Researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, are among the Viewpoint’s authors. All authors are with the Partnership for Research on Ebola VACcination (PREVAC). In addition to NIAID, the partnership, established in 2017, comprises experts from the French National Institute of Health and Medical Research (Inserm), the London School of Hygiene & Tropical Medicine (LSHTM), the West African Clinical Research Consortium and their collaborators. PREVAC is currently conducting a Phase 2 clinical trial in Guinea, Liberia, Sierra Leone and Mali to evaluate three Ebola vaccination strategies in people one year and older.

Ebola virus disease remains a public health threat — the Democratic Republic of the Congo (DRC) already has experienced two Ebola outbreaks in 2018 — underscoring the need for continued efforts to develop an effective vaccine. The authors note that 36 trials of Ebola vaccine candidates have been completed and another 14 are active, according to clinicaltrials.gov. The rVSV-ZEBOV experimental vaccine, which has been deployed in the DRC, is the only candidate with some clinical efficacy data, which were obtained in a clinical trial in Guinea conducted during the 2014-2016 Ebola outbreak in Guinea.

After reviewing the status of four additional vaccine candidates under study (Ad26.ZEBOV, MVA-BN-Filo, chAd3-EBO-Z, and the GamEvac-Combi vaccine), the authors highlight areas where more research is required. Specifically, they note the need for more data in pregnant women, children and immunocompromised populations, including people infected with HIV and the elderly. Additionally, they say more research is needed on the durability and rapidity of immune responses generated by various vaccine approaches. The experts also call for studies to identify reliable correlates of protection (the specific and measurable part of an immune response that would indicate a person is protected from Ebola) as well as large-scale trials to fully evaluate the safety and efficacy of experimental vaccines.

The authors conclude by underscoring the value of embedding social science research in clinical trial design to help build trust and engagement with the affected communities. They note that in addition to the need to investigate various vaccines and vaccination strategies to respond more effectively to future outbreaks, improving the global capacity to conduct clinical research and forming collaborative partnerships, such as PREVAC, are crucial for success.

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In metals, the connection of thermal and electrical conductivity is described by the Wiedemann-Franz law, which has first been formulated in 1853. In its modern form the law states that at a fixed temperature, the ratio between the two types of conductivity is constant. The value of that ratio is quite universal, being the same for a remarkably wide range of metals and conditions. That universality breaks down, however, when the carriers interact with one another. This has been observed in a handful of exotic metals hosting strongly correlated electrons. But Husmann, Corman and their co-workers have now explored the phenomenon in a system in which they had exquisite control over all relevant parameters, enabling them to monitor particle and heat transport in unprecedented detail.

Clean transport

The carriers in their experiments are fermionic lithium atoms, which they cooled to sub-microkelvin temperatures and trapped using laser beams. Initially, they confined a few hundred thousand of these atoms to two independent reservoirs that can be heated individually. Once a temperature difference between the two reservoirs had been established, they opened a tiny restriction between them — a so-called quantum point contact — thus initiating transport of particles and heat. The transport channel is defined and controlled using laser light as well. The experiment therefore provides an extraordinarily clean platform for studying fermionic transport. For example, in real materials, the lattice through which the electrons flow starts to melt at high temperatures. In contrast, in the cold-atom setup, with the structures defined by light, no such ‘lattice heating’ occurs, making it possible to focus on the carriers themselves.

Puzzling behaviour

When Husmann et al. determined the ratio between thermal and particle conductivity in their system, they found it to be an order of magnitude below the predictions of the Wiedemann-Franz law. This deviation indicates a separation of the mechanisms responsible for particle and heat currents, in contrast to the situation so universally observed for free carriers. As a result, their system evolved into a state in which heat and particle currents vanished long before an equilibrium between the two reservoirs in terms of temperature and particle number has been reached.

Moreover, another measure for thermoelectric behaviour, the Seebeck coefficient, was found to have a value close to that expected for a non-interacting Fermi gas. This is puzzling, because in some regions of the channel the strongly interacting atoms were in the superfluid regime (in which a gas or liquid flows without viscosity) and in the prototypical superfluid, helium-4, the Seebeck coefficient is zero. This discrepancy signals a different thermoelectric character for the fermionic gas studied by the ETH team.

