

The investigation from researchers at the universities of Bath and Durham suggest New Zealand's success can largely be ascribed to its drug agency PHARMAC. PHARMAC is unique because it not only assesses drugs scientifically, but also negotiates their prices with pharma companies.

Its equivalent in England is NICE, however whereas NICE focuses on the scientific assessment of drugs, price negotiations with drug companies rest with NHS England. There is speculation that given the attractiveness of the UK as a market for multinational drug companies, new trade deals being agreed by the UK could undermine NICE's ability to assess new drugs and determine whether they represent value for money.

For example, the researchers argue that if trade deals grant pharmaceutical companies new powers to challenge NICE's decisions through new forms of appeals mechanisms this could be a 'game changer', providing companies with additional tactics to drive up prices.

Their study, which involved analysis of policy documents produced alongside New Zealand's trade talks with other countries, freedom of information requests and interviews with key experts and policymakers, points to what could go wrong with drug prices and drug access in the UK post-Brexit.

Researcher, Dr Piotr Ozieranski from the University of Bath's Centre for the Analysis of Social Policy explained: "The implications of this study are particularly important post-Brexit and especially in the context of trade policy because of the potential impact these new deals will have on drug prices. The key issue is whether NICE is sufficiently protected for the independent, expert analysis it gives to ensure value for money for the NHS.

"Another key lesson from the study is that not only is PHARMAC protected from commercial influence, it is also trusted with maximum flexibility in negotiating drug prices with manufacturers. Depending on the situation, it can negotiate prices before a drug even reaches the market or, conversely, stall negotiations until it is about to lose patent protection and become cheaper. It also encourages price competition among companies by setting up competitive tenders and play-offs, as well as negotiating with multiple applicants at the same time."

Ben Main from the University of Durham, commented: "New Zealand's success in ensuring continued access to drugs whilst consistently driving down prices is not by accident; even more so because, unlike the UK, New Zealand cannot use the argument of a large population to secure lower prices. PHARMAC is a brilliant negotiator and uses flexibility to achieve good deals. Healthcare policymakers in the UK can learn from this model.

"However, our work raises an important question for UK policymakers: Is it worth granting NICE extra powers that would allow it to emulate some of the tactics used by PHARMAC? While price negotiations are typically shrouded in secrecy, New Zealand's evident success suggests that experts can be trusted not only with evaluating drugs scientifically but also striking favourable deals with the industry."

The paper also highlights the importance of protecting NICE from political interference.

Ben Main added: "Crucially, PHARMAC wields much policy authority, which is bolstered by social and political support even though some of its decisions may at times deny access to promising drugs to some patients. This contrasts with NICE's position, which on occasions has been challenged by politicians and NHS officials wanting to secure funding for specific therapies which did not pass - or were unlikely to pass - NICE's evaluation criteria. By and large, PHARMAC is not part of party politics."

Main also draws attention to how the industry has sought legal changes to the way PHARMAC operates: "One key lesson surrounds the issue of transparency. In other institutional contexts a lack of transparency surrounding decision making is a criticism levelled at policymakers. What we see is that over the last decade in New Zealand there is 'transparency' on industry's terms - a weapon to offset PHARMAC's authority - and a lack of transparency on PHARMAC's terms which has enabled their spending model and offset industry's dominant market position."

New Zealand's policymakers have sought to insulate PHARMAC's power by legally exempting its decisions from being potentially challenged as 'anti-competitive' by drug companies (Section 53 of the New Zealand Public Health and Disability Act 2000). On top of this, after lengthy negotiations, New Zealand refused to sign a Trans-Pacific Partnership treaty with the US, whose 'transparency and disclosure requirements' included provisions which could be used to challenge PHARMAC's decisions.

Instead, it signed a Progressive Trans-Pacific Trade Treaty (CPPTP) with eight other countries. CPPTP is unlikely to affect PHARMAC, however to further safeguard this, New Zealand subsequently suspended the application of its procedural rules in relation to PHARMAC.

###

To access the full paper and discussion see https://onlinelibrary.wiley.com/doi/10.1111/1467-9566.13343.

 

Bats in Tel Aviv enjoy the rich variety and abundance of food the city has to offer

Just like humans:

TEL-AVIV UNIVERSITY

Research News

IMAGE: A FRUIT BAT IN TEL AVIV view more 

CREDIT: S. GREIF.

A new Tel Aviv University study found that, like humans, bats living in Tel Aviv enjoy the wide variety and abundance of food that the city has to offer, in contrast to rural bats living in Beit Guvrin, who are content eating only one type of food. The study was led by research student Katya Egert-Berg, under the guidance of Prof. Yossi Yovel, head of Tel Aviv University's Sagol School of Neuroscience and a faculty member of the School of Zoology in the George S. Wise Faculty of Life Sciences and the Steinhardt Museum of Natural History, as well as a recipient of the 2021 Kadar Family Award for Outstanding Research. The study was published in the journal BMC Biology.

The researchers explain that despite the intensification of urbanization processes, which tend to lead animals to leave the city, there are animals that are able to thrive in an urban domain. One such example is the fruit bat. These bats, like humans, live in a variety of environments, including the city and the countryside; there are even some that forage in the city and then go home to roost in the country.

