Culture

A pioneering study has shed new light on how a group of novel organelle-based disorders affect cells.

The study led by Professor Michael Schrader from the University of Exeter, and featuring an international, multi-disciplinary team of scientists, has explored on peroxisome alterations and their contribution to the disease.

Organelles are the functional units of a cell. They perform specialised functions, and defects in their enzymes performing those functions can result in metabolic disorders.

However, organelles are not just cellular factories in a production line, but are also highly dynamic. They are able to move around in the cell to interact and cooperate with other organelles and multiply by increasing in size and then dividing to adapt their number and functions to cellular needs.

Recently, scientists have identified a new group of disorders, characterised by defects in the membrane dynamics and division of organelles rather than by loss of metabolic functions.

Those disorders are caused by mutations in genes encoding for the organelle division machinery, such as Mitochondrial fission factor (MFF) - a key component of the division machinery of two organelles, mitochondria and peroxisomes.

MFF functions as an adaptor protein to recruit a mechanochemical enzyme, Dynamin-related protein 1 (DRP1), to mitochondria and peroxisomes. This enzyme can constrict and divide membranes and is essential for membrane fission and organelle multiplication.

Defects in either MFF or DRP1 block the division of mitochondria and peroxisomes and result in highly elongated organelles unable to divide. Patients with MFF deficiency present with developmental and neurological abnormalities.

The majority of studies into MFF-deficiency have focused on mitochondrial dysfunction, but the contribution of peroxisomal alterations to the pathophysiology is largely unknown.

An international, multi-disciplinary team of scientists, led by Professor Michael Schrader from the University of Exeter, has now shed light on peroxisome alterations and their contribution to the disease.

Peroxisomes fulfil important protective functions in the cell and are vital for health; they contribute to cellular lipid metabolism and redox balance, which links them to the control of energy regulation, cellular ageing and age-related disorders. They also cooperate with mitochondria in the combat of viruses and anti-viral defence. Loss of peroxisome function leads to severe developmental and neurological defects such as those seen in MFF-deficiency.

"In this study, we show that MFF-deficiency impacts on the maturation of peroxisomes. Loss of MFF function results in an altered distribution of peroxisomal proteins and causes the accumulation of extremely long pre-peroxisomal membrane structures inside the cell, which have reduced import-competency for peroxisomal enzymes," said Professor Michael Schrader.

"We show that peroxisomes in MFF-deficient cells display alterations in peroxisomal redox state and intra-peroxisomal pH.

"Previous studies have shown that the peroxisomes in MFF-deficiency are largely functional, leading to the general assumption that defects in peroxisomal dynamics and division results only in elongated peroxisomes, which are otherwise unaltered. We have now revealed in MFF-deficient cells that this is not the case.

"Interestingly, we observed that the highly elongated peroxisomes in MFF-deficient cells are not fully static; their dynamics can be modulated, for example through the induction of organelle degradation.

"These experiments have provided us with new insights into the pathophysiology of MFF-deficiency and related disorders with impaired peroxisome plasticity.

"In peroxisomal disorders, we often see altered numbers, different shapes or even different distributions of peroxisomes in patient cells. We also developed a mathematical modelling approach to help understand this.

"Understanding why this happens and how to modulate peroxisome numbers or distribution can provide new possibilities to improve cell performance in those patients."

"This might also be relevant to age-related conditions like dementia, deafness and blindness, as peroxisomal dynamics are known to have important protective functions within sensory cells."

The international research team combined human cell biology (Professor Michael Schrader), clinical diagnostics (Dr Sacha Ferdinandusse, Amsterdam University Medical Centre, NL; Professor Peter Freisinger, Department of Pediatrics, Reutlingen, GER), redox biology (Professor Marc Fransen, University of Leuven, BE), neurobiology (Dr Markus Islinger, University of Heidelberg, GER) and mathematic modelling (Dr David Richards, Centre for Biomedical Modelling and Analysis, LSI, Exeter, UK) to shed further light into the physical processes disturbed in MFF-deficient cells.

People with severe peroxisomal disorders, also known as Zellweger Spectrum Disorders, often die as children or young adults, and the team cooperates with a charity called Zellweger UK to raise awareness and to support families and sufferers.

