Culture

New research from University of Warwick shows that knee replacement surgery using a tourniquet increases the risk of serious complications, and causes additional pain after surgery

A tourniquet is a device which is wrapped tightly around the thigh to stop blood flow to the rest of the leg

Researchers calculate that a change in knee replacement surgical practice might avoid nearly 2,000 serious complications a year in the UK alone

The research shows that when a tourniquet is used patients have on average nearly 20% more pain the day after the surgery

Use of a tourniquet is established practice amongst the majority of knee surgeons, however, a minority perform the surgery without a tourniquet

The risk of developing serious complications following a knee replacement could be up to 73% higher when a tourniquet is used, compared to surgery without a tourniquet.

Serious complications during knee replacement surgery are rare. However, researchers at the University of Warwick found that 5.9% of patients whose operations involved a tourniquet had serious complications needing additional health care, compared to 2.9% in those operated on without a tourniquet.

Research from Warwick Clinical Trials Unit has revealed that this common surgery, performed over 100,000 times a year in the UK, is likely to be safer and less painful for patients if surgeons do not use a tourniquet. A tourniquet is a device which is wrapped around the thigh and squeezes it to stop blood flow to the rest of the leg. It is typically applied for about an hour during the surgery.

The conclusions are drawn from a new systematic review publishing today (8 December) in the Cochrane Library and funded by the National Institute for Health Research, drawing on data from 41 previous clinical trials on the use of a tourniquet during knee replacement surgery. The differences became clear when the results from multiple studies around the world were combined.

The researchers conclude that surgeons should now discuss the benefits and risks of using a tourniquet with patients prior to surgery and offer a choice of whether to use a tourniquet or not. The report suggests that a change of surgical practice by not using a tourniquet might avoid up to 1,987 serious complications in the UK each year.

Many people with arthritis are successfully treated with painkillers, exercise and physiotherapy. When arthritis becomes severe, these may be less effective and patients are typically offered knee replacement surgery. This procedure is performed under anaesthetic when the knee joint is opened up, the worn joint surfaces are removed and replaced with artificial surfaces usually constructed from metal and plastic.

Widespread use of tourniquets may relate to surgeons' concerns about blood loss and improving the way that the cement used to hold the knee replacement in place attaches to the bone. However, modern anaesthetic and surgical techniques mean this is unlikely to be a problem. For example, hip and shoulder replacement surgery where the use of a tourniquet is not possible proceed safely, without undue concerns about bleeding or cement fixation of the components. The researchers found no evidence of any problem with the attachment between the cement and the bone when a tourniquet was not used, even in x-ray studies designed to measure this accurately.

The researchers pooled data from 41 previous randomised control trials up to March 2020, involving 2,819 patients, comparing the outcomes when the surgeon used a tourniquet during knee replacement surgery to those who didn't use a tourniquet. Knee function, quality of life, total blood loss and fixation of the components were measured and little difference was found between the two methods. However, where a tourniquet was used 5.9% of patients experienced serious complications such as blood clots, wound infection and the need for further surgery, compared to 2.9% where a tourniquet was not used. Patients who had a knee replacement where a tourniquet was used also reported on average 19% more pain the day after surgery than patients where no tourniquet was used.

Senior author Mr Peter Wall, Consultant Orthopaedic Surgeon from Warwick Clinical Trials Unit and University Hospitals Coventry and Warwickshire NHS Trust, said: "The evidence indicates that knee replacement surgery performed with a tourniquet increases the risk of serious complications needing additional healthcare, many of which might be avoided if a tourniquet is not used.

He emphasised that: "Most people do very well after knee replacement, but like any major surgery, there are risks and use of a tourniquet may exacerbate these."

Cancer drugs have side effects, so for many years, scientists have been exploring ways to transport the active substances to a tumour in the body as precisely as possible. That is the only place that drugs should take effect. One approach is to inject them into the bloodstream and control their transport in small vessels at tumour sites by locally altering the blood flow with tiny vehicles. Research laboratories have created microrobots whose shape and propulsion are inspired by bacteria and that are small enough to be inserted into blood vessels.

These microvehicles can be powered from outside the body by a moving magnetic field.

Simone Schürle, Professor at the Department of Health Sciences and Technology, is now going one step further: instead of microrobots inspired by bacteria, she wants to use real bacteria that are magnetic. Researchers discovered such magnetotactic bacteria in the sea 45 years ago. These microorganisms absorb iron dissolved in the water; iron oxide crystals form in their interior and line up in a row. Like a compass needle, these bacteria align themselves with the Earth's magnetic field so they can navigate in the water in a directed manner.

Precise control with magnetic fields

ETH Professor Schürle and her team investigated how to use a magnetic field to control these bacteria in the laboratory as a way to direct the flow of liquids in a controlled manner. In their experiments, they applied only relatively weak rotating magnetic fields to spin the bacteria along the desired directions. And with many bacteria in a swarm, it proved possible to move the fluid surrounding them. The bacteria produce an effect similar to that of a micropump, meaning they are able to move active substances present in the fluid in different directions, for example from the bloodstream into the tumour tissue. By using superimposed magnetic fields that locally reinforce or cancel each other out, this pumping activity can be confined to a small region with pinpoint accuracy, as Schürle's team has been able to show in simulations.

Moreover, the principle can be put to work outside the body to mix different liquids locally with each other in very small vessels without having to manufacture and control mechanical micropumps.

"One major advantage of bacteria over microrobots is that they are easy to produce. We can simply cultivate them in bioreactors," Schürle says.

Dead or alive

Their work is primarily focused on investigating the approach and describing how the bacteria can control the flow. Before such bacteria can be used in the human body, their safety must first be investigated. However, bringing bacteria into the body for medical reasons is an approach that science is already pursuing under the term "living therapeutics", albeit with other types of bacteria, such as E. coli.

