Culture

Evolutionary anthropologists from the University of Vienna and colleagues now present evidence for a different explanation, published in PNAS. A larger bony pelvic canal is disadvantageous for the pelvic floor's ability to support the fetus and the inner organs and predisposes to incontinence.

The human pelvis is simultaneously subject to obstetric selection, favoring a more spacious birth canal, and an opposing selective force that favors a smaller pelvic canal. Previous work of scientists from the University of Vienna has already led to a relatively good understanding of this evolutionary "trade-off" and how it results in the high rates of obstructed labor in modern humans. However, it has remained unclear what the advantage of a narrow birth canal is, given its disadvantage for childbirth. It has long been thought that a smaller birth canal is advantageous for bipedal locomotor performance. A different, less prominent explanation is that it enhances pelvic floor functionality. The muscles of the human pelvic floor play a vital role in supporting our inner organs and a heavy fetus, and in maintaining continence. A larger pelvic canal would increase the downward deformation of the pelvic floor, increasing the risk of pelvic floor disorders, such as pelvic organ prolapse and incontinence. However, this "pelvic floor hypothesis" has been challenging to prove.

A team of evolutionary anthropologists and engineers from the University of Vienna, the Konrad Lorenz Institute for Evolution and Cognition Research, and the University of Texas at Austin (USA) used a new approach to test this hypothesis. The researchers, led by Katya Stansfield and Nicole Grunstra from the Department of Evolutionary Biology, simulated a Finite Element model of a human pelvic floor across a range of different surface areas and thicknesses and investigated the deformation in response to pressure. "Finite Element analysis allowed us to isolate the effect of pelvic floor geometry by controlling for other risk factors, such as age, number of births, and tissue weakness," says Stansfield. This approach also enabled the team to model pelvic floor size across a broader range of variation than can be observed in the human population, "because natural selection may prevent the occurrence of such 'extreme' sizes precisely because of the disadvantages for pelvic floor functionality," explains Grunstra.

As predicted by the pelvic floor hypothesis, larger pelvic floors deformed disproportionately more than smaller pelvic floors. "Our results support the notion that smaller pelvic floors - and thus smaller birth canals - are biomechanically advantageous for organ and fetal support despite their disadvantage for childbirth," says Stansfield.

The researchers also found that thicker pelvic floors were more resistant to bending and stretching, which partly compensated for the increase in pelvic floor deformation as a result of increased surface area. So why did natural selection not result in a larger birth canal that eases childbirth, along with a disproportionately thicker pelvic floor that compensates for the extra deformation? "We found that thicker pelvic floors require quite a bit higher intra-abdominal pressures in order to undergo stretching, which is actually necessary during childbirth," says Grunstra. The pressures generated by women in labor are among the highest recorded intra-abdominal pressures and they may be difficult to increase further. "Being unable to push the baby through a resistant pelvic floor would equally complicate childbirth, and so we think we have identified a second evolutionary trade-off, this time in the thickness of the pelvic floor," concludes Grunstra. "Both the size of the birth canal and the thickness of the pelvic floor appear to be evolutionary 'compromises' enforced by multiple opposing selective pressures," says co-author Philipp Mitteroecker.

The (when stretched) two-metre-long DNA molecule in each human cell is continuously being unpacked and packed again to enable the expression of genetic information. When genes must be accessed for transcription, the DNA double helix unwinds and the strands separate from each other so that all the elements needed for gene expression can access the relevant DNA region. This process results in the accumulation of DNA supercoiling that needs to be resolved. A study recently published by Felipe Cortés, Head of the Topology and DNA Breaks Group at the Spanish National Cancer Research Centre (CNIO), and the members of his team, in cooperation with Silvia Jimeno González, Professor at the University of Seville and Head of the Transcription and mRNA Processing Group at the Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), reveals that DNA supercoiling is involved in regulating gene expression rather than just being collateral damage that must be fixed, as was previously believed. The results of the study were published in Cell Reports.

"Our results help us understand that DNA supercoiling is an important contributor to the control of gene expression and not just a problem related to DNA metabolism" says Cortés.

This study reveals that this type of regulation occurs mainly in specific genes that are massively activated (in the order of a hundred-fold) in a few minutes in response to different types of stimuli like cellular stress, cell division signals, hormones or neuronal activation.

TOP2A and the control of immediate early gene expression

Topoisomerases are proteins that relieve DNA topological stress by removing both positive and negative supercoiling, that is, over- and under-winding of DNA strand as compared to its relaxed state.

The authors of the research show that topoisomerase TOP2A relieves negative supercoiling at gene promoters, resulting thus in an increase in the number of twists of the DNA strands in these regions. This is an obstacle to the continuous opening of the helix that prevents the advance RNA polymerase, remaining in a poised state ready to trigger gene expression as soon as needed.

"Topoisomerases are considered to facilitate gene activation, but our study shows that TOP2A acts in promoter regions of genes like c-FOS [whose codified protein is involved in cell proliferation] silencing them and creating a topological context that facilitates rapid activation to respond quickly to stimuli," says Cortés.

The authors of the study point at the possibility that supercoiled DNA might have other functions, such as facilitating a three-dimensional configuration of the genome that enables the interaction of gene expression regulatory factors.

DNA supercoiling as a mechanism of gene regulation might be particularly relevant for fundamental biological processes that require a considerable rewiring of gene expression programmes, like cell differentiation or reprogramming, or tumour transformation and progression.

"Our work opens a way for the use of topoisomerase inhibitors as modulators in these processes and cell responses, and also even as cancer therapies," Cortés adds.

Altering a mosquito's gut genes to make them spread antimalarial genes to the next generation of their species shows promise as an approach to curb malaria, suggests a preliminary study published today in eLife.

The study is the latest in a series of steps toward using CRISPR-Cas9 gene-editing technology to make changes in mosquito genes that could reduce their ability to spread malaria. If further studies support this approach, it could provide a new way to reduce illnesses and deaths caused by malaria.

Growing mosquito resistance to pesticides, as well as malaria parasite resistance to antimalarial drugs, has created an urgent need for new ways to fight the disease. Gene drives are being tested as a new approach. They work by creating genetically modified mosquitoes that, when released into the environment, would spread genes that either reduce mosquito populations or make the insects less likely to spread the malaria parasite. But scientists must prove that this approach is safe and effective before releasing genetically modified mosquitoes into the wild.

