Culture

The final results of the randomized phase two trial E3311 will be presented at the American Society of Clinical Oncology (ASCO) annual meeting, to occur virtually from May 29-31. The trial, conducted in patients undergoing transoral robotic surgery (TORS), tested reduced postoperative radiation therapy in patients with human papillomavirus-associated oropharynx squamous cell carcinoma at intermediate risk for recurrence. ASCO is highlighting the importance of the positive results by making it the first presentation in its Head and Neck Oral Abstract Session (Abstract 6500). The ECOG-ACRIN Cancer Research Group designed and conducted the trial with funding from the National Cancer Institute, part of the National Institutes of Health.

"Transoral resection followed by low-dose radiation is safe in patients with intermediate-risk locally advanced oropharynx cancer, with very good oncologic outcome," said lead investigator Robert L. Ferris, MD, PhD, director, UPMC Hillman Cancer Center in Pittsburgh and a surgical oncologist specializing in head and neck cancer (pictured). "These results present a promising deintensification approach."

Most pharynx cancers caused by HPV have a very good outcome, and the cancer does not return or spread to other parts of the body after treatment. Dr. Ferris and colleagues sought to prove the benefits of using tumor pathologic features, obtained in specimens collected at surgery, to determine patients' risk of recurrence-low, intermediate or high. In particular, they sought to more clearly define the prognostic and predictive role of traditional pathologic biomarkers such as extensive nodal or extranodal disease, to give the right amount of postoperative treatment for each risk group.

Patients at low risk were observed. Patients at intermediate risk were randomized to two arms of radiation alone, both at doses lower (50Gy or 60Gy) than usual (60-66Gy). At the time the trial opened in 2013, the optimal dose of radiation therapy was not defined. Patients at high risk were assigned to usual radiation therapy plus chemotherapy.

"Study E3311 met its primary endpoint," said Dr. Ferris. "For intermediate risk patients-those with uninvolved surgical margins, less than five involved nodes, and less than 1mm extranodal extension-reduced-dose postoperative radiation therapy without chemotherapy appears sufficient. In our study, this group had better outcomes than the group on usual high-dose radiation plus chemotherapy, showing that our patient stratification identified low and intermediate risk patients well, preserving patients' throat function and sparing them unnecessary short- and long-term toxicities."

For patients with low-risk disease, two-year progression-free survival (PFS) was favorable without postoperative therapy (observation alone). All arms had two-year survival rates above 90% and there was no excess of local recurrences with reduction in radiation or chemotherapy (Arms B and C). Risk stratification appeared to appropriately select patients for observation (Arm A).

The overall intent of E3311 was to gather essential data for the design of a future, randomized phase three trial. The primary endpoint was to determine the feasibility and oncologic efficacy of a prospective multi-institutional study of TORS for HPV+ oropharynx cancer followed by risk-adjusted adjuvant therapy. The primary endpoint was two-year progression-free survival in patients determined to be at intermediate risk after surgical excision.

"The tissue samples and imaging studies collected in the course of this trial are a rich resource for studying the biology of intermediate- and high-risk disease, in work that is ongoing," said ECOG-ACRIN Head and Neck Committee Chair, Barbara A. Burtness, MD, Professor of Medicine, and Co-Leader, Developmental Therapeutics Program, Yale Cancer Center and Yale School of Medicine (pictured). "ECOG-ACRIN plans to pursue the current data with a randomized phase three trial of TORS-based treatment deintensification compared with conventional chemoradiation."

A lump in the neck and a sore throat are the most common signs of oropharynx cancer, a disease in which cancer cells form in the tissues of the oropharynx-the middle part of the throat (pharynx), at the base of the tongue and tonsils. About 60% of oropharynx cancers are associated with HPV infection. The incidence has been increasing in recent years, especially in individuals under the age of 45. This change is attributed to the increasing prevalence of HPV infection in developed countries, the practice of oral sex, and the rising number of sexual partners.

While surgeons and patients widely favor the organ-preservation approach of transoral robotic surgery, there remain serious concerns about both short- and long-term toxicities associated with chemotherapy. Besides, given the potential long-term consequences of radiation therapy for a younger population, re-evaluation of adjuvant treatment intensity is needed.

Earth-based experiments on iron-sulfur alloys thought to comprise the core of Mars reveal details about the planet's seismic properties for the first time. This information will be compared to observations made by Martian space probes in the near future. Whether the results between experiment and observation coincide or not will either confirm existing theories about Mars' composition or call into question the story of its origin.

Mars is one of our closest terrestrial neighbors, yet it's still very far away -- between about 55 million and 400 million kilometers depending on where Earth and Mars are relative to the sun. At the time of writing, Mars is around 200 million kilometers away, and in any case, it is extremely difficult, expensive and dangerous to get to. For these reasons, it is sometimes more sensible to investigate the red planet through simulations here on Earth than it is to send an expensive space probe or, perhaps one day, people.

Keisuke Nishida, an Assistant Professor from the University of Tokyo's Department of Earth and Planetary Science at the time of the study, and his team are keen to investigate the inner workings of Mars. They look at seismic data and composition which tell researchers not just about the present state of the planet, but also about its past, including its origins.

"The exploration of the deep interiors of Earth, Mars and other planets is one of the great frontiers of science," said Nishida. "It's fascinating partly because of the daunting scales involved, but also because of how we investigate them safely from the surface of the Earth."

