Culture

Research shows the sexes have equal spatial cognition skills

image: Research by Drs Mark Campbell and Adam Toth of Lero, the Science Foundation Ireland Research Centre for Software and University of Limerick, Ireland shows that men and women have equal spatial cognition skills. Pictured at the launch of the Lero Esports Science Research Lab are Jessica Mangione, Niall Ramsbottom, Dr Adam Toth, Yueying Gong and Dr Mark Campbell.

Image: 
Diarmuid Greene, TrueMedia

Men are not better than women at spatial cognition - such as map reading - is the principal finding from ground-breaking work by researchers at Lero, the Science Foundation Ireland Research Centre for Software, hosted at University of Limerick (UL), Ireland.

Employing cutting-edge eye-tracking technology researchers Dr Mark Campbell and Dr Adam Toth of the Lero Esports Science Research Lab at UL found that there is no male advantage in mental rotation abilities associated with spatial cognition competences.

Dr Campbell said the skill of spatial cognition or our ability to navigate our environment has been the battleground for almost 40 years for researchers claiming that males have a distinct performance advantage on tests of spatial cognition, notably the mental rotations test.

Studying the cognitive proficiency of individuals and gamers is a key aim of the Lero Esports Science Research Lab which opened in 2019 and is the first of its kind in Ireland.

"Better performance on these tests is strongly associated with higher IQ and better performance in STEM (Science Technology Engineering and Maths) subjects in schools and colleges," Dr Campbell explained.

Dr Toth sums up the results: "So males are better than females? Well no, actually. Our study found that there is no male advantage in mental rotation abilities. By lengthening the time allowed to complete the test, the male performance advantage diminished entirely suggesting that the so-called sex difference in mental rotation is simply not there or may be explained by other factors."

The research published in Nature Scientific Reports also found for the first time that both males and females frequently employed different gaze strategies during the cognitive tests to get to the correct answer. In other words, men and women approach the task in a different way to get the same result.

The research paper is entitled: "Investigating sex differences, cognitive effort, strategy, and performance on a computerised version of the mental rotations test via eye-tracking."

One hundred University of Limerick (UL) undergraduate and postgraduate level psychology and sports science students volunteered to take part in the test carried out by the Lero researchers. The 47 men and 53 women were in good health and had an average age of 23.

Credit: 
University of Limerick

A new model has been developed that simulates the accumulation of lipids in membranes

image: Vladimir Baulin, researcher of the URV's Department of Chemical Engineering, has led the study.

Image: 
URV

Cholesterol is crucial to the formation of the cell membranes of mammals and is part of many life processes. One of the most controversial concepts in biophysics is the hypothesis of the so-called lipid rafts: areas of high concentrations of cholesterol and glycosphingolipids in membranes. These lipid rafts, also known as lipid microdomains, are areas of the cell membrane in which lipids and cholesterol accumulate and play an important role in cell function. Currently, the presence of lipid rafts in live cells is only a hypothesis because although various laboratory studies have attempted to simulate them by mixing two types of lipid and cholesterol, none has managed to detect them or determine whether they really exist, how they are formed and how they function in live cells.

It is suspected that lipid rafts are also responsible for the onset of diseases such as Creutzfeldt-Jakob or AIDS, the pathogens of which pass through them to enter the cells. Therefore, understanding their mechanism is fundamental to determining how these diseases develop.

A team of physicists led by the researcher of the URV's Department of Chemical Engineering Vladimir Baulin has designed an experiment that simulates the formation of a new type of lipid raft on a nanometric scale around objects incrusted in the membranes such as proteins and ion channels. The results of this study have been published in the journal Physical Review Letters.

"Ion channels are a sort of transmembrane protein - that's to say, they span the whole cell membrane - which, in conjunction with proteins, allow specific ions to pass from one side of the membrane to the other. They are part of it and contain cholesterol. The role transmembrane proteins play in the possible formation of these cholesterol nanodomains is unknown," says Vladidimir Baulin about the research results.

In this research, the scientists have carried out an experiment with a lipid membrane very similar to human cells in terms of the size scale, and the dimension and composition of the cholesterol. They substituted the transmembrane protein for an ultra-short carbon nanotube - 10 nanometres long. And after a series of simulations they confirmed that these domains - the lipid rafts - are highly dynamic, they form and then disappear only to form again and they exist for approximately 10 nanoseconds.

The team also made another important discovery about the role of cholesterol in membranes: cholesterol may be responsible for destabilizing the membranes and helping nanometric-sized objects to enter the cells. "It was like finding the key for opening and closing doors through a membrane," said Vladimir Baulin. "We found that when there are high concentrations of cholesterol, nanotubes can spontaneously leave the membrane in a question of milliseconds. But if the membrane has no cholesterol, they remain trapped inside."

This study may serve to develop new crucial approaches for researching lipid rafts, so the development of some diseases and cell processes will also be better understood.

Credit: 
Universitat Rovira i Virgili

Sea level rise to cause major economic impact in the absence of further climate action

The Paris Agreement, adopted in 2015 by 175 parties, aims to limit global warming to well below 2°C compared to pre-industrial levels. However, the period 2010-2020 was the planet's hottest decade on record and the long-term trend is upward. Sea level rise is one of the most severe impacts of climate change, with rising waters amplifying coastal floods, threatening coastal communities, infrastructure, and agriculture.

New IIASA-led research for the first time assessed the economy-wide effects of sea level rise globally and in particular in G20 countries when jointly taking into account different climate mitigation and adaptation assumptions, using three different macroeconomic models. In the study, authors compared two different climate policy scenarios - one achieving well below 2°C warming by the end of this century (basically in line with the Paris Agreement), and one overshooting this target - in combination with two different adaptation scenarios (no adaptation and full adaptation to sea level rise) and estimated GDP impacts due to coastal flooding in all scenario combinations for 2050 and 2100. The study is also innovative in terms of looking at G20 countries explicitly, that is, countries that are big emitters and at the same time affected by climate change. The analysis thus corroborates the need for action on both mitigation and adaptation.

