Culture

One day in the near future dyes in electric motors might indicate when cable insulation is becoming brittle and the motor needs replacing. Scientists at Martin Luther University Halle-Wittenberg (MLU), together with ELANTAS, a division of the specialty chemicals group ALTANA, have developed a new process that enables the dyes to be directly integrated into the insulation. By changing colour, they reveal how much the insulating resin layer around the copper wires in the motor has degraded. The results were published in the journal "Advanced Materials".

Modern combustion engines have long had detectors that recognise, for example, when an oil change is needed, saving unnecessary inspections. Electric motors also show signs of wear. Inside, they are usually made up of tightly wound copper wires - and these in turn are coated with an insulating resin. "This insulation changes over time. It becomes brittle as it degrades dues to heat and chemical processes," explains Professor Wolfgang Binder from the Institute of Chemistry at MLU. However, it is not possible to tell from the outside whether the insulation around the wires inside is still intact or whether the entire motor needs to be replaced.

The scientists from MLU were tasked with finding a solution to this problem on behalf of the ELANTAS division of ALTANA, which produces special resin systems for such insulation. "Until now, developers have focused on the degree to which material degrades under specific conditions," explains Alexander Funtan, a chemist at MLU. Recommendations were then made as to how long it would take before a replacement would be necessary. However, the actual wear depends on the conditions under which it is used, most particularly temperature. Funtan therefore developed a test rig which he used to analyse four different resin systems over several months to determine which degradation products form at different temperatures.

He discovered that the four resin systems consistently released a specific alcohol under the different temperature conditions. "We then worked closely with the researchers and developers at ELANTAS to find a sensor molecule for this alcohol," he says. In other words, a substance that is easily detectable and whose properties change when the alcohol binds to it. The sensor molecule must also withstand high temperatures and normal production processes. Another requirement was that it did not change the insulation's electrochemical properties. The choice fell on a dye that normally glows reddish orange under UV light; but when alcohol binds to it, the colour spectrum shifts to a light green.

The different colour spectra could then be analysed using special devices that could be installed directly in the engine. "This way, you can see if a replacement is necessary without having to open up the engine," says Binder. This will hopefully avoid unnecessary motor replacements in the future. The new insulation could be used in the motors of electric vehicles as well as in machines and other equipment. "These results reveal what can be achieved by combining basic university research with commercial application know-how," says Dr Simon Rost, head of research & development at ELANTAS in Hamburg. "In the future, this will enable us to provide added value to our customers and further contribute to sustainable development."

ELANTAS filed a patent for the new process at the beginning of the year. The research was financed by the specialty chemicals group ALTANA and also funded by the EU's BAT4EVER project as part of the "Horizon 2020" programme.

Recently, Prof. WANG Junfeng from the High Magnetic Field Laboratory of the Hefei Institutes of Physical Science (HFIPS), together with international scholars, developed a novel circular permutated light-oxygen-voltage 2 (LOV2) to expand the repertoire of genetically encoded photoswitches, which will accelerate the design of novel optogenetic devices. The result was published in Nature Chemical Biology.

LOV2 domain is a blue light-sensitive photoswitch. In a typical LOV2-based optogenetic device, an effector domain is fused after the C-terminal Jα helix of LOV2, intending to cage the effector via steric hindrance in the dark. On photostimulation, light-triggered unfolding of the Jα helix exposes the effector domain to restore its function. Crafting a LOV2-based photoswitchable protein often takes tremendous engineering efforts to optimize each component and the connecting linker in between. Therefore, it is desirable to expand the current optogenetic toolbox by creating new modules that simplify these steps.

In this study, the researchers designed cpLOV2 using circular permutation, a robust protein engineering approach previously used to evolve new variants of genetically encoded fluorescent probes and biocatalysts. The nitrogen (N) and carbon (C) termini of cpLOV2 were created at the N-terminus of Jα helix while the old ones were connected by a glycine and serine-rich linker. Therefore, the effector could be fused before the N-terminal Jα of cpLOV2 in addition to the C-terminus in LOV2.

Using high resolution NMR spectroscopy and other techniques, the researchers demonstrated that the structural integrity and function of light-induced Jα dissociation of cpLOV2 are well maintained. cpLOV2 was also well worked in LOVTRAP and improved light-induced dimer (iLid), both are LOV2 based optical heterodimerization systems.

cpLOV2 provided more choices for optogenetic application developments. The researchers generated a series of hybrids by fusing LOV2 or cpLOV2 with different Ca2+ channel-activating and autoinhibition fragments derived from stromal interaction molecule 1, and found several novel cpLOV2 based optical actuators to gate ORAI1 Ca2+ channel, therefore they demonstrated that cpLOV2 could afford new caging surfaces to overcome limitations associated with wild type LOV2.

For effectors required a free N terminus to execute its full function, cpLOV2 is a better choice. A key protein involved in necroptosis, mixed lineage kinase domain-like (MLKL) protein, was the successful caged and uncaged in cpLOV2-MLKL but not MLKL-LOV2 to optical control of cell suicides.

Chimeric antigen receptor (CAR) T cell therapy has emerged as a promising immunotherapeutic approach. However, the uncontrollable CAR T cell activity during therapy would cause severe side-effects e.g. cytokine release syndrome in some patients. Researchers designed cpLOV2 based optical heterodimerization systems (cpLID), and constructed photo-tunable split CAR (optoCAR). The therapeutic optoCAR T cells can be specifically activated by CD19 tumor antigen and blue light, and then proliferate to kill CD19+ Raji lymphoma cells.

In mouse model implanted with CD19+ Raji cells, researchers used upconversion nanoparticles (UCNPs) to convert the high tissue penetrative near-infrared light to blue light and activate the injected optoCAR T cells and achieved highly effective therapy of lymphoma tumor. OptoCAR T cells developed in this study permit the spatiotemporal and reversible control of T cell activities and cytokine production.

