Culture

While most people dying from COVID-19 are elderly, up to 5 to 10 percent of younger adults and children can also be seriously infected by the SARS-CoV-2 virus. Researcher from all over the world have tried to determine why some people become very ill and others are barely affected with COVID-19.

Researchers from the University of Bergen and their French colleagues are getting closer to an answer.

"We found that persons with serious COVID-19 disease have antibodies that are blocking so-called interferons, which are an important part of the body´s defence mechanism," says Professor Eystein Husebye at the Department of Clinical Science, University of Bergen (UiB).

Enable possible treatment

Husebye was involved in this study because he has had long experience with patients suffering from the immune disease APS1. APS1 is a serious, but rare, immune disease. Patients with APS1 have a high concentration of antibodies against interferones.

If these patients then become infected with COVID-19, their bodies will work against their own immune systems. In addition, this response has also been seen in patients with milder immune diseases.

"It is relatively easy to see if young people with COVID-19 have these antibodies in their blood. If so, it might be possible to supply them with extra interferons as treatment," Husebye says.

May explain gender differences

The UiB-discoveries support other mysterious findings relating to COVID-19.

"Deaths and severe COVID-19 are more frequent among men than women. Our study has shown that men have more of these antibodies," Husebye says.

Even if it is easy to use blood tests to discover antibodies against interferons, Husebye does not recommend massive screening in healthy people. Most people with APS1 are diagnosed in their childhood, and most people with immune failure have been diagnosed already.

"Immune failure is just a piece in the puzzle when it comes to understand why young people may die of COVID-19. Old people generally die of more complex causes," says Eystein Husebye.

Tsukuba, Japan - End-of-life discussions, considered an essential part of high-quality end-of-life care for patients with life-threatening illnesses, make it easier to provide treatment and care that satisfy the patient's wishes. They also contribute to reducing depression and complicated grief among bereaved family members. In countries with increasing numbers of older people, such as Japan, there's a strong need to find how to have these discussions and how to make them effective.

A new study centered at Japan's University of Tsukuba found an important connection between the experience of caring for a loved one and the likelihood of having end-of-life discussions. Also, while experiencing someone's death may seem like another factor that would encourage these discussions, the study did not find such a connection. The findings were published in the Journal of Pain and Symptom Management.

"Compared with in Western nations, research has found people in Japan are less likely to engage in end-of-life discussions," study co-author Professor Takehiro Sugiyama says. "We wanted to find what factors relate to having these discussions, and what sort of people do and don't have them."

The research divided respondents into two groups based on their experience having end-of-life discussions: those who had engaged in such discussions and those who had not. The main predictors were the experiences of the death of and care for a loved one.

This appears to be the first study to clarify the association between the experience of caring for a loved one and the history of having engaged in one's own end-of-life discussions. The team used a nationwide survey to gather data on nearly 1,000 men and women, young and old. Then they further looked at where these experiences took place, along with possibly related factors, such as people's age, sex, and family makeup.

They found a clear connection between the experience of caring for a loved one and end-of-life discussions, irrespective of the caregiver's age. However, they found that experiencing a loved one's death was not associated with these discussions. They also found that men, both those under 65 and those aged 65 and older, were less likely to have such discussions.

The findings additionally revealed potential factors associated with being less likely to have end-of-life discussions: younger age and not having a family doctor. This means health-care providers may need to highlight the need for further education to promote the importance of end-of-life discussions, especially for younger people and for men.

"Caregiving involves factors such as managing a loved one's medication, supporting them, and advocating for them," first author Kyoko Hanari says. "These factors may motivate people to initiate end-of-life discussions. That and our other findings are a useful base to build on, seeing the beneficial impacts of these discussions."

Especially in aging societies, end-of-life discussions are increasingly needed. Researchers now need to dig deeper into the relation with caregiving and other factors, find how to motivate such discussions, and examine what they should include.

(Vienna, 14 October 2020) Numerous scientific studies indicate that inflammatory processes play a key role in the development of psychiatric disorders. One of the areas of particular interest is the interleukin 6/STAT3 signal transduction pathway, which is associated with depression, schizophrenia, and bipolar disorder. In a study published in leading journal Molecular Psychiatry, MedUni Vienna researchers led by Daniela Pollak from the Division of Neurophysiology and Neuropharmacology showed that STAT3 plays an important role in the serotonergic system as a molecular mediator for controlling emotional reactivity, thereby establishing a mechanistic link between the immune system, serotonergic transmission and affective disorders such as depression.

The STAT3 signal transduction pathway is activated in response to a series of immunogenic and non-immunogenic stimuli, i.e. those that can and those that cannot trigger an immune response. "It was found that STAT3 is involved in nervous system functions that are important for controlling behaviour in physiological and pathological situations. In an earlier study, we had managed to show that STAT3 also regulates the expression of the serotonin transporter gene (Note: SERT)," explains Pollak.