For a long time it has been theorized that the core of Mars probably consists of an iron-sulfur alloy. But given how inaccessible the Earth's core is to us, direct observations of Mars' core will likely have to wait some time. This is why seismic details are so important, as seismic waves, akin to enormously powerful sound waves, can travel through a planet and offer a glimpse inside, albeit with some caveats.

"NASA's Insight probe is already on Mars collecting seismic readings," said Nishida. "However, even with the seismic data there was an important missing piece of information without which the data could not be interpreted. We needed to know the seismic properties of the iron-sulfur alloy thought to make up the core of Mars."

Nishida and team have now measured the velocity for what is known as P-waves (one of two types of seismic wave, the other being S-waves) in molten iron-sulfur alloys.

"Due to technical hurdles, it took more than three years before we could collect the ultrasonic data we needed, so I am very pleased we now have it," said Nishida. "The sample is extremely small, which might surprise some people given the huge scale of the planet we are effectively simulating. But microscale high-pressure experiments help exploration of macroscale structures and long time-scale evolutionary histories of planets."

A molten iron-sulfur alloy just above its melting point of 1,500 degrees Celsius and subject to 13 gigapascals of pressure has a P-Wave velocity of 4,680 meters per second; this is over 13 times faster than the speed of sound in air, which is 343 meters per second. The researchers used a device called a Kawai-type multianvil press to compress the sample to such pressures. They used X-ray beams from two synchrotron facilities, KEK-PF and SPring-8, to help them image the samples in order to then calculate the P-wave values.

"Taking our results, researchers reading Martian seismic data will now be able to tell whether the core is primarily iron-sulfur alloy or not," said Nishida. "If it isn't, that will tell us something of Mars' origins. For example, if Mars' core includes silicon and oxygen, it suggests that, like the Earth, Mars suffered a huge impact event as it formed. So, what is Mars made of and how was it formed? I think we are about to find out."

Amsterdam, May 13, 2020- While history shows us that power tends to corrupt, a team of Swiss and German researchers have recently examined historical examples of large-scale business fraud and misconduct at the highest-levels of government in order to highlight how leaders sometimes lose all sense of morality. Inflicting serious harm on their company or society in the process.

This new study in The Leadership Quarterly, published by Elsevier, suggests a change in the selection process may mitigate the one key factor to blame: hubris.

Leaders often attribute their success to their superior ability and bask in their own brilliance. Drunk from power and overconfidence, they embark on endeavors that often begin to bring about detrimental outcomes. In recent times, we have witnessed accounting fraud at Enron, software fraud at Volkswagen, and corruption at FIFA - the list of misconduct by successful top managers is long.

"In classical Athens and medieval Venice, political positions were filled using a mixed procedure of targeted selection and drawing by lots," explained author Professor Katja Rost, University of Zurich, Switzerland. "We wanted to see how appointing leaders partly by random selection affected their performance."

Candidates were pre-selected according to conventional performance criteria. After conducting a large laboratory experiment and reviewing the existing literature, Dr. Berger, Assistant Professor, University of Bern, Switzerland and his research team including, Profs. Margit Osterloh, University Basel, Switzerland, Rost, and Thomas Ehrmann, University Münster, Germany confirm that partly random selection avoids hubris in leaders.

Their analysis found that overconfident leaders selected partly randomly are less prone to misusing their power and making decisions that are more beneficial to other members of the group, compared to overconfident leaders selected through the usual competitive selection process.

A competitive selection process typically triggers leadership hubris of overconfident people due to two factors. First, positions of power are often occupied by persons with overconfidence; and second, competitive selection methods confirm overconfident leaders' feeling that they are exceptional and perform far "above the average" of other candidates and feel entitled to enrich themselves.

In contrast, partly random selected leaders are more "humbled" than those selected by competitive methods without performing any less effectively.

"This study is intriguing and points to the problem of a current leaders selection methods. Yet, a potential better solution was discovered by city states and institutions of the past, who used, in part, random selection from a pool of candidates to appoint leaders," said Dr. John Antonakis, Editor-in-Chief of The Leadership Quarterly. "Dr. Berger and his colleagues now provide experimental evidence to support such a practice; this article should stimulate more research but more importantly, further reflection too by institutional legislators and selectors of leaders."

At a glance

Researchers have discovered the reason why the excessive amounts of mucus produced by patients with respiratory illnesses is thicker than usual.

Mucus viscosity is driven by proteins called 'trefoil factors' that bind to 'mucin glycoproteins' which are very long protein strands coated with unique sugar molecules.

Understanding these mechanisms could help to significantly improve airway-clearing treatments for patients with chronic respiratory diseases.

Worldwide, hundreds of millions of people are impacted by chronic respiratory disease. COPD alone affects more than 250 million people, causing 3 million deaths each year. People with chronic respiratory diseases typically produce an excessive amount of thick mucus in the lungs which obstructs their airways, making it difficult to breathe.

Significant leap in mucus biology

Mucus is mostly comprised of water and mucin glycoproteins which are very long protein strands coated with glycans - a type of sugar molecule. Associate Professor Goddard-Borger said the study's findings revealed that proteins called 'trefoil factors' interact with mucins by recognising and binding to the unique glycan signatures on their surface.

"Trefoil factors have long been known to make mucus more viscous (thicker), and it has been postulated that this thickening occurs in respiratory diseases. However, until now we did not completely understand how the trefoil factor proteins achieved this," he said.

