Culture

A new analysis of data from researchers at King's College London using information from the COVID Symptom Study app and patients admitted to St Thomas' Hospital in London, has shown that delirium - a state of acute confusion associated with a higher risk of serious illness and death - is a key symptom of COVID-19 in frail, older people.

The findings, published in the journal Age and Ageing, highlight that doctors and carers should be aware of delirium as a possible early warning sign of COVID-19 in the elderly, even in the absence of more typical symptoms such as cough or fever.

Led by clinical fellow and geriatrician Dr Rose Penfold at King's College London, the researchers analysed data from two groups of older people aged 65 or over from March through May. The first group included 322 patients admitted to hospital with COVID-19 who had tested positive for COVID-19, while the second comprised 535 users of the COVID Symptom Study app who reported having had a positive test result.

They found that older adults admitted to hospital who were classified as frail according to a standard scale were more likely to have had delirium as one of their symptoms than people of the same age who were not classed as frail. Delirium, along with tiredness and breathlessness, were also more common in frailer users of the COVID Symptom Study app with COVID-19, compared with fitter people of the same age.

A third of app users experiencing delirium did not report suffering the 'classic' COVID-19 symptoms of cough and fever, while delirium was the only symptom for around one in five (18.9%) of hospitalised patients.

Frailty in the group of hospitalised patients was measured using the Clinical Frailty Scale (CFS) test, which is administered by a doctor. COVID Symptom Study App users were asked to complete a short questionnaire asking about their health, which is comparable to the CFS.

This is the first study showing that delirium is a likely symptom of COVID-19 in frail older adults, although the precise biological connection between the two conditions still needs to be understood. The findings also highlight the need for systematic assessment of frailty for older people, along with awareness and screening for delirium for this vulnerable population in hospitals, care homes and the community.

Dr Rose Penfold from King's College London said: "Older, frailer people are at greater risk from COVID-19 than those who are fitter, and our results show that delirium is a key symptom in this group. Doctors and carers should watch out for any changes in mental state in elderly people, such as confusion or strange behaviour, and be alert to the fact that this could be an early sign of coronavirus infection."

Dr Claire Steves from King's College London said: "The past six months have shown us that COVID-19 can spread catastrophically through care homes. Knowing that delirium is a symptom in frail, elderly people will help families and carers spot the signs earlier of COVID-19 and act appropriately and put in place infection control measures such as isolation, increased hygiene and personal protective equipment to protect this highly vulnerable group."

Professor Tim Spector, Professor of Genetic Epidemiology at King's College London and COVID Symptom Study lead, said: "In April we upgraded the COVID Symptom Study app to allow users to log health reports on behalf of friends and family who aren't able to access the app. This significantly increased the number of older people in the study, providing vital insights. We're hugely grateful to all our users and urge everyone to download the app and log their health and that of their loved ones on a daily basis as we move towards the winter months."

Despite humanity's remarkable engineering prowess, sometimes completely unexpected or poorly understood physical phenomena can rapidly lead to catastrophic failures. Such was the case in Braniff International Airways Flight 542 in 1959 and Northwest Orient Airlines Flight 710 in 1960, where both aircrafts spontaneously disintegrated in mid-air due to a mechanical phenomenon known as "flutter."

In aerospace research, flutter generally refers to undesired and self-sustained vibrations in turbine blades that can readily grow out of control, destroying them along with the engine, and even the aircraft's wings. It is not very surprising that flutter remains an area of active research and one of the main concerns when designing turbines. In fact, flutter has been placed once again under the spotlight in a project (advanced-fan-jet-research: aFJR) launched by the Japan Aerospace Exploration Agency (JAXA) aimed at designing highly efficient and environment-friendly turbines.

In a new study published in Physical Review Applied, scientists from the Tokyo University of Science (TUS), in collaboration with researchers from JAXA, tackle the problem of developing a novel methodology for early detection of flutter in the design state of blades. Dr. Hiroshi Gotoda (corresponding author of the paper) from the Department of Mechanical Engineering at TUS explains the problem at hand and how they tried to solve it, "The onset of cascade flutter has impeded the technological development of advanced jet engines and its early detection is a long-standing problem in current aerospace propulsion engineering. Our main aim was to explore the applicability of a methodology combining complex networks and synchronization to detect a precursor of cascade flutter."

The main idea behind their approach is that the turbine fan can be mathematically modeled as a complex network of interrelated oscillators and that flutter is ultimately the result of the progressive synchronization of more and more blades as a result of increased airflow going through the turbine. In another study, published in the Journal of Applied Physics, the same group had explored an artificial intelligence-based method for detecting the onset of flutter from time-series data using the permutation entropy of the system, which is a measure of the randomness of the turbine's complex dynamics. In their current work, they demonstrate that a network representation of the system based on synchronization is closely related to the actual oscillatory behavior of the blades.

Through experiments on an actual turbine test rig conducted at JAXA's Altitude Test Facility, the research team found that, before the onset of flutter, one particular blade begins to act as a "central hub" in the network and adjacent blades start to oscillate in sync with it. This "local" synchronization quickly expands and leads to the collective synchronization of all blades, resulting in potentially catastrophic "flutter."

In this context, the network representation of the system proposed in this study serves two important purposes, as explained by Dr. Gotoda, "We demonstrate the applicability of two local and global measures as potential detectors of cascade flutter: the connecting strength between individual network nodes and the network's synchronization parameter. The former is valid for specifying the dominant blades for the onset of cascade flutter. In contrast, the latter, which ranges from 0 to 1, is more suitable for determining a threshold for this onset."

