Culture

EAST LANSING, Mich. - In a time where many are practicing "social distancing" from the outside world, people are relying on their immediate social circles more than usual. Does a sense of obligation - from checking on parents to running an errand for an elderly neighbor - benefit or harm a relationship? A Michigan State University study found the sweet spot between keeping people together and dooming a relationship.

"We were looking to find whether obligation is all good or all bad," said William Chopik, assistant professor of psychology at MSU and co-author of the study. "When we started, we found that people were responding to types of obligations in different ways. People distinguished between requests that were massive obligations and requests that were simple. There's this point that obligation crosses over and starts to be harmful for relationships."

According to Jeewon Oh, MSU doctoral student and co-author of the study, obligation is sometimes the "glue that holds relationships together," but it often carries negative connotations.

"We found that some obligations were linked with greater depressive symptoms and slower increases in support from friends over time," Oh said. "However, other obligations were linked with both greater support and less strain from family and friends initially."

Chopik and Oh's findings suggest that there's a distinct point at which obligation pushes individuals to the brink of feeling burdened, which can start to harm their relationships.

"The line in our study is when it crosses over and starts to be either a massive financial burden or something that disrupts your day-to-day life," Chopik said. "While engaging in substantive obligation can benefit others and make someone feel helpful, it is still costly to a person's time, energy and money."

Until now, similar research showed inconsistencies in how obligation impacts relationships, which Chopik attributes to the spectrum of obligation. This spectrum ranges from light obligation, like keeping in touch with a friend, to substantive obligation, like lending that friend a considerable amount of money.

"In a way, major obligations violate the norms of friendships," Chopik said. "Interestingly, you don't see that violation as much in relationships with parents or spouses."

Chopik explained that friendships are viewed as low-investment, fun relationships that make people feel good.

"Our longest lasting friendships continue because we enjoy them. But if obligations pile up, it might compromise how close we feel to our friends," Chopik said. "Because friendships are a relationship of choice, people can distance themselves from friends more easily than other types of relationships when faced with burdensome obligations."

Additionally, substantive obligations may create strain in a friendship as we try to encourage our friends to do the same even when they might not be able to do so, Oh said.

"Although we may feel good when we do things for our friends, and our friends are grateful to us, we may start to feel like we are investing too much in that relationship," Oh said.

On the other end of the spectrum, light obligation creates what Chopik calls a "norm of reciprocity."

"Those light obligations make us feel better, make us happier and make our relationships stronger," Chopik said. "There's a sense that 'we're both in this together and that we've both invested something in the relationship.'"

That's why, among the best relationships, low-level acts of obligation don't feel like obligations at all. Small acts of kindness, which strengthen the bonds of our relationships, are done without any fuss or burden.

Still, some types of relationships can make even minor obligations seem daunting. If someone doesn't have a great relationship with a parent, a quick phone call to check in isn't enjoyable, it's an encumbrance.

"Even for things we would expect family members to do, some in the study did them begrudgingly," Chopik said.

Chopik and Oh's findings reveal a spectrum of obligations as diverse as the relationships one has in life.

"It's the little things you do that can really enhance a friendship, but asking too much of a friend can damage your relationship," Chopik said.

A group of researchers led by Leif Schroeder from the Leibniz-Forschungsinstitut fuer Molekulare Pharmakologie (FMP) have found a way to detect metastases in certain types of cancer in the brain at an early stage, using only minimal amounts of contrast agent. To this end, the team uses a synthetic molecule that helps to detect the formation of new blood vessels, producing much more sophisticated imaging than is possible with conventional methods of diagnosis. The results have now been published in Advanced Biosystems.

Some types of cancer - including breast cancer - may induce the formation of brain metastases. Increased development of new small blood vessels (capillaries) is an early sign of abnormal tissue changes. Conventional contrast agents used in magnetic resonance imaging (MRI) for examining the brain are not suitable for the direct and early detection of newly forming cells. "For this, we need a contrast agent that considerably increases the sensitivity of MRI by greatly improving the contrast structure, and that is only needed in tiny amounts," explained FMP researcher Dr. Leif Schroeder.

His group has been working for a long time to develop new contrast agents that detect artificially magnetized xenon in tissue and that cause signals even in small quantities. In his efforts to create a contrast agent especially suited for use in vascular cells of the so-called blood-brain barrier, the physicist was able to draw on preliminary work undertaken by his FMP colleague Dr. Margitta Dathe, who had developed a similar structure for drug transport to these cells in inner vascular walls of the brain. This peptide structure forms so-called micelles, aggregates of around 19 molecules that cluster spontaneously.

To utilize micelles for diagnostic purposes, Schroeder and his team had them modified: "We inserted molecular cages - synthetic molecules shaped like a hollow soccer ball - that we can temporarily fill with xenon. We were therefore able to 'switch on' 19 xenon loads per micelle for the image contrast, enabling us to directly visualize this type of tumor-forming cells," reported Leif Schroeder.

First, he and his team tested whether the modified version of the structure developed by Margitta Dathe would still form micelles. "Fortunately, the molecules behaved in the same way, despite the insertion of cages, and formed micelles composed of 19 units each," the researcher remarked. The micelles were then supposed to interact with large amounts of xenon.

Having a high local density of cages is a prerequisite for visualizing blood vessel cells in MRI. In a further step, the researchers tested whether xenon could enter the cages inside the molecules - this also proved successful. Schroeder then investigated how micelles equipped with xenon behave in two cell cultures, one of which comprised cerebral cells. In this case, the micelles docked onto blood vessel cells and labeled them - the newly developed contrast agent worked. To check their findings, Leif Schroeder also tested the micelles in aortic cells. Since this type of cell is structured differently, however, there was much less binding of micelles in this case.

