Culture

Known as nature's own sonar system, echolocation occurs when an animal emits a sound that bounces off objects in the environment, returning echoes that provide information about the surrounding space.

While echolocation is well known in whale or bat species, previous research has also indicated that some blind people may use click-based echolocation to judge spaces and improve their navigation skills.

Equipped with this knowledge, a team of researchers, led by Dr Lore Thaler, of Durham University, UK, delved into the factors that determine how people learn this skill.

Over the course of a 10-week training programme, the team investigated how blindness and age affect learning of click-based echolocation. They also studied how learning of this skill affects the daily life of people who are blind.

The findings are published in the journal PLOS ONE.

The study involved blind and sighted participants between 21 and 79 years of age who trained over the course of 10 weeks. Blind participants also took part in a 3-month follow up survey assessing the effects of the training on their daily life.

Both sighted and blind people improved considerably on all measures, and in some cases performed comparatively to expert echolocators at the end of training. Somewhat surprisingly, in some cases sighted people even performed better than those who were blind.

Importantly, however, neither age nor blindness was a limiting factor in participants' rate of learning or in their ability to apply their echolocation skills to novel, untrained tasks. Furthermore, in the follow up survey, all participants who were blind reported improved mobility, and 83% reported better independence and wellbeing.

Overall, the results suggest that the ability to learn click-based echolocation is not strongly limited
by age or level of vision. This has positive implications for the rehabilitation of people with vision loss or in the early stages of progressive vision loss.

Currently, click-based echolocation is not taught as part of mobility training and rehabilitation for blind people. There is also the possibility that some people are reluctant to use click-based echolocation due to a perceived stigma around making the required clicks in social environments.

Despite this, the results indicate that blind people who use echolocation and people new to echolocation are confident to use it in social situations. The potential barriers relating to perceived stigma are perhaps much smaller than previously thought.

Dr. Lore Thaler, in the Department of Psychology at Durham University, said "I cannot think of any other work with blind participants that has had such enthusiastic feedback."

"People who took part in our study reported that the training in click-based echolocation had a positive effect on their mobility, independence and wellbeing, attesting that the improvements we observed in the lab transcended into positive life benefits outside the lab. "

"We are very excited about this and feel that it would make sense to provide information and training in click-based echolocation to people who may still have good functional vision, but who are expected to lose vision later in life because of progressive degenerative eye conditions."

The human brain continues to surprise us with its capabilities for complex learning strategies and the neuroplasticity to alter its very structure to better process information from its senses.

The work was funded by a grant of the Biotechnology and Biological Sciences Research Council United Kingdom, and a grant from the Network for Social Change.

Clinical trials published in high-profile medical journals rarely report on income or other key sociodemographic characteristics of study participants, according to a new study that suggests these gaps may create blind spots when it comes to health care, especially for disadvantaged populations.

The study, publishing June 2 in JAMA Network Open, analyzed 10 per cent of 2,351 randomized clinical trials published in New England Journal of Medicine, JAMA, The BMJ, The Lancet and Annals of Internal Medicine between Jan. 1, 2014 and July 31, 2020.

The most commonly reported sociodemographic variables were sex and gender (in 98.7 per cent of trials) and race/ethnicity (in 48.5 per cent). All other sociodemographic data, such as income, literacy or education level, language or housing status were reported in less than 15 per cent of the trials.

"Randomized trials can only work for everyone if they include everyone," said Dr. Aaron Orkin, a researcher and Emergency Physician at St. Joseph's Health Centre of Unity Health Toronto who led the study. "The results of randomized trials affect everybody because they determine how we promote health and how we diagnose and treat disease.

"If trials don't report on the characteristics of the people being studied, there is no way to know that the study's findings will apply to all populations. Trials can only serve populations made vulnerable by social and economic policies if they are included."

The research found that education level or literacy was reported in 14.3 per cent of studies examined, 5.9 per cent reported income or socioeconomic status and 4.6 per cent included participants based on a social determinant of health, such as health insurance or employment status which are social factors that impact health. Of the 237 studies examined, only six (2.5 per cent) reported gender. No studies reported non-binary gender descriptors.

Dr. Orkin used the rollout of the COVID-19 vaccine as an example to explain why these findings are important. Public health officials now know that communities who are most vulnerable to COVID-19 tend to also be those who face the most barriers in terms of access to vaccines.

"In Ontario, Manitoba and elsewhere, data on race, ethnicity, income and occupation were collected with cases of COVID-19, and this has informed the vaccine rollout," noted Dr. Andrew Pinto, a Scientist at the MAP Centre for Urban Health Solutions of St. Michael's, who co-led the study and was a co-author. "We need to ensure data on these important social determinants of health are included in COVID-19 treatment and vaccine studies as well," he noted.

Similarly, recently, including women in cardiovascular trials after years of exclusion has led to the discovery that women have different heart disease symptoms and pathologies - something that was not known until women were included in randomized clinical trials about the disease.

"People who face discrimination or disadvantages should have confidence that research being done to benefit them is inclusive," said Dr. Nav Persaud, a scientist at MAP and co-author on the paper.