These encouraging results suggest optoCAR T cells could mitigate potential side effects without losing therapeutic efficacy. In the future, they plan to try "optogenetic immunotherapy" to treat different types of cancer.

A research group at the University of Córdoba studied the molecular properties of the holm oak (Quercus ilex) in search of trees that are more resistant to drought and root rot.

One of the biggest problems affecting holm oaks is drought. The holm oak (Quercus ilex) boasts a high natural adaptability and resistance to inclement weather conditions in dry environments with high temperatures. However, drought is one of the main causes of mortality in holm oak plantations, with "drought stress" also an important factor contributing to root rot.

This is a multifactorial syndrome that causes the decay and death of holm oaks, consisting of a combination of stress due to drought, high temperatures, and attacks by soil pathogens (mainly Phytophthora cinnamomi), a situation that will tend to worsen in a scenario of climate change. However, not all holm oaks are equally affected. Some exhibit greater resistance and tolerance to these stresses, and are called "elite" specimens, thus being the most interesting to study.

The research group AGR-164 "Biochemistry, Proteomics and Biology of Plant and Agroforestry Systems" at the University of Cordoba carried out a study that will make it possible to identify the trees with the best chance of surviving under the most adverse circumstances.

This study, coordinated by Dr. María Ángeles Castillejo, together with Professor Jesús V. Jorrín-Novo and Dr. Lola Rey, focused on investigating this species, about which very little is known at the molecular level, despite the fact that, according to the Castillejo: "the holm oak is the most important and representative species of the Andalusian forest ecosystem, la dehesa, and of the Mediterranean forest". Working with forest species entails a great effort and is a challenge due to their high biological variability and long life cycles, she explained. To this it must be added that "currently there is not yet a sequenced holm oak genome, although we are working on it and hope to have it shortly. This will mean, without a doubt, a great advance in the molecular study of this species", Castillejo explained.

The importance of studying the oak lies in its ecological, environmental and economic value. In fact, in addition to serving as sustenance for pigs, in recent years there has been a renewed interest in the human consumption of acorns, "due to its beneficial nutritional and pharmacological properties, about which little is still known", according to Castillejo.

Therefore, the molecular study of specimens exhibiting a high tolerance to drought has great potential. Thus, the objective of this research project was to identify trees that are more tolerant of drought through the study of their proteome proteins in order to determine those that may be involved in said tolerance.

For this, four populations from different parts of Andalusia were chosen, and a drought stress experiment was carried out with their seedlings. Physiological studies (such as the measurement of leaf fluorescence) were carried out to determine the drop in photosynthesis, and, thus, select two sampling times for the subsequent molecular analysis. Those proteins that increased in response to the drought, which happened in at least two of the populations studied, were selected for a second analysis.

This dual strategy for the quantification of proteins and peptides (a type of molecule) made it possible to select those most stable over time, which may be involved in drought tolerance, such that they could be used as possible molecular markers. "Those trees whose genome is expressing the greatest number or quantity of these proteins are probably more tolerant to drought", added the researcher.

Thus, it was possible to propose a list of possible markers that will be used by growers to include them in their selection of specimens and reforestation programs to repopulate areas affected by drought.

Autism spectrum disorder is a neurodevelopmental condition involving impaired social abilities, and this makes it a fascinating subject for neuroscientists like Prof. Teiichi Furuichi of the Tokyo University of Science who study the neuroscience of social behavior. Prof. Furuichi and his colleagues have previously worked on developing mouse models of autism to unravel the condition's neurochemical mechanisms, and in a paper recently published in the prestigious Journal of Neuroscience, they provide evidence that a genetic mutation associated with autism can impair the release of a peptide called oxytocin that plays an important role in regulating social behavior. This finding promises to broaden our understanding of the neurobiology of social behavior.

The gene that Prof. Furuichi's team chose to study is Caps2, which encodes a protein called Ca2+-dependent activator protein for secretion 2 (CAPS2) that regulates the release of brain chemicals (or "neurotransmitters"). Previous studies have shown that CAPS2 deficiencies in mice cause behavioral impairments such as reduced sociality, increased anxiety, and disrupted circadian rhythms. Furthermore, a study of Japanese patients with autism spectrum disorder revealed that some of them had Caps2 mutations that adversely affect the CAPS2 protein's functions. Prof. Furuichi and his colleagues had previously discovered that the CAPS2 protein is expressed in neurons in the hypothalamus and pituitary gland that release the neuropeptide oxytocin. This information formed the basis of their recent study. As Prof. Furuichi explains, "We hypothesized that CAPS2 deficiencies in mice should alter oxytocin release, which should in turn result in impaired social behavior."

To test this hypothesis, researchers Shuhei Fujima, Graduate Student at Tokyo University of Science; Yoshitake Sano, Junior Associate Professor at Tokyo University of Science; Yo Shinoda, Associate Professor at Tokyo University of Pharmacy and Life Sciences; Tetsushi Sadakata, Associate Professor in Gunma University; Manabu Abe, Associate Professor at Niigata University; and Kenji Sakimura, a Fellow of Niigata University, among others, led by Prof. Furuichi conducted a series of experiments involving mice that carried genetic alterations that prevented them from expressing the CAPS2 protein. These mice had lower-than-normal oxytocin levels in their blood but higher-than-normal oxytocin levels in the hypothalamus and pituitary gland. The researchers interpreted this finding as evidence that CAPS2 deficiencies impede the normal release of oxytocin from these brain regions into the bloodstream.

Unsurprisingly, the reduced bloodstream levels of oxytocin had clear behavioral effects. When placed inside a rectangular box, the oxytocin neuron-specific CAPS2-deficient mice were unwilling to spend much time in the center of the box, and the researchers interpreted this as evidence of increased anxiety about the risk of a predator attacking them. The CAPS2-deficient mice also exhibited diminished willingness to engage in social interactions when introduced to unfamiliar mice. Interestingly, spraying an oxytocin solution into the noses of the CAPS2-deficient mice acted to restore their willingness to socially interact with unfamiliar mice.