The urban environment is fundamentally different from the rural environment in terms of the diversity and accessibility of food. Although the city has a larger variety of trees per area, there are many challenges that bats have to face, such as buildings and humans. In rural areas, on the other hand, most of the trees are concentrated in orchards without barriers, but have less diversity - the trees are mostly of one type. Because of the fundamental environmental differences between the city and the country with regards to the distribution and variety of fruit trees, the nature of the bats' movement when foraging in these areas differs as well.

In this new study, the researchers compared the nature of the movement of rural bats and city bats as they foraged for food. They used tiny GPS devices to track the bats, to see if the way they moved while searching for food was affected by their living environment, or the environment in which they were foraging.

CAPTION

Fruit Bat

CREDIT

Yuval Barkai.

They found that fruit bats foraging in the city are much more exploratory, enjoy the abundance of the urban environment, visit a variety of fruit trees every night, and feed from a wide a variety of trees. In contrast, the rural bats focus on only one or two fruit trees each night. Moreover, the researchers found that among the rural bats who roost in the countryside, there were many who left their rural homes every night in search of food in the city, and then flew back to the country after their meal. During their stay in the city, such bats share the same flight patterns as those of the bats that live in the city around the clock.

The study's findings led the researchers to assess that even bats that live in rural environments their entire lives will be able to orient themselves in an urban, industrialized environment. They explain that there are animal species that are flexible - for them, the ability to adapt to a new and unfamiliar environment such as an urban settlement is an acquired skill. Such species, of which the fruit bats are an example, will in many cases be able to adapt to life in urban areas.

Prof. Yovel: "How animals cope with urbanization is one of the most central and important questions in ecological research today. Understanding the ways in which animals adapt to urban areas can help us in our conservation efforts. The urban environment is characterized by much fragmentation, and we currently have little understanding of how animals, especially small animals, like the bats, move and fly in such areas."

###

Link to the article: https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-021-01060-x

 

Cosmic rays help supernovae explosions pack a bigger punch

ROYAL ASTRONOMICAL SOCIETY

Research News

IMAGE: FALSE COLOUR IMAGE OF ONE OF THE SUPERNOVA SIMULATIONS SHOWING HOT AND COLD PATCHES OF GAS (WHITE/GREEN) IN THE BUBBLE AND THE FILAMENTARY STRUCTURE OF COSMIC RAYS (BLUE) AROUND THE... view more 

CREDIT: CREDIT: F. RODRÍGUEZ MONTERO.

The final stage of cataclysmic explosions of dying massive stars, called supernovae, could pack an up to six times bigger punch on the surrounding interstellar gas with the help of cosmic rays, according to a new study led by researchers at the University of Oxford. The work will be presented by PhD student Francisco Rodríguez Montero today (19 July) at the virtual National Astronomy Meeting (NAM 2021).

When supernovae explode, they emit light and billions of particles into space. While the light can freely reach us, particles become trapped in spiral loops by magnetic shockwaves generated during the explosions. Crossing back and forth through shock fronts, these particles are accelerated almost to the speed of light and, on escaping the supernovae, are thought to be the source of the mysterious form of radiation known as cosmic rays.

Due to their immense speed, cosmic rays experience strong relativistic effects, effectively losing less energy than regular matter and allowing them to travel great distances through a galaxy. Along the way, they affect the energy and structure of interstellar gas in their path and may play a crucial role in shutting down the formation of new stars in dense pockets of gas. However, to date, the influence of cosmic rays in galaxy evolution has not been well understood.

In the first high-resolution numerical study of its kind, the team ran simulations of the evolution of the shockwaves emanating from supernovae explosions over several million years. They found that cosmic rays can play a critical role in the final stages of a supernova's evolution and its ability to inject energy into the galactic gas that surrounds it.

Rodríguez Montero explains: "Initially, the addition of cosmic rays does not appear to change how the explosion evolves. Nevertheless, when the supernova reaches the stage in which it cannot gain more momentum from the conversion of the supernova's thermal energy to kinetic energy, we found that cosmic rays can give an extra push to the gas, allowing for the final momentum imparted to be up to 4-6 times higher than previously predicted."

The results suggest that gas outflows driven from the interstellar medium into the surrounding tenuous gas, or circumgalactic medium, will be dramatically more massive than previously estimated.

Contrary to state-of-the-art theoretical arguments, the simulations also suggest that the extra push provided by cosmic rays is more significant when massive stars explode in low-density environments. This could facilitate the creation of super-bubbles powered by successive generations of supernovae, sweeping gas from the interstellar medium and venting it out of galactic discs.

Rodríguez Montero adds: "Our results are a first look at the extraordinary new insights that cosmic rays will provide to our understanding of the complex nature of galaxy formation."

CAPTION

The red, green and blue colours show low, intermediate and high energy X-rays observed with NASA's Chandra X-ray Observatory, and the star field is from the Digitized Sky Survey.

CREDIT

Credit: NASA / CXC / NCSU / JPL-Caltech / M. Burkey et al.