The authors argue that experiences and outcomes of a disease across cultures, races, income levels, living situations, genders, and other variables will be different. Studying a disease and its treatment in limited groups ultimately limits its applicability.

The authors hope to use the initial information reported in this study to focus on reporting of social determinants in trials in specific disease areas and to change standards in conducting research.

"Trials like the ones we studied have a great impact on clinical guidelines and often determine what gets funded. Inclusivity from the start is essential," Dr. Pinto said.

MINNEAPOLIS - Deep brain stimulation continues to be effective in people with Parkinson's disease 15 years after the device is implanted, according to a study published in the June 2, 2021, online issue of Neurology®, the medical journal of the American Academy of Neurology.

Researchers found that compared to before deep brain stimulation, study participants continued to experience significant improvement in motor symptoms, which are symptoms that affect movement, as well as a reduction in medications 15 years later.

Parkinson's disease can progressively affect speech, walking and balance due to a gradual reduction of a chemical in the brain called dopamine. Parkinson's symptoms of muscle stiffness, tremor and slowness of movement can be treated with a medication call levodopa that temporarily restores dopamine. However, that process of rising and falling levels of dopamine throughout the day can cause dyskinesia, a side effect of medication that may include twisting, swaying or head bobbing.

Deep brain stimulation controls motor symptoms from Parkinson's disease with electrodes that are placed in certain areas of the brain. The electrodes are connected to a device placed under the skin in the upper chest. The device controls the electrical impulses.

"Deep brain stimulation benefits seem to last for several years but not enough data have been available to show that these effects are still present more than 15 years after surgery," said study author Elena Moro, MD, PhD, of the Grenoble Alpes University in France and a Fellow of the American Academy of Neurology. "We wanted to know if people with Parkinson's disease continue to benefit from this treatment. It is exciting to report that our study found in the long run, deep brain stimulation continues to be effective in people with Parkinson's disease."

For the study, researchers identified 51 people who had a deep brain stimulation device implanted at the university hospital. The average age for diagnosis of Parkinson's disease was 40. The average age for device implantation was 51. Study participants had the device an average of 17 years.

Researchers reviewed data for each participant on movement problems, quality of life, medication and scores on tests that measure the severity and progression of Parkinson's disease.

Researchers found that when comparing data on participants before having a device implanted to data 15 years later, the amount of time participants experienced dyskinesia was reduced by 75%.

Researchers also found the amount of time spent in an "off state," when medication was no longer working well, was reduced by 59%. Also, the use of medications to control dopamine levels was reduced by 51%.

Researchers found few side effects of having the stimulation for 15 years and such side effects were mostly manageable.

"Our study also found that despite the natural progression of Parkinson's disease and the worsening of some symptoms that become resistant to medications over the years, participants still maintained an overall improvement in quality of life," said Moro. "Future studies should continue to examine the benefits of deep brain stimulation over longer periods of time and in larger groups of people."

A limitation of the study was that many of the people who had deep brain stimulation at the hospital were not available for study 15 years later, either because researchers were no longer able to contact them or because they had died. It is possible that the people in the study may have been healthier than those not included, meaning the results may not fully reflect the experience of all people using deep brain stimulation.

What The Study Did: Researchers investigated the effect of real-time continuous glucose monitoring on glycemic control among patients with insulin-treated diabetes.

Authors: Andrew J. Karter, Ph.D., of Kaiser Permanente in Oakland, California, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2021.6530)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Individuals at higher risk of developing pancreatic cancer could be identified earlier using machine learning (ML) techniques which would result in a greater number of patients surviving the disease, suggests a new study published in PLOS ONE.

The study was led by the London School of Hygiene & Tropical Medicine (LSHTM) and funded by the UK charity Pancreatic Cancer Research Fund (PCRF).

It used UK electronic health records for more than 1,000 patients aged 15-99 years who were diagnosed with pancreatic cancer between January 2005 and June 2009.

The researchers examined numerous symptoms and health statuses recorded by a GP among patients up to two years before the cancer diagnosis. They then developed an algorithm which 'learnt' how to distinguish patients who went on to develop pancreatic cancer from those who didn't.

The algorithm was then used to identify those at high risk of developing pancreatic cancer just from GP records.

Using this technique, 41% of patients under the age of 60 were identified as high risk, up to 20 months prior to diagnosis. Over 72% of people who went on to be diagnosed would have been successfully identified as high risk (sensitivity) whilst 59% of people who did not develop cancer were correctly identified as low risk (specificity). Results were similar for patients over 60, with 43% identified at 17 months, with 65% sensitivity and 57% specificity.

The team estimates that combining their algorithm with simple blood and urine tests which could potentially detect pancreatic cancer, currently under investigation, could result in 30 older and 400 younger patients per cancer being identified as 'potential patients'. This could lead to the earlier diagnosis of around 60% of all pancreatic cancer tumours.

The authors acknowledge that further work is required to confirm, refine and evaluate the potential use of these findings in practice.

Dr Ananya Malhotra, co-lead author from the London School of Hygiene & Tropical Medicine, said: "Each year, 460,000 people worldwide are diagnosed with pancreatic cancer, and only around 5% of those diagnosed survive for five years or more. This low survival is because patients are usually diagnosed very late. Recent progress has been made in identifying biomarkers in the blood and urine, but these tests cannot be used for population screening as they would be very expensive and potentially harmful due to the psychological distress of excess testing.