"Gene drives are promising tools for malaria control," says first author Astrid Hoermann, Research Associate at Imperial College London, UK. "But we wanted a clear pathway for safely testing such tools in countries where the disease most commonly occurs."

In the study, Hoermann and colleagues genetically modified the malaria-transmitting mosquito Anopheles gambiae. They used the CRISPR-Cas9 technology to insert a gene that encodes an antimalarial protein amidst genes that are turned on after the mosquito eats a blood meal. The team did this in a manner that allowed the whole section of DNA to also function as a gene drive that could be passed on to most of the mosquitoes' offspring. They initially inserted the gene along with a fluorescent marker to help them track it in three different spots in the DNA, and then later removed the marker, leaving only a minor genetic modification behind.

Next, the team bred the mosquitoes to see if they were able to successfully reproduce and remain healthy. They also tested how well the malaria parasite developed in the mosquitoes' guts. Their experiments provide preliminary evidence that this approach to genetic modifications could create successful gene drives.

"These genetic modifications are passive, and could be tested in the field and undergo a stringent regulatory process to ensure they are safe and effective in blocking the parasite without raising concerns of accidental spread in the environment," explains senior author Nikolai Windbichler, Senior Lecturer at the Department of Life Sciences, Imperial College London. "However, once we combine them with other mosquitoes with an active gene drive, they turn into gene drives themselves without the need for any further changes. Our approach thus brings gene drives one step closer to being tested in the field as a malaria elimination strategy."

Many consumers are willing to pay for improved environmental quality and thus non-market values of impacts of food production on e.g. water quality, C sequestration, biodiversity, pollution, erosion or GHG emissions may even be comparable to the market value of agricultural production. Diverfarming project elucidated how consumers value agroecosystem services enabled by diversification and provided consumer perspectives for developing future agricultural and food policies to better support cropping diversification.

The researchers quantified consumers' willingness to pay for the benefits of increased farm and regional scale diversity of cultivation practices and crop rotations. Three valuation scenarios were presented to a representative sample of consumers: the first one focused on agroecosystem services on cropland, the second on wider socio-cultural effects and the third was a combination of them. A total of 600 consumers finished the questionnaire.

It was found that 79% of households were willing to pay extra for cropping diversification and that this corresponds to a significant monetary value of ecosystem services. The calculated total non-market value of cropping diversification at the country level can be as high as 47-95% compared to the annual market revenues of cereals, and 15-32% compared to the total market revenues in agriculture in Finland. The sum the consumers were willing to pay was on the average €228 per household annually which equals to €245 per hectare of cultivated cropland.

The relatively high willingness to pay for both agroecological and socio-cultural benefits provide important messages for actors in the food chain and for policy makers on future targeting of economic resources within agri-environmental schemes. This study showed that positive societal implications of cropping diversification were valued slightly higher than direct field level effects of diversification. In particular, improved maintenance of domestic food production and processing, reduced nutrient runoffs from agriculture, maintained food culture and tradition, as well as improved carbon balance of agriculture and the number of jobs in rural areas were valued high.

The effectiveness of agroecological schemes needs to be developed further but a higher contribution by consumers can also likely fund future transition towards more sustainable food production. Findings on the valuation of different ecosystem services help different actors of the food chain or policy makers to stress the most valued consequences and use the related arguments when, e.g., motivating the use of public expenditures.

However, the results also indicate that 21% of consumers were not willing to pay anything to support more diverse cropping systems. Rather traditional arguments based on ecology have been used in promoting for example organic and low-input agriculture. Effects on carbon sequestration and more resilient food production with positive effects on rural jobs and local food culture have been less emphasized. Using a larger selection of arguments would help to reach a wider variety of consumer types.

The Diverfarming project seeks a change in paradigm in European agriculture towards a more environmentally and economically sustainable agriculture through crop diversification and the reduction of inputs.

With summer around the corner, a project shows how implementing an evidence-based mindfulness program in a summer camp setting decreases emotional distress in school age children and empowers campers and counselors alike - enhancing camper-counselor relationships. Mindfulness - a state of consciousness that fosters awareness - has the potential to help regulate emotions and behaviors.

Researchers from Florida Atlantic University's Christine E. Lynn College of Nursing implemented an eight-week program guided by the Mindful Schools© curricula in a large urban summer day camp program (ages 3 to seventh grade). Mindfulness-based practices are intentional exercises that cultivate mindfulness and engage youth to help develop attention to self and surroundings, social skills and emotional skills.

Results of the program evaluation, published in the Journal of Pediatric Nursing (online in December 2020 ahead of final publication in issue on March 1, 2021), showed that weekly mindfulness sessions appeared to empower campers with the ability to pay attention to self and surroundings while regulating emotions and behaviors. Mindfulness sessions for counselors empowered them to intentionally role model, utilize mindful strategies when dealing with difficult behaviors of campers and reinforced mindful practices to campers between weekly Mindful Schools© sessions.

According to the counselors' observations, 40 minutes of weekly mindful sessions were most influential in affecting campers' ability to self-regulate. Counselors also reported their own ability to increase classroom/cabin management and camper behavior management skills through the use of peace corners and portable mindfulness aids such as "calm down jars," stress balls and talking timers.

Campers attended an adapted 40-minute Mindful Schools© session once a week as part of the camp curriculum. Weekly sessions began with a didactic teaching related to select Mindful Schools© lesson topics. Then campers engaged in actual practice of mindfulness content; age-appropriate hands-on experiential activities were then implemented to reiterate and practice mindful content. To ensure learned material was retained, cabin peace corners containing material that reinforced mindfulness were designed and implemented into each cabin classroom.

All Mindful Schools© sessions were delivered by a pediatric nurse practitioner and/or a master's prepared registered nurse - both of whom were certified Mindful Schools© educators. The children participated in mindful breathing, daily use of peace corners and even used mindfulness tools like the calm down jars filled with water, glitter, clear glue and food coloring. For example, campers were instructed to shake their calm down jars and focus on the falling glitter while they practiced mindful breathing. Workstations that represented each mindful lesson were set up at the completion of the eight-week program and offered for campers to select their lesson of choice(s). The purpose of the workstations were to evaluate which mindfulness activities resonated most with campers for future camp program design.