The combined findings of these new studies shed light on the complex phenomenon of flutter, and contribute to the academic systemization of nonlinear problems in the field of aeronautical engineering and related nonlinear science. They could represent promising techniques for the early detection of flutter onset in the design state of blades. The efforts of this research team from TUS and JAXA would help the development of safer and more eco-friendly turbine designs.

A team of investigators from CDDEP, the Government of Tamil Nadu, and Andhra Pradesh studied disease transmission patterns in 575,071 individuals exposed to 84,965 confirmed cases of COVID-19. The study, based on data collected by tens of thousands of contact tracers in the states of Andhra Pradesh and Tamil Nadu is the largest and most comprehensive analysis of COVID-19 epidemiology to date.

Andhra Pradesh (population 50 million) and Tamil Nadu (population 68 million) are among the Indian states with the largest healthcare workforce and public health expenditures per capita, and are known for their effective primary healthcare delivery models. Both states initiated rigorous disease surveillance and contact tracing early in response to the pandemic. Procedures include syndromic surveillance and SARS- CoV-2 testing for all individuals seeking care for severe acute respiratory illness or influenza-like illness at healthcare facilities; delineation of 5km "containment zones" surrounding cases for daily house-to-house surveillance to identify individuals with symptoms; and daily follow-up of all contacts of laboratory-confirmed or suspect COVID-19 cases, with the aim of testing these individuals 5-14 days after their contact with a primary case, irrespective of symptoms, to identify onward transmission.

The AP-TN study found that:

COVID transmission

1. Risk of transmission from an index case to a close contact ranges from 2.6% in the community to 9.0% in the household and does not differ significantly with respect to the age of the index case.
2. Infection probabilities ranged from 4.7-10.7% for low-risk and high-risk contact types, respectively. Same-age contacts were associated with the greatest infection risk.
3. The study found a high prevalence of infection among children who were contacts of cases around their own age; this finding of enhanced infection risk among individuals exposed to similar-age cases was also apparent among adults.
4. Not all infected individuals transmit COVID-19. Prospective follow-up testing of exposed contacts revealed that 70% of infected individuals did not infect any of their contacts, while 8% of infected individuals accounted for 60% of observed new infections. This study presents the largest empirical demonstration of superspreading that we are aware of.

Mortality

1. Case-fatality ratios spanned 0.05% at ages 5-17 years to 16.6% at ages ?85 years.
2. Men were 62% more likely to die than women.
3. 63% of those who died had at least one co-morbidity. 36% had two or more co-morbidities. 45% of those who died were diabetic.
4. Unlike observations in high-income settings, deaths in India are concentrated at ages 50-64 years. The figure below shows case fatality ratios (CFR) at various age groups in India compared to other countries. The CFR is higher in the 40-70 age group in India than in any of the four comparison countries (see figure below). For the age category above 80, the CFR is India is in line with other countries indicating a potential survival effect.
5. Contrary to long hospital stays reported in high-income settings, the median time to death is 6 days following admission (compared to 13 in the United States).

Effect of the Lockdown

1. There are substantial reductions in the reproductive number Rt associated with the implementation of India's country-wide shutdown, which has not previously been shown empirically.
2. Case-fatality ratios (proportion of cases that died) have decreased over the course of the epidemic. Individuals who tested positive between in July were 26% less likely to die than those tested in March and April. Those who tested positive in May and June were 13% less likely to die than those tested in March and April.

According to the director of CDDEP, Dr. Ramanan Laxminarayan, "This study was made possible by the significant contact tracing effort in Andhra Pradesh and Tamil Nadu, which involved tens of thousands of healthcare workers. The results on disease transmission and mortality have the potential to inform policy to fight COVID-19. The study also speaks to the capacity of research emerging from India to help inform the global response to COVID-19".

UNIVERSITY PARK, Pa. -- If you've ever played an online video game, you've likely competed with a bot -- an AI-driven program that plays on behalf of a human.

Many of these bots are created using deep reinforcement learning, which is the training of algorithms to learn how to achieve a complex goal through a reward system. But, according to researchers in the College of Information Sciences and Technology at Penn State, using game bots trained by deep reinforcement learning could allow attackers to use deception to easily defeat them.

To highlight this risk, the researchers designed an algorithm to train an adversarial bot, which was able to automatically discover and exploit weaknesses of master game bots driven by reinforcement learning algorithms. Their bot was then trained to defeat a world-class AI bot in the award-winning computer game StarCraft II.

"This is the first attack that demonstrates its effectiveness in real-world video games," said Wenbo Guo, a doctoral student studying information sciences and technology. "With the success of deep reinforcement learning in some popular games, like AlphaGo in the game Go and AlphaStar in StarCraft, more and more games are starting to use deep reinforcement learning to train their game bots."

He added, "Our work discloses the security threat of using deep reinforcement learning trained agents as game bots. It will make game developers be more careful about adopting deep reinforcement learning agents."

Guo and his research team presented their algorithm in August at Black Hat USA - a conference that is part of the most technical and relevant information security event series in the world. They also publicly released their code and a variety of adversarial AI bots.

"By using our code, researchers and white-hat hackers could train their own adversarial agents to master many -- if not all -- multi-party video games," said Xinyu Xing, assistant professor of information sciences and technology at Penn State.

Guo concluded, "More importantly, game developers could use it to discover the vulnerabilities of their game bots and take rapid action to patch those vulnerabilities."

Important strides have been made in recent years in uncovering children's knowledge about hierarchical social relationships. Much of these have focused on dominance, a hierarchy in which individuals defer to others out of fear or intimidation.