Changes in serotonergic transmission, that is to say the transmission of information from one neuron to another using serotonin as a messenger substance, correlate closely with pathological changes in depression or other affective disorders. However, the interaction between the STAT3 signal transduction pathway and the neuronal information flow in the brain and its importance in regulating emotional behaviour has not yet been explored.

STAT3 deficiency reduces emotional reactivity

The published work therefore specifically investigated the significance of the STAT3
signal transduction pathway in the serotonergic system of the midbrain - an emotional regulation centre - by targeted inhibition of STAT3 in a mouse model. Says Pollak: "Where STAT3 was selectively absent from the serotonergic system of the midbrain, the mice displayed reduced, negative emotional reactivity in their behaviour and a diminished response to the effects of amphetamine in the brain. These effects could be detected in mice with reduced STAT3 expression both in a genetic and in a viral model, so that it was possible to rule out developmental changes and to show that an acute manipulation of STAT3 in the adult organism impacts on emotional behaviour."

In animals lacking in STAT3, there was also found to be a change in the neuronal activity of serotonergic cells of the midbrain. Changes in molecular networks that are significant in neuropsychiatric illnesses were also found on the level of gene expression. "The results of our study indicate that STAT3 plays an important role as a molecular mediator in the serotonergic system for controlling emotional reactivity, thereby establishing a mechanistic link between the immune system, serotonergic transmission and affective disorders."

Service: Molecular Psychiatry

"STAT3 in the raphe nuclei gates behavioural reactivity and regulates gene networks associated with neuropsychiatric disorders". Sonali N. Reisinger, Spyridon Sideromenos, Orsolya Horvath, Sophia Derdak, Ana Cicvaric, Francisco Monje, Martin Bilban, Martin Häring, and Micaela Glat and Daniela D. Pollak.

https://www.nature.com/articles/s41380-020-00904-2.

Fanconi anaemia (FA) is a genetic disease affecting small children characterized by bone-marrow failure, developmental abnormalities and predisposition to multiple forms of cancer. The molecular mechanisms behind FA are inherited mutations in genes encoding for DNA repair proteins, leading to irreversible bone marrow failure. The exact mechanisms how these genetic mutations lead to the exhaustion of stem cells from the bone marrow has been unknown.

Now, the researchers have identified a cause for this failure. The findings were published in the distinguished Cell Stem Cell journal.

"The results open new paths for developing novel therapies for the disease, for which the only curative treatment currently available is stem cell transplantation. Understanding the mechanism of bone marrow failure better can help to plan stem cell transplantations and to develop new therapies for milder forms of Fanconi anaemia," says Anniina Färkkilä, docent and clinical researcher at the University of Helsinki.

Expression of the MYC gene resulted in permanent bone marrow failure

In the study, researchers at the University of Helsinki analysed the gene expression of individual cells, and found, to their surprise, overexpression of the MYC gene in the bone marrow stem cells of patients with Fanconi anaemia. MYC is one of the best-known genes regulating the formation of malignant tumours.

Functional experiments demonstrated that MYC overexpression resulted in the division of stem cells and their detachment from the bone marrow.

"The overexpression of the MYC gene was caused by inflammation mediators, and it led to an abnormal presence of stem cells in the circulation of patients suffering from Fanconi anaemia. In mouse experiments, a MYC inhibitor reduced stem cell detachment, but at the same time it also reduced cell proliferation," Färkkilä notes.

This suggested that MYC, upregulated in the stem cells due to the inflammatory stress signals, was required for the survival of the stem cells, but as a side effect led to the detachment from the bone marrow niche, and the development of bone marrow failure in FA patients.

Identifying the mechanism associated with bone marrow failure helps to develop biomarkers also for premalignant states in patients with Fanconi anaemia.

"The DNA repair genes defective in FA often result in the development of a number of cancers, which also makes the findings potentially significant in relation to other cancer types, such as ovarian cancer," Färkkilä says.

A new study from the University of Eastern Finland shows that a bettor likely stays away from betting for a 27% longer time after a losing day than after a day on which they won or broke even. The study looked at how losing or winning on the previous betting day predicts how long it takes from a bettor to return to the next session of online horse race betting. The study also found that high wins or losses on the previous betting day do not predict the timing of the next betting session.

"A typical online horse race bettor seems to modify their betting behaviour according to how successful their previous betting day was. Earlier studies have found that bettors tend to reduce their stakes after a losing day. We were now able to show that a typical bettor also stays away from betting for a longer time after losing," Early Stage Researcher Tuomo Kainulainen from the University of Eastern Finland says.

Published in Journal of Gambling Studies, the study used individual-level gambling account data. The researchers analysed the betting behaviour of more than 9,000 individuals in Finland who placed bets on the Finnish horse race betting operator Fintoto's online betting platform in August 2012.