It should also be possible to use non-natural bacteria for future medical applications. Synthetic biology can be used to construct bacteria that feature optimised functional properties and are safe for use in the human body, for example by not causing allergic reactions. Schürle can envisage treatments using bacteria that are killed before they are introduced into the body as well as treatments using living bacteria.

Fine control through self-propulsion

It has also been known for several decades that certain types of anaerobic bacteria (which do not require oxygen to grow) preferably accumulate in cancer patients' tumours. In other words, these bacteria naturally prefer the low oxygen conditions in tumours over the rest of the body. While this was investigated in bacteria other than those used by Schürle's team, synthetic biology could be used to combine the advantages of several bacterial species. This might lead to the development of bacteria that approach the tumour powered by their own flagella (whip-like appendages) and can then be precisely transported deep into the tumour tissue using external magnetic forces.

Observations conducted by the Murikabushi Telescope of Ishigakijima Astronomical Observatory confirmed that dark coating can reduce satellite reflectivity by half. There are concerns that numerous artificial satellites in orbit could impair astronomical observations, but these findings may help alleviate such conditions.

Today's growing demand for space-based services has spawned a wave of satellite constellation projects which operate numerous artificial satellites in orbit. Since these satellites can shine by reflecting sunlight, the astronomy community has raised concerns about their potential impact on astronomical observations. In January 2020, SpaceX launched "DarkSat," an experimental satellite with an anti-reflective coating, and asked astronomers to assess how much this coating can reduce the satellite reflectivity. Brightness measurements of artificial satellites have already been conducted, but until now, there was no verification that a dark coating actually achieves the expected reflectivity reduction.

The Murikabushi Telescope of Ishigakijima Astronomical Observatory can observe celestial objects simultaneously in three different wavelengths (colors). Comparing multicolor data obtained under the same conditions provides more accurate insight into how much the coating can reduce the satellite brightness. Observations conducted from April to June 2020 revealed for the first time in the world that artificial satellites, whether coated or not, are more visible at longer wavelengths, and that the black coating can halve the level of surface reflectivity of satellites. Such surface treatment is expected to reduce the negative impacts on astronomical observations. Further measures will continue to be implemented to pave the way for peaceful coexistence between space industries and astronomy.

An international research team has clarified the regulatory mechanism of the ubiquitin-proteasome system (*1) in recognizing and repairing DNA that has been damaged by ultraviolet (UV) light. The investigators at Kobe University (Japan), the National Institute of Health Sciences (Japan), the Catholic University of Louvain (Belgium), Kyoto University (Japan), and the National Institute of Genetics (Japan) have published their results in the journal Scientific Reports.

Main Points

The researchers developed a microscope system whereby they could induce DNA damage to any intracellular location via UV light stimulation and observe cellular responses in real time.

They observed that proteasome, which is a multi-protein complex involved in protein degradation, quickly accumulated at the sites of the UV light-induced DNA damage.

This research has illuminated that the enzymatic activity and structural integrity of the proteasome are vital for the DNA damage recognition pathway, which is mediated by DDB2 proteins. Mutation in the DDB2 gene occurs in the genetic disorder xeroderma pigmentosum (*2).

Research Background

UV light from the sun is very harmful to living organisms because it can damage their genes. This is called DNA damage and normally it is fixed by the repair system in our cells, preventing us from experiencing adverse effects resulting from exposure to sunlight during the course of our daily lives. However, patients with xeroderma pigmentosum (XP) are born with malformations in this repair system, which means that their bodies are unable to sufficiently repair DNA damage caused by UV light. Consequently, they are predisposed to developing skin cancer in sun-exposed areas.

Intracellular proteins are generated and degraded as required, and the ubiquitin-proteasome system is known to play an important role in managing this degradation process. It has been previously shown that the ubiquitin-proteasome system coordinates cellular responses to repair the UV-induced DNA damage. However, the detailed mechanism behind this had not been clarified until now.

Research Findings

The international team, led by Prof. SUGASAWA Kaoru at the Biosignal Research Center, Kobe University, developed a custom microscope system (*3) which allowed them to successfully observe the dynamic behaviors of various intracellular proteins in response to UV-induced DNA damage (Figure 1, left).

The DDB2 protein is one of the gene products responsible for XP and is important for recognizing UV-induced DNA damage. Utilizing the custom microscope system enabled the researchers to make a new discovery: they found that the DDB2 protein works together with the ubiquitin-proteasome system to promote DNA repair. First of all, the multi-protein complexes, proteasomes, quickly accumulated at DNA damage sites depending on the presence of DDB2 proteins. This suggests that the proteasome's protein degradation function could be activated following the damage recognition and repair (Figure 1, right).

Furthermore, using an inhibitor to suppress this proteasome activity caused the proteasome to accumulate in a specific region of the nucleus, trapping the DDB2 protein and making it unable to participate in DNA damage repair (Figure 2). On the other hand, suppressing the expression of proteasome subunits compromised proper assembly of the proteasomes and the aforementioned proteasome aggregation was no longer observable. However, the absence of proteasomes severely suppressed the accumulation of DDB2 proteins at DNA damage sites.

These results revealed for the first time that proteasomes' protein degradation activity and architectural integrity are involved in the regulation of DDB2 protein-mediated DNA damage repair via separate mechanisms.

Further Developments

The results of this study show that the action of the DNA damage recognition mechanism is essential for enabling DNA damage to be efficiently repaired. Furthermore, this understanding will also contribute towards clarifying the onset mechanisms of diseases such as skin cancer, in addition to the development of treatments to suppress this onset.