These findings therefore pose new challenges for microscopic modelling of strongly interacting fermion systems. At the same time, the platform established with these experiments could help to explore novel concepts for thermoelectric devices, such as coolers and engines that are based on interconverting temperature differences into particle flow, and vice versa.

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A team of researchers led by the University of Tennessee, Knoxville conducted the measurement in a beam test facility at the Department of Energy’s Oak Ridge National Laboratory using a replica of the Spallation Neutron Source’s linear accelerator, or linac. The details are published in the journal Physical Review Letters.

“Our goal is to better understand the physics of the beam so that we can improve how accelerators operate,” said Sarah Cousineau, group leader in ORNL’s Research Accelerator Division and UT joint faculty professor. “Part of that is related to being able to fully characterize or measure a beam in 6D space — and that’s something that, until now, has never been done.”

Six-dimensional space is like 3D space but includes three additional coordinates on the x, y, and z axes to track motion or velocity.

“Right away we saw the beam has this complex structure in 6D space that you can’t see below 5D — layers and layers of complexities that can’t be detangled,” Cousineau said. “The measurement also revealed the beam structure is directly related to the beam’s intensity, which gets more complex as the intensity increases.”

Previous attempts to fully characterize an accelerator beam fell victim to “the curse of dimensionality,” in which measurements in low dimensions become exponentially more difficult in higher dimensions. Scientists have tried to circumvent the issue by adding three 2D measurements together to create a quasi-6D representation. The UT-ORNL team notes that approach is incomplete as a measurement of the beam’s initial conditions entering the accelerator, which determine beam behavior farther down the linac.

As part of efforts to boost the power output of SNS, ORNL physicists used the beam test facility to commission the new radio frequency quadrupole, the first accelerating element located at the linac’s front-end assembly. With the infrastructure already in place, a research grant from the National Science Foundation to the University of Tennessee enabled outfitting the beam test facility with the state-of-the-art 6D measurement capability. Conducting 6D measurements in an accelerator has been limited by the need for multiple days of beam time, which can be a challenge for production accelerators.

“Because we have a replica of the linac’s front-end assembly at the beam test facility, we don’t have to worry about interrupting users’ experiment cycles at SNS. That provides us with unfettered access to perform these time-consuming measurements, which is something we wouldn’t have at other facilities,” said lead author Brandon Cathey, a UT graduate student.

“This result shows the value of combining the freedom and ingenuity of NSF-funded academic research with facilities available through the broad national laboratory complex,” said Vyacheslav Lukin, the NSF program officer who oversees the grant to the University of Tennessee. “There is no better way to introduce a new scientist — a graduate student — to the modern scientific enterprise than by allowing them to lead a first-of-a-kind research project at a facility that uniquely can dissect the particles that underpin what we know and understand about matter and energy.”

The researchers’ ultimate goal is to model the entire beam, including mitigating so-called beam halo, or beam loss — when particles travel to the outer extremes of the beam and are lost. The more immediate challenge, they say, will be finding software tools capable of analyzing the roughly 5 million data points the 6D measurement generated during the 35-hour period.

“When we proposed making a 6D measurement 15 years ago, the problems associated with the curse of dimensionality seemed insurmountable,” said ORNL physicist and coauthor Alexander Aleksandrov. “Now that we’ve succeeded, we’re sure we can improve the system to make faster, higher resolution measurements, adding an almost ubiquitous technique to the arsenal of accelerator physicists everywhere.”

The PRL paper is titled “First Six Dimensional Phase Space Measurement of an Accelerator Beam.” The paper’s coauthors also include ORNL’s Alexander Zhukov.

“This research is vital to our understanding if we’re going to build accelerators capable of reaching hundreds of megawatts,” Cousineau said. “We’ll be studying this for the next decade, and SNS is better positioned to do this than any other facility in the world.”

According to the Centers for Disease Control and Prevention, about 1 in 10 infants in 2016 was preterm, born prior to completing 37 gestational weeks of pregnancy. Micro preemies are the tiniest infants in that group, weighing less than 1,500 grams and born well before their brain, lungs and organs like the liver are fully developed.

As staff reviewed charts for very low birth weight preterm infants admitted to Children’s NICU, they found dramatic variation in nutritional practices among clinicians and a mean decline in delta weight Z-scores, a more sensitive way to monitor infants’ weight gain along growth percentiles for their gestational age. A multidisciplinary team that included dietitians, nurses, neonatologists, a lactation consultant and a quality-improvement leader evaluated nutrition practices and determined key drivers for improving nutrition status.