"We found that mindful breathing, mindful bodies, and mindful listening assisted in bringing awareness to campers in the program and provided skills to address stressful experiences," said Andra S. Opalinski, Ph.D., APRN, co-author, an associate professor and assistant dean of graduate studies in FAU's Christine E. Lynn College of Nursing. "Since calm down jars and mindful pebbles were the two most preferred activities - both of which are in sync with the top three mindful practices implemented by the campers - offering such adapted age appropriate experiential activities may indeed reinforce and reiterate didactic teaching and be pertinent for the intersection of playing and learning for mindful practices in children."

Because studies have found mindfulness-based practices as an effective approach to addressing self-regulation/ behavior concerns in school age children and adolescents, Opalinski and Laurie A. Martinez, Ph.D., M.S.N., M.B.A., co-author, a registered nurse and a project coordinator in FAU's Christine E. Lynn College of Nursing, note that applying an evidence-based practice mindfulness program to summer camp programs, a setting in which large numbers of children participate, provides additional context for addressing and examining mental health promotion in pediatric populations.

"This application of an evidence-based program also showed that the use of Mindful Schools© allows for sustainability of the program because a nurse can be trained in the curriculum and adapt the lessons for an alternative setting to broaden the reach of mindfulness interventions to settings such as after school and summer activity programs, Boys and Girls Clubs as well as faith community programs that provide services for children and adolescents," said Martinez. "In fact, the Mindful Schools© educators are exploring the possibilities of conducting a research study to validate the effectiveness of curricula change."

New research by the University of Kent and the SWPS University has discovered that national narcissists are more likely to support greenwashing (misleading information about the environmental benefits of a product, a company or a policy) in order to improve their nation's public image.

Findings show that while national narcissists are not likely to support genuine pro-environmental campaigns, they are ready to support political greenwashing campaigns. In business greenwashing decreases consumers' trust and undermines both the image and the profits of the companies that use this strategy. In the realms of politics, it may garner support from those whose strong national attachment is rooted in feelings of underappreciation and belief in their nation's unrecognised greatness.

The study, published by the Journal of Environmental Psychology, highlights the importance of group-based underpinnings of anti-environmental attitudes. It shows that nation-based defensiveness is a significant barrier in introducing pro-environmental policies, as it is associated with the preoccupation of national image more than with taking actual pro-environmental action. National narcissism, characterised by a strong need to validate a grandiose ingroup image, is related to support for pretending to be green just to impress others. Thereby, those high in national narcissism support creating pro-environmental appearances (although only to the extent they believe it is a low-cost strategy).

The team of psychologists led by Dr Aleksandra Cislak (SWPS University) and Dr Aleksandra Cichocka (Kent) hypothesised that although national narcissists might not support pro-environmental actions, they would support promoting a pro-environmental image of their nation. In five studies, psychologists demonstrated that individuals high in national narcissism were less likely to support actual pro-environmental actions (Studies 2-5), but more likely to support greenwashing campaigns (Studies 1-3, 5), although not when greenwashing would involve financial costs incurred by the ingroup (Study 4). In Study 5, national narcissism predicted support for greenwashing as a political strategy. This was related to the preference for green image enhancement over green actions (controlling for pro-environmental attitudes and individual narcissism). Psychologists did not observe similar effects for national identification or right-wing political ideology.

Lead author, Dr Aleksandra Cislak from the Center for Research on Social Relations at SWPS University said: 'Greenwashing is appealing to those high in national narcissism, as it allows them to maintain external recognition while at the same time refrain from pro-environmental actions. In this, support for greenwashing, while rejecting genuinely green actions, is similar to anti-science attitudes such as vaccination hesitancy. For those high in national narcissism, it feels powerful to reject or undermine policies recommended by other groups, especially the elite.'

Dr Aleksandra Cichocka, a co-author of the research paper and a reader in political psychology at the University of Kent's School of Psychology, added: 'When it comes to green deeds that could actually help protect the environment, those with a narcissistic view of their nation may be reluctant to offer support, especially when those actions are costly or seen as being imposed by other countries.'

A five-year study of mule deer does and newborn fawns in western Wyoming shows that migrating deer have a lot to balance when it comes to birth timing.

The study led by University of Wyoming scientists challenges the long-held assumption that animals match offspring birth with the peak green-up of forage at the birth site. Instead, only deer that migrated long distances and followed the flush of spring green-up from low elevation winter ranges to higher-elevation summer ranges were able to match birth with peak green-up. Other deer migrated shorter distances and gave birth earlier, but birth was out of sync with green-up.

The researchers' work appears in the journal Ecology.

To examine the factors shaping birth timing, researchers integrated highly detailed data on female deer, including movement data from GPS collars, body condition and gestational development from ultrasonography of adult female deer, and intensive fieldwork to locate newborn fawns.

"In contrast to existing theory, which predicts that conditions at the birth site should shape optimal birth timing, our results provide a clear example of birth timing being shaped by trade-offs arising from events occurring away from the birth site and from other parts of the annual cycle," the researchers wrote.

Migration results in animals having to time important events, such as reproduction, within tight time schedules. In general, mule deer in western Wyoming give birth in early June, generally after migration is over but early enough for fawns to grow large enough to survive the onset of winter. The deer that were part of the study included animals that migrated long distances between winter and summer ranges, as well as those that migrated shorter distances.

Among the study's findings:

Most deer completed migration well before giving birth: Across the five-year period of the study, animals completed migration, on average, 23 days before giving birth.

Does that ended migration earlier gave birth earlier.

Only animals that surfed the green wave and ended migration just before giving birth matched birth with peak green-up, whereas most gave birth after peak green-up.

Although matching birth with peak green-up likely increased access to high-quality forage, doing so resulted in delayed birth and, therefore, less time for offspring to grow and develop before fall migration.

Does appear to trade off early birth and increased time of offspring growth with matching birth to peak green-up.

Animals that migrated long distances had less developed fetuses in March, thereby allowing them to complete migration before giving birth -- without sacrificing the ability to surf the green wave along their migratory route.

"Conceptualizing birth timing through the lens of the full annual cycle helps to illuminate additional trade-offs that migrants face when balancing reproduction with migration, foraging and accumulation of fat reserves," the researchers wrote.

They say the link between movement tactics and timing of birth has important conservation and management implications. For example, human-caused disturbances to migration patterns could harm deer reproduction until animals have time to adjust. Additionally, the diversity of movement behaviors among western Wyoming mule deer is important to preserve, as animal populations with greater life-history diversity have been found to be more able to withstand environmental changes.