Based on these findings, Prof. Furuichi and his colleagues conclude that the CAPS2 protein plays a critical role in facilitating the release of peripheral oxytocin into the bloodstream. They similarly suggest that CAPS2 is also involved in the release of central oxytocin into the brain regions relating to the control of sociality. Given the key role that oxytocin plays in regulating social behaviors, this could help to explain how mutations in the Caps2 gene could lead to atypical patterns of social behavior in persons with autism spectrum disorder. When asked about the social significance of his team's work, Prof. Furuichi remarks, "We believe that this research, although basic, is an important achievement that will contribute to the development of tools for the early molecular diagnosis and effective treatment of autism spectrum disorder."

Given the relatively high prevalence of autism and how extremely disabling severe cases can be, the development of effective treatments would have major benefits for people with autism and the society as a whole.

In the field of international business research, lobbying is considered a legitimate and legal political action conducted in a developed economy. Bribery, on the other hand, is seen as an outright corrupt practice in an emerging economy.

In a study published in the March issue of the journal Business & Society, a researcher from The University of Texas at Dallas examined the gray area between lobbying and bribery among multinational companies, especially in countries where lobbying is not regulated strongly or institutional development is insufficient.

The analysis found that firms based in developed countries, as opposed to developing countries or transition economies, are more likely to influence the institutional environment of host countries through lobbying, even when bribery is expected to be a more prevalent way of doing business in many of these countries.

"We wanted to address this and call for more attention to the issue of lobbying as an equally important issue as bribery in firm activities to influence the institutional environment in the international business context. For example, addressing institutional constraints overseas by shaping regulatory and policy environments in a more favorable way can increase performance benefits," said study author Dr. Seung-Hyun Lee, professor of organizations, strategy and international management in the Naveen Jindal School of Management.

"Moreover, while bribery has been largely seen as what firms from transition economies do, there has been little discussion of the lobbying attempts that firms from more developed economies are doing. We wanted to shed light on this, too."

In the study, Lee and co-author Dr. Jisun Yu of Concordia University in Montreal investigated what determines a multinational enterprise's propensity to engage in lobbying and bribery in countries where the overall institutional development for market exchanges is insufficient and overall country governance is relatively weak.

A transition economy is one that endeavors to change from a planned economy to a market economy. Examples include China and Vietnam. For the study, the researchers focused on the transition economies of central and eastern European countries and members of the Commonwealth of Independent States, a regional organization of countries from the former Soviet Union.

"While transition economies are full of uncertainty due to structural transitions and the uneven development of adequate institutions, these very characteristics are also a source of opportunities, such as low-cost production, highly educated labor forces and easy access to the European market," Lee said.

Using data from the Business Environment and Enterprise Performance Survey conducted in transition economy countries by the World Bank, the researchers aimed to further discussions concerning the ethical and social implications of corporate activities conducted to influence institutions.

Their analysis found that multinational enterprises based in a country with a strong governance system are less involved in bribery but have a higher tendency to lobby their hosts in transition-economy countries. The researchers found that this tendency holds true even when these enterprises rely on the host country's local market for much of their sales.

The study also found that firms from a home country with more developed governance also attempt to change the laws to a greater extent in host countries with weaker institutional development.

"Multinational enterprises behave consistently in host countries and tend to stick to the way business was done in their domestic markets, even when dependence on local sales in host countries increases," he said. "It is a good thing to find that multinational enterprises from countries with a stronger governance system are less likely to bribe in transition economies, compared to their counterparts with weaker governance."

Lee said it is important for policymakers to understand that home country governance can be an effective mechanism in controlling a multinational enterprise's illegal political activities, even outside its home boundaries.

"When it comes to host countries, governments there may want to make sure that lobbying is effectively governed and bribery is curbed to incentivize multinational enterprises hailing from stronger governance systems to invest in their countries," he said.

Policymakers might also consider strengthening their country's governance system as a way of reducing their multinational enterprises' unwanted involvement in corruption overseas, Lee said.

Counselling sessions improve long term mental health in primary-school aged children, according to a new study. The research has implications for reversing declining mental health in young people in a COVID-19 era.

A team from the University of Exeter and the University of Cambridge worked in partnership with Place2Be to assess the longer-term impact of its school-based service.

The study assessed the impact of Place2Be's programme, in which trained counsellors operated in 171 schools nationwide in the academic year 2015/16. Under the scheme, children could self-refer to the counsellors for any reason, or be referred by parents or teachers.

Researchers analysed data on 740 children who took up one-to-one counselling, collected before the counselling started, after the sessions finished, and approximately one year after this. The children did not have to have mental health disorders to take up the counselling, however a comparison with children who were being seen by NHS mental health services indicated that they had similar levels of poor mental health.

The research, published in European Child and Adolescent Psychiatry, used data from the Strengths and Difficulties Questionnaire (SDQ) completed by teachers and parents. One year later, this data showed that the children who spoke to counsellors had considerably better mental health than a comparative group of children who had poor mental health yet had not seen a counsellor.

Lead author Dr Katie Finning, of the University of Exeter, said: "We know that children's mental health is deteriorating, while access to child and adolescent mental health services is decreasing. Our research indicates that children who have access to a counsellor at primary school see benefits to their mental health over the longer term compared to children who don't. School-based counselling could help address the urgent need to support children's mental health, and could help reduce pressure on oversubscribed child mental health services."

Previously published research has concluded that Place2Be's counselling intervention has economic benefits resulting from higher employment output and lower spending on public services, amounting to over £5,700 per child. However, this amount was based on the intervention having short-term benefits that faded more quickly than the new research suggests. So the savings per child are likely to be an under-estimate, given the new finding that benefits are longer-term.