In a new study published in Child Development researchers from Central European University and Bar-Ilan University begin to explore how young children conceptualize leadership, a hierarchy that is based on voluntary deference and respect. Specifically, they examined whether children view leaders primarily as more entitled individuals (deserving preferential treatment) or more responsible individuals, relative to non-leaders. Such concepts could underlie children's predictions and evaluations of leaders' and non-leaders' behavior in a variety of situations.

The researchers presented five-year-old Israeli children stories about a group who elect a leader and go to an amusement park. Each story involved a collaborative situation. In one, rides required two protagonists - thus establishing a joint goal -- and to activate a ride, the protagonists must put coins into its piggy-bank box. Children were shown a hierarchical dyad (a leader and a non-leader) and an egalitarian dyad (two non-leaders), and their respective coins, in turn. Children anticipated how many coins each protagonist would contribute to activate the ride and judged the acceptability of two 'actual' contributions (small or large) by the leader (hierarchical dyad) and non-leader (egalitarian dyad). The other story was similar, except that protagonists only had to ride in dyads, and dyads fulfilling this requirement received a prize. Children's anticipation of relative withdrawals from the joint prize, and acceptability judgments of 'actual' small and large withdrawals by a leader (hierarchical dyad) and a non-leader (egalitarian dyad) were measured.

Results showed that children expected a leader to contribute more to a joint goal than its non-leader partner, expected a leader to withdraw an equal share (not more) from the common prize, and judged a leader more harshly than a non-leader for not adhering to these two behaviors. "These findings show that children view leaders as more responsible (not more entitled), relative to non-leaders, in two collaborative contexts," said the study's first author, Dr. Maayan Stavans, of Central European University, who collaborated on the research with Prof. Gil Diesendruck, of the Department of Psychology at Bar-Ilan University. "Our focus on collaborative situations, extends prior research presenting primarily competitive or neutral contexts. It is also a first demonstration that children understand conferred leadership by election."

"Because children were not asked about familiar kinds of authority figures, such as teachers and parents, nor about situations in their everyday lives, their responses reflect sophisticated ideas about leadership applied to novel protagonists and situations. While impressive, we have yet to understand how children come to think leaders have increased responsibility, at what point do they begin to represent leaders' increased entitlement (as adults do!), and how dependent are these representations on context," added Dr. Stavans.

Meanwhile, the researchers say that parents and educators can capitalize on the finding that children attribute leaders increased responsibility in two ways. First, they, as 'leaders', should behave toward their children 'followers' in line with these ideas, to reinforce them. Second, once children begin to attribute increased entitlement to leaders, parents and educators can explain how position perks come with increased responsibility and can be lost when responsibility is unfulfilled, upholding leaders when needed.

Researchers at the University of Maryland, Baltimore County (UMBC) have published new findings in Molecular and Cellular Proteomics on critical cellular processes triggered when cells respond to environmental stress. Mark Marten, professor of chemical, biochemical, and environmental engineering, led the research team, which identified three coordinated pathways involved in the response to cell wall stress in filamentous fungi. Cynthia Chelius, who recently earned her Ph.D. in chemical engineering at UMBC, is the first author on the paper.

A previous NSF grant supported the work that Marten conducted with Ranjan Srivastava, University of Connecticut, and Steven Harris, University of Manitoba.

Numerous species of filamentous fungi are pathogens that can make people sick, especially people who are immunocompromised. Different species of fungi play an important role in the development of pharmaceuticals and enzymes, and agriculture, where fungi can help improve the quality of soil and make nutrients more readily available for crops. By understanding how cells work and respond to stress, researchers can reverse-engineer processes that could have a broad range of applications.

To understand how the fungal cell walls respond to environmental stressors, Marten and his team studied what he describes as the cell's "software"--rules that control how the cell behaves. When fungi experience stress, Marten's team found an increase in the number of septa (or cross-hyphal bulkheads) created. "When you stress cells, they sense it and try to protect themselves," Marten explains. He adds that fungi try to repair damage to their cell walls so that they can resume normal growth and function.

The study used a multi-omic methodology, which researchers say can be applied to studying how signaling networks in cells work in general. The methodology allowed researchers to get a more detailed understanding of how cells respond to stressors. They found that when cell walls experience stress, there is a coordinated response through various pathways. By combining short time-scale phosphoproteomic sampling and longer scale transcriptomic sampling, the researchers were able to see a broader view of how cells respond to stress.

Marten, Srivatava, and Harris's teams will continue to collaborate on related research, which will be supported by a new three-year grant totaling $1.23 million grant from the National Science Foundation. This work will further explore how filamentous fungi repair their cell walls when exposed to stressors.

The team will examine how the parts of the fungal cell are assembled and how fungal gene regulatory networks function. They hope to understand how proteins in cells interact with each other, and how cells can turn on and off certain parts of their DNA to respond to stress.

"We were excited to see the results from this paper, as they both revealed a novel connection between different aspects of gene regulation in fungi and served as the basis for a new hypothesis regarding gene regulation in our most recent NSF Collaborative Research Award," says Marten.

British Columbia found that BC was better prepared for the pandemic and responded in a more coordinated and decisive manner, leading to far fewer deaths than in Ontario.

The article is published in CMAJ (Canadian Medical Association Journal).

As of September 10, 2020, Ontario had reported 5965 resident cases in LTC homes and 1817 resident deaths from COVID-19, compared with just 466 cases and 156 deaths in BC homes.