Despite increasing concern over the intrusion of algorithms in daily life, people may be more willing to trust a computer program than their fellow humans, especially if a task becomes too challenging, according to new research from data scientists at the University of Georgia.

From choosing the next song on your playlist to choosing the right size pants, people are relying more on the advice of algorithms to help make everyday decisions and streamline their lives.

"Algorithms are able to do a huge number of tasks, and the number of tasks that they are able to do is expanding practically every day," said Eric Bogert, a Ph.D. student in the Terry College of Business Department of Management Information Systems. "It seems like there's a bias towards leaning more heavily on algorithms as a task gets harder and that effect is stronger than the bias towards relying on advice from other people."

Bogert worked with management information systems professor Rick Watson and assistant professor Aaron Schecter on the paper, "Humans rely more on algorithms than social influence as a task becomes more difficult," which was published April 13 in Nature's Scientific Reports journal.

Their study, which involved 1,500 individuals evaluating photographs, is part of a larger body of work analyzing how and when people work with algorithms to process information and make decisions.

For this study, the team asked volunteers to count the number of people in a photograph of a crowd and supplied suggestions that were generated by a group of other people and suggestions generated by an algorithm.

As the number of people in the photograph expanded, counting became more difficult and people were more likely to follow the suggestion generated by an algorithm rather than count themselves¬ or follow the "wisdom of the crowd," Schecter said.

Schecter explained that the choice of counting as the trial task was an important one because the number of people in the photo makes the task objectively harder as it increases. It also is the type of task that laypeople expect computers to be good at.

"This is a task that people perceive that a computer will be good at, even though it might be more subject to bias than counting objects," Schecter said. "One of the common problems with AI is when it is used for awarding credit or approving someone for loans. While that is a subjective decision, there are a lot of numbers in there -- like income and credit score -- so people feel like this is a good job for an algorithm. But we know that dependence leads to discriminatory practices in many cases because of social factors that aren't considered."

Facial recognition and hiring algorithms have come under scrutiny in recent years as well because their use has revealed cultural biases in the way they were built, which can cause inaccuracies when matching faces to identities or screening for qualified job candidates, Schecter said.

Those biases may not be present in a simple task like counting, but their presence in other trusted algorithms is a reason why it's important to understand how people rely on algorithms when making decisions, he added.

This study was part of Schecter's larger research program into human-machine collaboration, which is funded by a $300,000 grant from the U.S. Army Research Office.

"The eventual goal is to look at groups of humans and machines making decisions and find how we can get them to trust each other and how that changes their behavior," Schecter said. "Because there's very little research in that setting, we're starting with the fundamentals."

Schecter, Watson and Bogert are currently studying how people rely on algorithms when making creative judgments and moral judgments, like writing descriptive passages and setting bail of prisoners.

An observational study of patients in London hospitals suggests that the B.1.1.7. variant is not associated with more severe illness and death, but appears to lead to higher viral load, consistent with emerging evidence that this lineage is more transmissible than the original COVID-19 strain.

A separate observational study using data logged by 37,000 UK users of a self-reporting COVID-19 symptom app found no evidence that B.1.1.7. altered symptoms or likelihood of experiencing long COVID.

Authors of both studies acknowledge that these findings differ from some other studies exploring the severity of the B.1.1.7. variant and call for more research and ongoing monitoring of COVID-19 variants.

Two new studies, published in The Lancet Infectious Diseases and The Lancet Public Health, found no evidence that people with the B.1.1.7. variant experience worse symptoms or a heightened risk of developing long COVID compared with those infected with a different COVID-19 strain. However, viral load and R number were higher for B.1.1.7., adding to growing evidence that it is more transmissible than the first strain detected in Wuhan, China, in December 2019.

The emergence of variants has raised concerns that they could spread more easily and be more deadly, and that vaccines developed based on the original strain might be less effective against them. Preliminary data on B.1.1.7. indicates that it is more transmissible, with some evidence suggesting it could also be associated with increased hospitalisations and deaths. However, because the variant was identified only recently, these studies were limited by the amount of data available.

Findings from the new studies, which spanned the period between September and December 2020, when B.1.1.7. emerged and began to spread across parts of England, provide important insights into its characteristics that will help inform public health, clinical, and research responses to this and other COVID-19 variants.

Increased viral load but no association with increased severity and death

The Article in The Lancet Infectious Diseases journal is a whole-genome sequencing and cohort study involving COVID-19 patients admitted to University College London Hospital and North Middlesex University Hospital, UK, between November 9 and December 20, 2020. This was a critical time point when both the original and B.1.1.7. variants were circulating in London, the vaccination programme was just starting, and before a significant surge in cases in early 2021 caused a strain on the NHS.

The authors compared illness severity in people with and without B.1.1.7 and calculated viral load. Among 341 patients who had their COVID-19 test swabs sequenced, 58% (198/341) had B.1.1.7 and 42% (143/341) had a non-B.1.1.7. infection (two patients' data were excluded from further analysis). No evidence of an association between the variant and increased disease severity was detected, with 36% (72/198) of B.1.1.7. patients becoming severely ill or dying, compared with 38% (53/141) of those with a non-B.1.1.7 strain.

Patients with the variant tended to be younger, with 55% (109/198) of infections in people under 60 compared with 40% (57/141) for those who did not have B.1.1.7. Infections with B.1.1.7. occurred more frequently in ethnic minority groups, accounting for 50% (86/172) of cases that included ethnicity data, compared with 29% (35/120) for non-B.1.1.7 strains.

In a regression analysis that included 289 patients, those with B.1.1.7 were no more likely to experience severe disease after accounting for hospital, sex, age, ethnicity, and underlying conditions.

Those with B.1.1.7. were no more likely to die than patients with a different strain, with 16% (31/198) of B.1.1.7. patients dying within 28 days compared with 17% (24/141) for those with a non-B.1.1.7. infection.

More patients with B.1.1.7 were given oxygen by mask or nasal cannula than those with a non-B.1.1.7. strain (44%, 88/198 vs 30%, 42/141, respectively). However, the authors say this is not a clear measure of disease severity, as patients may have received nasal prong oxygen for reasons unrelated to COVID-19, or as a consequence of underlying conditions.