Associate Professor Goddard-Borger said the research showed trefoil factors had two glycan-binding sites and could cross-link mucins strands to make the mucus gel more rigid. "Within mucus, trefoil factors essentially 'staple' the mucin strands into a mesh: the more staples, the denser the mesh and the thicker the mucus becomes."

Understanding what trefoil factors bind to and how they do this represents a significant leap forward in understanding mucus and how it functions in the respiratory, gastrointestinal and reproductive tracts.

Improving therapies for blocked airways

Associate Professor Goddard-Borger said that going forward the aim was to inhibit the bonds created between trefoil factors and mucin strands, and that the development of such a technology could lead to new therapeutics for the treatment of respiratory diseases.

"A healthy amount of mucus is very important for capturing and clearing potential threats to the lung, such as dust particles, dead cells and bacteria, so we're not looking to remove mucus altogether. We are seeking to develop innovative approaches for reducing the viscosity of the mucus to aid in clearing excess mucus from the lungs of patients with chronic respiratory disease.

"The next step is to work with commercial collaborators to progress our vision to develop new mucolytic drugs that can more effectively clear mucus from the airways. Achieving this could make a significant impact on the quality of life and life expectancy of people struggling with debilitating respiratory conditions," Associate Professor Goddard-Borger said.

Scientists have revealed the critical role that the chemical composition of bedrock plays in limiting vegetation growth in some of the world's most barren and rocky terrains.

A team of international scientists, including Professor Tim Quine from the University of Exeter, has conducted pioneering new research into vegetation productivity in a karst region of Southwest China.

Covering around 15 per cent of the Earth's land surface, karst terrains are usually characterised as being barren, rocky ground - usually with caves and sinkholes - and an absence of surface lakes and streams.

Crucially, the areas have well-jointed, dense limestone found near the surface, and a moderate to heavy rainfall - with the water being able to percolate away through the rock, dissolving and removing the limestone as it goes.

While this topography is known to hinder vegetation productivity, the role that geochemistry of the bedrock - that is its chemical composition - plays in reducing plant growth has not been extensively studied.

In the new study, the research team used a 'critical zone approach' - studying an area that extends from the base of the weathered bedrock to the top of the vegetation canopy - across a typical karst region of southwest china.

They found significant variations in the chemical composition of the bedrock across the region, which influenced both the amount and the distribution of soil. They discovered that this, in turn, also played a pivotal role in controlling plant growth.

The researchers showed not only that plant productivity is controlled not by both the soil and the bedrock's ability to retain water, but also this in turn is controlled by bedrock's geochemistry.

The research team believe this is especially important when water is in short supply - the hottest driest months of the year - and during droughts.

They also believe that the findings offer a pivotal tool in helping authorities to optimise land use, as well as assessing ecosystem resilience and sensitivity to climate change climate.

The study is published in Nature Communications on Wednesday, May 13th 2020.

Professor Quine said: "Our international team and interdisciplinary critical zone approach have given us invaluable insight into bedrock controls on vegetation growth in the iconic landscapes of China's Karst zone. We have been able to show that bedrock chemistry provides us with a valuable quantitative measure of the capacity of ecosystems to retain the water that is essential to sustain plant growth through dry seasons and droughts."

Professor Hongyan Liu of Peking University, and principle investigator, said: "Our research also shows the global significance of the bedrock influence on vegetation productivity. We selected 12 of the main karst regions in the world, 10 of which show significant differences in vegetation productivity due to bedrock geochemistry".

Professor Meersmans of the University of Liege said: "This study highlights the importance of interdisciplinary research across the boundaries of soil-, plant- and geosciences in order to unravel the impact and interplay of various key factors determining primary production in karst regions. Moreover, the present study offers a basis for future research assessing the resilience of these fragile ecosystems when facing climate change and other environmental threats."

The research was carried out as part of the UK-China (NERC-NSFC) SPECTRA project, called Soil Processes and Ecological Services in the Karst Critical Zone of Southwest China, which aims to enhance the sustainable development of one of the poorest regions of China, Guizhou.

The Guizhou karst region, with a population of 35 million, is one of the poorest regions in China with a GDP less than 50% of the national average. In response to the environmental deterioration and changing social conditions in the Guizhou karst region, the Chinese government has intervened to promote the abandonment of the most degraded cultivated land and its succession to grassland, shrub and forest.

The SPECTRA project is designed to identify the biological controls on nutrient availability, soil formation and loss, and their response to perturbation, providing the rich evidence base needed to inform land management decision-making in the Guizhou province.

Scientists at Japan's Institute for Integrated Cell-Material Sciences (iCeMS) are leading efforts to synthesize stronger and efficient materials for hydrogen fuel cell membranes. Most fuel cells currently on the market employ liquid membranes. A new coordination polymer glass membrane, reported in the journal Chemical Science, works just as well as its liquid counterparts with added strength and flexibility.

Hydrogen fuel cells are fed hydrogen and oxygen to produce electricity, with water as their only by-product. These fuel cells contain 'proton conducting membranes' that facilitate the separation of hydrogen's positive and negative particles, protons and electrons, a process that ultimately leads to the production of electricity.

Protons need to easily move across these membranes for the process to be efficient. Current proton conducting membranes are made from liquids and cannot operate effectively under dry conditions, making their fabrication complicated and expensive. Scientists are looking for ways to fabricate solid membranes made from water-free electrolytes that provide better mechanical and thermal stability than their liquid counterparts, but are also cost-effective and still conduct protons well.