Professor Tamsin Ford, from the University of Cambridge, who supervised the research, said: "We've previously found that children's mental health has worsened during the pandemic. We need to prioritise the provision of evidence-based mental health support in schools. Early intervention at this young age, before mental health problems become entrenched in adolescence and young adulthood, may help to prevent the long-term impacts of childhood mental health problems."

Catherine Roche, Chief Executive of Place2Be, said: "This study reinforces our evidence that high quality school-based mental health support not only helps children to get the most out of their education, but can also prevent problems from growing over time - impacting children's life chances. Schools are on the frontline and have the opportunity to make mental health services easily accessible for families. But school leaders and teachers cannot do this alone, they need quality training, easy referral routes and timely access to specialist mental health services - only when all parts of the system work together will children get the help they deserve."

HAMILTON, ON May 18, 2021 -- Five years after the disastrous wildfire in Fort McMurray, Alberta, researchers are warning that the complex role of peatlands, a factor critical to projecting the risk and behaviour of future fires, is missing from the forecasting model.

The Fort McMurray fire burned out of control from May 1 to July 5, 2016, though it continued to smoulder until it was finally declared extinguished Aug. 2, 2017.

Peat deposits - which are prevalent across Canada, especially in Alberta - are complex threats that can complicate and magnify the risk of severe, long-lasting fires and heavy smoke, but they are not yet part of the standard assessment tools that fire managers use.

It's a critical gap that should be addressed urgently, say the authors of a new paper published today in the International Journal of Wildland Fire, who have completed the first scientific assessment of peatland smouldering fire potential.

"Our understanding of this risk is advancing quickly because it needs to. Year on year, wildfires are becoming more severe and having greater impact," says researcher Sophie Wilkinson, lead author of the paper. "We need tools to understand this at every level of management and governance."

Wilkinson, a post-doctoral research fellow in McMaster's School of Earth, Environment and Society, authored the paper with McMaster colleagues Professor James Michael Waddington and Alex Furukawa, and Professor Mike Wotton of the University of Toronto.

The team looked most closely at peat deposits that are home to black spruce trees. The trees can burn quickly, throwing flaming embers into the air and across the landscape, while the peat, once lit, can smoulder for months and even move underground before re-emerging.

The compacted layers of dead Sphagnum moss and other vegetation, steeped in groundwater and topped by living moss and sometimes black spruce, are huge vaults of carbon.

Once viewed as benign wetland firebreaks, these complex ecosystems are not necessarily resistant to fire and can extend and accelerate wildfires. When climate change and human activity accelerate the drying of such wetlands, stored peat becomes even more dangerous fuel for smoky, stubborn and potentially devastating fires.

"I think the Fort McMurray fire really highlighted the lack of understanding of ecosystems in that area and the interplay between them," Wilkinson says. "It's concerning from a public health and safety perspective, and in terms of its feedback with climate change."

The researchers were able to perform a detailed study in Alberta because peatlands there are more thoroughly mapped, but they believe similar risks exist throughout the boreal peatlands of Canada.

The risk of peat fire is shaped by the type and depth of a peat deposit, the geological structure beneath it, and the presence of trees on its surface, all influenced by rain, wind and temperature - collectively known as "fire weather".

Sometimes fire moves swiftly over peatlands, while other times it digs in. Often, the researchers find, the potential for the worst peat fires is in the smallest, shallowest deposits, which are common in the more populated southern areas of the Boreal Plains.

"It's challenging because there are so many counterintuitive elements at play. These are wetlands that are burning," Wilkinson says.

"A good understanding of how fire is likely to behave in relation to these variables is not yet available to fire managers. I think awareness is growing, and peat fires are getting onto the radar of the public and policymakers more, but the actual scale of the carbon stored in peatlands and the potential to release it through fire is not well understood by the public."

A study published this May in the journal Clinical Infectious Diseases suggests that people who have had dengue in the past are twice as likely to develop symptoms of COVID-19 if they are infected by the novel coronavirus.

The findings of the study were based on an analysis of blood samples from 1,285 inhabitants of Mâncio Lima, a small town in the state of Acre, part of Brazil’s Amazon region. The principal investigator was Marcelo Urbano Ferreira, a professor at the University of São Paulo’s Biomedical Sciences Institute (ICB-USP) in Brazil. The study was supported by FAPESP.

“Our results show that the populations most exposed to dengue, possibly owing to socio-demographic factors, are precisely those that most risk falling very sick if they’re infected by SARS-CoV-2. This is an example of what has been called a syndemic [synergic interaction between two epidemic diseases so that one exacerbates the effects of the other]. On one hand, COVID-19 has hindered efforts to control dengue. On the other, the latter appears to increase the risk for those who contract the former,” Ferreira told Agência FAPESP.

For seven years Ferreira has been conducting research in Mâncio Lima with the aim of combating malaria. In 2018 he began work on a project involving a survey of 20% of the town’s population every six months. His team call on homes, apply questionnaires, and collect blood samples. In early 2020 the project received additional funding from FAPESP so that part of the research effort could be redirected to the monitoring and characterization of SARS-CoV-2 in the region (read more at: agencia.fapesp.br/34728).

“In September 2020, a study by another group was published suggesting that areas with many cases of dengue were relatively little affected by COVID-19. Because we already had blood samples collected from inhabitants of Mâncio Lima before and after the first wave of the pandemic, we decided to use the material to test the hypothesis that prior infection by dengue virus conferred some degree of protection against SARS-CoV-2. What we found was exactly the opposite,” Ferreira said.

Methodology

The blood samples analyzed had been collected in November 2019 and November 2020. They were submitted to tests capable of detecting antibodies against all four dengue serotypes and against SARS-CoV-2.

The results showed that 37% of the cohort studied had contracted dengue before November 2019 and 35% had been infected by the novel coronavirus before November 2020. Clinical data (symptoms and outcomes) of the volunteers diagnosed with COVID-19 were also analyzed.