"The BC long-term care system before the pandemic was better prepared to minimize SARS-CoV-2 transmission and respond to outbreaks," says lead author Michael Liu, medical and graduate student at Harvard University, Boston, Massachusetts, and the University of Oxford, Oxford, United Kingdom.

In a comparison of the two provinces' preparedness and response to COVID-19, the authors found that BC's health system had several strengths over Ontario's.

For example, before the pandemic, the average combined per diem funding per LTC resident in BC was $222 compared with $203 in Ontario. Long-term care residents were more likely to live in shared rooms in Ontario (63%) than in BC (24%). Links between hospitals, LTC and public health were stronger in BC, and the organizational structure of the health system was relatively stable compared with Ontario, which was undergoing significant change with the merging of regional entities and several provincial agencies into Ontario Health.

"BC overall was better prepared for the pandemic, and elected leaders and public health officials responded faster and more decisively with measures to limit transmission of SARS-CoV-2 into long-term care homes," says Dr. Irfan Dhalla, a physician at St. Michael's Hospital, Unity Health Toronto, and the University of Toronto.

The authors recommend governments should ensure clear, consistent communications; respond rapidly and proactively; ensure disparities between for-profit and non-profit homes do not affect quality of care; move to single rooms; ensure infection prevention and control teams can support LTC homes during outbreaks; and consider organizational structures to support integration between LTC, public health and hospitals.

"Residents of long-term care homes will always be vulnerable to infections," says Dr. Dhalla. "Our analysis highlights policies and practices that, if implemented, could help protect these vulnerable seniors from a second wave of COVID-19 as well as other infectious diseases."

A study published in Nature shows that a segment of DNA that causes their carriers to have an up to three times higher risk of developing severe COVID-19 is inherited from Neandertals. The study was conducted by researchers at Karolinska Institutet and Max Planck Institute for Evolutionary Anthropology.

COVID-19 affects some people much more severely than others. Some reasons for this - such as old age - are already known, but other as yet unknown factors also play a role. This summer, a large international study linked a gene cluster on chromosome 3 to a higher risk of hospitalisation and respiratory failure upon infection with the SARS-CoV-2 virus.

Hugo Zeberg and Svante Pääbo at Karolinska Institutet in Sweden and Max Planck Institute for Evolutionary Anthropology in Germany now report that the version of the gene cluster associated with a higher risk of severe COVID-19 is very similar to the corresponding DNA sequences of a roughly 50,000-year-old Neandertal from Croatia, and indeed comes from Neandertals.

"It turns out that this gene variant was inherited by modern humans from the Neandertals when they interbred some 60,000 years ago," says Hugo Zeberg. "Today, the people who inherited this gene variant are three times more likely to need artificial ventilation if they are infected by the novel coronavirus SARS-CoV-2."

The study also reveals considerable differences in how common this genetic risk variant is in different parts of the world. It is particularly common among people in South Asia where about half of the population carry the Neandertal risk variant. In Europe, one in six people carry the risk variant, while in Africa and East Asia it is almost non-existent.

The study provides no explanation as to why this genetic variant confers a higher risk.

"It is striking that the genetic heritage from the Neandertals has such tragic consequences during the current pandemic. Why this is must now be investigated as quickly as possible," says Svante Pääbo, director at the Max Planck Institute for Evolutionary Anthropology.

Homeless New Yorkers who menstruate face numerous challenges due to inadequate access to toilets, bathing spaces, and laundering services, as well as pervasive menstrual stigma. The study by researchers at Columbia University Mailman School of Public Health and the CUNY School of Public Health and Health Policy highlights the need for improved quality, supply, and accessibility of bathrooms for sheltered and street-dwelling homeless, and ease of access to bathing and laundering, particularly as the number of women in the city's shelter system is near record highs.

In partnership with the Coalition for the Homeless, the researchers conducted in-depth interviews with 22 individuals ages 18 and older living on the street and in shelters in New York City in 2019. They also interviewed 15 staff at government agencies, shelters, and service provider organizations and conducted field audits of public toilets.

Results, which include interview excerpts, are published in the journal Health and Place.

"Homelessness, and a lack of adequate access to bathing and laundering, particularly for those living on the street, intensifies the difficulties around the pressure 'to pass,' as someone who is not homeless in order to enable increased access to toilets, which you need even more when managing monthly menstruation," says first author Marni Sommer, DrPH, associate professor of sociomedical sciences at Columbia Mailman School. "A constant threat of feeling unclean, combined with pervasive menstrual stigma, takes a toll on these individuals' self-esteem, their confidence, their sense that they can be respected in the world around them, and even their ability to seek out services, training and work."

Among the study's findings:

Respondents report that shelter bathrooms are often dirty or flooded, making them unpleasant, unsafe, and sometimes, impossible to use. Gaining access to a private sector restroom is predicated on their ability to "pass" as someone who is not homeless.

Showering facilities across the city, made available by various service providers, are few in number for those living on the street, with limited hours and days of operation, and often seen as unclean and unsafe.

Few shelters offer laundry services, and for those that do, many require payment. Numerous study participants said they dispose of items that are bloodstained or heavily soiled given the laundering challenges.

Access to menstrual products is complicated by the embarrassment and shame of having to disclose one's menstruating status to shelter or service provider staff in order to meet one's basic needs.

"The subject of the menstruation management needs of individuals experiencing homelessness has received very little attention from researchers or policymakers in the U.S.," says Sommer. "Our research clearly demonstrates the injustice of this neglect, and the need to improve bathroom quality, supply and accessibility, as well as improve ease of access to bathing and laundering resources. Such actions are essential given the high numbers of those experiencing homelessness in New York City, and in the time of COVID, a clarion call for clean and accessible public toilets is especially timely."