"Our coordination polymer glass performed better than recently reported ionic liquids and crystalline coordination polymers," says Satoshi Horike, a materials scientist at Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS) who led the research.

Horike, Tomohiro Ogawa and colleagues in Japan fabricated their coordination polymer glass membrane by mixing a 'protic ionic liquid' with zinc ions. Protic ionic liquids are liquid salts made by mixing an acid and a base. The team used a protic ionic liquid called diethylmethylammonium dihydrogen phosphate. Adding zinc to this liquid led to the formation of a solid, elastic polymer glass.

The molecular structure of the coordination polymer glass facilitated the movement of protons across it under dry conditions at 120°C. When tested in a hydrogen fuel cell, it produced high voltage (0.96 volts), well within the range of typical polymer electrolyte membranes. Its power output was also similar to commonly used Nafion membranes.

Ogawa believes their findings offer an interesting approach for using glass polymers in fuel cell applications. The team plans to continue their work with the aim of achieving fuel cell membranes with higher performance and long-term stability.

Japanese researchers have succeeded in catalytic asymmetric iodoesterification from simple alkene substrates and carboxylic acids. Published in Angewandte Chemie International Edition on April 27, this new research, was accomplished by precisely controlling multiple interactions in a single catalytic reaction. This synthetic reaction is expected to contribute to the simplification of industrial processes and greater efficiency in optical active drug production.

Catalytic reactions are very important for the process of manufacturing chemical products and pharmaceuticals such as esters and halogen compounds, which are indispensable for everyday line. In particular, when the target compound has a chiral center, it is necessary to selectively obtain the correct optical isomer, and precise catalyst design is essential to the development of an asymmetric catalyst that achieves this. The research reported in the above article efficiently succeeds in obtaining an optically active ester incorporating iodine, and is expected to offer great value and huge potential to industry.

"Among the halogens, iodine is essential for developing and improving the functions of medicines, agrichemicals, and materials," says Professor Takayoshi Arai of Chiba University. "At the same time, the development of a catalyst technology that works to produce high-value-added iodine products is highly significant in Chiba, which is one of the world's leading iodine production sites."

For many years, Professor Arai has succeeded in developing asymmetric catalysts that utilize the properties of various metal complexes, and at the same time has employed a halogen bond as a catalyst design, expected to be capable of selective activation of soft-functionalities with a clear directionality. Professor Arai and his team have been researching catalyst design, and with this latest research, in addition to original catalyst design, they have succeeded in achieving a previously-inaccessible synthetic reaction by collaborating with a theoretical calculation research team.

Asymmetric iodolactonization, for which case studies have been reported, can easily be achieved because it involves an intramolecular reaction, but it requires a substrate synthesis and can be used only for particular purposes. By contrast, the iodoesterification reaction is industrially valuable as it combines two different inexpensive and readily available molecules in one reaction. However, in the iodoesterification reaction, both high-level activation and precise recognition of the three-dimensional molecule structure have to be compatible in the intermolecular reaction. Asymmetric iodoesterification reaction could not be realized so far due to the complexity of the reaction. This time, however, the research team developed a new strategy, and they achieved this combined with theoretical calculations in addition to applying the technology and know-how of stereoselective catalysts revealed in previous research. Furthermore, they found that four types of chemical bonds, namely metal carboxylate, halogen bond, hydrogen bond, and π-π stacking, collaborate catalytic asymmetric iodoesterification by coordinating the formation of one catalyst.

"In this research, we finally succeeded in accomplishing the asymmetric catalytic reaction of iodoesterification for the first time in the world by coordinating four different forces, much like playing a quartet on one catalyst," reports Professor Arai. "We hope that this practical new reaction will contribute significantly to the creation of optically active and highly functional iodine compounds and industrial application of such compounds."

It's "hammerhead" time according aerial drone footage of blacktip sharks fleeing to shallow waters when confronted by a huge predator along the coast of southeast Florida. Footage from the drone provides the first evidence of adult blacktip sharks (Carcharhinus limbatus) using shallow waters as a refuge from the great hammerhead shark, (Sphyrna mokarran) - proving you "can't touch this."

Several juvenile shark species use shallow water nursery sites where the young can grow with a reduced risk of predation. However, prior to a study by Florida Atlantic University, no documentation was available to show that large adult sharks also swim in shallower waters to avoid predation.

The use of unmanned aerial vehicles (UAVs) enabled FAU scientists to unobtrusively observe and allow natural behaviors to be documented in the wild, providing insight into seldom-seen predator-prey interactions. Results of the study are published in the Journal Fish Biology.

The blacktip shark is both an agile predator of teleost fishes, cephalopods and crustaceans and a prey for larger sharks, such as the great hammerhead, which can get as big as 18 feet long. Despite their large size, hammerheads are often found in relatively shallow waters that are likely an important area for their feeding. Their prey typically includes stingrays, bony fishes and other sharks, so it is no surprise that they have been spotted in and around the blacktip shark aggregations, which provide an abundance of possible prey.

On three separate occasions, a UAV recorded footage of a hammerhead shark approaching an aggregation of blacktip sharks in the nearshore waters of Palm Beach County. The average length of the blacktips captured in the area is under 6 feet, which the researchers used to calibrate the scale in the video footage to estimate the distance from shore for these interactions. Based on this estimate, all videos were recorded less than 150 feet offshore of the beach, in water no more than waist deep.