"We found that up to 2050 the global GDP losses in both climate futures are significant and similar given the effects of climate change that we are already experiencing. However, by 2100, without further mitigation and adaptation and assuming continued sea level rise, projected annual global economy-wide losses can amount to more than 4%," explains study lead author and IIASA Risk and Resilience Deputy Program Director Thomas Schinko. "With ambitious mitigation and adaptation, the model results show that this number can be reduced to below 0.5% of global GDP loss, despite the associated costs for adaptation measures and residual impacts. This confirms the importance and economic efficiency of adaptation in the long term: Making sure that coastal communities and their infrastructure are climate-resilient will affect economies across the globe much less than persistent climate impacts in the absence of climate action."

According to study coauthor Laurent Drouet, a senior scientist at the RFF-CMCC European Institute on Economics and the Environment, in terms of regional effects across the G20, the highest levels of annual GDP impacts in relative terms are projected for China. In 2050 and with no further adaptation, economic losses amount to 0.8-1.0%. Estimated GDP losses for India are slightly smaller (0.5-0.6%), followed by Canada (0.3-0.4%). Zoi Vrontisi, a senior researcher at the E3MLab of the National Technical University of Athens, highlighted that until 2050 the direct economic losses of sea level rise on a global level can still be balanced out by interregional trade and substitution effects in production processes at the macroeconomic level. However, after 2050 and up to 2100, the scale of economy-wide effects in G20 countries changes drastically.

China remains the country with the highest projected relative GDP loss if no further adaptation is undertaken, which is now a factor of ten higher than it was in 2050: According to the economic modeling undertaken, annual losses would amount to 9-10% in a well below 2°C scenario, and to 11-12% under a current mitigation policy scenario. Other regions with severe economy-wide damages by 2100 under no adaptation are Europe and Japan.

Macroeconomic impacts are analogous to the direct damages of sea level rise. However, Andries Hof from PBL Netherlands Environmental Assessment Agency, notes that this changes if stronger mitigation actions are undertaken and sea level rise adaptation efforts are strengthened. Similar to the global picture, all individual G20 countries could thereby limit the residual economy-wide impacts to below 1.0% of GDP if appropriate adaptation measures are taken. An important benefit of further mitigation efforts to be undertaken by G20 countries are strong reductions of impacts for the most vulnerable coastal countries across the globe. This effect will be further investigated in future research.

"The findings of this paper demonstrate that we need to think long term while acting swiftly. Macroeconomic impacts up to and beyond 2050 as a result of coastal flooding due to sea level rise - not taking into account any other climate-related impacts, such as drought - are severe and increasing. We, as a global society, need to further coordinate mitigation, adaptation, and climate resilient development, and consider where we build cities and situate important infrastructure," concludes Schinko.

Credit: 
International Institute for Applied Systems Analysis

Physicists develop a new experimental model for 'lipid rafts' in human cells

It is a rather trivial statement: if you want to enter the house through a door, it is best to take a key in your hand, open and go inside. But if you have no idea what the key looks like or where it is hidden - under the doormat, on the basement stairs? - it becomes much more difficult.
 

It is similar in biology. It goes without saying that there are doors that connect the interior of cells to the exterior. One of these doors, however, still puzzles scientists: so-called "lipid rafts". These are certain areas in the cell membrane in which lipids, which are important for the signal transmission of cells, accumulate. These are platform enriched with cholesterol that looks like rafts, these areas "float" through the cell membrane. Across lipid rafts, molecules can also enter and get out of the cell.
 

In particular, scientists suspect that these "lipid rafts" are also contributing to diseases such as Parkinson, Alzheimer or HiV infection, whose pathogens enter the cells via these lipid raft. An understanding of this mechanism is therefore fundamental to the emergence of such diseases.
 

However, no one has been able to fully characterize "lipid rafts" in living cells, so far their size and lifetime are still subject to vigorous debates. Only in model membranes have the "rafts" been observed and fully characterize but "these models were not very well transmissible to real cells", explains Dr. Jean-Baptiste Fleury (Saarland University). The expert in microfluidics explains why this is the reason: "On the one hand, previous experiments were very large, namely in the micrometer range. At the cell level, however, the processes take place at the nanometer level, i.e. again by a factor of 1000 below. In addition, the lipid rafts in the experiment have been much more short-lived than in real cells", Fleury explains. Instead of between one and 15 milliseconds, the previous experimental lipid rafts existed only for about 10 nanoseconds, i.e. about one millionth of the natural lipid rafts.
 

Jean-Baptiste Fleury has now developed an experiment system that brings both the size scale, the temporal dimension of these lipid rafts much closer to the natural conditions than has been the case up to now. To do this, he placed around 10 nanometer long carbon nanotubes, as a replacement of an artificial transmembranar protein, inside the model membrane to trigger the formation of ultra-small cholesterol region around this carbon nanotube. He was able to observe that the cholesterol concentration plays a decisive role in whether the nanotubes got through the cell or whether they remained trapped in the cell membrane. "We found that nanotubes in presence of high cholesterol concentrations can spontaneously emerge from the bilayer within a few milliseconds while remaining trapped in the membrane if the bilayer does not contain cholesterol."

Theoretical physicists from the University of Rovira i Virgili in Tarragona (Spain) and the Nanjing University in China developed the basis for this. In months of computer simulations, they calculated the behavior of the nanotubes and cholesterol and then used the Saarland expertise of Jean-Baptiste Fleury as an experimental physicist to check the theoretical knowledge in the experiment. In this way, the international research team has developed fundamental new approaches to researching lipid raft, so that the development of diseases and the cellular processes may also be better understood. They published their findings in the renowned journal "Physical Review Letters". 