Tail without a comet: the dusty remains of Comet ATLAS

ROYAL ASTRONOMICAL SOCIETY

Research News

IMAGE: HUBBLE SPACE TELESCOPE IMAGE OF COMET C/2019 Y4 (ATLAS), TAKEN ON APRIL 20 2020, PROVIDING THE SHARPEST VIEW TO DATE OF THE BREAKUP OF THE SOLID NUCLEUS OF THE COMET.... view more 

CREDIT: NASA / ESA / STSCI / D. JEWITT (UCLA)

A serendipitous flythrough of the tail of a disintegrated comet has offered scientists a unique opportunity to study these remarkable structures, in new research presented today at the National Astronomy Meeting 2021.

Comet ATLAS fragmented just before its closest approach to the Sun last year, leaving its former tail trailing through space in the form of wispy clouds of dust and charged particles. The disintegration was observed by the Hubble Space Telescope in April 2020, but more recently the ESA spacecraft Solar Orbiter has flown close to the tail remnants in the course of its ongoing mission.

This lucky encounter has presented researchers with a unique opportunity to investigate the structure of an isolated cometary tail. Using combined measurements from all of Solar Orbiter's in-situ instruments, the scientists have reconstructed the encounter with ATLAS's tail. The resulting model indicates that the ambient interplanetary magnetic field carried by the solar wind 'drapes' around the comet, and surrounds a central tail region with a weaker magnetic field.

Comets are typically characterized by two separate tails; one is the well-known bright and curved dust tail, the other - typically fainter - is the ion tail. The ion tail originates from the interaction between the cometary gas and the surrounding solar wind, the hot gas of charged particles that constantly blows from the Sun and permeates the whole Solar System.

When the solar wind interacts with a solid obstacle, like a comet, its magnetic field is thought to bend and 'drape' around it. The simultaneous presence of magnetic field draping and cometary ions released by the melting of the icy nucleus then produces the characteristic second ion tail, which can extend for large distances downstream from the comet's nucleus.

Lorenzo Matteini, a solar physicist at Imperial College London and leader of the work, says: "This is quite a unique event, and an exciting opportunity for us to study the makeup and structure of comet tails in unprecedented detail. Hopefully with the Parker Solar Probe and Solar Orbiter now orbiting the Sun closer than ever before, these events may become much more common in future!"

This is the first comet tail detection occurring so close to the Sun - well inside the orbit of Venus. It is also one of the very few cases where scientists have been able to make direct measurements from a fragmented comet. Data from this encounter is expected to contribute greatly to our understanding of the interaction of comets with the solar wind and the structure and formation of their ion tails.

CAPTION

Schematic reconstruction of a Solar Orbiter encounter with the ion gas tail from fragmented comet C/2019 Y4 (ATLAS). In the diagram, lines identify interplanetary magnetic field lines in the solar wind; these are draped around the comet and form the typical magneto-tail with opposing orientation at the two sides. Solar Orbiter data from the Imperial College MAG magnetometer are shown along the spacecraft trajectory through the structure: arrows indicate the direction of the magnetic field, and length its intensity. The identified sharp boundary between the tail and the ambient solar wind on the draped side is indicated by the magenta dashed line.

CREDIT

L. Matteini / Imperial College London

 

Human action, key to antibiotic resistance in giant tortoises of Galapagos

UNIVERSIDAD COMPLUTENSE DE MADRID

Research News

    SHARE

 PRINT  E-MAIL

IMAGE: GIANT GALAPAGOS TORTOISES MIGRATING view more 

CREDIT: JUAN MANUEL GARCÍA

UCC-UCM, 13 July. The Giant Galapagos tortoises which live in contact with human farming and tourism activities, or in urbanised zones, have more bacterial resistance to antibiotics than those that live in more isolated ecosystems.

This is the main conclusion of the research published in Environmental Pollution on which Universidad Complutense de Madrid participated together with the Charles Darwin Foundation (FCD), the Institute for Conservation Medicine of the Saint Louis Zoo (ICM), the Centre for Animal Health Research (INIA-CISA) and Universidad Europea de Madrid.

Ainoa Nieto, the lead author, researcher at ICM/FCD and collaborator in practical teaching and doctoral student at UCM, explains the new information provided by the study: "Human activities are facilitating the dispersal of resistance into the environment, which has already been observed in other parts of the world, but which has never been demonstrated on the Galapagos Islands."

Resistance to antibiotics is one of the major threats to public health on the planet. The WHO has estimated that by 2050 it could be leading to more deaths than cancer, diabetes or traffic accidents. The detection of these bacteria in the Galapagos archipelago for the first time turn them into environmental pollutants and the tortoises into potential "sentinels or bioindicators" of the health of ecosystems.

PCR to identify genes and bacteria

To carry out the study, samples were taken from 270 tortoises in 2018 and 2019 in two locations with different characteristics in the Galapagos Islands: the island of Santa Cruz, which has the largest human population, and the remote volcano of Alcedo on the island Isabela.

The analyses of resistance were carried out in the INIA-CISA laboratory in Madrid using a new methodology that allows the detection of resistance genes without the need to cultivate the bacteria, through PCR reactions in real time. This technique helps identify the genes and also the number of bacteria with resistant genes that are present in a sample. In total, 21 genes were analysed that codify resistance for eight of the antibiotic families most commonly used in human and animal medicine.