"Although preliminary, this study offers some hope for a new early diagnosis for pancreatic cancer which until now remains elusive."

Previous research has highlighted conditions associated with pancreatic cancer diagnosis such as jaundice, abdominal pain and new-onset diabetes. Whilst these new results are consistent with these findings, this approach is a step-change from these previous studies because the team examined whether it is possible to predict future pancreatic cancer based on the presence of a combination of symptoms or abnormalities more than 12 months before diagnosis, ignoring late-stage symptoms.

The case-control study used anonymised electronic health records from primary care linked to cancer registrations. Cases were comprised of 1,139 patients, aged 15-99 years, diagnosed with pancreatic cancer between January 2005 and June 2009. Each case was age-, sex- and diagnosis time-matched to four non-pancreatic (cancer patient) controls. Disease and prescription codes for the 24 months prior to diagnosis were used to identify 57 individual symptoms, with models then trained to predict patients who later developed pancreatic cancer.

The algorithm's greatest potential is within a multiple-testing model where pancreatic cancer is one of several malignancies of interest. Another important finding was the relative importance of diabetes, over time-varying symptoms, in predicting later pancreatic cancer diagnosis, which is consistent with previous research.

Dr Laura Woods, study senior author from the London School of Hygiene & Tropical Medicine, said: "Using machine learning techniques we developed a risk score for pancreatic cancer diagnosis in order to identify patients for whom biomarkers might detect the disease at an early and treatable stage. After further work this approach could be applied in the primary care setting and has the potential to be used alongside a non-invasive biomarker test to increase earlier diagnosis. This would result in a greater number of patients surviving this devastating disease."

Maggie Blanks, Pancreatic Cancer Research Fund's Chief Executive Officer, said: "Using machine learning to help improve earlier diagnosis is truly novel and we're extremely pleased that this pilot study has shown to have strong potential. We're looking forward to seeing where this research leads, as earlier diagnosis will be a game-changer for improving survival for patients."

The authors acknowledge limitations of the study including the poor specificity of the models arising principally from the use of cancer patients as controls that are not representative of the general population.

The research team is seeking further funding to develop this pilot study into a full investigation.

All the cells of an organism share the same DNA sequence, but their functions, shapes or even lifespans vary greatly. This happens because each cell "reads" different chapters of the genome, thus producing alternative sets of proteins and embarking on different paths. Epigenetic regulation--DNA methylation is one of the most common mechanisms--is responsible for the activation or inactivation of a given gene in a specific cell, defining a secondary cell-specific genetic code.

Researchers led by Dr. Modesto Orozco, head of the Molecular Modelling and Bioinformatics lab at IRB Barcelona, have described how methylation has a protein-independent regulatory role by increasing the stiffness of DNA, which affects the 3D structure of the genome, thus impacting gene activation. Present work reveals a cryptic mechanism connecting epigenetic footprinting and gene programming, which can help us to better understand development, ageing and cancer.

"The new model organism and the theoretical analysis framework that we have developed and published are really innovative and we hope they will facilitate research projects undertaken by many laboratories around the world studying DNA methylation and its impact on gene expression," explains Dr. Orozco, also an ICREA Academia Fellow and Professor of the University of Barcelona (UB).

3D structure and gene expression

The DNA inside the cell is folded and structured in a 3D manner to maintain its correct organisation and preservation. When a gene has to be "read", DNA unfolds in this region, allowing access to the cellular machinery. Therefore, the 3D structure increases or decreases accessibility to a gene, conditioning whether that gene will produce the protein it encodes for, or not. For this study, the Molecular Modelling and Bioinformatics group used next-generation sequencing methods and molecular simulations to model the whole genome structure.

"Using these techniques, we observed that we could recapitulate the characteristic distribution of DNA methylation seen in mammalian genomes, and we confirmed our earlier in vitro result on the relationship between 3D structure, DNA flexibility, and methylation, showing that this also occurs in vivo," explains Dr. Isabelle Brun Heath, director of the Experimental Bioinformatics Laboratory and codirector the study.

Autistic people's ability to accurately identify facial expressions is affected by the speed at which the expression is produced and its intensity, according to new research at the University of Birmingham.

In particular, autistic people tend to be less able to accurately identify anger from facial expressions produced at a normal 'real world' speed. The researchers also found that for people with a related disorder, alexithymia, all expressions appeared more intensely emotional.

The question of how people with autism recognise and relate to emotional expression has been debated by scientists for more than three decades and it's only in the past 10 years that the relationship between autism and alexithymia has been explored.

This new study, published in the Journal of Autism and Developmental Disorders, uses new techniques to explore the different impacts of autism and alexithymia on a person's ability to accurately gauge the emotions suggested by different facial expressions.

Connor Keating, a PhD researcher in the University of Birmingham's School of Psychology and Centre for Human Brain Health, is lead author of the study. He says: "We identified that autistic people had a specific difficulty recognising anger which we are starting to think may relate to differences in the way autistic and non-autistic people produce these expressions. If this is true, it may not be accurate to talk about autistic people as having an 'impairment' or 'deficit' in recognising emotion- it's more that autistic and non-autistic faces may be speaking a different language when it comes to conveying emotion".