No differences in the betting behaviour of women and men after a losing day

A typical online horse race bettor in Finland is a 51-year-old male who lives in an urban area and places a bet approximately every four days. The average betting volume per day was 43 euros (roughly 50 US dollars) and the average net loss per day was 12 euros (roughly 14 US dollars).

The study also examined whether different groups of bettors identified in the data had a different reaction to a losing day. The researchers analysed the association of individual characteristics, such as age and gender, with the next betting session after a losing day. They found that after a losing day, inexperienced bettors are likely to stay away from betting for a longer time than experienced ones.

"Despite women engaging in online horse race betting less frequently than men, we find no difference in how these two groups modify their behaviour after a losing day," Kainulainen points out.

The researchers found some differences in how different groups of bettors reacted to a losing day, but these differences were very small. The study suggests that all bettors, regardless of their individual characteristics, are likely to stay away from betting for longer after a losing day.

Scientists from Nanyang Technological University, Singapore (NTU Singapore) have modelled the cradle-to-grave environmental impact of using different types of shopping bags and report that in cities like Singapore, single-use plastic bags (made from high-density polyethylene plastic) have a lower environmental footprint than single-use paper and multi-use cotton bags.

Reusable plastic bags made from polypropylene non-woven plastic were the most eco-friendly option, followed by single-use plastic bags.

The model revealed that cotton and kraft paper bags have relatively bigger environmental footprints due to their greater contribution to global warming and eco-toxicity potential in their production.

However, the NTU team stressed that their model applied specifically to Singapore and might be applicable in cities such as Tokyo, Hong Kong, and Dubai. Reusable and single-use plastic bags would be a comparatively better environmental option only in these cities, due to the model's focus on densely populated metropolitan areas that have waste management structures with similar end-of-life incineration facilities.

The findings were published in the scientific Journal of Cleaner Production in August 2020.

Assistant Professor Grzegorz Lisak, Director of Residues & Resource Reclamation Centre at the Nanyang Environment and Water Institute (NEWRI), who led the research, said: "Our main message is that re-usable plastic bags are the best option, provided that they are re-used many times - over 50 times to be precise. However, one surprising conclusion is that, in our model, in a single-use case, plastic bags, if treated properly afterwards, are less environmentally detrimental than the other types of bags in this study."

"It is essential to evaluate the implications case by case for dealing with plastic waste. In a well-structured closed metropolitan waste management system with incineration treatment, using plastic bags may be the best option that is currently available, provided that there is no significant leakage of waste into the environment."

To reach their conclusions, the team carried out a life cycle analysis of five types of bags to evaluate the environmental impacts associated with their production, distribution, transportation, waste collection, treatment, and end-of-life disposal.

The research team found that the global warming potential of a single-use kraft paper bag was the highest, over 80 times that of reusable plastic bags. Single-use plastic and reusable cotton bags (reused 50 times) were calculated to have over ten times the global warming potential of reusable plastic bags (reused 50 times).

To offset the emission equivalent to equal that of the creation of one single-use plastic bag, a reusable plastic bag would need to be reused four times.

The team also observed that the relative negative environmental impacts of cotton and kraft paper bags in the model are due to their production processes that consume immense amounts of water and natural resources. Hence, improving the production methods, optimizing resource usage, and following sustainable practices could in future favour the usage of bags made from cotton and paper.

Relevance to cities and their waste reduction goals

In the case of Singapore, the team recommends the usage of reusable plastic bags to the greatest extent possible to reduce consumption of single-use plastic bags. Reprocessing single-use plastic bags would be a good policy goal to cut down on their environmental impact.

Asst Prof Lisak said that based on 2018 statistics in Singapore, reducing the single-use plastic grocery bag consumption by half could prevent over 10 million kg-CO2 equivalent emissions in a year.

Moving forward, the team will be embarking on further studies connected to plastic waste management, waste plastic upgrading and the development of new products

Artificial intelligence has arrived in our everyday lives--from search engines to self-driving cars. This has to do with the enormous computing power that has become available in recent years. But new results from AI research now show that simpler, smaller neural networks can be used to solve certain tasks even better, more efficiently, and more reliably than ever before.

An international research team from TU Wien (Vienna), IST Austria and MIT (USA) has developed a new artificial intelligence system based on the brains of tiny animals, such as threadworms. This novel AI-system can control a vehicle with just a few artificial neurons. The team says that the system has decisive advantages over previous deep learning models: It copes much better with noisy input, and, because of its simplicity, its mode of operation can be explained in detail. It does not have to be regarded as a complex "black box", but it can be understood by humans. This new deep learning model has now been published in the journal Nature Machine Intelligence.