A research group from Tohoku University led by current president Hideo Ohno has developed the world's smallest (2.3 nm) high-performance magnetic tunnel junctions (MTJs). This work is expected to accelerate the advancement of ultrahigh-density, low-power, high-performance non-volatile memory for a variety of applications, such as IoT, AI, and automobiles.

The development of STT-MRAM--non-volatile spintronics memory--helps reduce the increasing power consumption in semiconductor device scaling. Crucial to integrating STT-MRAM in advanced integrated circuits is scaling magnetic tunnel junction--a core component of STT-MRAM--while improving its performance in data retention and write operation.

Shape-anisotropy MTJ, proposed by the same group in 2018, has shown MTJ scaling down to single-digit nanometers while achieving sufficient data-retention (thermal-stability) properties. In the shape-anisotropy MTJ, thermal stability is enhanced by making the ferromagnetic layer thick. Once the thickness goes beyond a certain point, however, device reliability becomes degraded.

To address the issue in the conventional shape-anisotropy MTJ with a single ferromagnetic structure [Fig. 1(a)], the group employed a new structure that uses magnetostatically coupled multilayered ferromagnets [Fig. 1(b)]. The developed MTJs were successfully scaled down to 2.3 nm in diameter -the world's smallest MTJ size. They also exhibited high data retention properties up to 200°C and high-speed and low-voltage write operation down to 10 ns below 1 V at a single-digit-nanometer scale.

"The performance proves the developed MTJs' capability to work with the future-generation advanced integrated circuits," said Butsurin Jinnai, first author of the study. "Because of its material compatibility with the standard MTJ material system, CoFeB/MgO, the proposed MTJ structure can be easily adopted in existing MTJ technology." The group believes that this will speed up the development of ultrahigh-density, low-power, high-performance memory for a variety of applications, such as IoT, AI, and automobiles.

University of Tartu researchers and their collaborators from Finland and Spain investigated the relationship between the gut microbiome and polycystic ovary syndrome. Their study revealed that women with polycystic ovary syndrome in their late reproductive years have significant microbial changes in gut-related to their metabolic health.

Polycystic ovary syndrome is a complex hormonal disorder affecting up to 18% of women in reproductive age. Women with polycystic ovary syndrome often have irregularities in their menstrual cycle, excess of male sex hormones and polycystic ovarian morphology. It is associated with a variety of metabolic derangements, including obesity, insulin resistance and type 2 diabetes. The exact cause of polycystic ovary syndrome is unknown but it is believed to be multifactorial where genetics, lifestyle and possibly the gut microbiome could have a role.

This study aimed to assess whether the gut microbiome is associated with polycystic ovary syndrome in late fertile age women. "Our study population consisted of a subset of females from the longitudinal Northern Finland Birth Cohort 1966, which includes all expected births in 1966 in the two northernmost provinces of Finland," said the first author of the paper Kreete Lüll.

Results show that there are no significant differences in gut microbiome between women who have polycystic ovary syndrome and healthy women in their late fertile age. "Yet, we found differences between the microbial diversity and hormones," said Lüll. Furthermore, the results show that there are differences in microbiome profile in women with polycystic ovary syndrome in a pre-diabetic state compared to those with normal glucose tolerance.

"Although this study shed some light on the causes of polycystic ovary syndrome, further research with a larger sample set among younger women is needed in order to clarify the possible link between the gut microbiome, metabolites and development of polycystic ovary syndrome," added the last author, Senior Research Fellow of Molecular Biomedicine Elin Org.

The members of ACNP have been motivated by recent events to strengthen diversity and inclusivity programs within the College and find ways to promote change in our home institutions. Two Annual Meeting Study Groups provided both information and practical action steps for members. The first addressed the challenge of moving beyond diversity and inclusivity as "buzzwords" toward institutional change. Evidence-based strategies were discussed that can be used widely at academic institutions, in medical and scientific education specifically, within ACNP and at members' home institutions. The second Study Group addressed microaggressions, brief daily encounters that convey negative messages to members within specific biographical groups. While overt racism, sexism and classism in professional settings has decreased due to clear policies developed by institutions and professional organizations, microaggressions remain across all levels of scientific training and academic rank and contribute to the low representation of women and underrepresented minority groups among academic leadership. Women make up only 18% of medical school deans, while those from underrepresented minority groups account for 12% of deans. The Study Group provided insight into how and why microaggressions occur and discussed practical strategies to raise awareness and provided easy to remember and implementable strategies to eliminate them.

Inclusion and Diversity Efforts Within Large Scientific Organizations: Tangible Methods that Work

There is no clear consensus on how to enhance diversity and inclusivity at institutions, and these efforts are often assigned to members of underrepresented groups who are most affected and lack the authority and resources to effect institutional change. This study group co-Chaired by Dr. April Thames of the University of Southern California and Dr. Sade Spencer of the University of Minnesota addressed evidence-based methods to effect transformation in scientific institutions like the American College of Neuropsychopharmacology. Dr. April Thames discussed strategies including translating workgroup efforts into tangible outcomes and products, using social media and collaborating with colleagues and leadership. Dr. Erika Nurmi of UCLA illustrated challenges and successes at promoting diversity and inclusion in medical and scientific education at UCLA to provide examples to apply to ACNP and to members' place of work. Dr. Shawn McClintock showed how to infuse inclusion and diversity into the ACNP meeting programs. Finally, Dr. Sade Spencer led an interactive discussion with the audience. This study group set the stage for implementing and sustaining diversity and inclusions practices at ACNP and its members' institutions.