In the study, 31 autistic and 29 non-autistic participants were asked to identify emotions from a series of moving images made up of dots representing the key dynamic points of a facial expression - a little bit like the dots used to translate human movement into CGI animation. The images were displayed at a range of emotional intensities by varying the amount of movement in each expression, and at a variety of speeds.

The team found that both autistic and non-autistic participants had similar recognition capabilities at different speeds and intensities across all the emotions shown, except for one particular aspect - the autistic group were less able to identify angry expressions produced at normal speed and intensity. These represented the sorts of angry expressions that might be encountered in everyday life.

"When we looked at how well participants could recognise angry expressions, we found that it was definitely autistic traits that contribute, but not alexithymic traits," explained Connor. "That suggests recognising anger is a difficulty that's specific to autism."

A key trait that the team found was specific to participants with alexithymia was a tendency to perceive the expressions to be intensely emotional. Interestingly though, people with alexithymia were more likely to give higher correct and incorrect emotion ratings to the expressions. To give an example, those with alexithymia would rate a happy expression as more intensely happy and more intensely angry and sad than someone without alexithymia.

Connor explains: "One idea is that people with alexithymia are less able to gauge the intensity of emotional expressions and are more likely to get confused about which emotion is being presented."

He adds: "Everyone will know or meet somebody with autism at some point in their lives.By better understanding how people with autism perceive and understand the world we can start to develop training and other interventions for both autistic and non-autistic people to overcome some of the barriers to interacting successfully."

In the journal Nature Communications, an interdisciplinary team from the Max Planck Institute of Colloids and Interfaces presents for the first time a laser-driven technology that enables them to create nanoparticles such as copper, cobalt and nickel oxides. At the usual printing speed, photoelectrodes are produced in this way, for example, for a wide range of applications such as the generation of green hydrogen.

Previous methods produce such nanomaterials only with high energy input in classical reaction vessels and in many hours. With the laser-driven technology developed at the institute, the scientists can deposit small amounts of material on a surface and simultaneously perform chemical synthesis in a very short time using high temperatures from the laser. 'When I discovered the nanocrystals under the electron microscope, I knew I was onto something big,' says Junfang Zhang, first author of the study and doctoral researcher. The discovery turned into a new and environmentally friendly method for synthesizing materials that can, among other things, efficiently convert solar energy into electricity.

Without detours with sunlight to hydrogen: 'Nowadays most of green hydrogen is produced from water using electricity generated by solar panels and stored in batteries. By employing photoelectrodes we can use solar light directly,' says Dr. Aleksandr Savateev.

The newly developed principle works with so-called transition metal oxides, mainly copper, cobalt and nickel oxides, all of which are good catalysts. The special feature of these oxides is the variety of their crystal forms (nanocrystals such as nanorods or nanostars), which affect their surface energy. Each structure can have a different effect on catalytic reactions. Therefore, it is important that these nanostructures can be made targeted - or even untargeted, but repeatable. The developed technology could also be used to find quickly and efficiently new catalysts. 'Laser dot by laser dot, we can create different catalysts side by side by simply varying the composition and conditions, and then also test them in parallel right away,' says Dr. Felix Löffler adding, 'But now we need to work on making the catalyst systems more persistent in all applications'.

The method

Similar to the principle of a typewriter, material is transferred from a donor to an acceptor carrier. On the former is the 'ink', a solid polymer, which is mixed with metal salts, the latter consists of a thin carbon nitride film on a conductive electrode. Targeted laser irradiation transfers the salts to the acceptor along with the molten polymer. The brief high temperatures cause the salts to react within milliseconds and they transform into metal oxide nanoparticles with desired morphology.

SAN ANTONIO (June 2, 2021) -- Scientists from The University of Texas Health Science Center at San Antonio have discovered a mechanism by which SARS-CoV-2 exploits changes in metal ion concentrations to disguise itself in the body. Varying concentrations of metal ions -- positively charged atoms such as magnesium, manganese and calcium -- are observed in hospitalized COVID-19 patients.

"This is a newly described metal-dependent mechanism by which these ions help the virus to evade immune surveillance," said Yogesh Gupta, PhD, senior author of the research published June 2 in the journal Nature Communications. Dr. Gupta is assistant professor of biochemistry and structural biology at the UT Health Science Center San Antonio and investigator with its Greehey Children's Cancer Research Institute.

Dr. Gupta and colleagues captured atomic-level snapshots during various stages of camouflaging activity of the coronavirus. It turns out metal ions have an architectural purpose -- they form a bridge between viral messenger RNA (which are instructions for encoding the virus) and a protein complex consisting of viral proteins nsp16 and nsp10. The activity is sort of like a scaffold swaying in the wind and workers laying hands on it to steady it.

With the scaffold stabilized, the virus then uses nsp16 to modify its messenger RNA cap into a Trojan horse unrecognizable to the immune system. This tricks the defenses, protects the RNA code from being degraded and enhances viral growth in the body. This activity is required each time the virus multiplies.