“We tested a variety of strategies, including standardizing feeding practices; maximizing intended delivery of feeds; tracking adequacy of calorie, protein and micronutrient intake; and maximizing use of the mother’s own breast milk,” says Michelande Ridoré, MS, a Children’s NICU quality-improvement lead who will present the group’s findings during the Virginia Neonatal Nutrition Association conference this fall. “We took nothing for granted: We reeducated everyone in the NICU about the importance of the standardized feeding protocol. We shared information about whether infants were attaining growth targets during daily rounds. And we used an infographic to help nursing moms increase the available supply of breastmilk,” Ridoré says.

On top of other challenges, very low birth weight preterm infants are born very lean, with minimal muscle. During the third trimester, pregnant women pass on a host of essential nutrients and proteins to help satisfy the needs of the fetus’ developing muscles, bones and brain. “Because preterm infants miss out on that period in utero, we add fortification to provide preemies with extra protein, phosphorus, calcium and zinc they otherwise would have received from mom in the womb,” says Victoria Catalano, RDN, LD, CNSC, CLC, a pediatric clinical dietitian in Children’s NICU and study co-author. Babies’ linear growth is closely related to neurocognitive development, Catalano says. A dedicated R.N. is assigned to length boards for Children’s highest-risk newborns to ensure consistency in measurements.

Infants who were admitted within the first seven days of life and weighed less than 1,500 grams were included in the study. At the beginning of the quality-improvement project, the infants’ mean delta Z-score for weight was -1.8. By December 2018, that had improved to -1.3. And the number of lactation consultation ordered weekly increased from 1.1 to four.

“We saw marked improvement in micro preemies’ nutritional status as we reduced the degree of variation in nutrition practices,” says Mary Revenis, M.D., NICU medical lead on nutrition and senior author for the research. “Our goal was to increase mean delta Z-scores even more. To that end, we will continue to test other key drivers for improved weight gain, including zinc supplementation, updating infants’ growth trajectories in the electronic medical record and advocating for expanded use of birth mothers’ breast milk,” Dr. Revenis says.

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Adam van Casteren of the Max Planck Weizmann Center for Integrative Archaeology and Anthropology at the Max Planck Institute for Evolutionary Anthropology went out to compare the material properties of various plant foods eaten by chimpanzees in a tropical rainforest (Ngogo, Uganda) and a savannah woodland (Issa Valley, Tanzania). Using a portable mechanical tester, he measured the physical properties of plant tissues and found that some plant parts from the mosaic savannah woodland habitat, such as the outer casing of the Strychnos fruit, had much higher toughness and stiffness values than the plant tissues he tested from the rainforest. “I was surprised to see that some values even exceed those recorded for orangutan foods as they are generally considered to consume the most mechanically challenging diet of all the great apes,” says van Casteren.

The scientists also combined their plant food mechanical data with data from a stable isotope analysis from both plant and chimpanzee hair samples. Carbon stable isotopes are commonly used to reconstruct dietary ecology and habitat use of living and extinct primates. Although the carbon isotope values of plants were remarkably similar in both habitats, the isotope data obtained from chimpanzee hair suggested that savannah chimpanzees frequently feed on plants growing in open canopy areas. These likely include those plants which are particularly demanding when processed with the teeth.

The authors believe that the consumption of such tough foods is facilitated by the large front teeth of chimpanzees. “While some chimpanzee populations are using tools to crack open nuts, others like these savannah chimpanzees still rely on their teeth to get access to nutrients. Such differences in selection pressures acting on the teeth are likely to have played a key role during the evolution of hominins,” says Kornelius Kupczik, co-author and Track Leader of the Max Planck Weizmann Center.

Dental morphology, food mechanical properties and carbon stable isotopes are all highly relevant for reconstructing past diets of our early ancestors in Africa. “If we better understand the foundations and interactions of food material properties, dental wear processes and isotopes in extant chimpanzees this opens a window into the past and helps to interpret the data obtained from fossil specimens who lived in the African savannah several million years ago,” concludes co-author Vicky Oelze from the University of California in Santa Cruz and the Max Planck Institute for Evolutionary Anthropology, who conducted the stable isotope analysis.