The Mega Impact of Microaggression: Insights and Practical Solutions

The Study Group co-Chaired by Dr. Gretchen Neigh of Virginia Commonwealth University and Dr. Maria Oquendo of University of Pennsylvania discussed difficulties raised by microaggressions, how implicit bias can further perpetuate the cycle and outlined ways that bystanders and victims can break the cycle. Examples of common microaggressions were discussed including those related to gender (i.e. assumptions that absent female faculty members are home with children as opposed to traveling or attending conferences), race and/or culture (i.e. asking a colleague from an underrepresented group where they are 'really from'), and heteronormative behaviors (i.e. refusing to use preferred pronouns). Dr. VJ Periyakoi from Stanford University discussed ways microaggressions occur in academic settings. Dr. Catherine Njathi-Ori of the Mayo Clinic provided specific actions that individuals can use to address microaggression as they occur. Dr. Christine Moutier of the American Foundation for Suicide Prevention outlined communication strategies to change culture. Discussion after the presentations provided scenarios to help participants recognize microaggressions, appreciate their cost, and respond productively.

Since the early days of the COVID-19 pandemic, US science leaders and others have expressed frustration with the lack of an informed and coherent federal response, a sentiment that echoes objections to the handling of other pressing issues, such as climate change. Writing in BioScience, an assemblage of the past presidents of the American Institute of Biological Sciences (AIBS) have issued an appeal for the reinvigoration of sound policy and governance through the careful consideration of sound science.

This effort represents the culmination of decades of service on behalf of informed policymaking. "AIBS has long stood for the use of science to promote informed decision-making based on the best available evidence. We have helped secure new resources for science and education, defeated antiscience initiatives, and promoted integrity in the use of scientific information to make research funding decisions," write the authors. In addition, they highlight the importance of marshaling science to foster a better-informed public that makes decisions on the basis of vetted information rather than "advice from whomever they trust at the time."

The AIBS past presidents note the success of such approaches in addressing past challenges. They describe the discovery of acid rain and its attribution to Midwestern coal-fired power plants, then follow the story to the passage of the Clean Air Act Amendments of 1990 and the resultant reduction in environmental damage. Today, they argue, the stakes are high, but the best course of action is clear. Only by marshaling science for the benefit of society, they say, will we be able to "limit the spread of COVID-19; the disastrous disruption of the world's climate; the poisoning of global land, air, and water; and the extinction of a major portion of the biodiversity on which we ultimately depend for our survival."

Philadelphia, December 8, 2020 - As schools across the United States are grappling with remote and hybrid learning due to the COVID-19 pandemic, a new study in the Journal of Nutrition Education and Behavior, published by Elsevier, investigates the initial responses of child nutrition administrative agencies in all 50 US states and the District of Columbia (DC), five US territories, and the US Department of Interior Bureau of Indian Education (BIE).

"Our aim was to conduct a novel assessment of the responses and communications of these 57 unique jurisdictions," said lead author Gabriella M. McLoughlin, PhD, Implementation Science Center for Cancer Control and Prevention Research Center, Brown School at Washington University in St. Louis, St Louis, MO, USA.

"Based on our systematic coding of government websites (February-May 2020), we found most jurisdictions [kindergarten through 12th-grade] mentioned school meal provisions in school closure announcements; provided easily interpretable information and/or maps about meal sites; and included detailed information about school meal provisions in their COVID-19 landing webpages. Fewer provided updated and comprehensive implementation guidance; referenced school closures in emergency declarations; had clear communication/outreach to families; or partnered with anti-hunger organizations," added Dr. McLoughlin.

Although it is not surprising none of the jurisdictions examined executed a comprehensive plan to address food insecurity during a pandemic of this nature and school closures of this duration, the initial responses to COVID-19 should serve as important foundations for lessons learned as this pandemic persists and as jurisdictions work to better plan for future emergencies. Without question, ensuring participation in emergency school meal programs is of paramount concern as the COVID-19 pandemic-related school closures continue to place children and families at a greater risk for food insecurity. Innovative approaches are needed to mitigate increased food insecurity and help schools prevent further financial losses due to lack of participation.

"Translating this evidence into action is so important and the Society for Nutrition Education and Behavior (SNEB), among others, can play an instrumental role in establishing stronger communication pathways between students, families, schools, and governing entities," emphasized co-author and Society of Nutrition Education and Behavior Board member, Sheila Fleischhacker, PhD, JD, RDN, Georgetown Law, Washington, DC, USA.

Unplanned purchases are an important profit source for retailers. Because looking at products is always the first step in making a purchase decision, retailers apply various strategies in order to bring shoppers in juxtaposition with the store assortment. "Over the past decades, retailers have developed many sales strategies that focus on the visual attention of customers," says Mathias Streicher from the Institute for Strategic Management, Marketing and Tourism at the University of Innsbruck, Austria. "A popular strategy, for example, is to place product categories such as milk in the back of a store." Customers in need for everyday products therefore have to travel further into the store which naturally brings other products into the view of shoppers as they travel to stock their needs. Discount campaigns can also be used to lure customers into less frequented store areas. "All these strategies maximize the journey through the store and increase the probability to remember a forgotten need or discover a new product," says marketing expert Mathias Streicher. Together with Zachary Estes from the Cass Business School in London and Oliver Büttner from the University of Duisburg-Essen, Streicher investigated in several lab- and field studies how attention contributes to exploratory shopping and unplanned purchasing.