To gain insights into the transmissibility of B.1.1.7., the authors used data generated by PCR testing of patient swabs to predict their viral load - the amount of virus in a person's nose and throat. The data analysed - known as PCR Ct values and genomic read depth - indicated that B.1.1.7. samples tended to contain greater quantities of virus than non-B.1.1.7. swabs.

Dr Eleni Nastouli, from University College London Hospitals NHS Foundation Trust and the UCL Great Ormond Street Institute of Child Health, UK, said: "One of the real strengths of our study is that it ran at the same time that B.1.1.7. was emerging and spreading throughout London and the south of England. Analysing the variant before the peak of hospital admissions and any associated strains on the health service gave us a crucial window of time to gain vital insights into how B.1.1.7. differs in severity or death in hospitalised patients from the strain of the first wave. Our study is the first in the UK to utilise whole-genome sequencing data generated in real-time and embedded in an NHS clinical service and integrated granular clinical data.

"We hope that this study provides an example of how such studies can be done for the benefit of patients throughout the NHS. As more variants continue to emerge, using this approach could help us better understand their key characteristics and any additional challenges that they may pose to public health." [1]

The authors acknowledge some limitations to their study. Disease severity was captured within 14 days of a positive COVID-19 test, so patients who may have deteriorated after 14 days may have been missed in the analysis, though the authors sought to mitigate this by capturing deaths at 28 days. The analyses also did not take account of any other treatments that patients were receiving - such as steroids, antiviral medications, or convalescent plasma - or the possibility that some patients may have received ventilation for reasons other than COVID-19.

Writing in a linked comment, Sean Wei Xiang Ong, Barnaby Edward Young, and David Chien Lye, from the National Centre for Infectious Diseases, Singapore, who were not involved in the study, said, "[The authors'] observation that B.1.1.7 infections were associated with increased viral loads corroborates findings from two other studies and provides a mechanistic hypothesis that increased transmissibility is via increased respiratory shedding. Yet, disease severity and clinical outcomes between patients with B.1.1.7 and non-B.1.1.7 infections were similar after adjusting for differences in age, sex, ethnicity, and comorbidities. Importantly, this study was done from Nov 9 to Dec 20, 2020, before the late- December peak in UK COVID-19 infections, avoiding any confounding effect of the availability of health-care resources on mortality. This finding is in contrast with three studies that reported increased mortality associated with lineage B.1.1.7."

They continue, "Thus, although limited by a much smaller dataset, the study by Frampton and colleagues has important advantages over the three community studies. These advantages include the use of whole-genome sequencing, recruitment of hospitalised patients, and a population reflective of the spectrum of severity in whom increased virulence will have the greatest effect on outcomes. The finding that lineage B.1.1.7 infection did not confer increased risk of severe disease and mortality in this high-risk cohort is reassuring but requires further confirmation in larger studies."

Effective Control Measures

The Article in The Lancet Public Health journal is an ecological study that analysed self-reported data from 36,920 UK users of the COVID Symptom Study app who tested positive for COVID-19 between 28 September and 27 December 2020.

Test results and symptom reports submitted through the app were combined with surveillance data from the COVID-19 UK Genetics Consortium and Public Health England to examine associations between the regional proportion of B.1.1.7. infections and symptoms, disease duration, reinfection rates, and transmissibility.

The analysis covered 13 full weeks over the period when the proportion of B.1.1.7. grew most notably in London, South East and East of England. Users were included in a week if they had reported a positive test during the 14 days before or after that week. For each week in every region in the analysis (Scotland, Wales, and the seven NHS England regions), authors calculated the proportion of users reporting any of 14 COVID-19 symptoms.

Dr Claire Steves, Reader and Honorary Consultant Physician, King's College London, UK, who co-led the study, said "We could only do this by aggregating two large sources of data: the extensive genetic sequencing of viral strains performed in the UK, and symptom and testing logs from millions of users on the COVID-symptom Study App. Thanks to them, we confirmed the increased transmissibility but also showed that B.1.1.7. clearly responded to lockdown measures and doesn't appear to escape immunity gained by exposure to the original virus. If further new variants emerge, we will be scanning for changes in symptom reporting and reinfection rates, and sharing this information with health policymakers."

For each region and symptom, a linear regression was done to examine the association between the proportion of B.1.1.7. in that region and the proportion of users reporting the symptom during the study period. The analysis adjusted for age, sex, and seasonal factors (regional temperature and humidity) that could affect reporting of some symptoms.

The analysis revealed no statistically significant associations between the proportion of B.1.1.7. within regions and the type of symptoms people experienced. There was also no evidence of any change in the total number of symptoms experienced by people with B.1.1.7: in the South East region, which experienced the earliest rise in B.1.1.7, the correlation coefficient was -0.021. The proportion of people who experienced long COVID (here defined as symptoms persisting for more than 28 days without a break of more than 7 days) was also not altered by B.1.1.7., with a correlation coefficient of -0.003.

The reinfection rate was low, with 0.7% (249/36,509) of those who reported a positive test before October 1, 2020, testing positive again more than 90 days later. The analysis found no evidence that reinfection rate was altered by B.1.1.7: for all regions except Scotland (where less data was available due to fewer users of the app), reinfections were more positively correlated with the overall regional rise in cases than the regional rise in the proportion of B.1.1.7. infections. No difference in reinfection rates was reported across study regions.

However, the authors found that B.1.1.7. increased the overall reproduction number, or R number, by 1.35 times compared with the original strain. This estimate is similar to those from other studies investigating the variant's transmissibility. Despite this increase, the analysis indicates that the R number was below 1 - indicating falling transmission - during local and national lockdowns, even in the three regions (London, South East, and East of England) with the highest proportions of B.1.1.7., which accounted for 80% of infections.

Dr Mark Graham, from King's College London, UK, said: "The wealth of data captured by the COVID Symptom Study app provided a unique opportunity to look for potential changes in symptoms and length of illness associated with the B.1.1.7. variant. Reassuringly, our findings suggest that, despite being more easily spread, the variant does not alter the type or duration of symptoms experienced and we believe current vaccines and public health measures are likely to remain effective against it." [1]

The authors acknowledge some limitations to their study. It was not possible to assess causal effects of B.1.1.7. due to the lack of information on the disease strain of individual positive cases reported through the app. Users may also have made errors when inputting their information through the app. People who sign up to the app are likely to be more interested in health and COVID-19 than the wider population and may exhibit different behaviour to other members of the population.