In all three events, blacktip sharks used the shallow waters close to shore as a refuge from a great hammerhead. The hammerhead sharks in the videos were at least twice the size of the blacktip sharks making them approximately 12 feet long. The three separate videos were recorded during the day on Feb. 28, 2018, Feb. 28, 2019 and March 3, 2019.

"In two of the three videos, the hammerhead shark actively chased one or more blacktips toward the shore but was unsuccessful at capturing its prey," said Stephen Kajiura, Ph.D., senior author, a professor of biological sciences and director of the Elasmobranch Laboratory in FAU's Charles E. Schmidt College of Science. Kajiura co-authored the paper with his undergraduate student and lead author, Melanie D. Doan. "The chases ended with the hammerhead making a sharp turn away from its intended prey and the shore, back into deeper waters. The chasing events showed the hammerhead struggling as it experienced difficulty following the blacktips into the shallow waters."

Hammerheads are known to possess an exceptionally tall first dorsal fin, longer than their pectoral fins. Their large dorsal fin is proposed to generate lift when swimming on their side, instead of facilitating propulsion and precise turning, as seen in every other observed shark species. The caudal fin thrusts and propels the shark forward, but both the dorsal fin and upper lobe of the caudal fin are seen breaching the surface in each of the videos in the study.

"When the dorsal and caudal fins of hammerhead breach the surface, they are neither generating lift, providing thrust, nor helping to facilitate turning as efficiently as when they are completely submerged," said Kajiura. "The shallow water thus constrains the locomotion of the hammerhead, which provides the blacktip shark with a functional refuge because their smaller size allows them to continue to swim and maneuver effectively away from their larger predator."

Some of the footage analyzed in this study was generously provided by a local citizen scientist and film maker, Joshua Jorgensen. The increasing popularity of UAVs will likely lead to additional fortuitous observations that can further inform the understanding of behaviors that are difficult to observe or have been previously undocumented.

"The predictable seasonal occurrence of large numbers of blacktip sharks in clear, shallow waters close to the beach in Palm Beach County, Florida, provides an excellent opportunity to employ unmanned aerial vehicles to quantitatively explore the collective behaviors and swimming kinematics of large sharks during natural predator-prey interactions," said Kajiura.

SASKATOON - An innovative radiation treatment that could one day be a valuable addition to conventional radiation therapy for inoperable brain and spinal tumors is a step closer, thanks to new research led by University of Saskatchewan (USask) researchers at the Canadian Light Source (CLS).

Microbeam radiation therapy (MRT) uses very high dose, synchrotron-generated X-ray beams--narrower than a human hair--to blast tumours with radiation while sparing healthy tissue. The idea is that MRT would deliver an additional dose of radiation to a tumor after maximum conventional radiation therapy has been tried, thereby providing patients with another treatment that could extend their lives.

But the longstanding questions have been: What is the optimal X-ray energy range of the MRT radiation dose that will both penetrate the thickness of the human body and still spare the healthy cells? How can the extremely high radiation doses be delivered and measured with the accuracy necessary for human treatment?

In a just-published paper in Physics in Medicine and Biology, the research team is the first to show that MRT can be scaled up for human radiation treatment. The team has identified how the radiation can be optimally delivered to ensure the safety and effectiveness of the potential human cancer treatment.

"The challenge has been to determine the ideal energy range needed so that the therapy can be used in humans with the next generation of synchrotrons," said Farley Chicilo, a USask PhD student in bio-medical engineering and lead author of the paper.

The energy range that's available now at synchrotrons around the world is not sufficient to penetrate the thickness of the human body.

"We were able to identify the higher X-ray energy range needed to penetrate the thickness of the human body, validating predictions from mathematical modeling," said Chicilo, noting that mathematical modeling had indicated the optimal X-ray energy would be 150 to 250 kiloelectron volts (keV).

MRT has a key advantage over other types of radiation: because the microscopically narrow beam of bombarding X-rays is sectioned like the teeth on a comb, the unirradiated healthy tissue in the spaces between the fine microbeams is able to help heal the irradiated tissue in the microbeam path.

"For MRT to be successful, we need the parallel microbeams to be as sharply defined as possible," Chicilo said. "Imagine a tumour therapy using knife cuts so thin that they could cut completely through an animal's spinal cord, and not paralyze the animal. MRT is that thin knife cut."

The team's experiment showed that at 150 keV, the high-energy, high-intensity microbeams were not blurred, allowing the damaged cells in the microbeam path to be quickly repaired by adjacent healthy cells.

"One might think that at higher energy the electrons would scatter more and damage surrounding tissue but it's the opposite," said USask medical imaging expert Dean Chapman, Chicilo's co-supervisor. "This new knowledge will affect how dedicated machines for MRT will be developed in future."

Another significant challenge for scientists investigating MRT has been the lack of a detector that can accurately and precisely measure the extremely high radiation doses at micron scale resolution.

"What our team did was to develop a unique high-dose radiation measurement detector technique and use it to determine the exact radiation dose contour delivered by the microbeam," said USask engineering professor Safa Kasap, who has been working on X-ray imaging detectors for more than two decades and is Chicilo's supervisor.

The detector uses a special glass containing samarium, a rare Earth ion, that helped the team measure the radiation dose and ensure it is precise and controlled. The glass itself was prepared by Andy Edgar at the Victoria University of Wellington in New Zealand, a long-time collaborator of the USask group. The detector using this glass and the measurement apparatus were designed and developed at USask, the only place that uses this unique material for MRT measurement of ionizing radiation.