Attention can be easily influenced

"In looking at shelves shoppers always see a subset of the assortment and which subset they see critically depends on their visual attention," says Streicher. "We were able to show that attentional patterns can be unconsciously broadened or even narrowed down by simple in-store communications. For example, the researchers first manipulated the breadth of attention of volunteering participants in a mini-market on the university campus in Innsbruck, Austria, with the help of digital displays, which are now also widely used as advertising media in stores. For a broad focus, different images were shown randomly and consecutively on the left or right periphery of the screen, while for a narrow focus the same images appeared always in the middle. The participants were then equipped with mobile eye tracking glasses and placed in front of a candy shelf from which they were to select products. Those persons who were previously presented with images at the periphery of the screen looked at significantly more areas of the candy shelf than the control group, who were presented the same images in the middle of the screen. In a second study in a supermarket, the researchers equipped the customers with pedometers to measure their in-store travel. Here too, they were shown product images on a display before shopping. While those customers whose attention was narrowly focused walked approximately 240 meters in the store, customers with broad attention walked over 300 meters. Significantly, the proportion of unplanned purchases in customers' shopping carts doubled. "We show that a very simple intervention before shopping can have consequences for a person's shopping behavior," is how Mathias Streicher sums up the results of the study, which has now been published in the Journal of Consumer Research.

Better manage shopping habits

The results of the study not only make a valuable contribution to consumer research, but also offer interesting findings for practical use. Thus, the research work gives indications, how contents of communication on digital advertising media should be arranged, in order to positively affect purchase behavior. On the other hand, the research also offers recommendations for people who want to better control their purchasing behavior. "Our research shows that unplanned purchasing already begins at the level of visual attention," summarizes the Innsbruck-based consumer researcher, who also has a simple tip for customers: "To reduce unplanned purchases, it is therefore better to avoid wandering glances in shopping situations - preferably with the support of a shopping list."

One huge advantage of drones is that these little robots can go places where people can't, including areas that might be too dangerous, such as unstable structures after a natural disaster or a region with unexploded devices.

Researchers are interested in developing devices that can navigate these situations by sniffing out chemicals in the air to locate disaster survivors, gas leaks, explosives and more. But most sensors created by people are not sensitive or fast enough to be able to find and process specific smells while flying through the patchy odor plumes these sources create.

Now a team led by the University of Washington has developed Smellicopter: an autonomous drone that uses a live antenna from a moth to navigate toward smells. Smellicopter can also sense and avoid obstacles as it travels through the air. The team published these results Oct. 1 in the journal IOP Bioinspiration & Biomimetics.

"Nature really blows our human-made odor sensors out of the water," said lead author Melanie Anderson, a UW doctoral student in mechanical engineering. "By using an actual moth antenna with Smellicopter, we're able to get the best of both worlds: the sensitivity of a biological organism on a robotic platform where we can control its motion."

The moth uses its antennae to sense chemicals in its environment and navigate toward sources of food or potential mates.

"Cells in a moth antenna amplify chemical signals," said co-author Thomas Daniel, a UW professor of biology who co-supervises Anderson's doctoral research. "The moths do it really efficiently -- one scent molecule can trigger lots of cellular responses, and that's the trick. This process is super efficient, specific and fast."

The team used antennae from the Manduca sexta hawkmoth for Smellicopter. Researchers placed moths in the fridge to anesthetize them before removing an antenna. Once separated from the live moth, the antenna stays biologically and chemically active for up to four hours. That time span could be extended, the researchers said, by storing antennae in the fridge.

By adding tiny wires into either end of the antenna, the researchers were able to connect it to an electrical circuit and measure the average signal from all of the cells in the antenna. The team then compared it to a typical human-made sensor by placing both at one end of a wind tunnel and wafting smells that both sensors would respond to: a floral scent and ethanol, a type of alcohol. The antenna reacted more quickly and took less time to recover between puffs.

To create Smellicopter, the team added the antenna sensor to an open-source hand-held commercially available quadcopter drone platform that allows users to add special features. The researchers also added two plastic fins on the back of the drone to create drag to help it be constantly oriented upwind.

"From a robotics perspective, this is genius," said co-author and co-advisor Sawyer Fuller, a UW assistant professor of mechanical engineering. "The classic approach in robotics is to add more sensors, and maybe build a fancy algorithm or use machine learning to estimate wind direction. It turns out, all you need is to add a fin."

Smellicopter doesn't need any help from the researchers to search for odors. The team created a "cast and surge" protocol for the drone that mimics how moths search for smells. Smellicopter begins its search by moving to the left for a specific distance. If nothing passes a specific smell threshold, Smellicopter then moves to the right for the same distance. Once it detects an odor, it changes its flying pattern to surge toward it.

Smellicopter can also avoid obstacles with the help of four infrared sensors that let it measure what's around it 10 times each second. When something comes within about eight inches (20 centimeters) of the drone, it changes direction by going to the next stage of its cast-and-surge protocol.

"So if Smellicopter was casting left and now there's an obstacle on the left, it'll switch to casting right," Anderson said. "And if Smellicopter smells an odor but there's an obstacle in front of it, it's going to continue casting left or right until it's able to surge forward when there's not an obstacle in its path."

Another advantage to Smellicopter is that it doesn't need GPS, the team said. Instead it uses a camera to survey its surroundings, similar to how insects use their eyes. This makes Smellicopter well-suited for exploring indoor or underground spaces like mines or pipes.

During tests in the UW research lab, Smellicopter was naturally tuned to fly toward smells that moths find interesting, such as floral scents. But researchers hope that future work could have the moth antenna sense other smells, such as the exhaling of carbon dioxide from someone trapped under rubble or the chemical signature of an unexploded device.

"Finding plume sources is a perfect task for little robots like the Smellicopter and the Robofly," Fuller said. "Larger robots are capable of carrying an array of different sensors around and using them to build a map of their world. We can't really do that at the small scale. But to find the source of a plume, all a robot really needs to do is avoid obstacles and stay in the plume while it moves upwind. It doesn't need a sophisticated sensor suite for that -- it just needs to be able to smell well. And that's what the Smellicopter is really good at."