Learning from nature

Similar to living brains, artificial neural networks consist of many individual cells. When a cell is active, it sends a signal to other cells. All signals received by the next cell are combined to decide whether this cell will become active as well. The way in which one cell influences the activity of the next determines the behavior of the system--these parameters are adjusted in an automatic learning process until the neural network can solve a specific task.

"For years, we have been investigating what we can learn from nature to improve deep learning," says Prof. Radu Grosu, head of the research group "Cyber-Physical Systems" at TU Wien. "The nematode C. elegans, for example, lives its life with an amazingly small number of neurons, and still shows interesting behavioral patterns. This is due to the efficient and harmonious way the nematode's nervous system processes information."

"Nature shows us that there is still lots of room for improvement," says Prof. Daniela Rus, director of MIT's Computer Science and Artificial Intelligence Laboratory (CSAIL). "Therefore, our goal was to massively reduce complexity and enhance interpretability of neural network models."

"Inspired by nature, we developed new mathematical models of neurons and synapses," says Prof. Thomas Henzinger, president of IST Austria.

"The processing of the signals within the individual cells follows different mathematical principles than previous deep learning models," says Dr. Ramin Hasani, postdoctoral associate at the Institute of Computer Engineering, TU Wien and MIT CSAIL. "Also, our networks are highly sparse--this means that not every cell is connected to every other cell. This also makes the network simpler."

Autonomous Lane Keeping

To test the new ideas, the team chose a particularly important test task: self-driving cars staying in their lane. The neural network receives camera images of the road as input and is to decide automatically whether to steer to the right or left.

"Today, deep learning models with many millions of parameters are often used for learning complex tasks such as autonomous driving," says Mathias Lechner, TU Wien alumnus and PhD student at IST Austria. "However, our new approach enables us to reduce the size of the networks by two orders of magnitude. Our systems only use 75,000 trainable parameters."

Alexander Amini, PhD student at MIT CSAIL explains that the new system consists of two parts: The camera input is first processed by a so-called convolutional neural network, which only perceives the visual data to extract structural features from incoming pixels. This network decides which parts of the camera image are interesting and important, and then passes signals to the crucial part of the network - a "control system" that then steers the vehicle.

Both subsystems are stacked together and are trained simultaneously. Many hours of traffic videos of human driving in the greater Boston area were collected, and are fed into the network, together with information on how to steer the car in any given situation--until the system has learned to automatically connect images with the appropriate steering direction and can independently handle new situations.

The control part of the system (called neural circuit policy, or NCP), which translates the data from the perception module into a steering command, only consists of 19 neurons. Mathias Lechner explains that NCPs are up to 3 orders of magnitude smaller than what would have been possible with previous state-of-the-art models.

Causality and Interpretability

The new deep learning model was tested on a real autonomous vehicle. "Our model allows us to investigate what the network focuses its attention on while driving. Our networks focus on very specific parts of the camera picture: The curbside and the horizon. This behavior is highly desirable, and it is unique among artificial intelligence systems," says Ramin Hasani. "Moreover, we saw that the role of every single cell at any driving decision can be identified. We can understand the function of individual cells and their behavior. Achieving this degree of interpretability is impossible for larger deep learning models."

Robustness

"To test how robust NCPs are compared to previous deep learning models, we perturbed the input images and evaluated how well the agents can deal with the noise," says Mathias Lechner. "While this became an insurmountable problem for other deep neural networks, our NCPs demonstrated strong resistance to input artifacts. This attribute is a direct consequence of the novel neural model and the architecture."

"Interpretability and robustness are the two major advantages of our new model," says Ramin Hasani. "But there is more: Using our new methods, we can also reduce training time and the possibility to implement AI in relatively simple systems. Our NCPs enable imitation learning in a wide range of possible applications, from automated work in warehouses to robot locomotion. The new findings open up important new perspectives for the AI community: The principles of computation in biological nervous systems can become a great resource for creating high-performance interpretable AI--as an alternative to the black-box machine learning systems we have used so far."

Around 15% of Parkinson's disease cases are related to a known genetic background, out of which mutations in the Parkin and PINK1 genes are among the most frequent ones. Thus, revealing cellular mechanisms which are altered by these mutations is crucial for the development of new therapeutic approaches. In this study, the researchers analysed the blood serum of 245 participants from two independent cohorts and showed that patients carrying mutations in the Parkin or PINK1 genes have an increased level of circulating mitochondrial DNA and interleukin 6 (IL6).

These results indicate that deficiency in Parkin or PINK1 proteins - caused by a mutation on the corresponding gene - leads to impaired mitophagy. This dysfunction at the mitochondria level causes the release of mitochondrial DNA, thereby triggering inflammation and the elevation of interleukin 6 levels in the blood. When reaching the brain, IL6 is then thought to play a role in neurodegeneration. "Our study suggests that treatment with anti-inflammatory drugs holds the potential to alleviate the course of Parkinson's disease - at least for patients with mutations in the Parkin or PINK1 gene," explains Prof. Anne Grünewald, head of the Molecular and Functional Neurobiology group at the LCSB and one of the two senior authors of the study.