Writing in a linked comment, Dr Britta Jewell, from Imperial College London, UK, who was not involved in the study, said: "This study adds to the consensus that B.1.1.7 has increased transmissibility, which has contributed in large part to the sharp rise in cases in the UK over the study period and beyond, as well as ongoing third waves in European countries with growing burdens of B.1.1.7 cases. However, Graham and colleagues reach somewhat different conclusions about differences in symptoms than those of the UK Office for National Statistics, which reported that a higher proportion of individuals who tested positive for the B.1.1.7 variant had at least one symptom compared with those without the variant...Graham and colleagues acknowledge the limitations of using self-reported digital data for this type of analysis, including the inherent selection bias of app-based data, which could cause confounding that might explain some of the differences in findings.

However, Jewell continues: "The data suggest that, despite important changes in transmissibility and mortality, B.1.1.7 is similar enough to non-VOC lineages for current testing infrastructure and symptom profiles to identify new cases. Additionally, existing non-pharmaceutical interventions can reduce the Rt of B.1.1.7 to below 1, given adequate governmental planning. Fortunately, B.1.1.7 also appears to be quite effectively combatted by existing vaccines."

It has been long been known that cannabis users develop psychosis more often than non-users, but what is still not fully clear is whether cannabis actually causes psychosis and, if so, who is most at risk. A new study published in Translational Psychiatry by researchers at the Centre for Addiction and Mental Health (CAMH) and King's College London helps shed light on both questions. The research shows that while cannabis users had higher rates of psychotic experiences than non-users across the board, the difference was especially pronounced among those with high genetic predisposition to schizophrenia.

"These results are significant because they're the first evidence we've seen that people genetically prone to psychosis might be disproportionately affected by cannabis," said lead author Dr. Michael Wainberg, Scientist the Krembil Centre for Neuroinformatics at CAMH. "And because genetic risk scoring is still in its early days, the true influence of genetics on the cannabis-psychosis relationship may be even greater than what we found here."

Using data from the UK Biobank, a large-scale biomedical database containing participants' in-depth genetic and health information, the authors analyzed the relationship between genetics, cannabis use and psychotic experiences across more than 100,000 people. Each person reported their frequency of past cannabis use, and whether they had ever had various types of psychotic experiences, such as auditory or visual hallucinations. The researchers also scored each person's genetic risk for schizophrenia, by looking at which of their DNA mutations were more common among schizophrenia patients than among the general population.

Overall, people who had used cannabis were 50 per cent more likely to report psychotic experiences than people who had not. However, this increase was not uniform across the study group: among the fifth of participants with the highest genetic risk scores for schizophrenia, it was 60 per cent, and among the fifth with the lowest scores, it was only 40 per cent. In other words, people genetically predisposed to schizophrenia were at disproportionately higher risk for psychotic experiences if they also had a history of cannabis use.

Notably, because much less is known about the genetics of schizophrenia in non-white populations, the study's analysis was limited to self-reported white participants. "This study, while limited in scope, is an important step forward in understanding how cannabis use and genetics may interact to influence psychosis risk," added senior author Dr. Shreejoy Tripathy, Independent Scientist at the Krembil Centre for Neuroinformatics, who supervised the study. "The more we know about the connection between cannabis and psychosis, the more we can inform the public about the potential risks of using this substance. This research offers a window into a future where genetics can help empower individuals to make more informed decisions about drug use."

The "three-body problem," the term coined for predicting the motion of three gravitating bodies in space, is essential for understanding a variety of astrophysical processes as well as a large class of mechanical problems, and has occupied some of the world's best physicists, astronomers and mathematicians for over three centuries. Their attempts have led to the discovery of several important fields of science; yet its solution remained a mystery.

At the end of the 17th century, Sir Isaac Newton succeeded in explaining the motion of the planets around the sun through a law of universal gravitation. He also sought to explain the motion of the moon. Since both the earth and the sun determine the motion of the moon, Newton became interested in the problem of predicting the motion of three bodies moving in space under the influence of their mutual gravitational attraction (see attached illustration), a problem that later became known as "the three-body problem".

However, unlike the two-body problem, Newton was unable to obtain a general mathematical solution for it. Indeed, the three-body problem proved easy to define, yet difficult to solve.

New research, led by Professor Barak Kol at Hebrew University of Jerusalem's Racah Institute of Physics, adds a step to this scientific journey that began with Newton, touching on the limits of scientific prediction and the role of chaos in it.

The theoretical study presents a novel and exact reduction of the problem, enabled by a re-examination of the basic concepts that underlie previous theories. It allows for a precise prediction of the probability for each of the three bodies to escape the system.

Following Newton and two centuries of fruitful research in the field including by Euler, Lagrange and Jacobi, by the late 19th century the mathematician Poincare discovered that the problem exhibits extreme sensitivity to the bodies' initial positions and velocities. This sensitivity, which later became known as chaos, has far-reaching implications - it indicates that there is no deterministic solution in closed-form to the three-body problem.

In the 20th century, the development of computers made it possible to re-examine the problem with the help of computerized simulations of the bodies' motion. The simulations showed that under some general assumptions, a three-body system experiences periods of chaotic, or random, motion alternating with periods of regular motion, until finally the system disintegrates into a pair of bodies orbiting their common center of mass and a third one moving away, or escaping, from them.

The chaotic nature implies that not only is a closed-form solution impossible, but also computer simulations cannot provide specific and reliable long-term predictions. However, the availability of large sets of simulations led in 1976 to the idea of seeking a statistical prediction of the system, and in particular, predicting the escape probability of each of the three bodies. In this sense, the original goal, to find a deterministic solution, was found to be wrong, and it was recognized that the right goal is to find a statistical solution.

Determining the statistical solution has proven to be no easy task due to three features of this problem: the system presents chaotic motion that alternates with regular motion; it is unbounded and susceptible to disintegration. A year ago, Racah's Dr. Nicholas Stone and his colleagues used a new method of calculation and, for the first time, achieved a closed mathematical expression for the statistical solution. However, this method, like all its predecessor statistical approaches, rests on certain assumptions. Inspired by these results, Kol initiated a re-examination of these assumptions.

The infinite unbounded range of the gravitational force suggests the appearance of infinite probabilities through the so-called infinite phase-space volume. To avoid this pathology, and for other reasons, all previous attempts postulated a somewhat arbitrary "strong interaction region", and accounted only for configurations within it in the calculation of probabilities.