DALLAS - Dec. 8, 2020 - Two studies led by UT Southwestern researchers shed new light on how the brain encodes time and place into memories. The findings, published recently in PNAS and Science, not only add to the body of fundamental research on memory, but could eventually provide the basis for new treatments to combat memory loss from conditions such as traumatic brain injury or Alzheimer's disease.

About a decade ago, a group of neurons known as "time cells" was discovered in rats. These cells appear to play a unique role in recording when events take place, allowing the brain to correctly mark the order of what happens in an episodic memory.

Located in the brain's hippocampus, these cells show a characteristic activity pattern while the animals are encoding and recalling events, explains Bradley Lega, M.D., associate professor of neurological surgery at UTSW and senior author of the PNAS study. By firing in a reproducible sequence, they allow the brain to organize when events happen, Lega says. The timing of their firing is controlled by 5 Hz brain waves, called theta oscillations, in a process known as precession.

Lega investigated whether humans also have time cells by using a memory task that makes strong demands on time-related information. Lega and his colleagues recruited volunteers from the Epilepsy Monitoring Unit at UT Southwestern's Peter O'Donnell Jr. Brain Institute, where epilepsy patients stay for several days before surgery to remove damaged parts of their brains that spark seizures. Electrodes implanted in these patients' brains help their surgeons precisely identify the seizure foci and also provide valuable information on the brain's inner workings, Lega says.

While recording electrical activity from the hippocampus in 27 volunteers' brains, the researchers had them do "free recall" tasks that involved reading a list of 12 words for 30 seconds, doing a short math problem to distract them from rehearsing the lists, and then recalling as many words from the list as possible for the next 30 seconds. This task requires associating each word with a segment of time (the list it was on), which allowed Lega and his team to look for time cells. What the team found was exciting: Not only did they identify a robust population of time cells, but the firing of these cells predicted how well individuals were able to link words together in time (a phenomenon called temporal clustering). Finally, these cells appear to exhibit phase precession in humans, as predicted.

"For years scientists have proposed that time cells are like the glue that holds together memories of events in our lives," according to Lega. "This finding specifically supports that idea in an elegant way."

In the second study in Science, Brad Pfeiffer, Ph.D., assistant professor of neuroscience, led a team investigating place cells - a population of hippocampal cells in both animals and humans that records where events occur. Researchers have long known that as animals travel a path they've been on before, neurons encoding different locations along the path will fire in sequence much like time cells fire in the order of temporal events, Pfeiffer explains. In addition, while rats are actively exploring an environment, place cells are further organized into "mini-sequences" that represent a virtual sweep of locations ahead of the rat. These radar-like sweeps happen roughly 8-10 times per second and are thought to be a brain mechanism for predicting immediately upcoming events or outcomes.

Prior to this study, it was known that when rats stopped running, place cells would often reactivate in long sequences that appeared to replay the rat's prior experience in the reverse. While these "reverse replay" events were known to be important for memory formation, it was unclear how the hippocampus was able to produce such sequences. Indeed, considerable work had indicated that experience should strengthen forward, "look ahead" sequences but weaken reverse replay events.

To determine how these backward and forward memories work together, Pfeiffer and his colleagues placed electrodes in the hippocampi of rats, then allowed them to explore two different places: a square arena and a long, straight track. To encourage them to move through these spaces, they placed wells with chocolate milk at various places. They then analyzed the animals' place cell activity to see how it corresponded to their locations.

Particular neurons fired as the rats wandered through these spaces, encoding information on place. These same neurons fired in the same sequence as the rats retraced their paths, and periodically fired in reverse as they completed different legs of their journeys. However, taking a closer look at the data, the researchers found something new: As the rats moved through these spaces, their neurons not only exhibited forward, predictive mini-sequences, but also backward, retrospective mini-sequences. The forward and backward sequences alternated with each other, each taking only a few dozen milliseconds to complete.

"While these animals were moving forward, their brains were constantly switching between expecting what would happen next and recalling what just happened, all within fraction-of-a-second timeframes," Pfeiffer says.

Pfeiffer and his team are currently studying what inputs these cells are receiving from other parts of the brain that cause them to act in these forward or reverse patterns. In theory, he says, it might be possible to hijack this system to help the brain recall where an event happened with more fidelity. Similarly, adds Lega, stimulation techniques might eventually be able to mimic the precise patterning of time cells to help people more accurately remember temporal sequences of events. Further studies with "In the past few decades, there's been an explosion in new findings about memory," he adds. "The distance between fundamental discoveries in animals and how they can help people is becoming much shorter now."

Results from a new study co-led by researchers at Dartmouth's Geisel School of Medicine and the Department of Surgery at Kuma Hospital in Kobe, Japan show that active surveillance can be successfully implemented as a viable treatment option for patients with low-risk thyroid cancer. The study is the first to specifically analyze patient retention and adherence in an active surveillance program for thyroid cancer.

The incidence of small papillary thyroid cancers (less than 2 cm) has increased dramatically across the world over the past 25 years, without a proportional change in mortality. The research and medical communities now recognize this trend to be largely due to overdiagnosis--the detection of a disease that, had it not been detected, would have been unlikely to go on to cause symptoms or death.

In an effort to minimize the overtreatment of these small, localized cancers, many countries (led by Japan) have adopted more conservative treatment approaches. They already advocate partial rather than total surgical removal of the thyroid in certain cancers and developed the approach of active surveillance--which involves closely watching a patient's condition without doing surgery unless the cancer grows or changes. This approach is considered a viable option for carefully selected cancers, showing promise as a way to reduce harm from overtreatment.

"Prior to this study, there has been a lack of evidence about how well patients who select active surveillance will actually adhere to the approach over time, especially in countries like the U.S. that are only a few years removed from following traditional guidelines that called for more aggressive treatment approaches," says Louise Davies, MD, MS, associate professor of surgery and of The Dartmouth Institute at the Geisel School of Medicine at Dartmouth and lead author on the study.