"We don't know the real implications that this discovery could have for the health of giant tortoises, but resistance is considered environmental pollution, and the fact that species as iconic as Galapagos tortoises are entering into contact with these resistant bacteria implies that the ecosystem in which they live is being contaminated," explains Casilda Rodríguez, a researcher at the Department of Pharmacology and Toxicology at UCM.

Finally, Ainoa Nieto recalls that antibiotics can be bought in the Galapagos without a medical prescription, for both human and veterinarian use. The authorities do not restrict their use, as happens in Spain or other countries in the world.

###

Living near woodlands is good for children and young people's mental health

UNIVERSITY COLLEGE LONDON

Research News

Analysis of children and young people's proximity to woodlands has shown links with better cognitive development and a lower risk of emotional and behavioural problems, in research led by UCL and Imperial College London scientists that could influence planning decisions in urban areas.

In what is believed to be one of the largest studies of its kind, researchers used longitudinal data relating to 3,568 children and teenagers, aged nine to 15 years, from 31 schools across London. This period is a key time in the development of adolescents' thinking, reasoning and understanding of the world.

The study, published in Nature Sustainability, looked at the links between different types of natural urban environments and the pupils' cognitive development, mental health and overall well-being.

The environments were divided into what planners call green space (woods, meadows and parks) and blue space (rivers, lakes and the sea), with green space separated further into grassland and woodland. Researchers used satellite data to help calculate each adolescent's daily exposure rate to each of these environments within 50m, 100m, 250m and 500m of their home and school.

After adjusting for other variables, the results showed that higher daily exposure to woodland (but not grassland) was associated with higher scores for cognitive development, and a 16% lower risk of emotional and behavioural problems two years later.

A similar but smaller effect was seen for green space, with higher scores for cognitive development, but this was not seen for blue space. The researchers note though that access to blue space in the cohort studied was generally low.

Examples of other explanatory variables considered included the young person's age, ethnic background, gender, parental occupation and type of school, e.g., state or independent. The level of air pollution might have influenced adolescents' cognitive development, but researchers did not feel these observations were reliable or conclusive, and these require further investigations.

It is already estimated that one in 10 of London's children and adolescents between the ages of five and 16 suffer from a clinical mental health illness and excess costs are estimated between £11,030 and £59,130 annually for each person. As with adults, there is also evidence that natural environments play an important role in children and adolescents' cognitive development and mental health into adulthood, but less is known about why this is.

The results of this study suggest that urban planning decisions to optimise ecosystem benefits linked to cognitive development and mental health should carefully consider the type of natural environment included. Natural environments further away from an adolescent's residence and school may play an important role too, not just their immediate environment.

Lead author, PhD student Mikaël Maes (UCL Geography, UCL Biosciences and Imperial College London School of Public Health) said: "Previous studies have revealed positive associations between exposure to nature in urban environments, cognitive development and mental health. Why these health benefits are received remains unclear, especially in adolescents.

"These findings contribute to our understanding of natural environment types as an important protective factor for an adolescent's cognitive development and mental health and suggest that not every environment type may contribute equally to these health benefits.

"Forest bathing, for example (being immersed in the sights, sounds and smells of a forest), is a relaxation therapy that has been associated with physiological benefits, supporting the human immune function, reducing heart rate variability and salivary cortisol, and various psychological benefits. However, the reasons why we experience these psychological benefits from woodland remain unknown."

Joint senior author Professor Mireille Toledano (Director, Mohn Centre for Children's Health and Wellbeing and Investigator, MRC Centre for Environment and Health and Principal Investigator of the SCAMP study, Imperial College London) said: "It's been suggested previously that the benefits of natural environments to mental health are comparable in magnitude to family history, parental age and even more significant than factors like the degree of urbanisation around you, but lower than your parents' socio-economic status. Sensory and non-sensory pathways have been suggested as potentially important for delivering cognition and mental health benefits received from exposure to nature.

"It's critical for us to tease out why natural environments are so important to our mental health throughout the life course - does the benefit derive from the physical exercise we do in these environments, from the social interactions we often have in them, or from the fauna and flora we get to enjoy in these environments or a combination of all of these?"

Joint senior author Professor Kate Jones (UCL Centre for Biodiversity & Environment Research, UCL Biosciences) said: "One possible explanation for our findings may be that audio-visual exposure through vegetation and animal abundance provides psychological benefits, of which both features are expected in higher abundance in woodland. Even though our results show that urban woodland is associated with adolescent's cognitive development and mental health, the cause of this association remains unknown. Further research is fundamental to our understanding of the links between nature and health."

To arrive at the findings, researchers analysed a longitudinal dataset of 3,568 adolescents between 2014 and 2018, whose residence was known, from the Study of Cognition, Adolescents and Mobile Phones (SCAMP) across the London metropolitan area. They assessed adolescents' mental health and overall well-being from a self-reported Strengths and Difficulties Questionnaire (SDQ) - covering areas such as emotional problems, conduct, hyperactivity and peer problems - and the KIDSCREEN-10 Questionnaire taken by each adolescent for SCAMP.