The advantage of the new method is that the spread of malignant tumors to the brain can be detected early, before the onset of widespread metastasis. This is because, when metastasis occurs, brain areas exhibit increased formation of blood vessels, which are needed to supply nutrients to tumor tissue. In the case of breast cancer, this type of metastasis is often associated with a poor prognosis. Blood vessels absorb the micelles developed by Schroeder's and Dathe's team, and xenon enables the process of new vessel formation to be visualized directly - at an early stage. Conventional methods for labeling certain cells for MRI are much less sensitive. A comparison showed that alternatives involving fluorine contrast agents are around 16,000 times less efficient.

"The new contrast agent could be used for the safe and minimally invasive detection of early-stage cerebral metastases. This could have significant advantages, particularly in the diagnosis of breast cancer, because dangerous tumors can be detected much earlier, improving therapy outcomes," summarized Leif Schroeder. In the future, Schroeder and his group intend to utilize xenon-based contrast agents for other medical applications.

New York, NY--March 19, 2020--While beam steering systems have been used for many years for applications such as imaging, display, and optical trapping, they require bulky mechanical mirrors and are overly sensitive to vibrations. Compact optical phased arrays (OPAs), which change the angle of an optical beam by changing the beam's phase profile, are a promising new technology for many emerging applications. These include ultra-small solid-state LiDAR on autonomous vehicles, much smaller and lighter AR/VR displays, large-scale trapped-ion quantum computer to address ion qubits, and optogenetics, an emerging research field that uses light and genetic engineering to study the brain.

Long-range, high-performance OPAs require a large beam emission area densely packed with thousands of actively phase-controlled, power-hungry light-emitting elements. To date, such large-scale phased arrays, for LiDAR, have been impractical since the technologies in current use would have to operate at untenable electrical power levels.

Researchers led by Columbia Engineering Professor Michal Lipson have developed a low-power beam steering platform that is a non-mechanical, robust, and scalable approach to beam steering. The team is one of the first to demonstrate low-power large-scale optical phased array at near infrared and the first to demonstrate optical phased array technology on-chip at blue wavelength for autonomous navigation and augmented reality, respectively. In collaboration with Adam Kepecs' group at Washington University in St. Louis, the team has also developed an implantable photonic chip based on an optical switch array at blue wavelengths for precise optogenetic neural stimulation. The research has been recently published in three separate papers in Optica, Nature Biomedical Engineering, and Optics Letters.

"This new technology that enables our chip-based devices to point the beam anywhere we want opens the door wide for transforming a broad range of areas," says Lipson, Eugene Higgins Professor of Electrical Engineering and Professor of Applied Physics. "These include, for instance, the ability to make LiDAR devices as small as a credit card for a self-driving car, or a neural probe that controls micron scale beams to stimulate neurons for optogenetics neuroscience research, or a light delivery method to each individual ion in a system for general quantum manipulations and readout."

Lipson's team has designed a multi-pass platform that reduces the power consumption of an optical phase shifter while maintaining both its operation speed and broadband low loss for enabling scalable optical systems. They let the light signal recycle through the same phase shifter multiple times so that the total power consumption is reduced by the same factor it recycles. They demonstrated a silicon photonic phased array containing 512 actively controlled phase shifters and optical antenna, consuming very low power while performing 2D beam steering over a wide field of view. Their results are a significant advance towards building scalable phased arrays containing thousands of active elements.

Phased array devices were initially developed at larger electromagnetic wavelengths. By applying different phases at each antenna, researchers can form a very directional beam by designing constructive interference in one direction and destructive in other directions. In order to steer or turn the beam's direction, they can delay light in one emitter or shift a phase relative to another.

Current visible light applications for OPAs have been limited by bulky table-top devices that have a limited field of view due to their large pixel width. Previous OPA research done at the near-infrared wavelength, including work from the Lipson Nanophotonics Group, faced fabrication and material challenges in doing similar work at the visible wavelength.

"As the wavelength becomes smaller, the light becomes more sensitive to small changes such as fabrication errors," says Min Chul Shin, a PhD student in the Lipson group and co-lead author of the Optics Letter paper. "It also scatters more, resulting in higher loss if fabrication is not perfect--and fabrication can never be perfect."

It was only three years ago that Lipson's team showed a low-loss material platform by optimizing fabrication recipes with silicon nitride. They leveraged this platform to realize their new beam steering system in the visible wavelength--the first chip-scale phased array operating at blue wavelengths using a silicon nitride platform.

A major challenge for the researchers was working in the blue range, which has the smallest wavelength in the visible spectrum and scatters more than other colors because it travels as shorter, smaller waves. Another challenge in demonstrating a phased array in blue was that to achieve a wide angle, the team had to overcome the challenge of placing emitters half a wavelength apart or at least smaller than a wavelength--40 nm spacing, 2500 times smaller than human hair--which was very difficult to achieve. In addition, in order to make optical phased array useful for practical applications, they needed many emitters. Scaling this up to a large system would be extremely difficult.

"Not only is this fabrication really hard, but there would also be a lot of optical crosstalk with the waveguides that close," says Shin. "We can't have independent phase control plus we'd see all the light coupled to each other, not forming a directional beam."

Solving these issues for blue meant that the team could easily do this for red and green, which have longer wavelengths. "This wavelength range enables us to address new applications such as optogenetic neural stimulation," notes Aseema Mohanty, a postdoctoral research scientist and co-lead author of the Optics Letter and Nature Biomedical Engineering papers. "We used the same chip-scale technology to control an array of micron-scale beams to precisely probe neurons within the brain."