Credit: 
Saarland University

'Net' is closing in on more viable biological control options for fall armyworm menace

image: Fall armyworm (Spodoptera frugiperda) is seriously threatening food security as a pest of cereals

Image: 
Daniel Adjokatcher

The 'net' is closing in on more viable biological control agents to fight the scourge of the fall armyworm (FAW) pest which is already wreaking havoc in most African countries as well as more than a dozen Asian countries including China and India.

CABI scientists teamed up with colleagues from the International Institute of Tropical Agriculture (IITA) and the Plant Protection and Regulatory Services Directorate (PPRSD) in Ghana to conduct new research which is another step closer to finding more biological control options to fight the FAW menace.

The Food and Agriculture Organization of United Nations (FAO) states that, based on 2018 estimates from 12 African countries, up to 17.7 million tonnes of maize could be lost annually to FAW on the continent - enough to feed tens of millions of people. The most direct impact of these losses falls on smallholder maize farmers, most of whom rely on the crop to stave off hunger and poverty.

Lead authors Dr Lakpo Koku Agboyi, Dr Georg Goergen and Dr Marc Kenis led new research which focused on exploring the parasitoid complex of the FAW in Ghana and Benin where 10 species were found to have parasitized the pest. These included two egg parasitoids, one egg-larval, five larval and two larval-pupal parasitoids. In similar surveys carried out in Ethiopia, Kenya and Tanzania, seven parasitoid species were collected.

Outlining their findings in the journal Insects, the authors showed that the three most abundant parasitoids in both countries were two Braconidae: the egg?larval parasitoid Chelonus bifoveolatus and the larval parasitoid Coccygidum luteum, as well as the egg parasitoid Telenomus remus.

Dr Agboyi, who is based at CABI's centre in Ghana, said, "We determined the larval parasitism rates in three Ghanaian regions and averages varied from 5% to 38% between regions, with up to 75% parasitism found at single locations. This data provides an important baseline for the development of various biological control options for fall armyworm."

Back in April 2019 Dr Kenis was lead author on another paper in Insects which confirmed the first report of Telenomus remus in Africa and positioned the species as a 'great opportunity for the rapid deployment of a biological control agent' for fall armyworm on the continent.

The latest research adds weight to the scientists' suggestion that Chelonus bifoveolatus, Coccygidum luteum and Telenomus remus could all be used to fight the fall armyworm as part of an Integrated Pest Management plan, either as augmentative biological control agents through regular releases or in conservation biological control strategies in which cultural practices enhance the action of the main natural enemies.

Dr Kenis said, "In Latin America, field releases of Telenomus remus in maize can result in 80-100 percent parasitism, providing full control of fall armyworm. However, a challenge of using a larval parasitoid of fall armyworm in augmentative biological control will be to find alternate rearing hosts for mass production. Fall armyworm is not suitable for the mass production of larval parasitoids due to the cannibalistic behaviour of the larvae".

"Another consideration for a wider utilisation is to provide a product that is financially affordable for African farmers. Mass production on its natural hosts is costly but we believe rearing systems on factitious hosts can be developed."

"Understanding the parasitoid complex of the fall armyworm in Africa is also necessary before any development of classical biological control involving the introduction of parasitoids from the Americas. However, since FAW remains a huge problem for African farmers despite substantial parasitism by native parasitoids, the introduction of American parasitoids should not be ruled out since their successful establishment may lower pest population levels permanently, at no cost for the farmers."

Dr Agboyi adds that the use of broad-spectrum insecticides is not only unsustainable in the long-run, but also increases production costs, has biodiversity and environmental impacts, and poses health risks to the growers and consumers.

Biological control, on the other hand they say, can offer an economically and environmentally safer alternative to synthetic insecticides that are currently being used for management of the fall armyworm and a range of other crop pests.

Credit: 
CABI

Discovery of a new liquid-liquid interfacial deformation by partial miscibility

image: (a) Phase diagram of PEG 8000-Na2SO4-water system and solution systems used in the present study. Region I is a one-phase region and region II is a two-phase region. When the concentration is set in red triangle, the solution is separated into two phases, phase L and phase H. The solution compositions used in the immiscible, fully miscible, and partially miscible systems are indicated by red, black, and green circles, respectively. (b) When a more viscous liquid is injected from a single point into a Hele-Shaw cell (a gap between two parallel flat plates with a very small distance b (= 0.3 mm)) filled with a less viscous liquid, their interface becomes hydrodynamically stable and spreads out in a circle. (c) Hydrodynamically stable displacement in the immiscible, fully miscible, and partially miscible systems for a given flow rate. The pictures are taken when the longest radius of the displacement pattern is 42 mm and the injection time is shown at the lower right corner of each picture. The circles in the figure correspond to the circles in the phase diagram of (a). That is, in the immiscible system, the compositions of the more viscous solution and the less viscous solution are represented by open-circle in red and solid-circle in red. In the fully miscible system, the composition of the more viscous solution, of the less-viscous, and of their mixed solution are represented by open-circle in black, solid-circle in black, and star in black. In the partially miscible system, they are represented by open-circle in black, solid-circle in black, and star in green.

Image: 
Yuichiro Nagatsu/ TUAT

The international collaborative team of Tokyo University of Agriculture and Technology (TUAT) (Japan), IIT Ropar (India), Osaka Univ. (Japan) has discovered for the first time in the scientific development that "partially miscibility", in which the two liquids do not mix completely with finite solubility, is capable of deforming the liquid-liquid interface. This interfacial deformation originates due to the spontaneous motion driven by phase separation between the soluble species, and is a phenomenon that cannot be seen with completely mixed (fully miscible) with infinite solubility or (almost) immiscible with no solubility.

The researchers published their results in Physical Review Fluids on Oct 29th, 2019.