By studying the difference between patients carrying the Parkin or PINK1 mutation either on one (heterozygous) or both chromosomes, the researchers also showed that monitoring the level of systemic inflammation in the blood might be used as a biomarker for these genetic forms of Parkinson's disease. Whereas patients with mutations in both chromosomes showed elevated levels of interleukin 6 compared to heterozygous patients, the latter still displayed a significant increase compared to healthy controls. "This tells us that heterozygous mutations also constitute a strong risk factor for the onset of Parkinson's disease," explains Prof. Grünewald. "Even before the disease has broken out in these heterozygous carriers, we might be able to detect it at an early stage by monitoring IL6 in the serum." Similarly, the study showed that the level of circulating mitochondrial DNA could serve as a marker of the progression of the disease for heterozygous Parkin/PINK1 mutation carriers.

Prof. Grünewald concludes: "Our findings have a high value for potential clinical applications, be it biomarkers in the patient's serum that detect the state of the disease or new therapeutic approaches targeting the innate immune response in Parkin/PINK1-associated Parkinson's disease."

Wednesday, 14 October 2020: Scientists have developed, for the first time, a score that can accurately predict which patients will develop a severe form of Covid-19.

The study, led by researchers at RCSI University of Medicine and Health Sciences, is published in The Lancet's translational research journal EBioMedicine.

The measurement, called the Dublin-Boston score, is designed to enable clinicians to make more informed decisions when identifying patients who may benefit from therapies, such as steroids, and admission to intensive care units.

Until this study, no Covid-19-specific prognostic scores were available to guide clinical decision-making. The Dublin-Boston score can now accurately predict how severe the infection will be on day seven after measuring the patient's blood for the first four days.

The blood test works by measuring the levels of two molecules that send messages to the body's immune system and control inflammation. One of these molecules, interleukin (IL)-6, is pro-inflammatory, and a different one, called IL-10, is anti-inflammatory. The levels of both are altered in severe Covid-19 patients.

Based on the changes in the ratio of these two molecules over time, the researchers developed a point system where each 1-point increase was associated with a 5.6 times increased odds for a more severe outcome.

"The Dublin-Boston score is easily calculated and can be applied to all hospitalised Covid-19 patients," said RCSI Professor of Medicine Gerry McElvaney, the study's senior author and a consultant in Beaumont Hospital.

"More informed prognosis could help determine when to escalate or de-escalate care, a key component of the efficient allocation of resources during the current pandemic. The score may also have a role in evaluating whether new therapies designed to decrease inflammation in Covid-19 actually provide benefit."

The Dublin-Boston score uses the ratio of IL-6 to IL-10 because it significantly outperformed measuring the change in IL-6 alone.

Despite high levels in blood, using only IL-6 measurements as a Covid-19 prognostic tool is hindered by several factors. IL-6 levels within the same patient vary over the course of any given day, and the magnitude of the IL-6 response to infection varies between different patients.

Countries that sign up to improved financial transparency over oil, gas, and mining revenues benefit from significant reductions in carbon emissions, a new study by the University of Sussex Business School reveals.

Members of the Extractive Industries Transparency Initiative (EITI) have seen their carbon emissions reduce by 13% on average between 2000 and 2014 while the world average carbon footprint per capita grew by 23% over the same period, reveals the research from the Sussex Energy Group.

Study author Professor Benjamin K Sovacool said while the relationship between EITI membership and carbon reductions is not necessarily deterministic, the scheme allowed countries to use recovered funds no longer lost to corruption to invest in more sustainable forms of energy and other environmental practices.

More than half of countries signing up to EITI have used it to address environmental payments, highlight environmental policies, and promote better natural resource and environmental management.

Prof Sovacool, Professor of Energy Policy at the University of Sussex Business School, said: "The EITI has induced changes throughout the industry without the need for more standard tools or approaches such as carbon permits, environmental standards, timetables, and mandates.

"The initiative challenges property rights concerning information about oil, gas, and minerals; prior to its creation, data on revenues was not in the public domain. Putting it there has focused attention on companies, generated press stories, sparked dialogue with local communities, and given investors and regulators ways to measure relative performance."

The study compared the performance of the first 12 countries to attain EITI Candidacy Status against the median of 218 countries between 2000 and the most recent data available in 2020 on social, economic, and political metrics using a unique World Bank dataset.

The study found that EITI countries performed better than the global average on benchmarks related to regulatory quality, rule of law, control of corruption, foreign direct investment, and interest rates.