The researchers disclose several limitations, including that they were unable to include individuals experiencing homelessness who struggle with mental health conditions, who are also less likely able to "pass" and access public or commercial restrooms. And, although the recruitment sought to be inclusive, ultimately everyone who was available for and interested in participating in an interview identified as a woman; thus, the researchers were unable to capture the experience of transmasculine and gender non-binary individuals, for whom adequate menstrual management can be a serious safety issue.

Background on Homelessness in New York City

In 2019, New York City homeless shelters held an average of 62,391 people per night, with the shelter system serving 133,284 separate individuals in 2018, a 59 percent increase over the prior decade, according to Coalition for the Homeless. A point-in-time count in 2019 by the Department of Homeless Services estimated 3,588 more individuals sleeping on the street, a number that may be a significant underestimate due to the difficulties associated with locating this population.

Outer ear infections, which affect millions of people each year, are typically caused by the bacteria Pseudomonas aeruginosa or Staphylococcus aureus. Repeatedly administering antibiotic drops, the standard treatment, can be a problem for some people, and the only single-use suspension currently available needs to be kept and handled cold. Now, researchers reporting in ACS Biomaterials Science & Engineering have developed a single-use treatment that doesn't require refrigeration.

Treatment for ear infections usually involves a patient or caregiver administering antibiotic drops for 7-14 days, multiple times each day. However, this regimen can be difficult for some, especially for people with hand or head tremors, nursing home residents, those in the military and people lacking access to regular health care. Incorrect or missed applications can mean the infection lasts longer than it should, or keeps coming back. In addition, the microbes could develop resistance to the drug. The U.S. Food and Drug Administration recently approved a treatment for ear infections that can be administered in a single dose by healthcare workers, but the medication requires refrigeration and several preparation steps prior to application. This would limit its use, particularly in remote areas. Monica Serban and colleagues wanted to develop a simple, safe, single-dose drug delivery system for ear infections that wouldn't need to be kept cold.

The team tested two delivery systems by mixing activated tetraethyl orthosilicate with large molecular weight polymers. The materials are liquids when squeezed through a syringe, but they rapidly form gels upon entering the ear, where they can release an antibiotic by diffusion. The hydrogels are stable through a range of temperatures, from 39.2 F to 104 F. The antibiotic ciprofloxacin doesn't require refrigeration, and when added to the gels, the materials killed P. aeruginosa or S .aureus in cultures at a 100-times lower antibiotic dose than that used in most ear drops. Also, the gels didn't harm or irritate model human skin. When placed in mouse ears, the materials were eliminated within 10 days, and they didn't impact the mice's hearing more than traditional ear drops. 

The authors acknowledge funding from the National Institutes of Health.

The abstract that accompanies this paper can be viewed here.

A recent publication in the Journal of Neuroscience by a group of researchers at the University of Kentucky looks at Encoding the Odor of Cigarette Smoke. Tim McClintock, a physiology professor at UK, says their work lays a foundation for two things.

"One is basic knowledge of how we tell one smell from another. We call this odor discrimination. The other is blocking the detection of unwanted odors. Cigarette smoke is an unwanted odor due to its general - though relatively mild - offensiveness, and for its clinical significance. The odor of cigarette smoke triggers the desire to smoke in both smokers and reformed smokers. Now that we know the receptors that respond to this odor, we can start to work on blocking them."

McClintock says they expect blockers to improve smoking cessation, which has very low success rates and has sometimes involved approaches such as vaping that he says are also detrimental to one's health.

In addition to opening the door to developing blockers of odors, McClintock says this work will help researchers understand why formulating fragrances and flavors with specific properties is so difficult. "Ergo, the oft-used phrase 'the art of perfumery'. Eventually we will turn this art into science."

The study was made possible thanks to recent technological advances in this field, "It has only been six years since we announced the invention of a new technology that allows us to identify the receptors responding to odors. We've been gradually working up from single odors towards more complex mixtures ever since," said McClintock.

The sense of smell uses hundreds of receptors as the detectors for odor molecules. "They work like a gymnasium scoreboard where patterns of lights form numbers and words; or like a computer screen where the pixels are the units forming patterns. Every odor produces its own unique pattern on the scoreboard. We can now read the pattern even for complex odors like cigarette smoke," explained McClintock. Cigarette smoke is a complex odor with more than 400 types of odor molecules.

The study used the new technology for preclinical experiments with mice to identify responsive receptors. They also used human perception studies to evaluate which odor molecules in cigarette smoke matter most. The human studies also asked volunteers to judge several things about artificial mimics of cigarette smoke odor. The data from the volunteers then allowed researchers to identify one odor molecule that is very important for the perception of cigarette smoke. The receptors for this molecule are the most important ones to block in order to improve smoking cessation.

UNIVERSITY OF CENTRAL FLORIDA

AI Can Detect COVID-19 in the Lungs Like a Virtual Physician, New Study Shows

The new UCF co-developed algorithm can accurately identify COVID-19 cases, as well as distinguish them from influenza.

ORLANDO, Sept. 30, 2020 - A University of Central Florida researcher is part of a new study showing that artificial intelligence can be nearly as accurate as a physician in diagnosing COVID-19 in the lungs.

The study, recently published in Nature Communications, shows the new technique can also overcome some of the challenges of current testing.

Researchers demonstrated that an AI algorithm could be trained to classify COVID-19 pneumonia in computed tomography (CT) scans with up to 90 percent accuracy, as well as correctly identify positive cases 84 percent of the time and negative cases 93 percent of the time.