The nsp16/nsp10 protein complex stretches itself when the RNA cap is modified, which is a second finding the scientists reported. The stretching is facilitated by metal ion binding.

The understandings gleaned in this research can eventually aid treatment of all coronaviruses.

"The next step is to use this structural knowledge to develop novel therapies to treat COVID-19 and emerging coronavirus infections," Dr. Gupta said. "We are already studying how imbalances in metal concentrations regulate the host immune response to these infections."

In collaborative international effort, laser physicists at LMU have built the first hybrid plasma accelerator.

Particle accelerators have made crucial contributions to some of the most spectacular scientific discoveries of modern times, and greatly augmented our knowledge of the structure of matter. Now a team of laser physicists led by Prof. Stefan Karsch at the Ludwig-Maximilian University (LMU) in Munich and the Max Planck Institute for Quantum Optics, in cooperation with scientists based at the Helmholtz Centre in Dresden-Rossendorf (HZDR), the Laboratoire d'Optique Appliquée in Paris (LOA), Strathclyde University in Glasgow and the DESY Electron Synchrotron in Hamburg, have now achieved a significant breakthrough in accelerator miniaturization. They have built the first compact two-stage plasma-based accelerator in which particles in a plasma wave initiated by a powerful laser are used to accelerate a beam of electrons.

Particle accelerators have become an indispensable tool for studies of the structure of matter at sub-atomic scales, and have important applications in biology and medicine. Most of these systems make use of powerful radio-frequency waves to bring particles up to the desired energy. One drawback of this approach, which has been the standard methodology in the field for decades, lies in the risk of electrical breakdown when very high levels of electrical power at radio frequencies are coupled into the accelerator. This potential risk effectively limits the field strengths attainable, and is one of the reasons why these accelerator systems are typically many kilometers long. Physicists have therefore been exploring ways of reducing their size by exploiting the fact that a plasma can sustain much higher acceleration fields. In this case, the electric field generated by a powerful laser or a particle beam is used to strip electrons from the atoms in a gas and to create a wake similar to the one produced by a speedboat on water, Electrons surfing on that wake can get accelerated to nearly the speed of light within a distance of only a few millimeters.

Studies on plasma-based acceleration with the aid of lasers, i.e. Laser Wakefield Acceleration (LWFA), are now in progress in many research institutions around the world. In contrast, work with accelerators based on particle beams - a field which is known as Plasma Wakefield Acceleration (PWFA) - has so far been possible only in large-scale accelerator facilities (e.g. CERN, DESY and SLAC), although it offers a number of advantages over LWFA. For example, particle beams do not heat the plasma as much as laser beams and allow to use a longer accelerating distance. This in turn promises to improve the quality of the beam and increase its energy, parameters that are a very important in terms of the technique's potential range of applications.

In their experiments, the authors of the new study were able, for the first time, to build and successfully test a practical and compact particle-based plasma accelerator. The essential breakthrough lies in the fact that the PWFA, which accelerates the final electron beam, is driven by a particle beam from an LWFA. The latter is itself highly compact, so that the hybrid plasma accelerator is only a few centimeters long. Moreover, simulations indicate that the acceleration fields are more than three orders of magnitude higher than that attainable in conventional accelerators. Another promising result of the study is that the data obtained at LMU are confirmed by complementary tests performed with the DRACO laser at the HZDR.

Dr. Andreas Döpp, a member of the Munich group led by Prof. Stefan Karsch, points out that "only a few years ago, the practical realization of such a combination would have been unthinkable. The hybrid accelerator was made possible by subsequent developments in the design of laser-based accelerators, which have led to tremendous improvements in the stability of the beam and in other vital parameters." Much of this progress has been made at LMU, following the installation in the Centre for Advanced Laser Applications (CALA) of the ATLAS laser, which is one of the most powerful of its kind in Germany.

The successful demonstration of the hybrid plasma accelerator represents the latest advance ahead. "We had already shown that our compact plasma accelerator behaves very similarly to its conventional and far larger conventional cousins. So we are confident that we will be able to generate extremely bright electron beams with this set-up in the near future," says Stefan Karsch.

Before the technology can be applied on a wider scale, a number of outstanding challenges must be overcome, but the team are already considering a variety of possible contexts in which such instruments would highly advantageous. "For instance, research groups that have not had easy access to a particle accelerator could utilize the technique and develop it further. Secondly, our hybrid accelerator could serve as the basis for what is called a free-electron laser (FEL)," says Dr. Arie Irman, who coordinated the experiments at the HZDR.

FELs are highly prized radiation sources, which can be used for extremely precise characterizations of nanomaterials, biomolecules and geological samples. Competition for access to these sources, such as the European XFEL in Hamburg, has been correspondingly intense. If such large-scale X-ray lasers could be complemented by the new plasma-based technology in future, such more compact sources could potentially be made available for a broader user base, therefore boosting research with brilliant X-rays as a whole.

Smoking in early puberty in boys may have negative consequences for their future generations of offspring, a study from the University of Bergen (UiB) shows.

By continued analysis of data gathered in the large international RHINESSA, RHINE and ECRHS studies, researchers have found that the health of future generations depends on actions and decisions made by young people today. This is particularly relevant for boys in early puberty and mothers/grandmothers both pre-pregnancy and during pregnancy, the study shows.