Researchers found correlations between EITI membership and considerable growth in energy infrastructure investment and declines in rates of extreme poverty.

While the world saw a significant deterioration in regulatory quality over the past two decades of almost 50%, EITI countries slipped by only 4%. Similarly in terms of rule of law, most countries saw a median decline in performance of 60%, but EITI countries dropped by only 5%.

However EITI countries did not see universal improvement against the world average on all metrics. They performed worse in terms of voice and accountability, political stability and violence, governmental effectiveness, energy investment, and poverty gap.

EITI countries saw a 235 % decline in political stability while globally this improved by more than 11%. Countries on average enjoyed a 226% increase in private sector investment in energy, EITI countries just 30%.

Prof Sovacool believes the EITI's limited impact on economic governance is in part due to the scheme's narrow view of transparency, covering only a minor fraction of public sector revenues and excluding wider dimensions of the sector, such as environmental impact assessments, project siting, or community relocation, are not covered.

The EITI also only focuses on government oil revenue and not government spending, where the corruption is often far worse, the study author said.

The EITI is also flawed because of its voluntary approach which means countries are not legally mandated to adhere to the principles of transparency and face no fines, criminal charges, or other sanctions for noncompliance, Prof Sovacool explained.

He added: "The EITI is an important and necessary ingredient of a dish for sustainable development in natural resource dependent countries, but it is far from a complete diet. While it may enhance economic governance and foreign direct investment, EITI membership does not lead to increased stability, reduced poverty or improved democracy.

"But our findings do suggest that, when left to their own devices, corporations and governments in resource rich countries need not always race to the bottom to lower standards and perpetuate the resource curse."

Human impacts on the Lower Lakes of the Murray River estuary have made its ecosystem more vulnerable to drought, according to findings by University of Sydney geoscientists.

The new science shows that since the construction of the Goolwa Barrages in 1940, which effectively cut the estuarine ecosystem off from the ocean, the risk of acidification of its waters has increased.

Researchers led by Dr Thomas Job from the School of Geosciences said their findings need to be taken into account when setting environmental baselines for the management of the Murray estuary. Their work is published in The Holocene journal.

"The Millennium Drought from 1996 to 2010 saw historic lows in Lake Albert's water levels," Dr Job, a postdoctoral researcher at the University of Sydney, said. "This triggered widespread oxidation of exposed sulfide minerals, causing surface waters to become acidic."

Without ocean water entering the system during drought, as would have occurred before the Goolwa Barrages were built, lake levels can drop to low levels, causing major acidification.

"This isn't just an estimate," lead author on the paper Dr Job said. "We have seen direct evidence for this in the recent geological record going back thousands of years: droughts leave historic fingerprints deep in the lake sediments. We see these fingerprints more distinctly in sediments deposited after the barrages were built."

Increased acidity dissolves metals from soils into the lake waters, lowering water quality. Eventually, these metals end up back in the lake sediments.

"We looked at the geologic record for these metals. Combining these new data with our understanding of the shape of the lake system over time, we have created a more dynamic picture of how the system formed and how it responds to changes in climate," Dr Job said.

"We hope this information will improve management of the Murray-Darling estuary."

WETLAND OF INTERNATIONAL IMPORTANCE

Rather than looking to precolonial conditions, current baselines used by the Murray-Darling Basin Authority aim to conserve the system with reference to 1985, when the estuary was listed as a Wetland of International Importance under the Ramsar Convention.

Critically, this is after changes to the ecosystem that locked in its vulnerability to acidification during drought.

"When we look at the complexity of the Albert and Alexandrina lakes, it's important that baselines capture they system's natural conditions. Previous models have struggled to identify how the system has changed over time," Dr Job said.

Contested interpretations of the estuary's formation and uncertainty surrounding the sustainability of current water usage practice for farming and domestic use mean that a robust understanding of how the system has evolved is required.

"Half of Australia's farming - and two-thirds of its irrigated agriculture - relies on careful management of the Murray-Darling system," Dr Job said.

By combining environmental chemistry with studies of the system's geomorphology, Dr Job and colleagues found previously hidden complexity and dynamism in how the lakes formed.

"It's not clear yet what this means for how we manage the precious water resources of our greatest river system, but we are getting a much better understanding of how complex - and how sensitive to change - the Murray estuary is," Dr Job said.

The new model also shows that before about 5400 years ago, Lake Albert experienced very different conditions, due to higher sea levels and a more direct southern connection to the ocean, increasing tidal influences and inflows of saltwater.

"We have updated two previous studies, one published in 1994 and the other in 2007," Dr Job said. "Ours is the first to incorporate the historic environmental chemistry of the lakes."

The research team hopes the improved historic picture of Murray estuary can be applied to the environmental management of the system.