The new study, recently published in the scientific journal Celestial Mechanics and Dynamical Astronomy, focuses on the outgoing flux of phase-volume, rather than the phase-volume itself. Since the flux is finite even when the volume is infinite, this flux-based approach avoids the artificial problem of infinite probabilities, without ever introducing the artificial strong interaction region.

The flux-based theory predicts the escape probabilities of each body, under a certain assumption. The predictions are different from all previous frameworks, and Prof. Kol emphasizes that "tests by millions of computer simulations shows strong agreement between theory and simulation." The simulations were carried out in collaboration with Viraj Manwadkar from the University of Chicago, Alessandro Trani from the Okinawa Institute in Japan, and Nathan Leigh from University of Concepcion in Chile. This agreement proves that understanding the system requires a paradigm shift and that the new conceptual basis describes the system well. It turns out, then, that even for the foundations of such an old problem, innovation is possible.

The implications of this study are wide-ranging and is expected to influence both the solution of a variety of astrophysical problems and the understanding of an entire class of problems in mechanics. In astrophysics, it may have application to the mechanism that creates pairs of compact bodies that are the source of gravitational waves, as well as to deepen the understanding of the dynamics within star clusters. In mechanics, the three-body problem is a prototype for a variety of chaotic problems, so progress in it is likely to reflect on additional problems in this important class.

With 'Eyecam' they now present the prototype of a webcam that not only looks like a human eye, but imitates its movements realistically. "The goal of our project is not to develop a 'better' design for cameras, but to spark a discussion. We want to draw attention to the fact that we are surrounded by sensing devices every day. That raises the question of how that affects us," says Marc Teyssier. In 2020, the French scientist completed his doctorate on the topic of anthropomorphic design in Paris. Now he is a postdoctoral researcher in the Human-Computer Interaction Lab at Saarland University in Germany.

The research team at Saarland Informatics Campus has developed a webcam that not only looks like a human eye, but also realistically imitates unconscious eye movements such as blinking or raising the eyebrow. "With 'Eyecam' we are exploring the question of whether a technical device should reflect its function in its design," adds computer scientist Marion Koelle, who did her doctorate on the social acceptance of body-worn cameras. "There are different ways of seeing, all of which have their own unique connotations, such as observing, recognizing, watching, or even spying. Also, a camera designed as an eye can send nonverbal signals through facial expressions. This opens up a whole new layer of interaction that hasn't existed in technical devices before," Koelle adds.

"The research is part of a whole series of work within a large EU-funded project, the ERC Starting Grant 'InteractiveSkin'. Here we are researching how interfaces that have properties of the human body can improve the interaction between humans and computers," says lab director Professor Jürgen Steimle.

The researchers use the unique capabilities and optics of their new development to explore different facets of ubiquitous sensing. Already today, webcams are a potential privacy risk. 'Eyecam' exaggerates this aspect, acting as an observer by opening its eye and tracking the user with its gaze. Alternatively, the anthropomorphic camera could be used for self-reflection, with the artificial eye getting ever more tired and repeatedly falling shut as the user sits in front of the computer late at night. Or it could take on the role of a pet that is simply there, looking around from time to time and reacting with delight when its owner enters the room.

"Our application scenarios are fictional and are intended to encourage people to think about how we interact with technical devices today, but also in the future. What is special is that we can experience and recreate our imagined scenarios with the help of a physically existing prototype," says Marc Teyssier. To reach as many people as possible with their thought-provoking development, the group has published the blueprints for their device.

Almost all bacteria rely on the same emergency valves--protein channels that pop open under pressure, releasing a deluge of cell contents. It is a last-ditch effort, a failsafe that prevents bacteria from exploding and dying when stretched to the limit. If we understood how those protein channels worked, antibiotic drugs could be designed to open them on demand, draining a bacterium of its nutrients by exploiting a floodgate common to many species. 

But these channels are tricky to operate in the lab. And how precisely they open and close, passing through a sub-conducting state and ending in a desensitized state under the influence of mechanical forces, remains poorly understood. Now, new research from the laboratory of Rockefeller's Thomas Walz introduces a novel method to activate and visualize these channels, making it possible to explain their function. The findings shed light on key membrane proteins in bacteria, and the same method can be used to improve our understanding of similar channels in humans. 

"We were actually able to see the entire cycle of the protein channel passing through a series of functional stages," Walz says.  

Walz has long focused upon MscS, a protein embedded in bacterial membranes that opens in response to mechanical force. MscS proteins exist in a closed state while resting in a thick membrane. Scientists once suspected that, when fluid build-up causes the cell to swell and puts tension on the membrane, it stretches so thin that its proteins protrude. Thrust into an unfamiliar environment, the protein channels snap open, releasing the contents of the cell and relieving pressure until the membrane returns to its original thickness and its channels slam shut. 

But when Yixiao Zhang, a postdoctoral associate in the Walz group, tested this theory over five years ago, reconstituting MscS proteins into small custom-designed membrane patches, he discovered that it was impossible to prise the channel open by thinning membranes within the natural range. "We realized that membrane thinning is not how these channels open," Walz says. 

These custom patches, called nanodiscs, allow researchers to study proteins in an essentially native membrane environment and to visualize them with cryo-electron microscopy. Walz and Zhang resolved to push the limits of nanodisc technology, removing membrane lipids with β-cyclodextrin, a chemical used to excise cholesterol from cell cultures. This induced tension in the membrane, and Walz and his team could observe with cryo-electron microscopy as the channel reacted accordingly--eventually snapping closed for good, a phenomenon known as desensitization.  

What they observed matched computer simulations, and a new model for the function of MscS emerged. When fluid builds up inside the cell, they found, lipids are called in from all corners to help ease tension throughout the membrane. If the situation becomes dire, even lipids associated with the MscS channels flee. Without lipids keeping them closed, the channels have the legroom to pop open. 

"We could see that, when you expose the membranes to β-cyclodextrin, the channels open and then close again," Walz says.  

Walz and Zhang's new method of manipulating nanodiscs with β-cyclodextrin will allow researchers studying dozens of similar mechanosensitive protein channels to, at long last, test their hypotheses in the lab. Many such proteins play key roles in humans, from hearing and sense of touch to the regulation of blood pressure. Of more immediate interest, however, is the prospect of exploiting protein channels that many different bacteria rely upon to survive. Novel drug targets are a particular necessity, given the rise of dangerous antibiotic resistant bacteria such as MRSA.  