Limitations of the study include an assumption that living or going to school near natural environments means more exposure to them, which may not always be the case due to how easily they can be accessed by a child or young person or how usable they are.

Also, a considerable proportion of the participants (52.21%) were in the group whose parents had a managerial/professional occupation, so adolescents in less favourable socio-economic groups may be underrepresented and pupils requiring special needs may be differently affected compared with their peers. Crime rates, which may have influenced the results too, were not taken into account.

###

The study was supported by the Natural Environment Research Council, the Medical Research Council and the National Institute for Health Research, and involved researchers from UCL, Imperial College London and Birkbeck, University of London.

 

New material could mean lightweight armor, protective coatings

U.S. ARMY RESEARCH LABORATORY

Research News

IMAGE: ARMY-FUNDED RESEARCH IDENTIFIES A NEW MATERIAL THAT MAY LEAD TO LIGHTWEIGHT ARMOR, PROTECTIVE COATINGS, BLAST SHIELDS, AND OTHER IMPACT-RESISTANT STRUCTURES, view more 

CREDIT: MIT

RESEARCH TRIANGLE PARK, N.C. -- Army-funded research identified a new material that may lead to lightweight armor, protective coatings, blast shields and other impact-resistant structures.

Researchers at the U.S. Army's Institute for Soldier Nanotechnologies at the Massachusetts Institute of Technology, Caltech and ETH Zürich found that materials formed from precisely patterned nanoscale trusses are tougher than Kevlar and steel.

In experiments, the ultralight structures, called nanoarchitectured materials, absorbed the impact of microscopic projectiles accelerated to supersonic speeds.

"Increasing protection while simultaneously decreasing the weight that soldiers carry is an overreaching theme in our research," said Dr. James Burgess, ISN program manager for the U.S. Army Combat Capabilities Development Command, known as DEVCOM, Army Research Laboratory. "This project is a really good example of such efforts where projectile energy absorption is nanostructured mechanism based."

The research, published in Nature Materials, found that the material prevented the projectiles from tearing through it.

"The same amount of mass of our material would be much more efficient at stopping a projectile than the same amount of mass of Kevlar," said Dr. Carlos Portela, assistant professor of mechanical engineering at MIT, the study's lead author.

The researchers calculate that the new material absorbs impacts more efficiently than steel, Kevlar, aluminum and other impact-resistant materials of comparable weight.

"The knowledge from this work...could provide design principles for ultra-lightweight impact resistant materials [for use in] efficient armor materials, protective coatings, and blast-resistant shields desirable in defense and space applications," said co-author Dr. Julia R. Greer, a professor of materials science, mechanics, and medical engineering at Caltech, whose lab fabricated the material.

Nanoarchitected materials are known to feature impressive properties like exceptional lightness and resilience; however, until now, the potential for additional applications has largely been untested.

"We only know about its response in a slow-deformation regime, whereas a lot of their practical use is hypothesized to be in real-world applications where nothing deforms slowly," Portela said.

To help fill this vital knowledge gap, the research team set out to study nanoarchitected materials undergoing fast deformation, such as that caused by high-velocity impacts. At Caltech, researchers first fabricated a repeating pattern known as a tetrakaidecahedron--a lattice configuration composed of microscopic struts--using two-photo lithography, a technique that uses a high-powered laser to solidify microscopic structures in photosensitive resin.

To test the tetrakaidecahedron's resilience to extreme, rapid deformation, the team performed experiments at MIT using the ISN-developed laser-induced particle impact array. This device aims an ultrafast laser through a glass slide.. As the laser passes through the slide, it generates a plasma, an immediate expansion of gas that launches the particles toward the target.

By adjusting the laser's power to control the speed of the microparticle projectiles, the researchers tested microparticle velocities within the supersonic range.

"Some experiments achieved twice the speed of sound, easily," Portela said.

Using a high-speed camera, the researchers captured videos of the microparticles impacting the nanoarchitected material. They had fabricated material of two different densities. A comparison of the two materials' impact response, found the denser one to be more resilient, and microparticles tended to embed in the material rather than tear through it.

To get a closer look, the researchers carefully sliced through the embedded microparticles and nanarchitectured target. They found that the struts below the embedded particle had crumpled and compacted in response to the impact, but the surrounding struts remained intact.

"We show the material can absorb a lot of energy because of this shock compaction mechanism of struts at the nanoscale, versus something that's fully dense and monolithic, not nanoarchitected," Portela said.

Going forward, Portela plans to explore various nanostructured configurations other than carbon, and ways to scale up the production of these nanostructures, all with the goal of designing tougher, lighter materials.

"Nanoarchitected materials truly are promising as impact-mitigating materials," Portela said. "There's a lot we don't know about them yet, and we're starting this path to answering these questions and opening the door to their widespread applications."

###

The U.S. Army established the MIT Institute for Nanotechnologies in 2002 as an interdisciplinary research center to dramatically improve the protection, survivability and mission capabilities of the Soldier and of Soldier-supporting platforms and systems.

In addition to Army funding through the institute, the U.S. Office of Naval Research and the Vannevar Bush Faculty Fellowship supported the research.