The researchers say that the ecological health and function of Lake Albert, and the degree to which it has been altered, should be measured with reference to its natural estuarine state before the Goolwa Barrages cut the lakes off from tidal brackish waters and changed the system's hydrology.

Lustrous metallic paints are used to enhance the beauty of many products, such as home decorations, cars and artwork. But most of these pigments owe their sheen to flakes of aluminum, copper, zinc or other metals, which have drawbacks. Now, researchers reporting in ACS Omega have developed organic-only dyes that can form films resembling gold or bronze, without the need for metals.

In paints, metal flakes tend to settle to the bottom of the can, requiring regular stirring during use and storage. Multiple coats of metallic paint are often needed to provide good coverage, which adds weight to the object being painted. Also, when used in ink-jet printers, metallic pigments can clog ink nozzles. For these and other reasons, researchers are trying to develop nonmetallic, organic paints with metal-like luster. But so far, few candidates have displayed all of the desired qualities of solubility in solvents, good film-forming properties and excellent stability over time. Katsuyoshi Hoshino and colleagues from Chiba University in Japan recently introduced a perchlorate-doped 3-methoxythiophene oligomer that checked all of these boxes, but it had to be dissolved in solvents that are considered unsafe for painters. To develop an industrially acceptable metal-effect dye, the researchers wanted to make and test chloride-doped 3-methoxythiophene oligomers.

The team made two different versions of the chloride-doped oligomers, which, unlike their previously reported perchlorate-doped counterpart, dissolved in water. They coated glass plates with solutions of the new dyes and allowed them to dry. The two chloride-doped oligomers produced lustrous gold- or bronze-like films, respectively, but they each had a non-glossy dark stain, which resembled a coffee ring stain, near the center. Although more research is needed to determine how to prevent this stain from forming, both films had higher reflectance than the one made by the perchlorate-doped oligomer. The paints are soluble in water but can be made water-resistant by dehydration, which makes their industrial implementation feasible. The new dyes could be used in commercial ink-jet printers, and they also might someday be implemented in organic electronic systems, the researchers say.

The growing global demand for palm oil has led to a rapid spread of oil palm monoculture plantations in South East Asia. This is often associated with the loss of natural habitat and biodiversity. Oil palm monocultures are uniformly structured and therefore offer little space for different species. Diversification using indigenous tree species can contribute to maintaining biodiversity. A research team from the University of Göttingen (Germany) and the University of Jambi (Indonesia) has now shown that such diversification can be encouraged with the help of information campaigns and free seedlings. The study has been published in the Journal of Environmental Economics and Management.

Oil palm plantations cultivated by smallholder farmers account for about 40 percent of the total area of oil palms in Indonesia, which means they are an important target group for interventions. The study of the interdisciplinary German-Indonesian Collaborative Research Centre "EFForTS" involved 800 smallholder farmers. "Smallholder farmers have little access to information, advice and high-quality seeds," says study director Professor Meike Wollni, agricultural economist at the University of Göttingen. "Yet, there is a high level of interest in diversification, especially with native fruit trees, as expressed by the local population in focus group discussions."

Against this background, the researchers divided the participants in the study into different treatment groups. The groups received information and/or tree seedlings. The results show that the two measures being investigated increase the number of trees planted in smallholder oil palm plantations. "We see that both interventions motivate a small group of individuals to plant many trees," says first author Dr Katrin Rudolf from the University of Göttingen. "However, to reach a large number of farmers, it is necessary to distribute seedlings. Here, the farmers' preferences should be taken into account when selecting tree species in order to increase the tree survival."

Identifying policies to improve the environmental impact of oil palm cultivation is highly relevant in the context of ongoing species loss, according to the authors. In addition to the supply side, however, the demand side should be considered when designing policies. Consumers could, for example, contribute to the costs incurred through certification of more environmentally friendly plantations.

PHILADELPHIA - As the search for successful Alzheimer's disease drugs remains elusive, experts believe that identifying biomarkers -- early biological signs of the disease -- could be key to solving the treatment conundrum. However, the rapid collection of data from tens of thousands of Alzheimer's patients far exceeds the scientific community's ability to make sense of it.

Now, with funding expected to total $17.8 million from the National Institute on Aging at the National Institutes of Health, researchers in the Perelman School of Medicine at the University of Pennsylvania will collaborate with 11 research centers to determine more precise diagnostic biomarkers and drug targets for the disease, which affects nearly 50 million people worldwide. For the project, the teams will apply advanced artificial intelligence (AI) methods to integrate and find patterns in genetic, imaging, and clinical data from over 60,000 Alzheimer's patients -- representing one of the largest and most ambitious research undertakings of its kind.

Penn Medicine's Christos Davatzikos, PhD, a professor of Radiology and director of the Center for Biomedical Image Computing and Analytics, and Li Shen, PhD, a professor of Informatics, will serve as two of five co-principal investigators on the five-year project.