CT scans offer a deeper insight into COVID-19 diagnosis and progression as compared to the often-used reverse transcription-polymerase chain reaction, or RT-PCR, tests. These tests have high false negative rates, delays in processing and other challenges.

Another benefit to CT scans is that they can detect COVID-19 in people without symptoms, in those who have early symptoms, during the height of the disease and after symptoms resolve.

However, CT is not always recommended as a diagnostic tool for COVID-19 because the disease often looks similar to influenza-associated pneumonias on the scans.

The new UCF co-developed algorithm can overcome this problem by accurately identifying COVID-19 cases, as well as distinguishing them from influenza, thus serving as a great potential aid for physicians, says Ulas Bagci, an assistant professor in UCF's Department of Computer Science.

Bagci was a co-author of the study and helped lead the research.

"We demonstrated that a deep learning-based AI approach can serve as a standardized and objective tool to assist healthcare systems as well as patients," Bagci says. "It can be used as a complementary test tool in very specific limited populations, and it can be used rapidly and at large scale in the unfortunate event of a recurrent outbreak."

Bagci is an expert in developing AI to assist physicians, including using it to detect pancreatic and lung cancers in CT scans.

He also has two large, National Institutes of Health grants exploring these topics, including $2.5 million for using deep learning to examine pancreatic cystic tumors and more than $2 million to study the use of artificial intelligence for lung cancer screening and diagnosis.

To perform the study, the researchers trained a computer algorithm to recognize COVID-19 in lung CT scans of 1,280 multinational patients from China, Japan and Italy.

Then they tested the algorithm on CT scans of 1,337 patients with lung diseases ranging from COVID-19 to cancer and non-COVID pneumonia.

When they compared the computer's diagnoses with ones confirmed by physicians, they found that the algorithm was extremely proficient in accurately diagnosing COVID-19 pneumonia in the lungs and distinguishing it from other diseases, especially when examining CT scans in the early stages of disease progression.

"We showed that robust AI models can achieve up to 90 percent accuracy in independent test populations, maintain high specificity in non-COVID-19 related pneumonias, and demonstrate sufficient generalizability to unseen patient populations and centers," Bagci says.

The UCF researcher is a longtime collaborator with study co-authors Baris Turkbey and Bradford J. Wood. Turkbey is an associate research physician at the NIH's National Cancer Institute Molecular Imaging Branch, and Wood is the director of NIH's Center for Interventional Oncology and chief of interventional radiology with NIH's Clinical Center.

This research was supported with funds from the NIH Center for Interventional Oncology and the Intramural Research Program of the National Institutes of Health, intramural NIH grants, the NIH Intramural Targeted Anti-COVID-19 program, the National Cancer Institute and NIH.

Study co-authors also included first author Stephanie A. Harmon with the NIH Molecular Imaging Branch, National Cancer Institute and the Clinical Research Directorate, Frederick National Laboratory for Cancer Research; Thomas H. Sanford and Dominic Labella with the State University of New York-Upstate Medical Center; Sheng Xu, Victoria Anderson, Amel Amalou, Maxime Blain, Michael Kassin, and Dilara Long with the Center for Interventional Oncology, Radiology and Imaging Sciences, NIH Clinical Center and NIH National Cancer Institute, Center for Cancer Research; Evrim B. Turkbey, Dima Hammoud, Ashkan Malayeri, Elizabeth Jones, and Ronald M. Summers with NIH Clinical Center Radiology and Imaging Sciences; Holger Roth, Ziyue Xu Dong Yang, Andriy Myronenko, Daguang Xu, and Mona Flores with the NVIDIA Corporation; Nicole Varble with the Center for Interventional Oncology, Radiology and Imaging Sciences, NIH Clinical Center and NIH National Cancer Institute, Center for Cancer Research and Philips Research North America; Stephanie M. Walker and Peter L. Choyke with the NIH Molecular Imaging Branch, National Cancer Institute; Anna Maria Ierardi, Elvira Stellato, and Guido Giovanni Plensich with the Department of Radiology Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico Milano, in Milan; Giuseppe Franceschelli with the Diagnostic and Interventional Radiology Service, ASST Santi Paolo e Carlo, San Paolo Hospital in Milan; Cristiano Girlando and Giovanni Irmici with the Postgraduation School in Radiodiagnostics, Università Degli Studi di Milano; Kaku Tamura, Hirofumi Obinata, and Hitoshi Mori with the Self-Defense Forces Central Hospital in Tokyo; Francesca Patella and Maurizio Cariati with the Diagnostic and Interventional Radiology Service, ASST Santi Paolo e Carlo, San Paolo Hospital in Milan; Gianpaolo Carrafiello with the Department of Radiology Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico Milano and Department of Health Sciences, University of Milano in Milan; and Peng An with the Department of Radiology, Xiangyang NO.1 People's Hospital Affiliated to Hubei University of Medicine Xiangyang in Hubei, China.

Bagci received his doctorate in computer science from the University of Nottingham in England and joined UCF's Department of Computer Science, part of the College of Engineering and Computer Science, in 2015. He is the Science Applications International Corp (SAIC) chair in UCF's Department of Computer Science and a faculty member of UCF's Center for Research in Computer Vision. SAIC is a Virginia-based government support and services company.

CONTACT: Robert H. Wells, Office of Research, robert.wells@ucf.edu

A river's only consistent attribute is change. As the Greek philosopher Heraclitus remarked, "No man ever steps in the same river twice." Although this dynamic nature is often out of sight and mind, forgetting about it has led to many a historical catastrophe.