The team is now collaborating with Applied Physics Professor Nanfang Yu's group to optimize the electrical power consumption because low-power operation is crucial for lightweight head-mounted AR displays and optogenetics.

"We are very excited because we've basically designed a reconfigurable lens on a tiny chip on which we can steer the visible beam and change focus," explains Lipson. "We have an aperture where we can synthesize any visible pattern we want every few tens of microseconds. This requires no moving parts and could be achieved at chip-scale. Our new approach means that we'll be able to revolutionize augmented reality, optogenetics and many more technologies of the future."

Healthy ageing has become one of the priorities of research in Europe. University of Tartu researchers looked for differences in the immune systems of young and old people. They focused on monocytes and found that the monocytes of the elderly do not seem to produce as much energy, and there is an increase in inflammation markers compared to younger people. Looking into the future, this research gives food for thought as to how to slow down age-related changes.

White blood cells or leukocytes include many cells with various tasks. To get a better understanding of exactly what these cells do, they need to be observed separately. Therefore, researchers at the University of Tartu Institute of Biomedicine and Translational Medicine together with colleagues from Tartu University Hospital and Estonian Genome Centre studied a specific white blood cell type - monocytes.

Monocytes comprise about 5-10% of all white blood cells in human blood. As with all other leukocytes, they originate from the hematopoietic cells of bone marrow, but they have special properties which help them fight viruses and other pathogens. They are constantly changing through life together with general changes in the organism.

According to a professor of molecular immunology at the University of Tartu, Pärt Peterson, links between ageing and monocytes have been found before. "For example, they are known to be associated with inflammatory processes occurring in the body. A link between monocytes and vascular calcification or atherosclerosis is also known," said Peterson.

Vascular calcification means that, due to the deposition of dead cells, cholesterol, fatty acids and lipids, plaques are formed on the walls of arteries. Over years, these plaques become denser and make blood vessels narrower. As a result, blood flow in blood vessels becomes restricted. "Calcification is a long-term and complex change in the walls of blood vessels, but it is the monocytes that affect the inflammation originating from the walls of blood vessels and accumulate in atherosclerotic plaques," explained Peterson.

Primarily based on this background information, the researchers wanted to study which changes have occurred in the monocytes of young people, and which in the monocytes of the elderly. "We found that the expression of many genes varies in the monocytes of elderly people. Changes have mainly occurred in the genes related to protein synthesis and in the work of mitochondria, i.e. the power plants of cells. It might be said that the monocytes of older people do not seem to produce as much energy as the cells of younger people," noted the professor.

There was also a visible increase in the intracellular inflammation markers in older people, which is probably accompanied by a general increase in inflammation levels. There are also other intracellular metabolic changes, as a greater proportion of some lipids was noted in elderly people, for example. Many lipids are an important and natural part of cell membranes, but according to Peterson, this may lead to the idea that the excessive accumulation of lipidic compounds in monocytes may be related to the plaques forming on the walls of blood vessels, and thus to atherosclerosis.

"Time will show whether we will be able to do something to slow down age-related changes. This study at least gives an idea as to which direction we should look to next. In terms of the future, it would be a big achievement if we were able to postpone or even avoid the process of vascular calcification," said Peterson.

According to the scientist, new practical solutions will definitely be added in the future, taking into account that healthy ageing has become one of the priorities of research in Europe. Several European countries, including Denmark and the Netherlands, have already created specialised institutes and centres for solving the issues related to the ageing society.

Peterson noted that conducting such basic research studies in Estonia is convenient, because due to the small size of the country, we have very good contacts and cooperation possibilities, broad-based genetic data and great possibilities for developing digital health care.

CHAPEL HILL-- An analysis of evidence from multiple scientific studies found six substances that have a strong link to bladder cancer in the urine of people who had used electronic cigarettes and sometimes other tobacco products, researchers from the University of North Carolina Lineberger Comprehensive Cancer Center and NYU Langone Health reported.

In the study in the journal European Urology Oncology, researchers compiled the results of 22 different studies that analyzed the urine of people who used e-cigarettes or other tobacco products, including cigarettes, to check for evidence of cancer-linked compounds or biomarkers of those compounds. They found six biomarkers or compounds with a strong link to bladder cancer.

"Smoking is the No.1 modifiable behavioral risk factor for bladder cancer," said UNC Lineberger's Marc Bjurlin, DO, MSc, associate professor of urology in the UNC School of Medicine. "There is now evolving literature showing that people who vape may have similar carcinogens in their urine as combustible cigarette users."

While public health agencies including the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention have warned that there are health risks of vaping, including for e-cigarette-associated lung injury, their safety profile has not been "definitively characterized," according to Bjurlin and his colleagues.

"The first and foremost side effects that we're seeing from electronic cigarette use are lung and pulmonary related," Bjurlin said. "We won't see the side effects for these other kinds of carcinogenic pathways until much later down the exposure pipeline."

To develop a better understanding of the long-term risks of vaping, including cancer, researchers investigated possible exposure to substances that can cause bladder cancer in particular since carcinogens could be processed in the body and then passed in urine.

In their review, Bjurlin and his colleagues found 40 different parent compounds that can be processed in the body to produce 63 different toxic chemicals or carcinogenic metabolites, which are substances that remain after in the body after processing.

Six of those chemicals have a strong link to bladder cancer, according to researchers' analysis of carcinogens databases of the International Agency for Research on Cancer and the Collaborative on Health and the Environment Toxicant and Disease Database.

They found evidence in some studies that e-cigarette users had "significantly" higher levels of several carcinogens that can be metabolized into substances linked to bladder cancer in their urine compared to people who had never used them.