The process of displacing one fluid in a porous medium by injecting another fluid is important in reactions and separation in chemical processes, as well as in enhanced-oil-recovery and CO2 sequestration. In particular, when a less viscous fluid displaces a more viscous fluid, the interface between the two fluids becomes hydrodynamically unstable and deforms in a finger shape. This phenomenon is called "Viscous fingering", and it has been studied since the 1950s as one fluid dynamics problem. Now, it is widely known that the properties of these two fluids can be traditionally classified according to whether they are fully miscible or immiscible. On the other hand, when a more viscous fluid displaces a less viscous fluid, classically, the interface stably spreads, regardless of whether the two fluids are fully miscible or immiscible.

"It has long been known that two fluids are partially miscible in underground processes with high-pressure conditions, such as oil recovery and CO2 storage, "said Dr. Nagatsu, corresponding author on the paper and an associate professor in the Department of Chemical Engineering at TUAT. "However, the intricate understating of interfacial dynamics in partially miscible systems has not been well-studied. One of reasons is that fluid displacement research has been mainly conducted by fluid mechanics researcher so far, and they missed to find the experimental systems that are partially miscible at room temperature and atmospheric pressure."

The research team succeeded in changing the miscibility of the system to fully miscible, immiscible, and partially miscible with little change in the viscosities of high-viscosity or low-viscosity liquids at room temperature and atmospheric pressure by using an aqueous two-phase system consisting of polyethylene-glycol (PEG), sodium-sulfate, and water and by changing the salt (sodium-sulfate) concentration (see Fig. (a)). "We found that a new interfacial deformation is observed in the case where the two liquids are partially miscible (see Fig. (c)) when a more-viscous liquid displaces a less-viscous one in a Hele-Shaw cell (Fig. (b)) which is a model mimics flow in porous media. This is very much counter-intuitive because no deformation takes place in such situation when the two fluids are fully miscible or immiscible (Fig. (b)). We showed this interfacial instability originates due to spontaneous flow driven by phase separation between the soluble species", Nagatsu explains.

"Our result shows that the effect of partial miscibility of liquids on interfacial hydrodynamics is not in the middle of fully miscible and immiscible, but has completely different properties. We emphasize that this will open a new cross-disciplinary research area involving hydrodynamics and chemical thermodynamics. Also, the displacement with partial miscibility in a porous medium takes places in the oil recovery process from the formation and the CO2 injection process into the formation, and thus our finding is expected to contribute to improve the accuracy of the phenomena prediction of those processes, adds Nagatsu.

Credit: 
Tokyo University of Agriculture and Technology

Making sense of flexible sensor systems

image: Imperceptible magnetic sensor matrix system

Image: 
Osaka University

A team of researchers from Osaka University and Leibniz Institute for Solid State and Materials Research developed the world's thinnest and lightest magnetic sensor matrix sheet system that visualizes the two-dimensional distribution of magnetism on various surfaces.

Conventional magnetic sensor circuits consist of silicon-based hard electronic elements integrated on a substrate with a hardness similar to that of glass, meaning they can be only placed on flat surfaces.

Conversely, flexible soft magnetic sensors have also been developed, but there is no device integrating a driving circuit, sensor scanning mechanism, signal processing circuit, and wireless measurement unit, all of which are required to form a system. "This is because the fabrication of a flexible magnetic sensor element is difficult. Furthermore, it is hard to integrate the fabrication process with circuit technology," explains lead author Masaya Kondo.

Now, this joint research team has developed a thin and soft ("skin-like") magnetic sensor matrix sheet system by integrating flexible electronic elements called organic transistors and giant magnetoresistive elements on a 1.5-μm-thick plastic film. This imperceptible circuit fabricated on a thin plastic film can be attached onto the skin of a person without causing discomfort and can function properly even when folded (Fig. 1).

The magnetic sensor matrix sheet system, with a sensitivity ten times higher than that of conventional systems, not only detects and amplifies weak magnetic signals, but also visualizes the two-dimensional distribution of magnetism in real time by automatically scanning magnetic sensor elements arranged in a matrix pattern (Fig. 2).

Among physical information, magnetic information obtained via a two-dimensional sheet-type magnetic sensor system is much more precise than electrical information because magnetic sensors have high spatial resolution due to the high permeability of magnetism in substances. A sheet-type sensor provides high-precision physical information as it can be adhered to a variety of objects regardless of shape.

"Attaching our sheet-type sensor to a reinforced structure identifies the precise locations of damage by mapping the distortion of magnetism caused by deteriorated reinforcing steel bars. Also, once the sensitivity of the sensor is improved further, higher precision cardiac diagnosis will be achieved by magnetic mapping than by conventional electrocardiography," says Prof. Sekitani, who led the study.

Credit: 
Osaka University

Experimental versus formal mathematics in the 21st century

Computers have helped mathematical research accelerate in multiple directions and increased the presence of mathematics in everyday life.

Patients suffer invasive treatments for harmless cancers

image: Research, led by Professor Paul Glasziou, the Director of the Institute for Evidence-Based Healthcare at Bond University, drew on data from the Australian Institute of Health and Welfare to compare how the lifetime risk of five cancers had changed between 1982 and 2012.

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Bond University, Australia

Australians are increasingly being diagnosed with cancers that will do them no harm if left undetected or untreated, exposing them to unnecessary surgeries and chemotherapy, says a new study published online today in the Medical Journal of Australia.

The research, led by Professor Paul Glasziou, the Director of the Institute for Evidence-Based Healthcare at Bond University, drew on data from the Australian Institute of Health and Welfare to compare how the lifetime risk of five cancers had changed between 1982 and 2012.

The study shows compared to 30 years ago, Australians are much more likely to experience a cancer diagnosis in their lifetime.

The figures suggest that in 2012 24 percent of cancers or carcinomas in men were overdiagnosed. These included 42 percent of prostate cancers, 42 percent of renal cancers, 73 percent of thyroid cancers and 58 percent of melanomas.