Visit the laboratory's Media Center to discover more Army science and technology stories

As the Army's national research laboratory, ARL is operationalizing science to achieve transformational overmatch. Through collaboration across the command's core technical competencies, DEVCOM leads in the discovery, development and delivery of the technology-based capabilities required to make Soldiers more successful at winning the nation's wars and come home safely. DEVCOM Army Research Laboratory is an element of the U.S. Army Combat Capabilities Development Command. DEVCOM is a major subordinate command of the Army Futures Command.

Study shows why second dose of COVID-19 vaccine shouldn't be skipped

STANFORD MEDICINE

Research News

The second dose of a COVID-19 vaccine induces a powerful boost to a part of the immune system that provides broad antiviral protection, according to a study led by investigators at the Stanford University School of Medicine.

The finding strongly supports the view that the second shot should not be skipped.

"Despite their outstanding efficacy, little is known about how exactly RNA vaccines work," said Bali Pulendran, PhD, professor of pathology and of microbiology and immunology. "So we probed the immune response induced by one of them in exquisite detail."

The study, published July 12 in Nature, was designed to find out exactly what effects the vaccine, marketed by Pfizer Inc., has on the numerous components of the immune response.

The researchers analyzed blood samples from individuals inoculated with the vaccine. They counted antibodies, measured levels of immune-signaling proteins and characterized the expression of every single gene in the genome of 242,479 separate immune cells' type and status.

"The world's attention has recently been fixed on COVID-19 vaccines, particularly on the new RNA vaccines," said Pulendran, the Violetta L. Horton Professor II.

He shares senior authorship of the study with Kari Nadeau, MD, PhD, the Naddisy Foundation Professor of Pediatric Food, Allergy, Immunology, and Asthma and professor of pediatrics, and Purvesh Khatri, PhD, associate professor of biomedical informatics and of biomedical data science. The study's lead authors are Prabhu Arunachalam, PhD, a senior research scientist in Pulendran's lab; medical student Madeleine Scott, PhD, a former graduate student in Khatri's lab; and Thomas Hagan, PhD, a former postdoctoral scholar in Pulendran's Stanford lab and now an assistant professor at the Yerkes National Primate Research Center in Atlanta.

Uncharted territory

"This is the first time RNA vaccines have ever been given to humans, and we have no clue as to how they do what they do: offer 95% protection against COVID-19," said Pulendran.

Traditionally, the chief immunological basis for approval of new vaccines has been their ability to induce neutralizing antibodies: individualized proteins, created by immune cells called B cells, that can tack themselves to a virus and block it from infecting cells.

"Antibodies are easy to measure," Pulendran said. "But the immune system is much more complicated than that. Antibodies alone don't come close to fully reflecting its complexity and potential range of protection."

Pulendran and his colleagues assessed goings-on among all the immune cell types influenced by the vaccine: their numbers, their activation levels, the genes they express and the proteins and metabolites they manufacture and secrete upon inoculation.

One key immune-system component examined by Pulendran and his colleagues was T cells: search-and-destroy immune cells that don't attach themselves to viral particles as antibodies do but rather probe the body's tissues for cells bearing telltale signs of viral infections. On finding them, they tear those cells up.

In addition, the innate immune system, an assortment of first-responder cells, is now understood to be of immense importance. It's the body's sixth sense, Pulendran said, whose constituent cells are the first to become aware of a pathogen's presence. Although they're not good at distinguishing among separate pathogens, they secrete "starting gun" signaling proteins that launch the response of the adaptive immune system -- the B and T cells that attack specific viral or bacterial species or strains. During the week or so it takes for the adaptive immune system to rev up, innate immune cells perform the mission-critical task of holding incipient infections at bay by gobbling up -- or firing noxious substances, albeit somewhat indiscriminately, at -- whatever looks like a pathogen to them.

A different type of vaccine

The Pfizer vaccine, like the one made by Moderna Inc., works quite differently from the classic vaccines composed of live or dead pathogens, individual proteins or carbohydrates that train the immune system to zero in on a particular microbe and wipe it out. The Pfizer and Moderna vaccines instead contain genetic recipes for manufacturing the spike protein that SARS-CoV-2, the virus that causes COVID-19, uses to latch on to cells it infects.

In December 2020, Stanford Medicine began inoculating people with the Pfizer vaccine. This spurred Pulendran's desire to assemble a complete report card on the immune response to it.

The team selected 56 healthy volunteers and drew blood samples from them at multiple time points preceding and following the first and second shots. The researchers found that the first shot increases SARS-CoV-2-specific antibody levels, as expected, but not nearly as much as the second shot does. The second shot also does things the first shot doesn't do, or barely does.

"The second shot has powerful beneficial effects that far exceed those of the first shot," Pulendran said. "It stimulated a manifold increase in antibody levels, a terrific T-cell response that was absent after the first shot alone, and a strikingly enhanced innate immune response."

Unexpectedly, Pulendran said, the vaccine -- particularly the second dose -- caused the massive mobilization of a newly discovered group of first-responder cells that are normally scarce and quiescent.

First identified in a recent vaccine study led by Pulendran, these cells -- a small subset of generally abundant cells called monocytes that express high levels of antiviral genes -- barely budge in response to an actual COVID-19 infection. But the Pfizer vaccine induced them.