“We deployed statistical analysis to conclude that prior infection by dengue virus doesn’t alter the risk of being infected by SARS-CoV-2. On the other hand, our study also shows that people who have had dengue are more likely to have symptoms if they’re infected by SARS-CoV-2,” said Vanessa Nicolete, first author of the article. Nicolete is a researcher with a postdoctoral fellowship at ICB-USP.

The causes of the phenomenon described in the article are unclear. There may be a biological basis for it, in the sense that antibodies against dengue virus somehow exacerbate COVID-19, or it may simply be due to socio-demographic factors that make certain population groups more vulnerable to both diseases for various reasons.

“The results evidence the importance of reinforcing both the social distancing measures introduced to contain the spread of SARS-CoV-2 and efforts to control the dengue vector, as the two epidemics are occurring at the same time and affecting the same vulnerable population. This should be getting more attention from the federal government,” Ferreira said.

The article “Interacting epidemics in Amazonian Brazil: prior dengue infection associated with increased COVID-19 risk in a population-based cohort study” by Vanessa C. Nicolete, Priscila T. Rodrigues, Igor C. Johansen, Rodrigo M. Corder, Juliana Tonini, Marly A. Cardoso, Jaqueline G. de Jesus, Ingra M. Claro, Nuno R. Faria, Ester C. Sabino, Marcia C. Castro and Marcelo U. Ferreira is at: academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab410/6270997.

Journal

Clinical Infectious Diseases

DOI

10.1093/cid/ciab410

MINNEAPOLIS/ST. PAUL (03/18/2021) -- A research team, led by the University of Minnesota Medical School, found that regardless of socioeconomic status, Twin Cities residents of underrepresented racial and ethnic backgrounds endure worse COVID-19 outcomes compared to people who are white.

The study was just published in the Journal of General Internal Medicine and is one of the first papers to discuss which social and cultural factors, including non-English speaking, may or may not contribute to racial and ethnic health disparities related to COVID-19.

"For people of color, even in the highest socioeconomic status, our data shows they still have worse COVID-19 outcomes compared to people who are white," said Nicholas Ingraham, MD, a third-year fellow in the Department of Medicine at the U of M Medical School who led the study. "We also found that, independent of race, ethnicity and socioeconomic status, non-English speaking is also associated with worse clinical outcomes in COVID-19. It puts patients at higher risk of disease not only across racial and ethnic populations but also within those populations."

Using a data system developed over the last two years by the Minnesota Critical Care Outcomes and Research Effort (a multidisciplinary and national collaboration founded at the University of Minnesota), the team analyzed 5,577 de-identified patient records from the M Health Fairview system between March 4 and Aug. 19, 2020. A subset of these patients required hospitalization within 45 days of diagnosis, which were used in the study. Researchers evaluated socioeconomic status through a proxy by matching those patients' nine-digit ZIP codes to an area deprivation index - a measure that uses 17 different markers of socioeconomic status from the U.S. Census data, including levels of education, poverty and safe housing, to assess the severity of deprivation within neighborhoods.

"When doing this analysis, we did see that there are differences in COVID-19 severity by race and ethnicity, just as many other national studies have already shared," Ingraham said. "But then, we adjusted for socioeconomic status to test the hypothesis that racial and ethnic disparities stem from differences in socioeconomic factors. When we did that, the race signal should have gone away, and we should have seen socioeconomic status as the cause for higher risk of hospitalization for certain patients. We actually saw the opposite. Socioeconomic status was not associated with severe disease, and race continued to be significant."

The study team recognizes that many other factors, including job type, genetics, testing access and systemic racism, may all play a role in COVID-19 health disparities. To provide more insight, Ingraham plans to expand on the study to determine which of the 17 factors within the area deprivation index may make patients more vulnerable to the disease. The team will also partner with the U of M School of Public Health to link their patient data set to other social determinants of health like environmental pollution and food deserts.

"Seeing an increased risk of severe COVID-19 disease in people of color and non-English speaking, independent of other known risk factors, these populations should be considered high priority for the continued vaccination rollout," Ingraham said.

More than three quarters of Iran's land is under extreme groundwater overdraft, where the rate of human uptake is higher than the rate of natural recharge. This is according to a new study led by Concordia researchers published in the Nature journal Scientific Reports.

The article was co-authored by Samaneh Ashraf, a former Horizon postdoctoral researcher now at the Université de Montréal, and Ali Nazemi, an associate professor in the Department of Building, Civil and Environmental Engineering. Amir AghaKouchak of the University of California, Irvine, also contributed to the paper.

The researchers write that mismanagement by the country's authorities is exacerbating existing strains on the semi-arid country's aquifers by an inefficient agriculture industry. Without urgent action, they note, the country faces multiple national crises.

"The continuation of unsustainable groundwater management in Iran can lead to potentially irreversible impacts on land and the environment, threatening the country's water, food and socioeconomic security," Ashraf says.

The authors write that an estimated 74 km3 of groundwater has been depleted from the country's 500 basins and sub-basins between 2002 and 2015. This has contributed to both growing soil salinity and an increase in land subsidence -- basically, land sinking. Among the most at-risk regions of land subsidence is the Salt Lake Basin, which includes Iran's capital Tehran, home to some 15 million people and already at risk of severe seismic activity.

Human role is clear

The researchers used publicly available data published by the Iranian Ministry of Energy as the basis for the study.

"We wanted to quantify how much of Iran's groundwater was depleted," Nazemi explains. "Then we diagnosed why it was depleted. Was it driven by climate forces, by a lack of natural recharge or because of unsustainable withdrawal?"

After looking at all the data they had available, the researchers concluded that heavy agricultural demands were the overwhelming leading cause of groundwater depletion. The country's west, southwest and northeast, where farmers grow strategic crops like wheat and barley, experienced the most severe drops.