For women, 18 percent of cancers or carcinomas were overdiagnosed, including 22 percent of breast cancers, 58 percent of renal cancers, 73 percent of thyroid cancers and 58 percent of melanomas.

The figures are significant because of the harm that can occur from cancer treatment of patients who would never have had symptoms in their lifetime.

"Cancer treatments such as surgery, radiotherapy, endocrine and chemotherapy carry risks of physical harms," the authors of the study reported.

"In the absence of overdiagnosis, these harms are generally considered acceptable.

"In the context of overdiagnosed cancers, however, affected individuals cannot benefit but can only be harmed by these treatments."

The authors also refer to separate studies showing overdiagnosis could be linked to psychological problems.

"For example, men's risk of suicide appears to increase in the year after receiving a prostate cancer diagnosis."

The new study, which was led by Professor Glasziou in conjunction with co-authors Professor Alexandra Barratt and Associate Professor Katy Bell of University of Sydney, Associate Professor Mark Jones of Bond University, and Dr Thanya Pathirana of Griffith University, calls for urgent policy changes to address overdiagnosis.

Professor Glasziou said increasing rates of diagnosis were a result of improvements and wider use of testing and screening.

"The problem is that some screening identifies abnormal cells that look like cancer but don't behave like cancer. However, reducing that problem is not easy, as some types of screening are important".

Professor Glasziou said the best option to reducing melanoma deaths may not be ever-more screening "but applying daily sunscreen" and research on better treatments.

"While much of the overdiagnosis is due to screening, many overdiagnosed cancer cases are incidental findings, that is, the patient is being tested for something else when the cancer is detected," Professor Glasziou said.

"Getting the balance right between too little and too much screening and testing will not be easy, but this is an important step.

It is the first time that the risk of overdiagnosis has been quantified across five cancers, anywhere in the world."

Associate Professor Bell said that the findings also suggest an important role for health services such as the Australian Institute of Health and Welfare, in detecting potential overdiagnosis and alerting health policy decision makers to the problem early on.

"Patterns of increased test use, cancer incidence, or treatment rates, without corresponding rises in mortality could indicate emerging areas of overdiagnosis," she said.

"People still need to remain vigilant when it comes to early detection of cancers, however they need to be informed and engage in shared decision making with their medical professionals about the harms of cancer screening and other associated procedures."

Credit: 
Bond University Australia

Prescription drug improves symptoms of autism by targeting brain's chemical messengers

Bumetanide - a prescription drug for oedema (the build-up of fluid in the body) - improves some of the symptoms in young children with autism spectrum disorders and has no significant side effects, according to a new study from researchers in China and the UK.

Published today in Translational Psychiatry, the study demonstrates for the first time that the drug improves the symptoms by decreasing the ratio of the GABA to glutamate in the brain. GABA and glutamate are both neurotransmitters - chemical messengers that help nerve cells in the brain communicate.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder estimated to affect one in 160 children worldwide. It is characterised by impairments in social communication, which manifest as problems with understanding emotions and with non-verbal communication, such as eye contact and smiling, and in failures to develop, maintain and understand social relationships. People with ASD also tend to have restricted interests and show repetitive behaviour. In mild cases of ASD, people are able to live independently, but for some the condition can be severe, requiring life-long care and support.

Although the biological mechanisms underlying ASD remain largely unknown, previous research has suggested that it may result from changes in brain development early in life, and in particular in relation to GABA, a neurotransmitter, a chemical in the brain that controls how nerve cells communicate. In the adult brain, GABA is inhibitory, which means it switches nerve cells 'off'. In fetal life and early postnatal development, it is mostly excitatory, switching nerve cells 'on' and making them fire, playing a key role in the development and maturation of nerve cells. Alterations in the GABA-switch (from excitatory to inhibitory) can cause a delay in when the developing neural circuits reach functional maturity, with consequences for network activity. This implies that intervening at an early age may help reduce some of the symptoms that can make life challenging for people with ASD.

Current treatments for ASD at preschool age are mainly behavioural interventions, such as using play and joint activities between parents and their child to boost language, social and cognitive skills. However, with limited resources there is an inequality in access to these treatments across the globe, particularly in developing countries.

Previous studies in rats and small clinical trials involving children with ASD suggest that the drug bumetanide, which has been approved for use in oedema, a condition that results in a build-up of fluid in the body, could help reduce symptoms of ASD.

Now, an international collaboration between researchers at a number of institutions across China and at the University of Cambridge, UK, has shown that bumetanide is safe to use and effective at reducing symptoms in children as young as three years old. ASD can be reliably diagnosed at age 24 months or even as early as 18 months of age.

The team recruited 83 children aged three to six years old and divided them into two groups. A treatment group of 42 children received 0.5mg of bumetanide twice a day for three months, while a control group of 41 children received no treatment. The researchers assessed symptoms using the Childhood Autism Rating Scale (CARS), which is used to rate behaviour such as imitation, emotional response and verbal and non-verbal communication. Children scoring above 30 on the scale are considered to have ASD.

Before treatment, both groups had similar CARS scores, but afterwards, the treatment group now had a mean total score of 34.51 (compared to the control group mean score of 37.27). Also, importantly, the treatment group showed a significant reduction in the number of items on the CARS assigned a score greater than or equal to three, with the average number of 3.52 items in the treatment group compared to 5.49 items in the control group.

Dr Fei Li from Xinhua Hospital, Jiao Tong University School of Medicine, the clinical lead of the study, said: "I have many children with autism spectrum disorder under my care, but as psychological treatment resources are not available in many places, we are unable to offer them treatment. An effective and safe treatment will be very good news for them.

"The mother of a four year old boy living in a rural area outside Shanghai who received the treatment told me that he was now better at making eye contact with family members and relatives and was able to participate more in activities. In future, we hope to be able to ensure all families, regardless of where they are living, can receive treatment for their child."