This special group of monocytes, which are part of the innate museum, constituted only 0.01% of all circulating blood cells prior to vaccination. But after the second Pfizer-vaccine shot, their numbers expanded 100-fold to account for a full 1% of all blood cells. In addition, their disposition became less inflammatory but more intensely antiviral. They seem uniquely capable of providing broad protection against diverse viral infections, Pulendran said.

"The extraordinary increase in the frequency of these cells, just a day following booster immunization, is surprising," Pulendran said. "It's possible that these cells may be able to mount a holding action against not only SARS-CoV-2 but against other viruses as well."

###

Pulendran is a member of the Institute for Immunity Transplantation & Infection and Stanford Bio-X and a faculty fellow of Stanford ChEM-H.

Other Stanford study co-authors are basic life science research scientist Chunfeng Li, PhD; research scientists Natalia Sigal, PhD, Sangeeta Kowli, PhD, and Sheena Gupta, PhD; postdoctoral scholars Yupeng Feng, PhD, Florian Wimmers, PhD, Vamsee Mallajosyula, PhD, and Fei Gao, PhD; graduate student Lilit Grigoryan; life science research professionals Sofia Maysel-Auslender, Meera Trisal and Allan Feng; former life science research professional Shaurya Dhingra; undergraduate student Sarah Chang; clinical research assistant Mihir Shah; clinical and laboratory research assistant Allie Lee; Sharon Chinthrajah, MD, associate professor of medicine; Sayantani Sindher, MD, clinical associate professor of medicine; Holden Maecker, PhD, professor of microbiology and immunology and director of Stanford's Human Immune Monitoring Center; Scott Boyd, PhD, associate professor of pathology; Mark Davis, PhD, professor of microbiology and director of Stanford's Institute for Immunity, Transplantation and Infection; and PJ Utz, MD, professor of medicine.

Researchers at Billerica, Massachusetts-based Quanterix and Emory University also participated in the study.

The work was funded by the National Institutes of Health (grants U19AI090023, U19AI057266, U24AI120134, P51OD011132, S10OD026799, R01AI123197-04, U01AI150741-01S1 and AI057229), Open Philanthropy, the Sean Parker Cancer Institute, the Soffer Endowment, the Violetta Horton Endowment, Stanford University, the Henry Gustav Floren Trust, the Parker Foundation, the Cooperative Centers on Human Immunology and the Crown Foundation.

Stanford's Institute for Immunity, Transplantation and Infection also supported the work.

The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://med.stanford.edu/school.html. The medical school is part of Stanford Medicine, which includes Stanford Health Care and Stanford Children's Health. For information about all three, please visit http://med.stanford.edu.

 

Experts challenge current understanding of transition dairy cow health

Comprehensive review in the Journal of Dairy Science® examines the riskiest period for dairy cow health, between giving birth and milk production, in a new light

ELSEVIER

Research News

Champaign, IL, July 19, 2021 - For dairy cows, the transition period--the time between a cow giving birth and beginning to produce milk--brings the greatest possibility of health problems. The current widespread belief is that the effects of excess nonesterified fatty acids (NEFA) in the bloodstream and the ensuing hyperketonemia during this period, coupled with low levels of available calcium, are largely responsible for disorders such as mastitis, metritis, retained placenta, and poor fertility. Much attention has therefore been devoted to regulating NEFA and calcium levels in transition cows--yet all these efforts have not made the transition period less of a challenge to cows and, hence, to farmers, with approximately 75 percent of disease occurring during the first months postpartum. Dairy producers literally pay the price in terms of reduced milk production, costs of treatment, early culling of cows, reduced reproductive abilities, and animal welfare.

In a new review in the Journal of Dairy Science, a team from the Iowa State University Department of Animal Science, Ames, IA, USA, led by Lance H. Baumgard, PhD, Norman L. Jacobson Endowed Professor in Dairy Nutrition, critically reviews the current accepted understanding of cow health during the transition period to investigate the reasons for these persistent problems and suggests lines of inquiry and perspectives on dairy cow health that may prove more effective. Their findings call into question the methods and conclusions of a large body of previous research and how such work has been applied in the dairy industry.

"During the last 50 years, dairy scientists have increasingly viewed elevated circulating NEFA and ketones and hypocalcemia as pathological and causal toward negative outcomes," Baumgard observed.

The team found that this tenet is largely based on observational studies, epidemiology, correlations, and ex vivo immune cell function assays. "It is becoming increasingly evident that periparturient diseases and disorders cannot be explained by the severity of changes in these simple metabolites. Interpreting biomarkers as causal agents of metabolic disorders deviates from the purpose of epidemiological studies," Baumgard added. In their review of previous research, Baumgard and colleagues emphasized the fundamental scientific principle that "correlation does not equal causation."

Examining data both from dairy cows and across species, the team concluded that postcalving changes to energetic and calcium metabolism reflect normal biological processes. Healthy animals use these processes to maximize milk production. In other words, conditions that have been widely regarded as indicating poor health may in fact represent normal and even advantageous functions--and some of the ways in which the challenges of the transition period are addressed may actually make problems worse. Unhealthy cows (metritis, mastitis etc.) utilize similar processes to support an effective immune system. Thus, the unhealthy cow and high-producing healthy cow share similar metabolic profiles.