The paper "Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generation study using a causal modelling approach" was recently published in the European
Respiratory Journal. The study highlights the importance of putting greater focus on smoking in young people (defined as before 15 years of age) to prevent potential damage on lung function in future generations. It also suggests including the use of moist oral tobacco (snus) and e-cigarette use.

According to the World Health Organization (WHO), roughly 6 million people die from tobacco-related ailments every day. The number is projected to rise over 8 million by 2030. The UiB-study underlines that the smokers not only jeopardize their own health, but also the health of their children and possibly their grandchildren.

Changes in the male germ cells

The study finds that both the pre-natal period and the pre-puberty period are times of high importance for the growing of cells, in particular germ cells. The researchers suggest that lifestyle and environmental factors impact respiratory health by epigenetic changes transmitted through male germ cells. Further, the study finds that lifestyle-related exposures during these periods influence the health of future generations.

In addition to reduced lung-function, the RHINESSA study finds that prepubertal smoking in boys can lead to obesity in their sons. However, interventions that aim to prevent smoking (nicotine use) in the most vulnerable time-windows, might have potential benefits for several generations.

Humans can observe what and where something happens around them with their hearing, as long as sound frequencies lie between 20 Hz and 20 000 Hz. Researchers at Aalto University have now developed a new audio technique that enables people to also hear ultrasonic sources that generate sound at frequencies above 20,000 Hz with simultaneous perception of their direction. The results have been published in Scientific Reports on 2 June 2021.

'In our study, we used bats in their natural habitat as sources of ultrasonic sound. With our new technique, we can now hear the directions-of-arrival of bat sounds, which means we can track bats in flight and hear where they are - we're essentially giving ourselves super hearing,' says Professor Ville Pulkki from Aalto University.

Small devices have been used before to listen to bats but previous versions haven't allowed listeners to locate the bats, just hear them. With their device the researchers record ultrasound using an array of microphones flush mounted and uniformly distributed on the surface of a small sphere. After the signal has been pitch-shifted to audible frequencies, the sound is played back on the headphones immediately. Currently, the pitch-shifting is performed on a computer, but, in the future, it could be done with electronics attached to the headphones.

'A sound-field analysis is performed on the microphone signals, and as a result we obtain the most prominent direction of the ultrasonic sound field and a parameter that suggests that the sound comes only from a single source. After this, a single microphone signal is brought to the audible frequency range of human hearing and its single-source signal is played back on the headphones so that the listener can perceive the source from the direction the sound was analysed to arrive,' Pulkki says.

On top of its popular appeal, the technique has tangible real-world applications.

'In science and art, people have always been interested in how they could improve their senses. Finding sources of ultrasonic sound is also useful in many practical situations, such as finding leaks in pressurised gas pipes. Minor pipe leaks often produce strong ultrasound emissions not detected by normal hearing. The device allows us to spot the sound source quickly,' Pulkki explains.

'Sometimes, damaged electrical equipment also emit ultrasound, and the device could be used for locating faulty equipment faster in places such as data centres,' he continues.

What drives the feasibility of climate scenarios commonly reviewed by organizations like the Intergovernmental Panel on Climate Change (IPCC)? And can they actually be achieved in practice? A new systematic framework can help understand what to improve in the next generation of scenarios and explore how to make ambitious emission reductions possible by strengthening enabling conditions.

While the IPCC is in the midst of the drafting cycle of the Sixth Assessment Report, whose publication will start in the second half of 2021, there is an ongoing debate on how to assess the feasibility of ambitious climate mitigation scenarios developed through integrated assessment models and to what extent they are actually achievable in the real world. In their new study published in Environmental Research Letters, researchers from IIASA and the RFF-CMCC European Institute on Economics and the Environment (EIEE) developed a systematic framework that allows identifying the type, timing, and location of feasibility concerns raised by climate mitigation scenarios.

"Feasibility - in other words, how plausible it is that a scenario materializes in the real world - is a complex concept that is currently getting significant academic attention. In our research, we built on past advancements in theoretical discussions and propose to operationalize feasibility in terms of the timing, disruptiveness, and scale of transformation across geophysical, technological, economic, institutional, and sociocultural feasibility dimensions," explains the paper's first author, Elina Brutschin, researcher in the IIASA Transformative Institutional and Social Solutions Research Group.

"Another major insight concerns the necessity to improve the assessment of socio-cultural feasibility concerns by including more indicators and incorporating insights on attitudes and behavioral changes from the social sciences," says Silvia Pianta, a postdoctoral researcher at EIEE and PhD fellow at Bocconi University.

"We found that the current generation of scenarios does not explore demand-side mitigation to its full potential and that more research is necessary in this area," adds coauthor Bas van Ruijven, IIASA Sustainable Service Systems Research Group leader.

To address these issues, the researchers developed a feasibility evaluation of indicators in each decade, with a flexible aggregation procedure that allows assessing feasibility concerns across dimensions and time. This flexible approach enabled them to look at the "big picture" to, for instance, assess which dimension raises major feasibility concerns, but also to analyze more detailed questions such as trade-offs over time, both within and across different dimensions. The resulting systematic framework is extremely useful, not only to understand what to improve in the next generation of scenarios, but also to analyze more systematically what type of enabling factors might bring us closer to more ambitious mitigation paths in the future.