To understand the mechanisms underlying the improvements, the researchers used a brain imaging technique known as magnetic resonance spectroscopy to study concentrations of neurotransmitters within the brain. They found that in two key brain regions - the insular cortex (which plays a role in emotions, empathy and self-awareness) and visual cortex (responsible for integrating and processing visual information) - the ratio of GABA to glutamate decreased over the three-month period in the treatment group. GABA and glutamate are known to be important for brain plasticity and promoting learning.

Professor Ching-Po Lin of National Yang-Ming University said: "This is the first demonstration that bumetanide improves brain function and reduces symptoms by reducing the amount of the brain chemical GABA. Understanding this mechanism is a major step towards developing new and more effective drug treatments."

Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge said: "This study is important and exciting, because it means that there is a drug that can improve social learning and reduce ASD symptoms during the time when the brains of these children are still developing. We know that GABA and glutamate are key chemicals in the brain for plasticity and learning and so these children should have an opportunity for better quality of life and wellbeing."

The team say the discovery that bumetanide changes the relative of concentrations of GABA to glutamate could provide a useful biomarker - a tell-tale biological measure - of how effective a treatment is. However, they cautioned that further research is needed to confirm the effectiveness of bumetanide as a treatment for ASD.

Dr Qiang Luo from Fudan University said: "These findings are very promising and suggest we will be able to use the biomarker measure to identify which children with ASD will benefit most from bumetanide. Further studies in a larger number of children will hopefully confirm whether bumetanide is an effective treatment for children with autism spectrum disorder."

Credit: 
University of Cambridge

Going with the flow: New insights into mysterious fluid motions

image: Left: da Vinci's sketch of eddies in a turbulent pool. Right: schematic of the energy spectrum corresponding to the flow inside the marked region in da Vinci's sketch.

Image: 
OIST

Water issuing from an ordinary faucet tells a complex tale of its journey through a pipe. At high velocities, the faucet's gushing stream is turbulent: chaotic, disorderly -- like the crash of ocean waves.

Compared to orderly laminar flows, like the faucet's steady stream at low velocities, scientists know little about turbulence. Even less is known about how laminar flows become turbulent. A mix of orderly and disorderly flows, transitional flows occur when fluids move at intermediate velocities.

Now, Dr. Rory Cerbus, Dr. Chien-chia Liu, Dr. Gustavo Gioia, and Dr. Pinaki Chakraborty, researchers in the Fluid Mechanics Unit and the Continuum Physics Unit at the Okinawa Institute of Science and Technology Graduate University (OIST), have drawn from a decades-old conceptual theory of turbulence to develop a new approach for studying transitional flows. The scientists' findings, published in Science Advances, may help furnish a more comprehensive, conceptual understanding of transitional and turbulent flows, with practical applications in engineering.

"Turbulence is often touted as the last unsolved problem in classical physics - it has a certain mystique about it," said Cerbus. "And yet, under idealized conditions, we have a conceptual theory that helps explain turbulent flows. In our research, we're striving to understand if this conceptual theory might also shed light on transitional flows."

Finding order in disorder

Scientists have long been captivated by turbulent flows. In the fifteenth century, Leonardo da Vinci illustrated turbulent flows as collections of swirling eddies, or circular currents, of varying sizes.

Centuries later in 1941, mathematician Andrey Kolmogorov developed a conceptual theory that revealed order underlying the energetics of seemingly disordered eddies.

As depicted in DaVinci's sketch, a stream plunging into a pool of water initially forms a large, swirling eddy, which quickly becomes unstable and breaks apart into progressively smaller eddies. Energy is transferred from the large to ever-smaller eddies, until the smallest eddies dissipate the energy via the water's viscosity.

Capturing this imagery in the language of mathematics, Kolmogorov's theory predicts the energy spectrum, a function which describes how the kinetic energy - the energy from motion - is apportioned across eddies of different sizes.

Importantly, the theory says that the energetics of the small eddies is universal, meaning that although turbulent flows may look different, the smallest eddies in all turbulent flows have the same energy spectrum.

"That such simple concepts can elegantly elucidate a seemingly intractable problem, I find it truly extraordinary," said Chakraborty.

But there is a catch. Kolmogorov's theory is widely thought to apply only to a small set of idealized flows, and not the flows of everyday life, including the transitional flows.

To study these transitional flows, Cerbus and his collaborators conducted experiments on water flowing through a 20-meter-long, 2.5-centimeter-diameter glass cylindrical pipe. The researchers added small, hollow particles with approximately the same density as water, allowing them to visualize the flow. They used a technique called laser doppler velocimetry to measure the velocities of the eddies in the transitional pipe flows. With these measured velocities, they computed the energy spectrum.

Surprisingly, the researchers found that, despite seeming distinct from turbulent flows, the energy spectrum corresponding to the small eddies in the transitional flows conformed to the universal energy spectrum from Kolmogorov's theory.

Beyond furnishing a new conceptual understanding of transitional flows, this finding has applications in engineering. Over the past two decades, Gioia and Chakraborty's research has shown that energy spectra can help predict friction between the flow and the pipe - a major concern for engineers. The more friction in a pipe, the more difficult it is to pump and transport fluids like oil.

"Our study combines esoteric mathematical ideas with factors that engineers care about," said Chakraborty. "And, we've found that Kolmogorov's theories have wider applicability that anyone thought. This is an exciting new insight into turbulence as well as into the transition to turbulence."

Credit: 
Okinawa Institute of Science and Technology (OIST) Graduate University

Assessing risk of chemicals to wildlife is huge challenge that requires new approach

image: Yellow hazardous chemicals sign

Image: 
Pixabay

Computer modelling and long-term ecological monitoring will be essential to assess the environmental risks of the rapidly growing number of chemicals across the world, according to a new review paper in the journal Science.