To assess patient retention in the program, adherence to a schedule of follow-up ultrasounds, and the patient experience in a well-established thyroid cancer surveillance program, the researchers conducted a cohort analysis of 1,179 patients at Kuma Hospital in Kobe, Japan between February 2005 and December 2017, the largest and longest known program of its kind. The analysis evaluated attendance data, and during 2018 Dr. Davies conducted patient and physician interviews and gathered field observation data.

Patients were considered adherent if they underwent an ultrasonographic exam within at least 13 months of their previous exam, and were considered retained if they came for their ultrasound examination at least every two years.

After completing their data analysis, the study team found that 91 percent of the patients adhered to the prescribed ultrasonography schedule. Retention in the program was also high--with only 4.5 percent of patients choosing surgery after two years and 8.5 percent stopping their follow-up care after a median of four years.

A number of factors were identified as key to program success by patients and physicians in the study--including prebiopsy education, receiving detailed test results (confirming stability of the cancer) at follow-up visits, and a supportive and collaborative communication style between physicians and patients.

Since active surveillance is a pronounced de-escalation of thyroid cancer care for many settings, those programs looking to implement it may benefit from this specific educational and supportive approach to care, which Davies and her colleagues propose be called the "guide framework."

"It's analogous to a traveler (the patient) and their guide (clinician)," she explains. "The clinician advises on options and advocates for the optimal path over time, and supportively reaffirms the care plan or recommends alternatives as conditions change and they continue on the care path together."

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

1. Hydroxychloroquine shows no benefit for postexposure prophylaxis for preventing SARS-CoV-2 infection

Clinical trials have ruled out the role of hydroxychloroquine in the treatment of COVID-19, but some believe that it may have a role in preventing SARS-CoV-2 infection in people after exposure to someone with known infection. Researchers from the University of Washington, Fred Hutchinson Cancer Research Center, New York University Grossman School of Medicine, and the University of Maryland School of Medicine conducted a randomized controlled trial among 671 households. 337 households were given 400mg of hydroxychloroquine daily for 3 days, followed by 200mg for 11 days. 334 households served as the control group and were given 500mg of vitamin C for 3 days, followed by 250mg for 11 days. The researchers note the risk for SARS-CoV-2 infection within the households was high, but there was no statistically significant difference in the development of SARS-CoV-2 infection between the hydroxychloroquine and control group.

The researchers conclude hydroxychloroquine should not be used to prevent SARS-CoV-2 infection after exposure to a close contact with infection.

Read the full text: https://www.acpjournals.org/doi/10.7326/M20-6519. A free summary for patients is also available: https://www.acpjournals.org/doi/10.7326/P20-0015.

Media contacts: A PDF for this article is not yet available. Please click the link to read the full text. The corresponding author, Ruanne V. Barnabas, MBChB, MSc, DPhil, can be reached through Bobbi Nodell at bnodell@uw.edu.

2. Patients with COVID-19 may develop an array of symptoms that evolve over time

COVID-19 can persist in persons and result in prolonged illness, sometimes referred to as "long COVID." Public health messages around persisting symptoms could help reinforce measures to avoid the spread of infection. In a brief research report, authors from Geneva University Hospitals and the University of Geneva present their findings from reviewing COVID-19 symptom evolution and persistence in an outpatient setting in Geneva, Switzerland, from day 1 through day 30 to 45 after diagnosis.

The study's findings show that patients with COVID-19 develop an array of symptoms that evolve over time. Fatigue, dyspnea, and loss of taste or smell were the main persistent symptoms. Recognizing the persistence of symptoms could legitimize patients' concerns about an unknown and new disease.

Read the full text: https://www.acpjournals.org/doi/10.7326/M20-5926.

Media contacts: A PDF for this article is not yet available. Please click the link to read the full text. The corresponding author, Mayssam Nehme, MD, can be reached at Mayssam.Nehme@hcuge.ch.

3. Wuhan study helps researchers better understand SARS-CoV-2 positivity and the disease course of COVID-19

Knowledge is limited about the patterns of viral persistence and host response in patients with COVID-19. Researchers from Wuhan, China conducted a large, retrospective study to describe patterns of viral polymerase chain reaction (PCR) positivity and evaluate their correlations with seroconversion and disease severity. They found the rate of viral PCR positivity peaked within the initial few days. Seroconversion rates peaked within four to five weeks. Dynamic laboratory index changes corresponded well to clinical signs, the recovery process, and disease severity.

The researchers note the data would be valuable for developing effective, preventive, and treatment strategies against COVID-19. Appropriate prevention and therapeutic approaches should be established on the basis of viral kinetics, clinical manifestations, and laboratory testing. They note further work is urgently needed to improve our understanding of the potential effects of the virus, host innate and adaptive immune responses, and their interactions during the acute and convalescent phases of COVID-19.

Read the full text: https://www.acpjournals.org/doi/10.7326/M20-3337.

Media contacts: A PDF for this article is not yet available. Please click the link to read the full text. The corresponding authors, Gang Chen, PhD, Chaoyang Sun, PhD, Ding Ma, PhD, and Peng Wu, PhD, can be reached through Chaoyang Sun, PhD at suncydoctor@gmail.com.

4. Simultaneous COVID-19 infection in identical twins helps to explain differences in illness severity

Although we are rapidly learning more about COVID-19, we still know little about why some infected persons have severe disease and others are asymptomatic or have mild disease. Authors from Italy describe a case report describing the differences in clinical illness between male identical twins who tested positive for SARS-CoV-2. Neither twin had a history of chronic disease, cardiovascular risk factors, or long-term therapy. They lived at the same address and worked at the same location. The same medical team provided care to both brothers during the first 2 weeks of their hospital stays. Despite having similar presentations and early treatment, Twin 1 was discharged without complications and recovered uneventfully, and Twin 2 required more care and had four days of invasive ventilation. The authors suggest the differences in the virus, such as differences in the infecting dose or viruses with different mutations, may explain differences in illness severity.