Kanazawa, Japan - Hand-foot-and-mouth disease (HFMD) is an acute viral infection that usually affects infants and children below five years. In a study published in Scientific Reports in January 2020, an international research team including Kanazawa University, the Vietnam National Hospital of Pediatrics, Tokyo Metropolitan Institute of Medical Science, Nagasaki University and Hanoi Medical University, has demonstrated the emergence of a new enterovirus (EV) A71-C4 lineage during the 2015-2016 outbreak of HFMD in northern Vietnam. Further, through clinical studies and an experimental mouse model, they have shown that EV-A71 C4 subgenotype may be more virulent than the B5 subgenotype.

HFMD is a common contagious childhood illness caused by enteroviruses of the family picornaviridae, the most frequently reported being EV-A71, coxsackievirus A16 (CV-A16), and CV-A6. It typically runs a mild self-limiting course; however, in rare cases it may cause inflammation of the meninges and the hindbrain, resulting in paralysis, cardiopulmonary complications, or even death. While most cases resolve within a few weeks, EV-A71 infections may be more severe, with serious complications.

To determine the epidemiological characteristics and identify the various enterovirus strains responsible for HFMD in northern Vietnam, the research team collected and analyzed throat and rectal swabs from 488 affected children in Hanoi.

Son T. Chu, lead author of the study, explains: "CV-A6 was the most common strain, followed by EV-A71. Of these EV-A71, 92.1% were the B5 subgenotype and 7.9% were the C4 subgenotype. Whole-genome sequencing showed that seven of the eight C4a strains formed a new lineage, including two possible recombinants between EV-A71-C4 and CV-A8 strains."

The researchers evaluated the proportion of inpatients as a clinical measure of virulence. Hospitalized children with EV-A71 significantly outnumbered those with CV-A6. Further analysis among the EV-A71 infected children showed that the proportion of inpatients among C4-infected was significantly higher than that among B5-infected, implying greater virulence of C4 than B5.

"As the number of C4-infected patients was small, we applied another technique to compare virulence," says Kyousuke Kobayashi, neurovirologist and lead author. "We inoculated transgenic mice susceptible to EV-A71 infection with viral isolates and monitored them for limb weakness, acute flaccid paralysis, body weight and death. We found increased paralysis and significantly higher mortality among mice infected with C4 strains than those infected with B5 strains."

HFMD is an emerging public health problem with periodic large outbreaks in pediatric populations in East and Southeast Asia. Currently, there is no approved antiviral drug against EV-A71 and the best strategy to mitigate its impact is to develop appropriate vaccines. Though inactivated vaccines exist, more suitable candidate strains may be identified from among the newly emerged EV-A71-C4 strains for developing live attenuated vaccines.

It's time to encourage people to wear face masks as a precautionary measure on the grounds that we have little to lose and potentially something to gain, say experts in The BMJ today.

Professor Trisha Greenhalgh at the University of Oxford and colleagues say despite limited evidence, masks "could have a substantial impact on transmission with a relatively small impact on social and economic life."

The question of whether masks will reduce transmission of covid-19 in the general public is contested.

Although clinical trial evidence on the widespread use of facemasks as a protective measure against covid-19 is lacking, at the time of writing increasing numbers of agencies and governments, including the US Centers for Diseases Control and Prevention, are now advocating that the general population wears masks, but others, such as the World Health Organization and Public Health England are not.

Some researchers argue that people are unlikely to wear masks properly or consistently, and may ignore wider infection control measures like handwashing. Others say the public should not wear them since healthcare workers need them more.

But Greenhalgh and colleagues challenge these arguments and suggest that in the context of covid-19, many people could be taught to use masks properly and may well do this consistently without abandoning other important anti-contagion measures.

What's more, they say if political will is there, mask shortages can be quickly overcome by repurposing manufacturing capacity - something that is already happening informally.

They conclude that it is time to act without waiting for randomised controlled trial evidence.

"Masks are simple, cheap, and potentially effective," they write. "We believe that, worn both in the home (particularly by the person showing symptoms) and also outside the home in situations where meeting others is likely (for example, shopping, public transport), they could have a substantial impact on transmission with a relatively small impact on social and economic life."

In a linked editorial, Babak Javid at Tsinghua University in Beijing and colleagues agree that the public should wear face masks because the benefits are plausible and harms unlikely. And they say cloth masks are likely to be better than wearing no mask at all.

As we prepare to enter a "new normal," wearing a mask in public may become the face of our unified action in the fight against this common threat and reinforce the importance of social distancing measures, they conclude.

In an opinion piece, researchers recommend that health care workers should not be caring for covid-19 patients without proper respiratory protection, and that cloth masks are not a suitable alternative for health care workers.