The analysis, led by the UK Centre for Ecology & Hydrology (UKCEH), says the sheer number of chemicals and substances is making it increasingly challenging to carry out the risk assessments required to check all products are completely safe for wildlife.

The EU's REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) regulation 2006 set an important precedent - that the onus to demonstrate a chemical was safe for humans and the environment should lie with the manufacturer.

However, out of more than 100,000 chemicals on the market in Europe, only a small fraction have been thoroughly evaluated for their potential harmful impacts on humans and the environment.

Professor Andrew Johnson of UKCEH, lead author of the paper, explains that, for example, there has been a lot of evaluation of the effects of pesticides on the environment but not washing detergents, despite their widespread use. He adds pharmaceuticals do not need an environmental risk assessment, and there has been little research into the potential impacts of several key classes of drugs on wildlife.

Meanwhile, weak regulations or inconsistent local enforcement have contributed to the creation of severe pollution hotspots in some parts of the world, particularly Asia where chemical sales are more than 60% higher than the US and EU combined, according to Professor Johnson and his co-authors.

He says: "Given the many chemicals that entered the market before REACH came into force, a retrospective authorisation process is trying to catch up.

"An ever-growing number of chemicals and uses for them means the challenge is enormous, and regulators are struggling to keep up. But it isn't necessarily a lost cause. We've learned from the past and chemicals are generally safer."

Along with progress in the regulation and management of chemicals, Professor Johnson and his co-authors say another reason for optimism is the improvement in analytical techniques in recent years. Computer modelling enables scientists to predict the effects of chemicals without animal testing but regulators are reluctant to rely entirely on these theoretical models.

The paper's authors - from UKCEH, the China National Environmental Monitoring Centre, Kyoto University and Brunel University - also recommend a more consistent retrospective risk assessment. This would involve long-term ecological monitoring to establish the trends in wildlife populations that are exposed to chemicals, and then carrying out forensic scientific analysis to establish if these are linked to chemical pollutants.

The paper's authors say this approach requires greater co-operation between scientists across different disciplines, and are calling on ecotoxicologists and environmental chemists to collaborate with ecologists.

One example of best practice of retrospective risk assessment and multidisciplinary collaboration, cited in the paper, is the investigative research carried out after declines were noted in bee populations. Several global studies, including UKCEH's pan-European field trial in 2014/15, showed that exposure to certain neonicotinoids had a negative impact on bees, resulting in EU bans on those pesticides.

Professor Johnson explains: "Our current system of chemical risk assessment is based on prospective rather than both prospective and retrospective analysis. Long-term environmental monitoring is not normally at the front of the queue for receiving funding, but it's cost effective and can provide the most compelling evidence of whether our use of chemicals is sustainable."

Credit: 
UK Centre for Ecology & Hydrology

Advanced practice registered nurses to have a greater role in national response to opioid epidemic

January 24, 2020 - As we enter a new year and a new decade, many states have enacted legislation affecting the roles of advanced practice registered nurses (APRNs) in terms of practice authority, reimbursement, and prescriptive authority, according to the 32nd Annual Legislative Update in the January issue of The Nurse Practitioner, published by Wolters Kluwer.

"This year, states have again placed an emphasis on enacting policy focused on the national opioid crisis," writes Susanne J. Phillips, DNP, APRN, FNP-BC, FAANP, of the University of California, Irvine, in her annual report on legislative developments in APRN practice. "APRNs in greater numbers participate in state prescription drug monitoring programs and opioid prescribing programs to improve access to safe and effective care for patients with chronic pain."

Expanded Roles for APRNs in Opioid Prescribing, Practice Authority and More

As the nation grapples with the challenges of effectively responding to the opioid epidemic, APRNs continue to play an expanded role. Three states - Arkansas, Florida, and South Carolina - advanced APRNs' prescriptive authority for prescribing opioids and schedule II controlled substances under certain circumstances. Wyoming introduced new limits on opioid prescribing for acute pain, affecting all prescribers including APRNs.

In Iowa and Wyoming, new regulations were passed related to APRNs' participation in state prescription drug monitoring programs (PDMPs). Two states enacted new laws related to continuing education requirements for prescriptive authority renewal: Delaware removed some redundant hours of pharmacology CE, while Oklahoma added two hours of education in pain management, opioid use, or addiction.

New legislation related to APRN practice authority was enacted in 12 states, including laws improving or clarifying APRN scope of practice. In Connecticut, APRNs were added to statutes regarding several areas of practice - behavioral health, healthcare facility admissions, and others - that previously mentioned only physicians or other healthcare providers.

Other states enacted specific scope of practice improvements or clarifications, in some cases including signature authority, including Montana, Nevada, North Dakota, Oklahoma, South Carolina, and Texas. New laws related APRNs' medical staff membership, credentialing, and privileging were passed in Nevada, New Mexico, and Washington. In Kentucky, the legislature authorized the Board of Nursing to regulate the practice of certified professional midwifery.

Several states adopted new policies regarding APRN involvement in telehealth, including full Medicaid reimbursement for telehealth services provided by APRNs in Kentucky. Additional APRN reimbursement policies were introduced in Colorado and Virginia. Other changes include tax incentives for APRN preceptors in South Carolina, new transition-to-practice statutes in South Dakota, and a delay to implementation of rules limiting APRNs practice authority in providing home health services in Washington.

The Nurse Practitioner's Annual Legislative Update provides a milestone marking nationwide efforts to take full advantage of the care provided by APRNs in their efforts to improve access to high-quality, safe, and effective healthcare. Through an "exceedingly active" 2018-19 legislative session, APRNs now have full, autonomous practice and prescriptive authority in 14 states, and full practice authority following a transition to practice period in another 10 states.

Credit: 
Wolters Kluwer Health

Opioid dependence found to permanently change brains of rats

Approximately one-quarter of patients who are prescribed opioids for chronic pain misuse them, with five to 10 percent developing an opioid use disorder or addiction. In a new study, published Jan. 14, 2020 in PNAS, researchers at University of California San Diego School of Medicine found that opioid dependence produced permanent changes in the brains of rats.