The paper notes that the number of registered wells that draw groundwater for agriculture has almost doubled in a decade and a half, from around 460,000 in 2002 to roughly 794,000 in 2015. Anthropogenic groundwater withdrawals decreased in 25 of the country's 30 basins during that same period. This suggests that the aquifers are being overexploited by human activity.

The researchers looked at soil electrical conductivity as a proxy for measuring salinity levels across the country and found that they were rising as well.

Urgent action required

Compounding all these problems are governments at the local and national levels that are not equipped to address the growing crisis for a variety of reasons, including international sanctions, local corruption and general mistrust of authorities among the population. But the authors say the country is in acute need of both short- and long-term solutions.

"In the short term, the unregistered wells need to be shut down," Nazemi says. "But longer term, Iran clearly needs an agricultural revolution. This requires a number of elements, including improving irrigation practices and adopting crop patterns that fit the country's environment."

While Iran is uniquely at risk due to its natural environment, growing population and ineffective governance, Nazemi warns that its experiences offer warnings to other countries, including Canada.

"Iran's example clearly shows that we need to be careful how we manage our water because one bad decision can have a huge domino effect. And if the problem is ignored, it will easily get out of control," he says. "It also illustrates the importance of environmental justice and stewardship. These are even more important when addressing the problem of climate change."

Medication-assisted treatment, or MAT, is an important tool in the ongoing fight against opioid use dependence in the United States. Employing certain medications in combination with counseling and behavioral therapy, MAT offers a comprehensive, "whole-patient" approach to addressing opioid use.

According to a new study from researchers at the UConn School of Social Work and the Connecticut Department of Mental Health and Addiction Services, Connecticut's MAT programs have higher-than-average patient retention rates - more people who enter Connecticut's programs stay in the program to completion.

But the study - recently published in the journal Substance Use and Misuse - also found that younger patients and patients who reported cocaine or crack use in addition to opioid dependence had a harder time sticking with the MAT treatment program than those who were older or those who might also be using other substances, which has implications for both program providers and policymakers as the country continues to grapple with the opioid epidemic.

"One of the things you look at when folks are coming into a program like this is what kinds of drugs they were using right before this started," says Michael Fendrich, a professor and associate dean for research at the School of Social Work who focuses on policies, services, interventions, and risk factors related to substance misuse and mental health and is the lead author of the new study. "A lot of programs are focused on one substance, but a lot of folks come in there not just using one substance."

The study looked at information about clients enrolled in four federally funded MAT programs in Connecticut over a three-year period, from December 2016 to August 2019, and included 423 clients that followed the same treatment model. In addition to medication, the programs included cognitive behavioral therapy and employed a recovery support coach - a person in recovery from opioid use disorder - as part of the treatment model.

Clients were considered to be "retained" if they were still receiving services from the program at the six-month interview or if they had a successful discharge before the six-month interview. The researchers found that, at six months, 58.9% of participants has been retained in the program. Most of these participants - 71% - were still receiving services. Others had completed services or had successful discharges at six-month follow-ups.

Prior use of other substances did not necessarily lead to lower retention - a finding that Fendrich says he found surprising. In particular, those who reported using benzodiazapines actually had a higher probability of success in the program.

"I don't have a solid reason for that," Fendrich says, "but we do know that benzodiazapine is a dangerous medication to be taken at the same time that you're taking opioid treatment medications, so there might have been a little bit more focus on making sure that those folks were using the treatment medication in the way they were supposed to be using it."

But reported cocaine or crack use was correlated with reduced retention, an area that Fendrich says merits greater study.

"Prior substance use is a complex issue," he says. "You can't just say, 'all prior drug use is going to decrease the chances for success.' But you need to look at what specific drugs are being used. And I would suggest that we just need some more follow up on that one."

Overall, rates of retention did not vary despite differences in location and in the demographics of the clients who sought treatment at the four sites.

"They were dealing with diverse clients, and they were pretty similar kinds of outcomes that they experienced," Fendrich says, "which speaks highly to the implementation of the program in the state."

Demographics, though, did influence success: older clients had higher retention rates than younger clients, suggesting that strategies specifically designed to support younger people who are struggling with opioid dependence are needed.

"I really think that the emerging adult, young adult, group is a group that's at risk for so many things, and I think we need to think about them in an even more focused way," Fendrich says. "As we emerge from the pandemic, this is a group that's struggling on many issues. It's a really difficult time, in terms of employment opportunities, in development - folks are not stabilized in their life - in relationships, and in just general direction in life. And so, it becomes harder when there's also substance dependence that's added into the picture."

While the role of peers employed as recovery support coaches in Connecticut's program was not specifically evaluated as part of the study, the researchers suggested their participation in the treatment model could contribute to Connecticut's higher retention rates. This hypothesis was supported by focus groups the researchers conducted with the program clients; many of the client comments were about the importance of peer support. While not unique to Connecticut, use of recovery support coaches in MAT programs is not universal, Fendrich says.

Programs need to think about the potential unique needs of people coming into the program, he notes, and look comprehensively at supports they might need to be successful.

"It's never just one thing," Fendrich says. "You know, people are complicated. And there is an opioid crisis, but folks who are who are dependent on opioids have lots of other problems. Some are addiction-related, and some are more in what I call the 'psychosocial adjustment realm,' but they all need attention. I think we've been good at attending to those in our programs in Connecticut, and it's a real feather in our cap."

He continues, "We have great programs here in the state, and we'll hopefully continue to build on the success that we've seen in our programs so far. But policy-wise, we need to be comprehensive in our approach to treatment for people who are coming into programs with opioid dependence."

Classic computers use binary values (0/1) to perform. By contrast, our brain cells can use more values to operate, making them more energy-efficient than computers. This is why scientists are interested in neuromorphic (brain-like) computing. Physicists from the University of Groningen (the Netherlands) have used a complex oxide to create elements comparable to the neurons and synapses in the brain using spins, a magnetic property of electrons. Their results were published on 18 May in the journal Frontiers in Nanotechnology.