The authors specifically applied the framework to the publicly available scenario set from the IPCC Special Report on Global Warming of 1.5°C and found that many scenarios currently assume a relatively fast overall decarbonization rate in regions that have a relatively low mitigation capacity. According to Brutschin, this suggests that many feasibility concerns are related to institutional constraints such as government effectiveness. While improving the quality of governance in many regions might be complicated, targeted capacity building and investments can significantly contribute to overcoming this challenge.

The authors highlight that the framework allows tracing important trade-offs over time, noting that while past studies focused on mitigation costs, the new research clearly shows that delayed climate action might generally be much more risky than an early disruptive transformation as delayed action requires an overall larger system to be transformed much faster and by relying on new technologies. In this regard, a better understanding of inter-temporal and inter-dimensional trade-offs incorporating insights from experts and policymakers is essential to take the overall understanding of the feasibility concepts to the next level.

"The new versatile framework that emerged from this collaborative project can be applied to any set of scenarios and can be constantly improved by incorporating new insights from the empirical literature on what is feasible in the real world. Although it was originally developed to evaluate global scenarios, it can be adjusted to have a more systematic evaluation of regional or national feasibility concerns in the future," notes IIASA Energy, Climate, and Environment Program Director, Keywan Riahi, who is also a coordinating lead author in Working Group III of the IPCC Sixth Assessment Report.

In addition to the new framework, the researchers also developed an interactive visual tool with key contributions by Giacomo Marangoni, a researcher at EIEE and Assistant Professor at Politecnico di Milano.

"A new data visualization method is extremely valuable when looking at multidimensional concepts such as feasibility. The tool we developed allows us to visualize our feasibility evaluations for different scenarios and to assess the sensitivity of our results to the definition of different feasibility concern thresholds," he says.

The data visualization tool can be accessed here: https://data.ece.iiasa.ac.at/climate-action-feasibility-dashboard/

Reference
Brutschin, E., Pianta, S., Tavoni, M., Riahi, K., Bosetti, V., Marangoni, G., & van Ruijven, B. (2021) A multidimensional feasibility evaluation of low-carbon scenarios. Environmental Research Letters DOI: 10.1088/1748-9326/abf0ce

Contacts:
Researcher contact
Elina Brutschin
Research Scholar
Transformative Institutional and Social Solutions Research Group
Energy, Climate, and Environment Program
Tel: +43 2236 807 350
brutschin@iiasa.ac.at

Press Officer
Ansa Heyl
IIASA Press Office
Tel: +43 2236 807 574
Mob: +43 676 83 807 574
heyl@iiasa.ac.at

About IIASA:
The International Institute for Applied Systems Analysis (IIASA) is an international scientific institute that conducts research into the critical issues of global environmental, economic, technological, and social change that we face in the twenty-first century. Our findings provide valuable options to policymakers to shape the future of our changing world. IIASA is independent and funded by prestigious research funding agencies in Africa, the Americas, Asia, and Europe.

About: RFF-CMCC European Institute on Economics and the Environment (EIEE)
RFF-CMCC European Institute on Economics and the Environment leverages two leading international centers for economic and environmental research: RFF - Resources for the Future and CMCC - Euro-Mediterranean Center on Climate Change. EIEE's research aims to improve environmental, energy, and natural resource decisions through impartial economic research and policy engagement to facilitate the transition to a sustainable, inclusive society. The focus is on issues surrounding but not limited to climate change, including a wide range of environmental, energy, natural resource, and societal issues.

One-quarter of people who take the drug methotrexate for common immune system disorders -- from rheumatoid arthritis to multiple sclerosis -- mount a weaker immune response to a COVID-19 vaccine, a new study shows.

Published (online May 25) recently in Annals of the Rheumatic Diseases, the study addressed disorders that result when the immune system, meant to fight disease and drive healing, is triggered abnormally. This in turn causes inflammation, the pain and swelling that come as immune cells rush into damaged or infected tissue, but often in the wrong amount or context. Called immune-mediated inflammatory disorders, they are typically treated with drugs that reduce inflammation, including methotrexate.

Led by researchers at NYU Grossman School of Medicine, the new study looked specifically at patients' responses to the Pfizer-BioNTech mRNA COVID-19 vaccine, which they measured by looking at the antibodies produced in each patient by the vaccine. Once injected into the body, vaccine ingredients are meant to trigger the production of antibodies, immune proteins that specifically glom onto this viral target protein, disabling it and tagging it for removal from the body.

The lower antibody response in patients who take methotrexate does not necessarily mean that these patients are not protected against COVID-19, cautions co-first study author Rebecca Haberman, MD, clinical instructor in the Department of Medicine at NYU Langone Health.

"It is most important to state that patients should not be concerned about our study findings as the majority of patients with immune system disorders are responding well to the mRNA vaccines," Dr. Haberman says. "It is also possible that methotrexate is delaying, rather than preventing, an adequate immune response against COVID-19."