"This finding shows us that people who vape will be exposed to a variety of different carcinogens," Bjurlin said. "People who have decades of exposure to these carcinogens from vaping may be at risk for developing malignancies, especially bladder cancer."

There were several limitations to the study, including that researchers did not know the levels of all of the cancer-causing substances in the urine of users from the studies.

In addition, some studies included people who were "dual users," or people who both smoked and vaped e-cigarettes. There were also cases when users smoked cigarettes and switched to e-cigarettes.

"The study population was quite heterogeneous, meaning that often studies looked at dual users, meaning those who used e-cigarettes and combustible cigarettes," Bjurlin said. "That made it difficult to assess whether the carcinogen found in the urine was actually from the e-cigarette use or from the cigarette use."

Further research is needed, said Bjurlin, who wants to determine the threshold of exposure to carcinogens that would lead to development of bladder cancer or other cancer types. He plans to lead a study that will evaluate carcinogens in the urine of e-cigarette users, smokers and non-users.

"Although there is no definitive case yet linking bladder cancer to vaping, it may be reasonable to suspect that decades down the road after exposure to these byproducts, people who vape may be at risk of developing bladder cancer," he said.

New Rochelle, NY, March 19, 2020--A new study has shown a novel peptide antagonist, given in combination with a PD-1 inhibitor, to be safe and well-tolerated in patients with advanced, refractory pancreatic and rectal cancer. The highest dose tested had a good safety profile and was recommended for use in future patient trials, as reported in Journal of Pancreatic Cancer, a peer-reviewed open access publication from Mary Ann Liebert, Inc., publishers. Click here to read the full-text open access article free on the Journal of Pancreatic Cancer website.

"Safety and Pharmacokinetics of CXCR4 Peptide Antagonist, LY2510924, in Combination with Durvalumab in Advanced Refractory Solid Tumors" was coauthored by Mark O'Hara, MD, Abramson Cancer Center at the University of Pennsylvania, and colleagues from University of Colorado School of Medicine, The University of Chicago Medicine, Eli Lilly and Company, Astra Zeneca, and Washington University Medical School in St. Louis.

The purpose of this open label phase 1a study was to determine the maximum tolerated dose, safety, and tolerability of LY2510924, a CXCR4 peptide antagonist with proven, significant antitumor activity in preclinical studies, given in combination with the PD-1 inhibitor durvalumab. The study patients had advanced pancreatic or rectal cancer that did not respond to other treatment. Patients received 20, 30, or 40 mg of LY2510924 daily together with 1500 mg of durvalumab on day 1 of each 28-day cycle. No adverse events resulted in death or the need to discontinue treatment with any of the three doses, leading to the conclusion that the highest dose of LY2510924, 40 mg, daily is safe and well-tolerated and should be used in the next phase of studies. The researchers also reported that a best response of stable disease was seen in 44% of patients in the trial.

Journal of Pancreatic Cancer Editor-in-Chief Charles J. Yeo, MD, Department of Surgery, Thomas Jefferson University, states: "The Journal was pleased to publish this phase 1 study using a CXCR4 peptide antagonist with a PD-1 inhibitor in eight patients with advanced pancreatic cancer. The combination yielded tolerable side effects and some patients showing a certain degree of disease stability."

ROCHESTER, Minn. -- Homelessness has become a social crisis and public health problem around the world, affecting people of all ages. Most homeless people are at a disadvantage with few resources, and may or may not have adequate health insurance. Mental illness and substance abuse are common issues in the homeless community. People living on the streets have a high likelihood of developing heart disease. Yet they have little ability to take care of their health.

A new study published in Mayo Clinic Proceedings examined in-hospital outcomes and 30-day readmission rates of 3,937 homeless patients from more than 1.5 million people admitted for a heart attack. Researchers used two years of data (2015-2016) from the National Readmission Database. The findings show that homeless patients often receive less treatment and are more likely to end up readmitted to the hospital within a month.

"The differences in patterns of care and clinical outcomes between homeless and nonhomeless patients are likely a reflection of the differences in risk profile at baseline," says Mohamad Alkhouli, M.D., a Mayo Clinic cardiologist and senior author of the study.

Compared to those with stable housing, homeless patients admitted with a heart attack tended to be male, about 10 years younger, and had fewer traditional risk factors for heart disease. Homeless patients in the study had a higher incidence of congestive heart failure, anemia, chronic kidney disease, and liver and lung diseases. Anxiety, depression, substance abuse and HIV infections were substantially higher for this group, as well.

Looking at matched outcomes for each group, homeless patients received less treatment in the hospital, as shown through a lower rate of angiography and revascularization. The in-hospital mortality rate and median cost of hospitalization were similar for the homeless versus patients who were not homeless.

Other differences emerged when comparing length of stay and readmission. Homeless patients were in the hospital longer. Yet they were more likely to leave against medical advice and be discharged to an intermediate care facility. They were also more likely to be readmitted. The 30-day readmission rates differed significantly, with 22.5% of homeless patients readmitted, compared to only 10% of patients who were not homeless. Cardiovascular causes were the most common reasons for readmission in both groups. However, 18% of homeless patients were readmitted for psychiatric causes, compared to 2% of patients who were not homeless.

"Addressing cardiovascular disease in the growing population of the homeless comes with a unique set of challenges," says Dr. Alkhouli. "The high burden of psychiatric illness among the homeless emphasizes the need for a holistic approach to address both the clinical and social needs of these patients."

An international team of scientists, led by the University of Bristol, has found that current estimates of flood risk rely upon methods for calculating flood damage which are inadequately verified and match poorly with observations.

Instead, building damage at a given flood depth is highly variable and can be characterized by a beta distribution.