Recently, UC Santa Barbara geomorphologist Vamsi Ganti and his collaborators published a study finding that sea level rise will cause rivers to jump course, or avulse, more often on deltas than in the past. Now his team has discovered that a perfect storm of factors -- including larger floods and finer sediment size -- will enable these destructive events to occur farther and farther inland. Their results, which appear in Geophysical Research Letters, warn of major disasters poised to hit many urban centers that historically never had to worry about these issues.

On large, relatively flat rivers, avulsions tend to occur in the backwater region, Ganti explained. "This is the zone over which the river flow feels the effect of the sea level." This region begins at the river mouth and can extend relatively far inland. For instance, the Mississippi River's backwater reach stretches 500 kilometers from the coast.

The team was looking through satellite and remote sensing data for historical avulsions and came across the unique deltas of Madagascar. The island has a host of short rivers that course down from the mountains carrying very fine sediment. This is due to the saprolitic soils -- loose, soft soils made of silt and disintegrating rock -- that dominate the country's highlands. Exacerbated by rampant deforestation on the island, the exposed soils feed the island's turbid, red rivers and make it one of the fastest eroding places on Earth, according to lead author Sam Brooke, a postdoctoral scholar in the Department of Geography.

Using multiple satellite images taken since the late 1970s, Brooke created time series animations that communicate just how fast Madagascar's river deltas are evolving. Using this data, he was able to obtain the rivers' discharge rates as well as the amount of time the channels remained full during floods.

Combining the data with the satellite imagery led to a surprising conclusion. The avulsions weren't occurring anywhere near the rivers' backwater zones. "[Instead, they were] about 20 times [farther] upstream," Brooke recalled, "way outside of where we'd expect them to be based on [...models] using simple backwater scale." The researchers realized they had to update their models of where avulsions occur on deltas.

A better model

The team's expanded theory boils down to a simple relationship. Two processes are at work in river channels -- the duration of floods, and the time it takes for the river to adjust to changes. The relative timescales of these phenomena dictate where avulsions occur.

If floods are shorter than the time the river takes to adjust, then erosion and deposition are limited to the backwater zone. However, if floods last longer than it takes the river to adjust, erosion during floods can travel far upstream of the river mouth, which makes it possible for the river to avulse much farther inland.

Large flat rivers, like the Mississippi, change slowly, but steep rivers with lots of fine sediment can adjust quite quickly. "The whole channel can be resurfaced within the backwater zone in a given flood," said Ganti, "and erosion can propagate much farther upstream." This is the case for rivers like those in Madagascar, which are relatively steep and have a lot of fine sediment.

A river floods when it's carrying enough water to overtop its banks. And for most of its length, a flooded waterway will do just that. But water level is constrained by sea level near the river's mouth up through the backwater zone. So the increased volume of water during floods begins moving faster, increasing erosion, and scouring the river bed deeper.

This wave of erosion can then spread upstream as flood conditions continue, enabling the river to avulse far upstream from the backwater zone -- much farther than anticipated.

A foreboding picture emerges

"Climate models predict that extreme floods will occur more often in a warming world," said Ganti. As a result, avulsions could begin moving even farther inland on rivers around the world.

But greenhouse gas emissions are not the only human activity affecting rivers. Sand and gravel are critical components in construction and infrastructure, and humans are now mining these resources on massive scales. Unfortunately, these make up the coarse fraction of alluvial sediment, which means that our activities are leading to finer sediment in many locations. Rivers can carry more of this fine-grained material, and the increased load reduces the amount of time it takes channels [?] to change. Once again, this enables avulsions to occur farther upstream.

What's more, sea level rise is pushing the backwater zone itself farther inland. These three factors combine to create the perfect recipe for major avulsions to occur ever farther inland on deltas, Ganti explained. This could lead to an increasing trend of homes, lives and livelihoods lost due to extreme flooding, likely in locations that never had to deal with these hazards historically.

And according to the team's previous paper these events will also become more frequent as the sea level rises.

"We should brace ourselves for avulsion as a serious flood hazard in the future," Vamsi cautioned.

River deltas have always been a critical resource for humanity, harnessed for agriculture, transportation and industry. Many of civilization's largest cities have grown along the banks of the world's great waterways. Their dynamism has always posed a challenge to society, but as rivers become less predictable and more volatile, researchers say, we will need to take more precautions to ensure our safety and wellbeing.

University of Maryland entomologists discovered that a gene critical for survival in other insects is missing in mosquitos--the gene responsible for properly arranging the insects' segmented bodies. The researchers also found that a related gene evolved to take over the missing gene's job. Although laboratory studies have shown that similar genes can be engineered to substitute for one another, this is the first time that scientists identified a gene that naturally evolved to perform the same critical function as a related gene long after the two genes diverged down different evolutionary paths.

The work emphasizes the importance of caution in genetic studies that use model animals to make conclusions across different species. It also points to a new potential avenue for research into highly targeted mosquito control strategies. The research study was published in the September 30, 2020, issue of the journal Communications Biology.

"Every single arthropod has a segmented body plan. And you would think it develops the same way in all of them. But what we found is that it doesn't," said Alys Jarvela, a postdoctoral associate in the UMD Department of Entomology and the lead author of the study. "We learn a lot in biology by studying a process in a model organism and assuming that it works essentially the same way, using the same genes, in other organisms. That is still an incredibly useful approach. But, now we know that there is also a possibility for gene substitutions to be made in nature."