MscS and the related bacterial protein channel MscL are "extremely interesting drug targets," Walz says. "Almost every bacterium has one of these proteins. Because these channels are so widely distributed, a drug that targets MscS or MscL could become a broad-spectrum antibiotic."  

A study done in rooms where COVID-19 patients were isolated shows that the virus's RNA - part of the genetic material inside a virus - can persist up to a month in dust.

The study did not evaluate whether dust can transmit the virus to humans. It could, however, offer another option for monitoring COVID-19 outbreaks in specific buildings, including nursing homes, offices or schools.

Karen Dannemiller, senior author of the study, has experience studying dust and its relationship to potential hazards like mold and microbes.

"When the pandemic started, we really wanted to find a way that we could help contribute knowledge that might help mitigate this crisis," said Dannemiller, assistant professor of civil, environmental and geodetic engineering and environmental health sciences at The Ohio State University.

"And we've spent so much time studying dust and flooring that we knew how to test it."

The study, published today (April 13, 2021) in the journal mSystems, found some of the genetic material at the heart of the virus persists in dust, even though it is likely that the envelope around the virus may break down over time in dust. The envelope - the crown-like spiked sphere that contains the virus's material - plays an important role in the virus's transmission to humans.

The study offers another non-invasive avenue for monitoring buildings for COVID-19 outbreaks, especially as more people are vaccinated and return to communal spaces.

Municipalities and others have tested wastewater to evaluate the prevalence of COVID-19 in a given community - gene copies and fragments of the virus live in human waste, and by testing wastewater, local governments and others can determine how widespread the virus might be, even if people are asymptomatic.

Dust monitoring could offer similar understanding on a smaller scale - say, a specific nursing home, hospital or school.

"In nursing homes, for example, you're still going to need to know how COVID is spreading inside the building," said Nicole Renninger, lead author of the paper and an engineering graduate student in Dannemiller's lab. "For surveillance purposes, you need to know if you are picking up an outbreak that's going on right now."

For this study, the research team worked with the crews responsible for cleaning the rooms at Ohio State where students who tested positive for COVID-19 were isolated. They also collected samples from two homes where people who tested positive for COVID-19 lived. They gathered vacuum bags of dust from the cleaning crews and from the homes.

The researchers also tested swabs collected from surfaces in the rooms.

They found genetic material from the SARS-CoV-2 virus - the virus that causes COVID-19 - in 97% of the bulk dust samples and in 55% of the surface swabs.

The cleaning crews sprayed a chlorine-based disinfectant in the rooms prior to cleaning; the researchers believe that disinfectant destroyed the envelope and/or capsid - the outer coat surrounding the virus - likely defanging it for transmission.

The research team tested the samples when they arrived at the lab, shortly after the rooms were cleaned, then tested the samples again weekly. After four weeks, the virus's RNA did not significantly decay in the vacuum bags.

"We weren't sure that the genetic material would survive - there are many different organisms in dust, and we weren't sure we'd see any viral RNA at all," Renninger said. "And we were surprised when we found that the actual RNA itself seems to be lasting a pretty long time."

Testing dust to monitor for COVID-19 outbreaks would likely be most useful for smaller-scale communities with a high-risk population - a nursing home, for example, Dannemiller said. Testing indoor dust is also likely less expensive at that scale than testing wastewater or all individuals directly on a routine basis.

"We wanted to demonstrate that dust could be complementary to wastewater for surveillance," Dannemiller said. "Wastewater is great for a large population, but not everybody sheds the virus in feces, and you have to collect wastewater samples, which not everyone wants to do. People are already vacuuming these rooms, so dust may be a good option for some groups."

Even before this study was published, Dannemiller said the researchers presented their findings to an industry group that represents maintenance and cleaning staff, with a recommendation: "If they can wait at least an hour or more after a person leaves the room to clean, they should," she said, citing previous studies of viral viability on other materials and in aerosols.

WHAT:

Many people who have COVID-19 make a full recovery and return to their baseline state of health; however, some people have symptoms or other sequelae weeks or months after initial SARS-CoV-2 infection. These heterogeneous symptoms were the subject of the virtual "Workshop on Post-acute Sequelae of COVID-19" hosted on Dec. 2 and 4, 2020, by the National Institute of Allergy and Infectious Diseases (NIAID), in collaboration with other institutes and centers of the National Institutes of Health. A paper published recently in Annals of Internal Medicine describes the workshop. Over 1,200 registered participants including researchers, clinicians, and affected community members discussed what is known about sequelae after COVID-19 and the knowledge gaps that need to be addressed in future research.

The constellation of symptoms and other effects experienced by those who do not return to their baseline state of health after COVID-19 has been referred to by many names, including post-acute sequelae of COVID-19 (PASC), and long or long-haul COVID. Symptoms can be wide-ranging in severity and duration, and may affect numerous organ systems. Reported symptoms include severe fatigue, cognitive dysfunction, and shortness of breath, as well as psychological symptoms, such as anxiety and depression. Longer term effects of COVID-19 have been reported in all age groups and demographics and in persons with asymptomatic, mild, or severe initial COVID-19 illness. If only a small fraction of SARS-CoV-2 infections lead to longer term effects, the global burden of disease will be significant.

In addition to reviewing existing data the workshop presenters identified important knowledge gaps. Notably, the epidemiology is not fully characterized, and it will need to be expanded in order to identify and help vulnerable groups of people. The full clinical spectrum of post-acute COVID-19 is not yet known, nor the reasons why the symptoms manifest so differently in individuals. Underlying pathophysiology is not determined and may be due to SARS-CoV-2 itself, or the immune response to infection.

Since COVID-19 is a new disease, researchers are still documenting the spectrum of recovery and trying to understand the different outcomes patients may experience. People who do not return to their baseline state of health have diverse clinical conditions that will require individualized and multidisciplinary approaches to treatment.

Workshop discussions highlighted that longitudinal studies, ideally including systematic assessments of different organ systems, and including diverse populations, will be needed in order to properly characterize post-acute COVID-19. Careful study of the virus and the immune response to infection may help researchers understand how manifestations of post-acute COVID-19 arise. These research efforts will need to involve a collaboration among clinicians, researchers, advocacy groups and patient communities.