More specifically, researchers reported that dependence on oxycodone, a potent opioid painkiller, led to permanent neuro-adaptations of the central nucleus of the amygdala (CeA) at the level of the nociceptin system, a brainwide network that modulates transmission of pain. Downregulation or suppression of the nociceptin system in the CeA led to an increase in activation of GABA receptors in rats highly addicted to opioids. The discovery is consistent with previous findings reporting CeA neuroa-daptations after cocaine and alcohol dependence.

When researchers restored nociceptin levels in the CeA, it resulted in normalization of GABAergic transmission and a reduction of the rats' opioid consumption.

"This suggests the nociceptin system may be a promising target for the treatment of opioid use disorder," said senior author Giordano de Guglielmo, PharmD, PhD, assistant professor in the Department of Psychiatry at UC San Diego School of Medicine.

"To reveal the role of nociceptin in the central nucleus of the amygdala, we used a multidisciplinary approach with behavioral models, molecular biology and electrophysiology," said first author Marsida Kallupi, PharmD, PhD, assistant professor in the Department of Psychiatry. "That allowed us to conclude that downregulation of this peptide may be partially responsible for excessive opioid addiction-like behaviors."

Currently, opioid maintenance therapy is the first-line treatment for opioid dependence, which involves using alternative, less damaging medications, such as methadone, buprenorphine and naltrexone. These three drugs are the only treatments approved by the U.S. Food and Drug Administration, but all have limitations, either because they act against different receptors, pose safety concerns or are less effective due to the need for strict adherence to treatment.

Both methadone and buprenorphine target mu-opioid receptors in the brain. The new research builds upon past behavioral and neurochemical studies suggesting the nociceptin system and its receptors (NOP) are also involved in opioid tolerance and reward, addiction to multiple drugs and modulation of stress. Interestingly, while the research demonstrates that NOP is implicated in development of opioid dependence, it conversely blocks effects of morphine-based opioids.

De Guglielmo said several efforts are already underway testing small molecule drugs that target the nociception system, and have produced positive effects in reducing alcohol-seeking behaviors and biology in rats. The new findings indicate they may offer similar potential therapeutic benefit for opioid addiction.

Every day, according to the National Institute on Drug Abuse, more than 130 people in the United States die after overdosing on opioids. Two out of three drug overdose deaths involve an opioid. From 1999 to 2017, the last year for which data is available, almost 400,000 Americans lost their lives to opioids, with 47,600 fatal overdoses in 2017 alone. It's estimated 2.1 million Americans have an opioid use disorder.

Credit: 
University of California - San Diego

UCI researchers identify a connection between early life adversity and opioid addiction

image: Individuals with a history of early life adversity (ELA) are disproportionately prone to opioid addiction. A new UCI-led study examines how early adversities interact with factors such as increased access to opioids to directly influence brain development and function, causing a higher potential for opioid addiction

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School of Biological Sciences / UCI

Irvine, CA - January 24, 2020 - Individuals with a history of early life adversity (ELA) are disproportionately prone to opioid addiction. A new UCI-led study reveals why.

Published in Molecular Psychiatry, the study titled, "On the early life origins of vulnerability to opioid addiction," examines how early adversities interact with factors such as increased access to opioids to directly influence brain development and function, causing a higher potential for opioid addiction.

"We already know that genetics plays a major role in addiction vulnerability. But, this factor alone cannot account for the recent exponential rise in opioid abuse," said Tallie Z. Baram, MD, PhD, the Danette Shepard Chair in Neurological Sciences at the UCI School of Medicine and one of the senior researchers for the study. "Our team was determined to find out if environmental factors, like early life adversity, were contributing."

Until now, it was unclear whether alterations of the maturation and function of pleasure/reward circuits in the brain, resulting from ELA, actually caused individuals to be more vulnerable to opioid use disorder.

"Our work creates, for the first time, a direct causal link between early life adversity and opioid addiction vulnerability," said Stephen V. Mahler, an assistant professor in the Department of Neurobiology & Behavior at the UCI School of Biological Sciences and a senior researcher for the study. "This is key to the development of predictive biomarkers and possible prevention strategies aimed at addressing the growing opioid abuse epidemic."

Prior studies involving rodents demonstrated that ELA is characterized by chaotic, unpredictable maternal signals to the developing pups. Converging evidence from both humans and rodents shows that such unpredictable, fragmented early life environments may lead to abnormal maturation of certain brain circuits, which profoundly impacts brain function and persists into adolescence and adulthood.

For this study, researchers simulated ELA in rats by limiting bedding and nesting materials during a short, postnatal period of time. In female rats, this led to striking opioid addiction-like characteristics including an increased relapse-like behavior. Remarkably, as observed in addicted humans, the rats were willing to work very hard (pay a very high price) to obtain the drug.

"Our study provided novel insights into potential origins and nature of a reward circuit malfunction in the brain," said Baram. "Ultimately, we found that conditions during sensitive developmental periods can lead to vulnerability to the addictive effects of opioid drugs, especially in females, which is consistent with the prevalence of ELA in heroin addicted women."

The findings highlight the importance of attention to sex differences in future ELA-related studies on opioid addiction, and in future prevention or intervention strategies being developed to address the growing opioid crisis.

According to the National Institute on Drug Abuse, more than 130 people in the United States die each day after overdosing on opioids. The misuse of and addiction to opioids--including prescription pain relievers, heroin, and synthetic opioids such as fentanyl--is a serious national crisis that affects public health as well as social and economic welfare. The Centers for Disease Control and Prevention estimates that the total "economic burden" of prescription opioid misuse alone is $78.5 billion a year, including the costs of healthcare, lost productivity, addiction treatment, and criminal justice involvement.

Credit: 
University of California - Irvine