"Brain aging and neurodegenerative diseases, among which Alzheimer's is the most frequent, are highly heterogeneous," said Davatzikos. "This is an unprecedented attempt to dissect that heterogeneity, which may help inform treatment, as well as future clinical trials."

Diversity within the Alzheimer's patient population is a crucial reason why drug trials fail, according to the Penn researchers.

"We know that there are complex patterns in the brain that we may not be able to detect visually. Similarly, there may not be a single genetic marker that puts someone at high-risk for Alzheimer's, but rather a combination of genes that may form a pattern and create a perfect storm," said Shen. "Machine learning can help to combine large datasets and tease out a complex pattern that couldn't be seen before."

That is why the project's first objective will be to find a relationship between the three modalities (genes, imaging, and clinical symptoms), in order to identify the patterns that predict Alzheimer's diagnosis and progression -- and to distinguish between several subtypes of the disease.

"We want to redefine the term 'Alzheimer's disease.' The truth is that a treatment that works for one set of patients, may not work for another," Davatzikos said.

The investigators will then use those findings to build a predictive model of cognitive decline and Alzheimer's disease progression, which can be used to steer treatment for future patients.

This undertaking will also utilize data from the Alzheimer's Disease Sequencing Project, an NIH-funded effort led by Gerard Schellenberg, PhD, and Li-San Wang, PhD, at Penn, along with colleagues from 40 research institutions. That project aims to identify new genomic variants that contribute to -- as well as ones that protect against -- developing Alzheimer's.

ITHACA, N.Y. - An injury to the anterior cruciate ligament (ACL) can lead to severe osteoarthritis in both animal and human patients. Now, a new interdisciplinary study on the protein that lubricates our joints says that lubricant may actually be a precursor of joint disease.

The paper, published Oct. 7 in Scientific Reports, is the first that investigates the role of a protein, known as lubricin, in ACL-type injuries in dogs. It may also have larger implications for similar injuries in humans as well as the potential for treatments and therapeutics.

"Lubricin is crucial for normal joint function and the lubrication of cartilage," said Heidi Reesink, Ph.D. '16, the Harry M. Zweig Assistant Professor in Equine Health at the College of Veterinary Medicine (CVM) and senior author on the paper. "We know that if a person or animal doesn't make that protein, they will develop devastating joint disease affecting all the major weight-bearing joints."

Lubricin is universal to mammals, including humans, though there is conflicting data regarding its role in joint injuries. Reesink's study found that, in canine patients that had suffered a ligament tear in the knee, lubricin increased within the joint - the opposite of conventional assumptions in medicine. "The dogma in this field has been that lubricin decreases in joint disease," Reesink said.

In three canine patients that had a joint injury, lubricin dramatically increased in the time between their initial injury but before any signs of arthritis in their X-rays.

"This indicates that the presence of increased lubricin might actually be a biomarker for predicting future osteoarthritis," said Reesink. "We also saw increased lubricin in dogs months to years after they injured their ACLs, suggesting that lubricin might be an indicator of ongoing joint instability."

Reesink said increased lubricin could consequently be a signal for clinicians to intervene or try a different treatment approach.

Reesink and her collaborators laid the groundwork for this new study by completing a systematic review of the literature surrounding lubricin in both human and veterinary medicine. The review waspublished this summer in the journal Osteoarthritis and Cartilage.

The overall finding of the review: There is no unified consensus on how lubricin is altered in other domestic veterinary species and in human joint injury, demonstrating the need for further study - which Reesink's new paper has done.

"In looking at horses and dogs, we're seeing the same pattern," she said. "The strongest piece of data would be to show it in humans as well."

Reesink and her collaborators worked with the Cornell Veterinary Biobank to obtain samples. The biobank supports CVM researchers as well as scientists across the globe, using biological samples collected from both ill and healthy animals at the Cornell University Hospital for Animals (CUHA). The samples are processed, catalogued and provided to researchers, which accelerates biomedical research.

Among the motivators for this study, said Reesink, is that a large number of cases in the small animal orthopedic section at CUHA is knee ligament injury, which is common in dogs.

"We can help both animals and humans by potentially coming up with better diagnostics, by more fully understanding how these molecules work and designing therapies beneficial to both, by taking advantage of these naturally occurring cases and improving orthopedic care," Reesink said.

In the veterinary realm, Reesink's team plans to do a follow-up longitudinal study in dogs, examining multiple time points in a patient's injury, treatment and recovery process. They also hope to draw similar connections in human ACL and other orthopedic injuries.

Currently, Reesink is examining parallel samples from both the Cornell Veterinary Biobank and the Hospital for Special Surgery, using funding from a pilot grant from the Weill Cornell Medicine Clinical and Translational Science Center.