When calculating flood risk - that is, translating modelled representations of the physical of phenomenon of flooding to its impacts - it is common to apply a 'depth-damage function' or curve, which relates a given water depth to a proportional building loss (for example one metre of water equals 50 per cent loss of building value).

Academics have understood that this depth-damage relationship is variable and that there is no perfect fit, but it is still common to apply such curves which are inadequately verified.

The new study, published today in the journal Nature Communications, used commonly applied curves, developed by various US government agencies, and examined how they compare to millions of actual flood insurance claims made in the US.

The study's aim was then to find out if ubiquitous curves have any skill in replicating real measured losses and, if not, find the true relationship between depth and damage in the claims record.

It found that universally applied depth-damage curves show low skill in the replication of property-level damages, rendering the results of projects where they have been applied (for example the justification of billions of dollars of infrastructure investment) suspect.

Instead, depth-damage is highly variable: damages per depth are generally concentrated at high (>90 per cent) and low (

At low inundation depths, most damages are somewhat minimal (90 per cent) damage. But as depth increases, the distribution shifts and swings towards greater probability of high (>90 per cent) damage and lower probability of low (

Lead author, Dr Oliver Wing from Bristol's School of Geographical Sciences, said: "This relationship can be represented with a beta distribution, meaning future flood risk analyses can employ a function which properly captures the true stochastic relationship between depth and damage."

There is an implication that flood risk assessments which have relied on existing 1:1 depth-damage curves may be significant misestimates. Decisions for billions of dollars of infrastructure investment, where benefits (mitigated damages) are calculated to have exceeded costs (installing said infrastructure), are commonly green-lit even if benefits are marginally greater - yet, these benefits may have been quantified using inadequate functions.

In the development of the beta distribution-based functions, future analyses can be more robust for a plethora of applications: infrastructure investment, insurance pricing, planning decisions, and much else.

Co-author, Professor Paul Bates, also from the University of Bristol's School of Geographical Sciences, added: "We can integrate these new depth-damage functions into existing flood risk calculation architecture.

"However, the insurance claims data used to generate these do not contain information on vulnerability for non-residential buildings or enough information to incorporate secondary modifiers such as how depth-damage changes given the building is made from wood rather than concrete.

"To generate a complete suite of depth-damage information, we will need to find a way of fusing engineering knowledge with such empirical datasets so that we can compute flood risk accurately for all types of building."

Automated Scanning Probe Microscopy (SPM) controlled by artificial intelligence

First demonstration of fully autonomous, long-term SPM operation

An Australian-German collaboration has demonstrated fully-autonomous SPM operation, applying artificial intelligence and deep learning to remove the need for constant human supervision.

The new system, dubbed DeepSPM, bridges the gap between nanoscience, automation and artificial intelligence (AI), and firmly establishes the use of machine learning for experimental scientific research.

"Optimising SPM data acquisition can be very tedious. This optimisation process is usually performed by the human experimentalist, and is rarely reported," says FLEET Chief Investigator Dr Agustin Schiffrin (Monash University).

"Our new AI-driven system can operate and acquire optimal SPM data autonomously, for multiple straight days, and without any human supervision."

The advance brings advanced SPM methodologies such as atomically-precise nanofabrication and high-throughput data acquisition closer to a fully automated turnkey application.

The new deep learning approach can be generalised to other SPM techniques. The researchers have made the entire framework publicly available online as open source, creating an important resource for the nanoscience research community.

FULLY-AUTONOMOUS DeepSPM

"Crucial to the success of DeepSPM is the use of a self-learning agent, as the correct control inputs are not known beforehand," says Dr Cornelius Krull, project co-leader.

"Learning from experience, our agent adapts to changing experimental conditions and finds a strategy to keep the system stable," says Dr Krull, who works with Dr Schiffrin at Monash School of Physics and Astronomy.

The AI-driven system begins with an algorithmic search of the best sample regions and proceeds with autonomous data acquisition.

It then uses a convolutional neural network to assess the quality of the data. If the quality of the data is not good, DeepSPM uses a deep reinforcement learning agent to improve the condition of the probe.

DeepSPM can run for several days, acquiring and processing data continuously, while managing SPM parameters in response to varying experimental conditions, without any supervision.

The study demonstrates fully autonomous, long-term SPM operation for the first time by combining:

an algorithmic approach for sample area selection and SPM data acquisition;

supervised machine learning using convolutional neural networks for quality assessment and classification of SPM data, and

deep reinforcement learning for dynamic automated in-situ probe management and conditioning.

They are among the most common ailments for those residing at post-acute and long-term care (PALTC) centers, yet diagnosing and managing urinary tract infections (UTIs) remains a challenging prospect for caregivers at these facilities.

In an effort to address the issue, the Infection Advisory Committee of the American Medical Directors Association - The Society for Post-Acute and Long-Term Medicine (AMDA) convened in late 2016 to devise consistent guidelines for treating UTIs. The Journal of the American Medical Directors Association published the group's consensus statement in its January issue.

According to the statement, many of the issues related to UTI treatment at PALTCs, including overdiagnosis and overtreatment, may stem from rapidly evolving advances in evidence-based UTI treatment recommendations that fail to reach busy practitioners and staff working in an environment where "fast-paced" is an understatement. This often results in the continuation of established and deeply rooted practice methods or pressure from senior staff and concerned family members to move ahead with a treatment plan that may no longer be recognized as the most effective.

As a member of AMDA's Infection Advisory Committee, Kalin Clifford, Pharm.D., an assistant professor for the Texas Tech University Health Sciences Center Jerry H. Hodge School of Pharmacy, helped develop the statement. He said the last major update to UTI treatment recommendations occurred in 2007, and though an update was issued in 2011, the discovery of new antibiotics and modifications to preferred diagnosis and treatment methods made it necessary and crucial to overhaul the guidelines.