Journal of Public Policy & Marketing has dedicated the second issue of its 2020 volume to better understanding and defining the uniquely related concepts of consumer power and consumer access. The guest editors and articles authors show how both concepts are in a constant state of change. They are influenced by technology, wealth, industry organization, and public policy.

Questions of access and power are particularly relevant in the context of today's United States with consumers simultaneously isolated and connected in ways never before imagined. Many of the articles in this issue offer prophetic insights though they were written well before and accepted only in the very early stages of the COVID-19 world health crisis.

"Denial Without Determination: The Impact of Systemic Market Access Denial on Consumer Power and Market Engagement"

Consumers may have access to a product or service, but that does not mean the consumer has the power to make ownership and usage a reality. Even when intervention levels the playing field, it still may take multiple purchase cycles before some consumers may attempt to take advantage of the new opportunities.

https://doi.org/10.1177/0743915619885393

"Access Granted? An Examination of Financial Capability, Trait Hope, Perceived Access, and Food Insecurity in Distressed Census Tracts"

Interestingly increasing a belief in hope is an effective way to improve the perception of access to adequate food sources among residents of food deserts. The authors suggest communication strategies that encourage this trait and improve the effectiveness of food and nutrition assistance programs.

https://doi.org/10.1177/0743915619889341

"The Effect of Consumers' Perceived Power and Risk in Digital Information Privacy: The Example of Cookie Notices"

Despite recent regulation (i.e., the GDPR), the design of cookie notices varies strongly in practice, with many websites providing cookie notices with low visibility and no or very limited choice. These most common designs are likely to increase consumers' risk perception, which reduces their purchase intent; website providers might, in contrast, benefit from offering consumers more choice over their private data.

https://doi.org/10.1177/0743915620902143

"Service Captivity: No Choice, No Voice, No Power"

This examination of "service captivity" offers insights into how consumers may feel trapped in a scenario where they can't exit a service relationship. The authors offer examples of how these consumers may gain access to new service providers.

https://doi.org/10.1177/0743915619899082

"Sound and Fury: Digital Vigilantism as a Form of Consumer Voice"

Via a pool of over 70,000 tweets associated with the 2017 Charlottesville Unite the Right rally, the authors categorize tweets into five categories and offer a perspective on how digital vigilantism was represented.

https://doi.org/10.1177/0743915620902403

"Sense of Power: Policy Insights for Encouraging Consumers' Healthy Food Choice"

Incorporating simple messages such as, "you are powerful" or "we all feel powerful sometimes" is enough to increase a consumer's sense of power and subsequently nudge them to make healthier food choices, particularly for consumers lower in socioeconomic status.

https://doi.org/10.1177/0743915620902148

"Children and Online Privacy Protection: Empowerment from Cognitive Defense Strategies"

Children and teens were already spending a growing amount of time online, but in the last several weeks, this seems to have increased even more. The authors investigate methods for improving safety beliefs and decisions to share personal videos on YouTube suggesting a combination of education and parental intervention empowers children and teens to protect their personal information online.

https://doi.org/10.1177/0743915619883638

"When Does the Social Service Ecosystem Meet Consumption Needs? A Power-Justice-Access Model of Holistic Well-Being from Recipients' Perspectives"

Research suggestions that respect is another dimension of consumer access and power. They show the fallacy of scorning low-income individuals' access to "luxuries," such as Starbucks coffee, and the importance of going beyond simple access and power and include the level of perceived justice (e.g., respect).

https://doi.org/10.1177/0743915620903318

"Consumer-Level Perceived Access to Health Services and Its Effects on Vulnerability and Health Outcomes"

Policymakers, health care organizations, and insurance providers can use perceived access to healthcare measure to better identify communities or populations that lack access, design programs and systems that reduce perceptions of health vulnerability in target populations, and ultimately improve consumers' health outcomes.

https://doi.org/10.1177/0743915620903299

Scientists report that the combined effects of rare, damaging mutations present at birth have a negative impact on healthspan and longevity, according to a study published this week in eLife.

The findings suggest one additional inherited damaging mutation could carve off six months of life, and combinations of these rare mutations determine how soon someone will develop diseases such as cancer, heart disease and dementia.

Most of the genetic variants linked to lifespan that researchers currently know about have been found in people who live long, such as centenarians who live to 100 or older. The variants responsible for survival of the rest of the population remain poorly understood.