Although computers can do straightforward calculations much faster than humans, our brains outperform silicon machines in tasks like object recognition. Furthermore, our brain uses less energy than computers. Part of this can be explained by the way our brain operates: whereas a computer uses a binary system (with values 0 or 1), brain cells can provide more analogue signals with a range of values.

Thin films

The operation of our brains can be simulated in computers, but the basic architecture still relies on a binary system. That is why scientist look for ways to expand this, creating hardware that is more brain-like, but will also interface with normal computers. 'One idea is to create magnetic bits that can have intermediate states', says Tamalika Banerjee, Professor of Spintronics of Functional Materials at the Zernike Institute for Advanced Materials, University of Groningen. She works on spintronics, which uses a magnetic property of electrons called 'spin' to transport, manipulate and store information.

In this study, her PhD student Anouk Goossens, first author of the paper, created thin films of a ferromagnetic metal (strontium-ruthenate oxide, SRO) grown on a substrate of strontium titanate oxide. The resulting thin film contained magnetic domains that were perpendicular to the plane of the film. 'These can be switched more efficiently than in-plane magnetic domains', explains Goossens. By adapting the growth conditions, it is possible to control the crystal orientation in the SRO. Previously, out-of-plane magnetic domains have been made using other techniques, but these typically require complex layer structures.

Magnetic anisotropy

The magnetic domains can be switched using a current through a platinum electrode on top of the SRO. Goossens: 'When the magnetic domains are oriented perfectly perpendicular to the film, this switching is deterministic: the entire domain will switch.' However, when the magnetic domains are slightly tilted, the response is probabilistic: not all the domains are the same, and intermediate values occur when only part of the crystals in the domain have switched.

By choosing variants of the substrate on which the SRO is grown, the scientists can control its magnetic anisotropy. This allows them to produce two different spintronic devices. 'This magnetic anisotropy is exactly what we wanted', says Goossens. 'Probabilistic switching compares to how neurons function, while the deterministic switching is more like a synapse.'

The scientists expect that in the future, brain-like computer hardware can be created by combining these different domains in a spintronic device that can be connected to standard silicon-based circuits. Furthermore, probabilistic switching would also allow for stochastic computing, a promising technology which represents continuous values by streams of random bits. Banerjee: 'We have found a way to control intermediate states, not just for memory but also for computing.'

Alzheimer's disease shares some key similarities with healthy aging, according to a new mathematical model described today in eLife.

The model provides unique insights into the multiscale biological alterations in the elderly and neurodegenerative brain, with important implications for identifying future treatment targets for Alzheimer's disease.

Researchers developed their mathematical model using a range of biological data - from 'microscopic' information using gene activity to 'macroscopic' information about the brain's burden of toxic proteins (tau and amyloid), its neuronal function, cerebrovascular flow, metabolism and tissue structure from molecular PET and MRI scans.

"In both aging and disease research, most studies incorporate brain measurements at either micro or macroscopic scale, failing to detect the direct causal relationships between several biological factors at multiple spatial resolutions," explains first author Quadri Adewale, a PhD candidate at the Department of Neurology and Neurosurgery, McGill University, Canada. "We wanted to combine whole-brain gene activity measurements with clinical scan data in a comprehensive and personalised model, which we then validated in healthy aging and Alzheimer's disease."

The study involved 460 people who had at least four different types of brain scan at four different time points as part of the Alzheimer's Disease Neuroimaging Initiative cohort. Among the 460 participants, 151 were clinically identified as asymptomatic or healthy control (HC), 161 with early mild cognitive impairment (EMCI), 113 with late mild cognitive impairment (LMCI) and 35 with probable Alzheimer's disease (AD).

Data from these multimodal scans was combined with data on gene activity from the Allen Human Brain Atlas, which provides detail on whole-brain gene expression for 20,267 genes. The brain was then split into 138 different gray matter regions for the purposes of combining the gene data with the structural and functional data from the scans.

The team then explored causal relationships between the spatial genetic patterns and information from their scans, and cross-referenced this to age-related changes in cognitive function. They found that the ability of the model to predict the extent of decline in cognitive function was highest for Alzheimer's disease, followed in order by the less pronounced decline in cognition (LCMI, ECMI) and finally the healthy controls. This shows that the model can reproduce the individual multifactorial changes in the brain's accumulation of toxic proteins, neuronal function and tissue structure seen over time in the clinical scans.

Next, the team used the model to look for genes that cause cognitive decline over time during the normal process of healthy aging, using a subset of healthy control participants who remained clinically stable for nearly eight years. Cognitive changes included memory and executive functions such as flexible thinking. They found eight genes which contributed to the imaging dynamics seen in the scans and corresponded with cognitive changes in healthy individuals. Of note, the genes that changed in healthy aging are also known to affect two important proteins in the development of Alzheimer's disease, called tau and amyloid beta.

Next, they ran a similar analysis looking for genes that drive the progression of Alzheimer's disease. Here, they identified 111 genes that were linked with the scan data and with associated cognitive changes in Alzheimer's disease.

Finally, they studied the functions of the 111 genes identified, and found that they belonged to 65 different biological processes - with most of them commonly linked to neurodegeneration and cognitive decline.

"Our study provides unprecedented insight into the multiscale interactions among aging and Alzheimer's disease-associated biological factors and the possible mechanistic roles of the identified genes," concludes senior author Yasser Iturria-Medina, Assistant Professor at the Department of Neurology and Neurosurgery at McGill University. "We've shown that Alzheimer's disease and healthy aging share complex biological mechanisms, even though Alzheimer's disease is a separate entity with considerably more altered molecular and macroscopic pathways. This personalised model offers novel insights into the multiscale alterations in the elderly brain, with important implications for identifying targets for future treatments for Alzheimer's disease progression."

A global effort to reduce sulfur and greenhouse gas (GHG) emissions from ships has researchers from the National Renewable Energy Laboratory (NREL) and other Department of Energy facilities investigating the potential use of marine biofuels.