Samarium glows orange when excited by a blue laser, but when exposed to X-rays, the ions gain an electron and glow red. By observing the ratio of orange to red light, the team was able to measure the dose deposited at a very high resolution over the large dose range of MRT.

"This is one of the best detectors that has been developed for measuring the detailed contour of the edges of the microbeam," said Kasap.

The new-found ability to predict both an ideal energy range of X-rays and the ideal width of the microbeams for human therapy will be "critical in future for treatment planning in clinical trials," said USask adjunct professor and team member Dr. Fred Geisler, a nuclear physicist and neurosurgeon who is an internationally renowned expert in spinal cord injury and spinal surgery.

"These are important and exciting steps in a process to make MRT available for human cancer treatment," Geisler said, adding this could take a decade.

Synchrotrons are the only means of generating high enough strength of parallel X-rays for MRT research. The CLS is one of only a few facilities in the world that can produce microbeams with the appropriate energy range for testing biological and medical applications.

Having the CLS located on the USask campus along with the Western College of Veterinary Medicine and the Saskatchewan Cancer Agency (SCA) creates a critical mass of multi-disciplinary researchers to continue to advance MRT.

In fact, Chicilo and some of his co-authors are currently working with the SCA on a mouse model to determine when to perform MRT after standard radiation therapy has already been tried.

Air pollution in China has received great attention due to its effects on climate and human health. A recent study showed the contrasting variation of air pollutants in China using long-term comprehensive data sets from 2013 to 2017, during which Chinese government took major efforts to reduce anthropogenic emission in polluted regions. A significant decreasing trend in the PM2.5 concentration in heavily polluted regions of the eastern China was happening. As a consequence, the heavily polluted days decreased in corresponded regions. However, surface ozone showed increasing trends in most of the cities from 2013 to 2017, which indicates a stronger photochemical pollution. 'It is so inspiring that the blue sky is coming back. However, surface ozone is increasing, which is a new challenge for future air pollution control. For the scientists, I think it is a unique opportunity to advance our current atmospheric chemistry and physics knowledge about influence of anthropogenic activity on our atmosphere' says Yonghong, the first author of the work.

In addition, using long-time measurements of aerosol chemical composition in urban Beijing, they revealed that concentrations of organic aerosol, nitrate, sulfate, ammonium and chloride showed a remarkable reductions from 2013 to 2017, connecting the decreases in aerosol precursors with corresponding chemical components closely.

New imaging technology allows scientists to see the widespread loss of brain synapses in early stages of Alzheimer's disease, a finding that one day may help aid in drug development, according to a new Yale University study.

The research, published May 13 in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, compared the density of synapses, which transmit signals between neighboring brain cells, in people with early stages of Alzheimer's with those of people who have no evidence of the disease. As expected, the loss of synapses in those with an early stage of Alzheimer's was particularly high in areas surrounding the hippocampus, an area of the brain crucial to formation of memory, the scientists report.

"However, our new methods enable us to detect widespread synaptic losses thoughout the brain," said Yale's Adam Mecca, assistant professor of psychiatry and first author of the paper. "This gives us confidence that we may use these results as a biomarker outcome for therapeutic trials, which could help speed development of new drugs to combat the disease."

To get a clearer picture of the early effects of Alzheimer's, the researchers used positron emission tomography (PET) imaging of a protein found in almost all brain synapses. Previous imaging technologies had been able to show in broad strokes the loss of brain tissue or reduced brain metabolism in Alzheimer's. However, the new PET scans show the distribution of synaptic damage, a more specific disease pathology present at early stages of the disease, the authors say.

"These methods will allow us to examine synaptic loss at still earlier stages of disease -- when people have evidence of Alzheimer's pathogenesis but have not yet manifested symptoms," said Christopher van Dyck, professor of psychiatry, neurology, and neuroscience, and senior author of the study.

The Yale team recently received a grant to conduct more synaptic imaging and relate synaptic loss to other disease markers for Alzheimer's, including amyloid and tau accumulation.

COVID-19, the disease caused by coronavirus SARS-Cov-2, has infected over 4 million people in 212 countries, of whom at least 272,000 have died. The ongoing economic and social impact of the pandemic is staggering, but despite a daily flood of news on the disease, few laypeople know that paradoxically, COVID-19 mostly kills through an overreaction of the immune system, whose function is precisely to fight infections.

In a new review article - explicitly targeted to non-specialists as well - in Frontiers in Public Health, a team of experts from Zunyi Medical University review the epidemiology, disease pathway, symptoms, diagnosis, and current treatment of severe COVID-19. They stress the key role of a potentially lethal overreaction of the immune system in the progression of the disease.

They explain step-by-step what is known about how the virus infects the airways, multiplies inside cells, and in severe cases causes the immune defenses to overshoot with a "cytokine storm". This storm is an over-activation of white blood cells, which release too-great amounts of cytokines - inflammation-stimulating molecules - into the blood.

"Similar to what happens after infection with SARS and MERS, data show that patients with severe COVID-19 may have a cytokine storm syndrome. The rapidly increased cytokines attract an excess of immune cells such as lymphocytes and neutrophils, resulting in an infiltration of these cells into lung tissue and thus cause lung injury," explains author Professor Daishun Liu from Zunyi Medical University, China.

The cytokine storm ultimately causes high fever, excessive leakiness of blood vessels, blood clotting inside the body, extremely low blood pressure, lack of oxygen and excess acidity of the blood, and build-up of fluids in the lungs ("pleural effusion").