"We realized there is a gap in the literature of what really needs to be addressed when treating urinary tract infections," Clifford said. "There's been so much change that it was time to come up with something to help today's providers, especially our nursing home colleagues, identify if a patient is truly having a UTI."

In past studies, investigators have concluded that more than 50% of antibiotics prescribed for UTI treatment in PALTC facilities may be inappropriate. In addition, Centers for Disease Control and Prevention (CDC) estimates stated that organisms that have developed resistance to multiple drugs caused more than 2 million infections in 2013 and resulted in death for more than 1% of those affected. One of the primary culprits is Clostridioides difficile (C diff), a bacterium that often appears during or shortly after treatment with antibiotics. It can cause diarrhea, an inflamed colon and, in the most severe cases, death.

PALTC residents often face an increased risk for bacterial colonization and infection from multidrug-resistant microbes like C diff than do non-PALTC residents. Proper antibiotic prescribing and use can reduce the health risks associated with these bacteria, and Clifford said the need to do so compounded the Infection Advisory Subcommittee's urgency to develop a new consensus statement to assist health care providers in diagnosing, treating and preventing UTIs.

"A lot of times urinary tract infections are diagnosed later and then overtreated, or we're treating something that's not really there," Clifford said. "This consensus statement is a reminder of what we're really looking for with urinary tract infections and what the options are to approach and treat them."

Some of the current study-related literature suggests younger adults are better able to communicate symptoms often associated with UTIs like painful urination, increased frequency or changes in urine appearance and content. Clifford said there is some observational evidence that suggests a link between UTIs and certain cognitive changes that many older adults experience, but additional research is needed to determine if such a link exists.

"We don't know what comes first; is the urinary tract infection causing confusion and the dulling of cognition or is it the confusion that is causing the UTI," Clifford explained. "That's never been addressed and never been found, it's just an association made from seeing more confusion in some older adults and then they happen to have a urinary tract infection."

In addition to the largely unstudied and unproven confusion-UTI link, Clifford said the tendency to check for a UTI has increased because testing generally requires urine analysis, a process that is not particularly difficult or expensive. If the urine analysis reveals the presence of bacteria, the inclination is to diagnose a UTI and begin antibiotic treatment without knowing for certain if the pathogen is causing a problem.

"When we overtest, there is a likelihood to also overtreat," Clifford added. "We might see there's new confusion, so let's just get a urine analysis and see if something's growing, and if there is an infection, even if we may not be sure what it is, it might cause us to go ahead and try this antibiotic anyway."

Cognition difficulties and dementia may have rendered some PALTC residents unable to communicate verbally. Others may have a history of UTI-related pathology or may be otherwise perceived as vulnerable or immune compromised. In some circumstances, Clifford said, residents presenting these conditions may prompt a clinician to test for a UTI and then prescribe antibiotic treatment without having a complete picture of the infection. However, he cautions, simply identifying bacteria in urine in a person experiencing one or more of these factors doesn't always mean an antibiotic is required.

In creating its consensus statement, Clifford said the committee's primary objective was to encourage clinicians to go beyond reflexively ordering a urine analysis and antibiotics. Rather than focusing solely on symptoms like confusion and urine samples, the committee advises looking for additional factors. For instance, is the person using the restroom more often? If they have been diagnosed with dementia, is the dementia getting worse? Do you have to change their undergarments more often?

"Let's try to make sure the indication for starting antibiotics is truly there and that they're truly needed," Clifford emphasized. "First, let's look for a couple other symptoms before going straight to that. That's what we're going for with this document. We're trying to effectively explain what's been found over the last few years. The goal is to try to protect the antibiotics that we have and try to use everything appropriately."

Now that the statement has been published, Clifford said the committee is in the process of getting the recommendations into the hands health care providers, especially those in PALTC settings. As is the case with most other medical literature, it takes time to get the information disseminated. To aid the process, AMDA is developing a mini-brochure that practitioners can carry in their lab coat pocket or work bag so they can more quickly and easily reference the statement's main recommendations.

"This can't just be a one-off thing; you really do have to look for other changes, you do have to look for other symptoms. That's really what we're going on with this statement," Clifford stressed. "It's not thinking, 'Hey, they're confused and they weren't yesterday; so check for a UTI.' It's about trying to encourage everybody to take a minute and think about it before throwing on an antibiotic. It's really about stressing the need to know your patient as much as you can."

A study has uncovered a new neurodegenerative disorder in which children experience developmental regression and severe epilepsy.

The study, led by the Murdoch Children's Research Institute (MCRI) and published in The American Journal of Human Genetics, found a variation in a gene causes a severe childhood-onset neurodegenerative disorder that has never before been described.

MCRI and Victorian Clinical Genetics Services (VCGS) Associate Professor Sue White said this newly discovered condition was different from other chronic neuroinflammation implicated in other neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease and frontotemporal dementia.

Associate Professor White said the study participants started with normal or mild developmental delay, and the onset of seizures started within the first year of life.
All had a severe and progressive developmental regression following a seizure, she said.

The study looked at six children from four families with the gene variant who had a similar degenerative condition, the cause of which was unlocked by genomic testing.

The genomic testing and data analyses were conducted for four participants at VCGS in Melbourne and one each at Ospedale Pediatrico Bambino Gesù in Italy and at Baylor College of Medicine in the US.

Associate Professor White said the disorder, with features suggestive of neuroinflammation, appeared to require two copies of the defective gene, meaning both parents had to be carriers of one altered copy.