Baumgard and colleagues provide a basis for further investigating this perspective, with the suggestion that future research might focus on preventing immune system activation in cows, thereby reducing the negative effects of inflammation. Proceeding thus, with careful attention to scientific rigor, they hope to make progress in overcoming the transition cow health problems that remain key obstacles to profitable dairy farming and improving overall agricultural sustainability.

###

A new metric for designing safer streets

UNIVERSITY OF PENNSYLVANIA

Research News

A new study published in Accident Analysis & Prevention shows how biometric data can be used to find potentially challenging and dangerous areas of urban infrastructure before a crash occurs. Lead author Megan Ryerson led a team of researchers in the Stuart Weitzman School of Design and the School of Engineering and Applied Science in collecting and analyzing eye-tracking data from cyclists navigating Philadelphia's streets. The team found that individual-based metrics can provide a more proactive approach for designing safer roadways for bicyclists and pedestrians.

Current federal rules for installing safe transportation interventions at an unsafe crossing--such as a crosswalk with a traffic signal--require either a minimum of 90-100 pedestrians crossing this location every hour or a minimum of five pedestrians struck by a driver at that location in one year. Ryerson says that the practice of planning safety interventions reactively with a "literal human cost," has motivated her and her team to find more proactive safety metrics that don't require waiting for tragic results.

Part of the challenge, says Ryerson, is that transportation systems are designed and refined using metrics like crash or fatality data instead of data on human behavior to help understand what makes an area unsafe or what specific interventions would be the most impactful. This reactive approach also fails to capture where people might want to cross but don't because they consider it too dangerous and that, if it were safe, more people would utilize.

"Today we have technology, data science, and the capability to study safety in ways that we didn't have when the field of transportation safety was born," says Ryerson. "We don't have to be reactive in planning safe transportation systems; we can instead develop innovative, proactive ways to evaluate the safety of our infrastructure."

The team developed an approach to evaluate cognitive workload, a measure of a person's ability to perceive and process information, in cyclists. Cognitive workload studies are frequently used in other fields of transportation, such as air traffic control and driving simulations, to determine what designs or conditions enable people to process the information around them. But studies looking at cognitive workload in bicyclists and pedestrians are not as common due to a number of factors, including the difficulty of developing realistic cycling simulations.

The researchers in Ryerson's lab looked at how different infrastructure designs elicit changes in cognitive workload and stress in urban cyclists. In 2018, the team had 39 cyclists travel along a U-shaped route from JFK Boulevard and Market Street, down 15th Street to 20th Street, then returning back to 15th and Market. Riders wore Tobii eye-tracking glasses equipped with inward- and outward-facing camera and a gyroscope capable of collecting eye- and head-movement data 100 times per second.

Along with the route being one of Philadelphia's newest protected bicycle lanes at the time, and therefore a new experience for all of the study participants, it also has a dramatic change in infrastructure along the 8-10-minute route, including a mix of protected bike lanes, car-bike mixing zones, and completely unprotected areas. "We felt that, in a short segment of space, our subjects could experience a range of transportation-infrastructure designs which may elicit different stress and cogitative workload responses," Ryerson says.

One of the study's main findings is the ability to correlate locations that have disproportionately high numbers of crashes with a consistent biometric response that indicates increased cognitive workload. If a person's cognitive workload is high, Ryerson says, it doesn't necessarily mean that they will crash, but it does mean that a person is less able to process new information, like a pedestrian or a driver entering the bike lane, and react appropriately. High cognitive workload means the threat of a crash is heightened.

In addition, the researchers found that stressful areas were consistent between expert cyclists and those less experienced or confident. This has implications for current approaches to managing safety, which typically focus on pedestrian- and cyclist-education interventions. Education is still important, Ryerson says, but these results show that infrastructure design is just as important in terms of making spaces safe.

"Even if you're a more competent cyclist than I am, we still have very similar stress and workload profiles as we traverse the city," says Ryerson. "Our finding, that safety and stress are a function of the infrastructure design and not the individual, is a shift in perspective for the transportation-safety community. We can, and must, build safety into our transportation systems."

The Ryerson lab is now analyzing a separate eye-tracking dataset from cyclists traveling Spruce and Pine streets before and after the 2019-20 installation of protected bike lanes, an experiment that will allow closer study of the impacts of a design intervention.

Overall, Ryerson says, the research shows that it's possible to be more proactive about safety and that city planners could use individual-level data to identify areas where a traffic intervention might be useful--before anyone is hit by a car. "The COVID-19 pandemic encouraged so many of us to walk and bike for commuting and recreation. Sadly, it also brought an increase in crashes. We must proactively design safer streets and not wait to count more crashes and deaths. We can use the way people feel as they move through the city as a way to design safer transportation systems," she says.

###

The complete author list is Megan Ryerson, Carrie Long, Michael Fichman, Joshua Davidson, Kristen Scudder, George Poon, and Matthew Harris from Penn; Michelle Kim from Swarthmore; and Radhika Katti from Carnegie Mellon University.