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The University of Stirling study provides clues as to why the abundance of Himalayan balsam — which has an adverse impact on native plants and river habitats — varies dramatically from place to place.

The work could help mitigate the impact of the pink-flowered plant, which outcompetes native species, causes shading and reduces the stability of riverbanks, enabling silt to enter the water.

Dr Zarah Pattison, of the Faculty of Natural Sciences, led the research, published in Ecosystems.

She said: “Our research has found that Himalayan balsam dislikes overly moist conditions, unlike the native plants — such as nettles, butterbur and canary grass — which dominate our lowland riverbanks. It prefers drier, steeper riverbanks where it can compete more effectively with the native plants.

“This knowledge offers a gateway to managing Himalayan balsam indirectly, by manipulating conditions on riverbanks.”

River engineering often involves straightening and over-deepening rivers and, combined with the abstraction of water, this leads to drier riverbanks during the summer, benefitting Himalayan balsam growth. This effect of riverbank drying may also be exacerbated with future climate change and drought conditions, as seen this summer across the UK.

In contrast, the restoration of rivers often results in gently sloped banks, meaning water is retained and riverbanks are therefore moister, favouring native species.

The authors also found that riverbanks with a large abundance of native plants are more likely to resist invasion by Himalayan balsam.

Dr Pattison believes the findings will aid river management by helping to pinpoint resources in attempt to control Himalayan balsam.

“The UK spends an estimated £1.7 million on managing invasive alien species, including thousands of man-hours manually removing or spraying species such as Himalayan balsam,” she said.

“Therefore, understanding the conditions which benefit the growth and spread of this species will enable better management and use of resources, in order to control the amount and spread of Himalayan balsam.”

The research involved field surveys conducted along 20 rivers across the Central Belt of Scotland.

The team used a technique, structural equation modelling, to assess the data and understand the effects of the environment and resident plant community on the abundance of Himalayan balsam.

Funded by Scottish National Heritage, the Scottish Environment Protection Agency and the University of Stirling, the research — Riverbanks as battlegrounds: Why does the abundance of native and invasive plants vary — involved Stirling academics Professor Nigel Willby and Dr Mario Vallejo-Marin.

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Pulmonary fibrosis is associated with the increased formation of connective tissue in the lungs, resulting in scarring (fibrosis) of functional lung tissue. This leads to a decrease in the inner surface of the extremely fine alveoli and the extensibility of the lungs, which, in turn, impedes the intake of oxygen and the release of carbon dioxide. The result is impaired lung function. IPF is a particularly aggressive form of the disease that cannot be attributed to a specific cause. The symptoms worsen rapidly. Existing drugs can slow progression of the disease but are unable to stop it permanently.

Research is therefore continuing to focus on elucidating the mechanisms underlying the pathological tissue changes associated with IPF. One approach that has been intensively pursued for several years now in the Department of Lung Repair and Regeneration (LRR) and the Institute of Lung Biology and Disease (ILBD) at Helmholtz Zentrum München aims to influence the so-called WNT signaling pathway. It is already known that the signaling molecule WNT5A is responsible for stimulating the proliferation of connective tissue cells in the lungs.

Vesicles transport scarring signals

The LRR Research Group headed by Dr. Dr. Melanie Königshoff has found that extracellular vesicles are very likely also involved in IPF. “Simply put, extracellular vesicles are tiny pouches released by cells that can contain a large number of messenger substances, such as proteins and nucleic acids,” describes Dr. Mareike Lehmann, one of the authors of the study. “They are an important means of communication between cells and organs and help to ensure that the substances reach completely new sites.”

Until recently, it was unclear whether and how extracellular vesicles are implicated in IPF. “We were able to show in the study that increased levels of extracellular vesicles occur in IPF patients, which then act as carriers of WNT5A,” explains lead author Aina Martin-Medina. “We were also able to confirm these results in our experimental model.” In addition, the authors showed in Petri dish experiments that reducing the number of vesicles decreases tissue scarring.

In further preclinical studies, the researchers now want to examine the suitability of extracellular vesicles as a pharmacological biomarker, as well as a possible therapeutic target.

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Materials provided by Helmholtz Zentrum München – German Research Center for Environmental Health. Note: Content may be edited for style and length.