"In our study the same gene variant was identified in three children of the same ethnic background," she said.

"While the families do not report that their two families are directly related, they are presumed to be distantly related due to the overlap of their family histories, with common ancestors originating from the same town."

The researchers used advanced molecular techniques to dissect the likely cellular pathway affected by the mutation in the NRROS gene. By inserting the gene into cells in the laboratory, they identified other molecules that NRROS interacts with. These molecules are crucial for a number of brain cell functions, including adding the insulating layers around nerve fibres, and producing brain immune cells.

"In line with these laboratory findings, our study participants had neurodegenerative symptoms with difficult to control epilepsy, developmental regression, and delayed myelination," Associate Professor White said.

"The myelination process is vitally important to healthy central nervous system functioning, enabling nerve cells to transmit information faster and allows for more complex brain processes."

MCRI Professor John Christodoulou said the outcomes of this research highlighted the power of new genomic sequencing technologies that had ended a diagnostic odyssey that for some families may take years.

"Now that we know the causative gene, we are in a better position to understand the underlying biology behind the disorder, which we hope in future may translate to targeted treatments specific for the disorder," he said.

Researchers from the University of Melbourne, The Royal Children's Hospital, Università degli Studi di Palermo in Italy, Texas Children's Hospital and Austin Health also contributed to the findings.

A Giant Right Atrial Myxoma with Blood Supply from the Left and Right Coronary Arteries: Once in a Blue Moon

In a new publication from Cardiovascular Innovations and Applications; DOI https://doi.org/10.15212/CVIA.2019.0566, Yichao Xiao, Zhenfei Fang, Xinqun Hu, Qiming Liu, Zhaowei Zhu, Na Liu, Xiaofan Peng and Shenghua Zhou from the Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China consider Cardiac myxomas.

In this case report the authors discuss cardiac myxomas, which are the commonest primary benign cardiac tumors, they are extremely rare, with an incidence ranging from 0.0017 to 0.19% and only about one-fifth of them originate from the right chambers of the heart. A 60-year-old woman was admitted because of recurrent attacks of chest tightness and shortness of breath. Transthoracic echocardiography detected a giant mass in the right atrium; myxoma was indicated by [18F]fluorodeoxyglucose PET/CT. Preoperative selective coronary angiography was performed to assess the extent and severity of coronary stenosis, and showed a strongly neovascularized right atrial mass supplied by two feeding vessels with multiple branches from the left and right coronary arteries. The myxoma was successfully excised with open heart surgery and the patient was free of myxoma recurrence during the 3-year follow-up.

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Lasers are becoming one of the dominant tools in the current manufacturing industry. Much effort has been devoted to improving the processing accuracy, and spatial resolutions as low as micrometers have been achieved in laser cutting, wedding, marking and stereolithography in an atmospheric environment. The femtosecond laser (fs-laser) is a particularly promising approach from this point of view, in addition to its three-dimensional (3D) processing capability and broad-spectrum material usability. Super-diffraction-limited feature sizes at a level of tens of nanometers based on multiphoton absorption thresholding, shrinkage and stimulation emission depletion effects have also been realized in fs-laser induced photocuring of polymers, which unfortunately are not applicable to solid materials. Optical near-field techniques provide an alternative super-resolution scheme by localizing light fields to nanometer scales with the physical shapes of sharp tips, tiny apertures, nanoparticles and small protrusions. Nevertheless, these approaches often rely on heavy movement and alignment systems to maintain precise probe-substrate spacing for practical fabrication/patterning throughput due to the evanescent nature of the near field. An innovative optical patterning technology that permits vacuum-free high-resolution processing comparable to conventional FIB processing is highly desired.In a new paper published in Light Science & Application, scientists from the State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing, China, the State Key Laboratory of Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun, China, and the Nanotechnology facility, Swinburne University of Technology, John st., Hawthorn, Australia reported an optical far-field-induced near-field breakdown (O-FIB) approach, allowing the nanofabrication applicable to almost any solid materials in atmosphere. The writing is initiated from nano-holes created by femtosecond laser induced multiphoton absorption and its cutting "knife edge" is sharpened by far-field regulated enhancement of the optical near field. A spatial resolution of sub-20 nm (λ/40 for light wavelength λ) is readily achieved. O-FIB is empowered by a simple polarization control of the incident light for steering nano-groove writing along the designed pattern.

"According to the continuous boundary condition of the normal component of electric displacement, we experimentally observed the light field nano-localization and polarization-vertical enhancement around the nanohole, which permits direct control of the near-field enhancement for nanoablation by far field. Based on this idea, we have realized free nano-writing with resolution as high as 18 nm by manipulating laser polarization and beam's trajectory in real time."

"Since for the self-regulation effect induced by the feedback between light and the initial seeds, our approach has the inherent robustness against the stochastic nature of initial ablation and the ability to manipulate line width. Besides, our approach demonstrates free-form stitchless writing of nano-grooves with controllable length, separation and trajectory. Meanwhile, the universality of seeding effect enables a large-area printing mode which is superior to the conventional FIB."

"Our presented technique has opened a new era of high-efficient nanomachining. It is applicable for various materials and surface in the fields of nanoelectronics, nanofluids, and nanomedicines. The possibility we show here to direct manipulating the near field through the far field, may inspire the researchers to push the femtosecond laser nanofabrication or even other domains of the optical processing to a higher level." The scientists forecast.