Researchers have known that rheumatoid arthritis patients who take methotrexate have a reduced response to seasonal flu vaccines. Because mRNA vaccines use a new mechanism of action that patients with these common immune disorders have not seen before, the researchers wanted to determine how well these patients are protected.

The research was conducted at NYU Langone and at Friedrich-Alexander University Erlangen Nuremberg in Germany and enrolled healthy people and patients treated for common immune-mediated disorders, including rheumatoid arthritis, psoriatic arthritis and psoriasis. Study participants received two doses of Pfizer-BioNTech mRNA COVID-19 vaccine. The researchers analyzed blood samples to determine the amount of antibodies patients produced after receiving the vaccine and measured the activation of key immune system cells, including CD8 killer T cells, which are generated as part of the body's immune response.

The researchers found that over 90 percent of healthy subjects and patients taking drugs other than methotrexate to control inflammation in both the New York and German study groups mounted strong antibody responses. Patients with immune-mediated inflammatory disorders who were taking methotrexate achieved an adequate response in only 62 percent of cases. Similarly, while healthy patients and those with common immune disorders who were taking anti-inflammatory drugs other than methotrexate produced CD8 T cells, patients taking methotrexate did not show an increase in CD8 T cell activation after vaccination.

"More research is needed to understand why such a significant proportion of people with common immune disorders who take methotrexate have deficiencies in mounting an antibody and cellular response," says study co-senior author Jose U. Scher, MD, an associate professor in the Department of Medicine at NYU Langone. "This may not necessarily mean that the vaccine is not efficacious, but that alternate vaccine strategies need to be investigated."

These alternate vaccine strategies include potentially discontinuing methotrexate during the time these patients receive the vaccine, changing the dosage of methotrexate or possibly administering a booster shot to the vaccine, says Dr. Scher, who is also director of the Psoriatic Arthritis Center at NYU Langone. The research team is currently leading studies to determine the best course of action for these patients.

Zebrafish exposed to the leading cannabinoids found in cannabis in the earliest stages of development suffer a significant drop in neural activity later in life, according to a University of Alberta study that has implications for prenatal development in humans.

Richard Kanyo, the lead author on the study and post-doctoral fellow in the Faculty of Medicine & Dentistry, said despite the popular narrative that the health benefits of cannabis are many, it turns out there is a surprisingly large knowledge gap.

"Once the legalization happened, people got really excited about it and there's a lot of bias in the media about positive effects, so we began wondering about the negative implications," said Kanyo.

Kanyo teamed up with Declan Ali, a biological sciences researcher in the Faculty of Science, whose lab had an ongoing interest in how certain chemicals and compounds alter development in young animals "when their neurons are contacting each other and trying to communicate."

For the study, developing zebrafish embryos were left to incubate for 10 hours in a solution containing one of the two main active cannabinoids found in cannabis--tetrahydrocannabinol (THC) or cannabidiol (CBD)--or a combination of these two compounds, immediately after fertilization.

Ali explained that 10 hours represents a period in animal development that includes a stage of development known as gastrulation, when the multiplying cells start to form multiple tissue layers. In zebrafish it happens between five and 10 hours after the egg has been fertilized; in humans it lasts about a week and occurs roughly three weeks after egg fertilization.

The amount of drug used would be equivalent to someone consuming cannabis or the active compounds every day for two to three weeks at the very start of a pregnancy.

On the fourth day of development, Kanyo looked at brain activity using cutting-edge fluorescing calcium sensors that measure calcium, which is increased in active neurons.

He found that neural activity decreased by 60 to 70 per cent in the group bathed in THC and by more than 70 per cent in the group immersed in CBD. The decrease was even more pronounced in zebrafish that developed in a solution containing both compounds.

"The interesting part is when combined, like how it is found in a cannabis edible or cigarette, we needed much less to get the same reduction in neural activity," said Kanyo.

Ali said the concentrations used in the experiment are a little bit on the high side for just a single cigarette, to make up for the fact that the compounds have to work their way through an outer egg casing to get to the embryo.

"By the time that happens, we don't know what the exact concentrations are, but they're definitely going to be much lower than what we put in the baths themselves."

Compared with one of the control compounds, MS222, a local anesthetic that blocks activity along nerves, the drop in neural activity on the high end of the concentrations tested was the equivalent to the drop in animals that have been anesthetized, Kanyo noted.

At five days after fertilization, when the larvae slowly begin to swim, the reduction in activity compared with normally developed zebrafish was about 20 per cent for CBD and THC individually, but 80 per cent or higher when in combination.

"This reduction in locomotion is consistent with earlier studies as well," said Ali.

Ali said the research follows earlier studies showing that exposure of young organisms to THC and CBD, either alone or in combination, could have a detrimental impact on overall brain and neural activity that could be manifested in different ways.

And though more work is needed to better understand the mechanism behind the effects on neural activity, Ali said people who are thinking of having children would certainly want to limit exposure to any of these compounds in the same way they would limit exposure to nicotine and alcohol.

"We're not saying that these compounds are bad for you," he said. "I think in some contexts--pain relief or reducing seizures--there's a great potential there.

"However, what we're seeing is cannabis is not all good for everyone all the time and probably should not be taken during pregnancy."