White blood cells are misdirected to attack and inflame even healthy tissue, leading to failure of the lungs, heart, liver, intestines, kidneys, and genitals (Multiple Organ Dysfunction Syndrome, MODS). This may worsen and shutdown the lungs (Acute Respiratory Distress Syndrome, ARDS) due to the formation of a so-called hyaline membrane, composed of debris of proteins and dead cells, lining the lungs, which makes absorption of oxygen difficult. Most deaths due to COVID-19 are therefore due to respiratory failure.

Liu et al. explain how in the absence of a specific antiviral cure for COVID-19, the goal of treatment must be to the fight the symptoms, lowering the mortality rate through intensive maintenance of organ function, for example an artificial liver blood purification system or renal replacement therapy to filtrate the blood through mechanical means.

Especially important are methods to supplement or replace lung function, for example through non-invasive mechanical ventilation through a mask, ventilation through a tube into the windpipe (if possible with the refinement of Positive End Expiratory Pressure, PEEP, where the ventilator delivers extra pressure at the end of each breath of keep the lung vesicles open throughout), the administration of heated and humidified oxygen via a tube in the nose ("transnasal high-flow oxygen"), or a heart-lung bypass.

The authors conclude by stressing the importance of preventing secondary infections: SARS-Cov-2 also invades the intestines, where it causes inflammation and leakiness of the gut lining, allowing the opportunistic entry of other disease-causing microorganisms. They advocate that this should be prevented with nutritional support, for example with probiotics - beneficial bacteria that protect against the establishment of harmful ones - and nutrients and amino acids to improve the immune defenses and function of the intestine.

"Because treatment for now relies on aggressive treatment of symptoms, preventative protection against secondary infections, such as bacteria and fungi, is particularly important to support organ function, especially in the heart, kidneys, and liver, to try and avoid further deterioration of their condition," concludes Liu.

Blockchain, the technology that underpins digital currency and has acquired a slightly tainted reputation as a useful tool for organised crime, is coming out of the shadows and is set to become a friend to consumers, protecting them from tainted food, fake medicine, fraud and products with illegal or unethical origins, a new study from the University of Bath shows.

"Blockchain technologies are likely to form part of supply chain solutions in the same way that bar and QR codes and RFID tags are now mainstream. But blockchain offers much more in terms of product visibility and traceability, helping consumer safety and allowing the public to make more informed choices about what, how and where they buy from," Michael Rogerson, researcher at the University's School of Management, said.

Rogerson's research and case studies showed blockchain - essentially a system that creates a list or record of actions that is very difficult to change - can bring particular advantages to the food industry, not only in terms of ensuring food quality but also in giving visibility into how the food was produced, and its environmental footprint.

"Recent years have seen a spate of environmental, social, and health scandals as well as persistent abuses and fraud. Consumers are increasingly paying attention to the impact food production has on the environment and on the people working in the supply chain. Cases of modern slavery have been discovered in Vietnamese fisheries, and child labour in cocoa supply chains shows no sign of abating," Rogerson said.

"Perhaps the best known fraud was the 2013 horsemeat scandal in the UK, where up to 60% of products labelled as beef were in fact horse. There have also been instances of infected chicken being sold in UK supermarkets and a long-standing issue in the United States of Romain lettuce causing E.coli poisoning has only recently ended," he added.

Existing technologies allow firms and consumers to know where products have been and when, or their nutritional value and allergens, but they do not offer any information about what actually happens at each point in the supply chain - something blockchain can remedy if deployed correctly. This can give companies a competitive advantage by offering data and reassurance about the provenance of goods, Rogerson said.

Larger companies have begun to recognize that potential but have been reticent about sharing the outcomes of their trials with blockchain, which means industry has been slow to share and learn, delaying advances in food safety and denying potential benefits to consumers, Rogerson said. He found smaller organizations were more willing to share their experience for his research - "Blockchain:case studies in food supply chain visibility".

The research paper studied several cases, including a Shanghai-based company Techrock, which has developed a package that can assure parents that a particular baby formula is safe. A string of Chinese infant formula scandals beginning in 2008 killed at least 18 babies, affected 300,000, and destroyed confidence in a product many parents relied upon to feed their children.

Parents can scan the product with a mobile phone and instantly see data on the baby formula's production, logistics and a picture of what it should look like - crucial for combatting fake products. They can also see if the product has been opened and resealed.

In Australia, an agricultural commodity management platform Agridigital provides consumers with data that enables them to verify a marketing claim. Their system digitally captures inputs from farmers, data from supply processes and uses RFID tags to monitor product movements. Data is stored on a Quorum blockchain. They match the data against operational best practices to show conformance, which consumers can view using a mobile app.

And in Fiji the World Wildlife Fund has partnered with blockchain provider TraSeable to protect the sustainability of fisheries. The partnership collects data on fishing grounds, location and route, catch logs, and crew details using smartphones and stores it on a public Ethereum blockchain. Once fish are unloaded, QR-tagging is used to track fish to stores, where consumers can access these data using a mobile app.

"These positive uses and developments bode well for the future of blockchain although it is important to note that there has been much hype, and much myth, surrounding its potential. With this research we hope to show industry what is actually possible and give a realistic appraisal of the limitations of this safety-enhancing technology," Rogerson said.

Rogerson said it was important to understand the limitations around the technology and have an honest discussion about the issues to be resolved. In particular, to reduce fraud or error supply chains need to be digitized from origin to end user. And while the technology can improve visibility of what happens to a product at each point in the supply chain, that visibility will still rely on humans putting in the correct information, he said.