Jarvela discovered the missing gene in mosquitos by accident. She was studying crickets and attempting to cross-check her genetic samples by comparing the gene sequences of crickets with those of other insects. She was specifically interested in a gene called paired, one of a handful of genes that guides the pattern of repeated parts in segmented animals like insects. Laboratory studies had shown that when paired is knocked out or silenced in fruit flies, every other segment of the insect's body fails to develop, and it doesn't survive.

"I was just trying to find the mosquito version of paired to use as a reference point, and I couldn't find, it," Jarvela said.

When she searched for paired in all publicly available databases of mosquito genomes, she discovered it was missing from every mosquito species represented.
"Once we accepted that the gene was really absent, we thought that was a pretty wild mystery and immediately changed gears to satisfy our curiosity," Jarvela said.

Jarvela's team searched the genomes of fly species closely related to mosquitos and found they all contained the paired gene. This indicated that the loss of paired is a recent evolutionary event that took place only in mosquitos. It was clear to the researchers that some other gene in mosquitos must be performing the same function as paired does in other insects.

They found clues suggesting which gene could be involved in a 1996 experiment on fruit flies. In that study, scientists knocked out paired and replaced it with a closely related gene called gooseberry, which normally has a distinct role at a later time in development. That was a highly engineered experiment, but it showed that when gooseberry was manipulated to express at the right time during development, fruit flies without the paired gene developed normal alternating segments and survived.

To find out if gooseberry had naturally evolved as a substitute for paired in mosquitos, Jarvela and her team used CRISPR to edit gooseberry out of a mosquito species called Anopheles stephensi. The mutated mosquito embryos looked like laboratory fruit fly embryos that had paired knocked out.

"This work shows that even when different species share a trait or feature, the genetic mechanisms underlying this shared trait may be different," said Leslie Pick, professor and chair of the Department of Entomology at UMD and the study's senior author. "In the case reported in this paper, segmentation still happens even though a gene we thought was essential is lost. Our next steps will be to search for additional examples of variation in gene regulatory networks in insects and try to determine how genetic rewiring occurs in nature."

Jarvela is also interested in probing other aspects of mosquito development that may be affected by the loss of the paired gene. In addition to controlling segmentation, which is critical for survival, paired influences male fertility in fruit flies.

"That means different genes probably regulate male fertility in mosquitos, and they might be unique to the mosquito, which could potentially provide a powerful avenue for controlling mosquitoes without harming other insects such as butterflies and bees," Jarvela said.

While dinosaurs ruled the land in the Mesozoic, the oceans were filled by predators such as crocodiles and giant lizards, but also entirely extinct groups such as ichthyosaurs and plesiosaurs.

Now for the first time, researchers at the University of Bristol have modelled the changing ecologies of these great sea dragons.

Mesozoic oceans were unique in hosting diverse groups of fossil reptiles, many of them over 10 metres long.

These toothy monsters fed on a variety of fishes, molluscs, and even on each other. Yet most had disappeared by the end of the Cretaceous, 66 million years ago, when the dinosaurs also died out. There are still some marine crocodiles, snakes and turtles today, but sharks, seals, and whales took over these ecological roles.

In a new study, completed when she was studying for the MSc in Palaeobiology at the University of Bristol's School of Earth Sciences, Jane Reeves, now a PhD student at the University of Manchester, used modern computational methods to explore how all these marine reptiles divided up the spoils.

Jane said: "It's difficult to work out the ecology and function of fossil animals but we decided to focus mainly on their feeding and swimming styles. I tracked down information on 371 of the best-known Mesozoic marine tetrapods, and coded each one for 35 ecological traits, including body size, diet, likely hunting style, tooth type, presence or absence of armour, limb shape and habitat."

The numerical analysis showed that all these marine reptiles could be divided into just six ecological categories linking how they moved, where they lived, and how they fed: pursuit predators that chased their prey, ambush predators that lurked and waited for the prey to swim past (two groups, one in deep water, one in shallow), a fourth group of reptiles that could still walk on land, shallow-water shell-crushers and foragers, and marine turtles with a variety of life modes.

Professor Mike Benton, who co-supervised the study, said: "A problem with studies of form and function of fossils is that we have to be careful in reconstructing the behaviour of ancient animals. But in Jane's study, she used ecological characters from the start where their function had already been established. For example, sharp pointy teeth mean fish-eating, whereas broad, flat teeth mean shell crushing."

Dr Ben Moon, another co-supervisor, said: "We knew that the different marine reptile groups came and went through the 186 million years of the Mesozoic.

"I'm especially interested in ichthyosaurs, and we wanted to test an idea that they had migrated through ecospace during the Mesozoic. Jane's study shows definite movement through time from being semi-terrestrial at the beginning of the Triassic to a wide range of ecologies, including ambush hunting, and finally pursuit predation in the Jurassic and Cretaceous."

Dr Tom Stubbs, another co-supervisor, said: "We also wanted to test whether all these animals were competing with each other. But in fact, they seem to have avoided competition.

"For example, after a substantial extinction of marine reptiles around the end of the Triassic, the surviving ichthyosaurs and plesiosaurs showed considerable conservatism. They didn't expand their ecological roles at all, and many niches were left empty until new groups of crocodiles and turtles emerged later in the Jurassic to take over these roles."

Jane Reeves added: "It was a great experience being able to study a large variety of creatures, and to then reconstruct the ecological lifestyles of extinct animals from just their fossils.

"You do have to be very careful in doing these kinds of studies, not to make any unfounded assumptions. We know animals can be opportunistic, and don't always behave exactly how we think they should, but we're confident that the data we collected reflects the most common, day-to-day, behaviours of each animal. These results give us a great insight into what was really happening under the surface of the Mesozoic seas."