The retrieval of phase of electromagnetic fields is one of the most important problems in optics as it allows the shape of transparent objects, including cells, to be quantified using visible light. Phase is a quantity that relates to the wave nature of light; it is not directly detectable by our eyes or common cameras, and yet carries important information about objects the light went through. Measuring the phase with very little light can be even more interesting and useful. With low light incidence, light toxicity to biological samples, for example, is reduced; however, the problem of recovering the phase also becomes much more difficult. Previous deep learning-based algorithms did improve over traditional methods under low light conditions, but displayed a tendency to over-represent the low spatial frequencies in the reconstructions, meaning that the reconstructions looked blurry.

In a new paper published in Light Science & Application, scientists from the 3D Optical Systems Group of Massachusetts Institute of Technology (MIT) proposed the Learning to Synthesize by DNN (LS-DNN) approach to combat this uneven fidelity by splitting the input signal into low and high spatial frequency bands. It then became possible for deep neural networks to process these two frequency bands, respectively; subsequently, a third neural network learned to synthesize the two frequency bands into the final reconstruction that is of high fidelity in all frequency bands. The authors discovered that the LS method is particularly robust at handling extremely noisy intensity signals.

The scientists summarize the impact of their LS-DNN algorithm as:
"We proposed a framework such that when we intentionally operate the learning algorithms outside their zone of comfort, i.e. with types of examples different than the algorithms were trained with, does not lead to disaster as with alternate approaches. That's thanks to the splitting and recombining structure of the architecture that we came up with. For example, the low frequency bands are processed by a neural network that knows how to handle low frequencies but doesn't necessarily care what type of objects the low frequencies came from. Similarly for the high frequencies. The synthesizer is also trained to recombine the two bands optimally. This kind of robustness suggests that the algorithm is readily applicable in practical situations."
"The main advantage of operating in the low light regime is that you can reduce to amount of light you deliver to the specimen. Our experiments were carried out with visible light; however, the same principles apply to other bands of electromagnetic radiation, e.g. x-rays. We know that x-rays are harmful, so if you can obtain the same image quality but with much lower dose of radiation, that would be a big advance."
"The LS method is versatile and adaptable to a great variety of such problems that we call inverse, meaning you have an indirect and incomplete or noisy observation of an object, and you're trying to reveal the object itself correctly. From x-rays we mentioned before to sonograms, MRI, geoscience investigations to discover petrol, all these are examples where similar problems occur. Our technique, in principle, is applicable because the competition between low and high frequencies is common to all these problems, and so is the noise and limited signal. So we have high hopes that very soon clearer images will be obtained in all these diverse domains," they concluded.

The law on keeping dangerous snakes as pets should be tightened up, animal welfare experts demand in this week's issue of the Vet Record.

The call follows an investigation by the journal, showing that several species of venomous and potentially lethal snakes, such as cobras, vipers, and rattlesnakes, can easily be bought through pet shops in England, but that the licensing arrangements for ownership are somewhat lax.

What's more, these reptiles are difficult for owners to manage properly at home, and few vets are sufficiently insured or have the relevant expertise to treat them, the investigation reveals.

Under the Dangerous Wild Animals (DWA) Act, it's perfectly legal to sell venomous snakes to people who don't have a licence to keep them: the legal onus is, instead, on the purchaser to have obtained a DWA licence from their local authority.

And animal welfare charity, the RSPCA, says that DWA licences may sometimes be issued retrospectively by councils, so enabling reptile collectors to obtain venomous snakes before they become licenced.

President of the British Veterinary Zoological Society (BVZS), Peter Kettlewell, points out that there aren't any legal controls when venomous snakes are purchased in EU countries and brought into the UK either.

"Pet shops are currently excluded from the requirements of the DWA Act and are therefore able to keep dangerous species without a DWA licence. BVZS strongly believes the legislation should be changed to prevent this," he told Vet Record.

But the BVZS is also concerned about the welfare of these animals once in private ownership.

"The husbandry of reptiles is challenging, and even commonly kept reptile species kept in people's homes are given inadequate care - as shown by the high proportion of reptiles presented to veterinary practices with husbandry-related diseases," he explains.

"Providing good husbandry would be made more difficult in the case of venomous animals due to the challenges in handling and managing them safely," he adds.

"BVZS believes that both the keeping of dangerous species by private individuals is likely to compromise both animal welfare and human safety, and as such, the selling of such species to private individuals should be carefully regulated and restricted," he contends.

The RSPCA also told Vet Record that it is "deeply concerned" about the number of venomous snakes being kept as pets, describing the DWA Act as "weakly drafted and poorly enforced." Many owners either don't bother to get a licence or don't realise they need one, it says.

Vet Record asked several exotics vets whether they would be prepared to deal with venomous snakes. Many said they wouldn't, citing health and safety issues and a lack of access to antivenom.

In a linked editorial, Vet Record senior news reporter, Josh Loeb, explains that the UK government (Defra) has now concluded a public consultation on the welfare of pet primates, and looks set to ban the keeping of these animals as pets.

"If written into law, such a ban would set a precedent. For the first time the UK would be banning a species or group of species from being kept as pets primarily because of welfare concerns. There are currently some legal restrictions on keeping certain species in private households - however, existing laws are based primarily on public safety or conservation reasons, not welfare grounds," he writes.

Given the risks and welfare issues involved, he questions whether venomous snakes shouldn't be included in this ban.

Such a move would be pushing at an open door, he suggests, as there's cross party agreement on the principle that certain types of wild animal just aren't suitable as pets.

There may also be a sound public health reason for reviewing regulations around the exotic animal trade, in view of the source of the current Covid-19 pandemic, he argues.

"If we want fewer exotic diseases to be imported into the UK going forward, perhaps we should rethink the keeping of exotic pets," he writes.

"When the current Covid-19 crises pass and when, hopefully, the government gains more headspace, the issue of dangerous and exotic wild animals being stocked as pets is surely an issue that merits greater political attention," he concludes.