"Biofuels turned out to be very good options because they have zero or very, very low sulfur compared to fossil fuels," said Eric Tan, a senior research engineer at NREL and lead author of a new article published in the journal Environmental Science and Technology.

His co-authors of "Biofuel Options for Marine Applications: Techno-Economic and Life-Cycle Analyses" are Ling Tao, also from NREL, along with scientists with Argonne National Laboratory, Pacific Northwest National Laboratory, and the U.S. Department of Transportation's Maritime Administration.

The International Marine Organization (IMO) has been ratcheting down the allowed amount of sulfur oxides emissions from ships since 2005. The newest upper limit, which took effect at the start of 2020, reduced the sulfur content of ships' fuel oil to 0.5% from 3.5%. IMO said the reduction should have major benefits for the environment and the health of people, particularly those living near ports and along coasts. Additionally, IMO has set aggressive targets to decarbonize marine shipping, targeting at least a 50% reduction in GHG emissions from international shipping by 2050, relative to 2008 levels.

The new regulation, which is enforced by individual countries, requires changes to bring ships into compliance. Ship owners can either install sulfur scrubbers to reduce emissions, or they can adopt a different, low-sulfur fuel. Both options carry an additional cost.

The NREL-directed research provides a starting point for establishing the feasibility of ships using biofuels. Fueling costs already account for a significant part of running a shipping line, so the researchers examined both prices and emissions.

The economics are weighed against the cost of burning heavy fuel oil (HFO), which accounts for about three-quarters of the fuel used by ships. A low-sulfur HFO costs slightly more a gallon than traditional HFO. The low-sulfur HFO prices would be the maximum ship owners are willing to pay for biofuels for a one-to-one replacement. The biofuels are considered to be potential drop-in fuels compatible for use in marine engines, but further work is needed to confirm that compatibility.

Upon examining different types of fuels for their ability to reduce emissions of greenhouse gases and air pollutants, the researchers found biofuels produced entirely from biomass offer much higher reductions in life-cycle greenhouse gas emissions--from 67% to 93% less than HFO. Biomass-derived fuels also are mostly free of sulfur and exhibit reductions in criteria air pollutant emissions such as particulate matter.

Tan's research concluded that, if shipping had no competition, the United States has a large supply of bio-feedstocks for producing substantial amounts of marine biofuels to displace fossil fuels. With ships using 400 million metric tons of fuel annually, a blend of 5% biofuels translates to about 5 billion gallons.

The research was funded by the U.S. Department of Energy's Bioenergy Technologies Office and by the U.S. Department of Transportation Maritime Administration.

NREL is the U.S. Department of Energy's primary national laboratory for renewable energy and energy efficiency research and development. NREL is operated for the Energy Department by the Alliance for Sustainable Energy, LLC.

NEW YORK, NY (May 18, 2021) - An expert panel convened by the Alzheimer's Drug Discovery Foundation (ADDF) and The Association for Frontotemporal Degeneration (AFTD) provides guidance on best practices for the design of early drug trials for Alzheimer's disease, frontotemporal degeneration (FTD), and other neurodegenerative dementias. Their guidance was published in the May 18, 2021 issue of Neurology®, the medical journal of the American Academy of Neurology ("Value-Generating Exploratory Trials in Neurodegenerative Dementias").

These efficiencies in clinical trials can help to achieve proof of concept more rapidly and at lower costs. The estimated cost of developing an Alzheimer's drug is eight times more than a cancer drug and takes nearly twice as long to develop. The panel, which comprised clinicians, researchers, and statisticians from academia, biotech, and pharmaceutical companies, as well as ADDF and AFTD scientific staff, focused on early phase 1 and 2 exploratory trials, which assess a drug's safety and pharmacologic effects on patients. Exploratory studies with optimized study designs can terminate programs not likely to succeed and efficiently move promising programs through the clinical trial process. Later phase 2 and phase 3 trials measure clinical outcomes such as memory and ability to perform daily functions.

"The majority of clinical development costs come from later stage phase 2b and phase 3 studies, which require long treatment periods and a large number of patients to detect meaningful changes in cognitive, behavioral, and functional endpoints," said Howard Fillit, M.D., ADDF founding executive director and chief science officer. "Results from exploratory phase 2a trials are the critical inflection point when researchers decide which drugs to move into these larger and more expensive trials, so clearly these phase 2a trials need to be as rigorous and well-designed as possible."

Panel makes four key recommendations for exploratory trial study designs

By adopting best practices in designing exploratory trials, researchers and companies can be more confident in using their results to make the all-important go/no-go decisions about advancing drugs to larger later-stage trials. The four key panel recommendations are to:

1. Employ rigorous statistical analyses and procedures, engaging statisticians in trial design as early as possible.

2. Incorporate the appropriate biomarker and clinical endpoints that reflect the drug's mechanism of action and the specific study population.

3. Leverage historical data to determine appropriate outcome measures that are well-aligned with the disease and mechanism of action for the treatment.

4. Consider novel clinical development plans to increase efficiency in moving a drug candidate into larger clinical trials or determining that it is ineffective as quickly as possible; avoid "cookie cutter" trial designs that are not optimized or tailored.

"These four recommendations can lead to more efficient trials, with substantial financial savings, as well as more strategic and effective engagement of patients," said AFTD CEO Susan L-J Dickinson. "The latter is a key concern for a rare disease like FTD where the low number of patients pushes the need for strategic study design, with patients enrolled only in studies that will provide a clear and accurate readout of therapeutic efficacy."

"We clearly need exploratory trials to be rigorous and efficient," said Dr. Fillit. "But this is about working toward the ultimate success--effective treatment strategies, which will likely be a combination drug approach that hits several of the biological pathways involved in the neurodegenerative process of dementia. That means being able to take multiple shots on goal--testing a wide variety of plausible drug candidates to identify the most promising ones."