Read the full text: https://www.acpjournals.org/doi/10.7326/L20-1207.

Media contacts: A PDF for this article is not yet available. Please click the link to read the full text. The corresponding author, Davide Lazzeroni, MD, can be reached at davide.lazzeroni@gmail.com.

5. Caring for dying patients during the pandemic shows the human side of medicine

The COVID-19 pandemic has affected the hospital experience for patients, visitors, and staff. Researchers from McMaster University and St. Joseph's Healthcare sought to understand clinician perspectives on adaptations to end-of-life care for dying patients and their families during the pandemic. They identified themes from semi-structured clinician interviews and found many barriers to end-of-life care arose because of infection control practices that mandated visiting restrictions and PPE. During hospitalization, family visits inside or outside the patient's room were possible 80 percent of the time. At the time of death, more than 44 percent of patients had a family member at the bedside.

Researchers found that clinicians were inspired to express humanity, seek each patient's story, ensure dignity-conserving care, adopt new roles, and catalyze connections.

Read the full text: https://www.acpjournals.org/doi/10.7326/M20-6943.

Media contacts: A PDF for this article is not yet available. Please click the link to read the full text. The corresponding author, Deborah J. Cook, MD, MSc, can be reached at debcook@mcmaster.ca.

A new study provides the first detailed documentation of a shallow water fish diving 450 feet deep to spawn. Uncovering this very rare spawning behavior in bonefish (Albula vulpes) is unprecedented. Using active acoustic telemetry and sonar data along the southern shore of Abaco, The Bahamas, a team of scientists led by Florida Atlantic University's Harbor Branch Oceanographic Institute in collaboration with Bonefish & Tarpon Trust, and University of Massachusetts Amherst, has discovered that although bonefish live in shallow waters less than 6 feet, they dive "deep" into the abyss to spawn.

While prior research in 2013 showed that bonefish descended approximately 164 feet to spawn, this new scientific finding reveals that bonefish descended to depths reaching 450 feet, and moved below 325 feet for two hours before spawning in a rush upward to 220 feet deep. Findings from the study, published in the journal Marine Biology, will be instrumental for conservation efforts for this economically and culturally important fish species.

"We were stunned by this discovery because the bonefish moved out beyond the incredibly abrupt and steep shelf drop off into the Providence Channel in Abaco," said Steven Lombardo, first author and a Ph.D. candidate who works with Matt Ajemian, Ph.D., senior author, an assistant research professor at FAU's Harbor Branch and head of the Fisheries Ecology and Conservation (FEC) Lab. "Data from our acoustic telemetry tags showed us in real time that bonefish were capable of handling extreme pressures. When they reached 334 feet in the first dive, we were floored, and 45 minutes later when they reached 450 feet deep, we were absolutely astonished."

Active acoustic telemetry enabled the scientists to observe the spawning movements and is a method that employs small pill-like tags that are surgically implanted into the fish's abdominal cavity, emitting an ultrasonic ping every three seconds. Researchers listened for the pings emitted from the tags using a boat-mounted directional hydrophone, using the strength of the signal communicated from the tag to the hydrophone to determine what direction to move the boat and follow the fish. Each ping transmitted by the tag inside the fish relayed data to the scientists, informing them of the depth of the fish's location and the water temperature.

The researchers spent four days from sunrise to sunset observing the bonefish pre-spawning aggregation in hopes that they would move offshore to spawn. At sunset on the final scheduled night of their research cruise, bonefish began "porpoising," where they gulped air at the surface, and then proceeded to move offshore following the edge of the continental shelf. The successful observation of bonefish spawning capped an 18-hour shift on the water, spanning two days.

"Following the bonefish on their offshore spawning migration was a marathon for the science team as well as the fish," said Aaron Adams, Ph.D., co-author, senior scientist at FAU's Harbor Branch and director of science and conservation at Bonefish & Tarpon Trust. "Most importantly for conservation, now that we know the conditions bonefish require to spawn we can better focus our efforts for habitat conservation."

When many species of coastal marine fish spawn, they spawn in groups known as spawning aggregations, which are mixed males and females. These fishes follow a process known as "broadcast spawning" in which the males and females eject sperm and eggs into the open water where the eggs are fertilized. The eggs hatch in about a day, and the tiny larvae that hatch from the eggs live in the open ocean as plankton for days to months, depending on the species, before finding shallow water and becoming juveniles. Adults of many of these species migrate long distances from their home ranges to spawning locations, often spawning on the edges of reefs adjacent to deep water.

Unlike other coastal marine fishes, the bonefish partakes in a unique three-point spawning migration, traveling up to 70 miles from shallow water home flats to form nearshore pre-spawning aggregations before moving offshore to reproduce. Once at the pre-spawning location, they gather in large groups often numbering anywhere from 5,000 to 10,000 bonefish.

"Despite their economic and cultural importance, there are concerns about the long-term health of the bonefish fishery. Because of habitat loss and harvest in some locations, bonefish are classified as 'Near Threatened,' therefore information on their reproduction is critical to conservation efforts," said Ajemian. "We are continuing our work on the offshore spawning movements of bonefish. We will be observing more spawning events at different locations and also will characterize what larval bonefish may be feeding on at these great depths."

This research will support the ongoing efforts of the Bonefish Reproduction Research Project at FAU's Harbor Branch, informing techniques used to rear captive spawned bonefish larvae through the feeding phase of development and beyond.