Additionally there are currently a variety of blockchain systems in use in supply chains but no agreed standards which could cause interoperability problems with data, particularly when it comes to consumers reading them on a variety of smartphone types and apps. And the cost of implementing such systems may restrict their use to higher value food products, medicines or goods where consumers are prepared to pay a premium, such as for baby formula.

"But possibly the largest obstacle might be the reputational issues attached to blockchain and the negative media coverage of cryptocurrencies. It would appear that blockchain, which the Economist once called 'the trust machine', has a trust issue and companies will have to work hard to overcome that - but our research shows that this work will pay off," Rogerson said.

To some, farming might seem simple: plant seeds, help them grow, then sell the product. But the reality is much different. Farming requires many complex decisions throughout the year.

One such decision is seeding rate - the number of seeds planted per acre. The best seeding rate for soybean fields is one of the most debated topics for those involved in agriculture.

Researchers have long tried to help farmers find a clear answer. A recent study by soybean scientists at Corteva Agriscience and universities across the U.S. might provide the most complete answer yet. They set out to determine what is called the optimal seeding rate for soybean growers.

"The optimal soybean seeding rate is a commonly discussed topic with many opinions, based on individual experience and regional experiments," says Adam Gaspar of Corteva Agriscience. "Our study is the largest soybean seeding rate study ever conducted. We hope to provide help to soybean growers based on where they are farming to help reduce risk and optimize yield potential."

A farmer could plant too little seed and not get maximum production. Or, they could plant too much and not make up the extra money spent. Optimum seeding rate is the ideal amount of seed to use to maximize production and minimize risk.

"Farm margins are very tight," Gaspar explains. "Growers are looking for ways to most efficiently use resources and control associated expenses, while not unnecessarily increasing their risk. Their seed purchase is a large investment, and one that has big implications. If they don't get it right, they are putting profitable returns at risk."

This collaborative research project is the first to determine seeding rates in different environments with low, medium, or high productivity. Medium productivity is average yield with low and high being below or above average. The productivity is influenced by various factors like soil type, topography and climate.

Researchers gathered data on the effects of seeding rate on soybean yield in 12 states plus Ontario, Canada from 2005 to 2007 and 2012 through 2017. The seeding rates, productivity and yield were analyzed.

Overall, the results showed that farmers should increase seeding rates in areas of lower productivity and reduce them in areas of higher productivity. As farmers know, these areas may vary in different parts of the farm. The productivity can even vary within different areas of each field.

Farmers can use this information to guide their decisions regarding how many seeds to plant per acre to maximize yield. Their seeding rate decisions may change from field to field, based on soil type, topography and previous yields. The seeding rate can even be changed within each field using variable rate planter technology.

"These findings will ultimately help growers use the optimal seeding rate between and within each field to optimize production, while limiting their risk of adverse yields due to seeding rates that are too high or too low," Gaspar says. "Also, it will emphasize the importance of establishing and maintaining an adequate plant stand until harvest. This is especially true in fields or areas of a field with low to medium productivity."

The work is unique because it brings together so many public and private researchers to share knowledge and resources. This directly helps soybean growers across North America.

"The annual seed purchase is one of the farmers' larger costs," says Gaspar. "It is critical for their success to make sure their seeding rate maximizes production and limits their downside risk. Our work will help soybean farmers manage their seed investment by being able to accurately adjust their seeding rates."

Researchers at Orygen and La Trobe University in Melbourne, Australia have completed a rapid review of contemporary epidemic and pandemic research to assess the potential impact of COVID-19 on people with psychosis.

The review, published online ahead of print in Schizophrenia Research, found an increase in the prevalence of psychosis as a result of COVID-19 would likely be associated with viral exposure, pre-existing vulnerability and psychosocial stress. The review also suggested that people with psychosis may present a major challenge and potential infection control risk to clinical teams working with them.

Orygen research fellow and co-lead author on the study, Dr Ellie Brown looked at published research on viruses such as MERS, SARS, swine influenza and other influenzas that have occurred in the past 20 years, to examine if there was any connection to how these viruses might impact people with psychosis.

"COVID-19 is a very stressful experience for everyone, particularly those with complex mental health needs," Dr Brown said. "We know that psychosis, and first episodes of psychosis, are commonly triggered by substantial psychosocial stresses. In the context of COVID-19, this could include stress relating to isolation and having to potentially remain within challenging family situations.

"People with psychosis are a population that are particularly vulnerable in the current COVID-19 pandemic and their needs are often overlooked.

"This research shows that their thoughts around contamination, and their understanding around concepts such as physical distancing may be different from the wider population."

Co-lead author of the research, Professor Richard Gray of La Trobe University said another important finding from the research was that psychotic symptoms, such as hearing voices, may occur in a small number of people with COVID-19.

"Maintaining infection control procedures when people are psychotic is challenging," Professor Gray said. "In order for them not to become potential transmitters of the virus, clinicians and service providers may benefit from specific infection control advice to mitigate any transmission risk."

Dr Brown said that although mental health disorders such as depression and anxiety were important to focus on during the COVID-19 pandemic, the community needed to be aware that the smaller but more severe spectrum of mental health conditions could be impacted as well.

Professor Gray agreed. "This is a group that's probably going to need more support, with isolation, physical distancing, hand washing etc, and clinicians may be the ones who need to be thinking and working on this to assist this vulnerable population," he said.