Now, researchers have proposed that the remaining variance that contributes to lifespan could be attributed to the combination of very rare but highly damaging mutations that are present in every person's genome. "The role of ultra-rare damaging mutations that decrease lifespan and healthspan has been largely overlooked," says co-senior author Vadim Gladyshev, Professor at Brigham and Women's Hospital and Harvard Medical School, Boston, US. "They are different in different people, but in combination, they exhibit an unexpectedly large effect on lifespan."

"Until recently, only common gene variants could be probed in genetic studies due to a small number of participants," explains co-first author Anastasia Shindyapina, a postdoctoral researcher at Brigham and Women's Hospital, Harvard Medical School. "However, large datasets that sequenced tens of thousands of people now allow us to assess the effects of DNA variation that appear in less than one out of 10,000 subjects."

Ultra-rare protein-truncating variants (PTVs) are known to be some of the most damaging genetic variants. These tend to have a larger impact than more common genetic variants, and can dramatically change the amount and function of important proteins in the body. Increased frequency of PTVs has been linked to complex diseases such as schizophrenia, epilepsy and autism. In this study, Shindyapina, along with co-first author Aleksandr Zenin, researcher at Gero, Singapore, and their colleagues set out to learn how the number of PTVs a person is born with influences their lifespan. They also wanted to see whether accumulating additional PTVs throughout life can affect overall health and length of survival.

The team analysed genomic data from more than 40,000 people registered in the UK Biobank who on average were in their mid-fifties. They compared the individual 'burden' of PTVs (the total number of PTVs per each person's genome) with their lifespan and their 'healthspan': the time taken to develop complex diseases including cancer, heart disease, chronic obstructive pulmonary disease, stroke and dementia.

The team found that people who had a high burden of ultra-rare PTVs had a shorter healthspan and lifespan. Each additional ultra-rare PTV in a person's genome accounted for a reduction in lifespan of six months and a reduction in healthspan of two months.

In addition to the genetic variants we are born with, we accumulate more as we age. The research predicted that the natural accumulation of PTVs increases proportionally with age but their effects are likely to be minor compared with the effects of PTVs we are born with. "This implies that the genetic variation we accumulate throughout life only accounts for a small fraction of the increased risk of disease and death that we all face as we grow older, if our theoretical calculations are correct," explains author Andrei Tarkhov, researcher at Gero and PhD student at Skolkovo Institute of Science and Technology, Moscow, Russia.

"Our finding that accumulated mutations during a lifetime do not accelerate disease or death contradicts previous hypotheses," adds co-senior author Peter Fedichev, Principal Investigator at Gero. "Together our results illustrate the surprising role of rare mutations previously inaccessible for genetic studies in the aging process. They also demonstrate the power of whole exome and genome sequencing to uncover the genetic architecture of complex diseases in the interest of developing future therapeutics."

FAYETTEVILLE, Ark. - The antimicrobial properties of silver have been known for centuries. While it is still a mystery as to exactly how silver kills bacteria, University of Arkansas researchers have taken a step toward better understanding the process by looking at dynamics of proteins in live bacteria at the molecular level.

Traditionally, the antimicrobial effects of silver have been measured through bioassays, which compare the effect of a substance on a test organism against a standard, untreated preparation. While these methods are effective, they typically produce only snapshots in time, said Yong Wang, assistant professor of physics and an author of the study, published in the journal Applied and Environmental Microbiology.

Instead, Wang and his colleagues used an advanced imaging technique, called single-particle-tracking photoactivated localization microscopy, to watch and track a particular protein found in E. coli bacteria over time. Researchers were surprised to find that silver ions actually sped up the dynamics of the protein, opposite of what they thought would happen. "It is known that silver ions can suppress and kill bacteria; we thus expected that everything slowed down in the bacteria when treated with silver. But, surprisingly, we found that the dynamics of this protein became faster."

The researchers observed that silver ions were causing paired strands of DNA in the bacteria to separate, and the binding between the protein and the DNA to weaken. "Then the faster dynamics of the proteins caused by silver can be understood," said Wang. "When the protein is bound to the DNA, it moves slowly together with the DNA, which is a huge molecule in the bacteria. In contrast, when treated with silver, the proteins fall off from the DNA, moving by themselves and thus faster."

The observation of DNA separation caused by silver ions came from earlier work that Wang and colleagues had done with bent DNA. Their approach, now patent pending, was to put strain on DNA strands by bending them, thus making them more susceptible to interactions with other chemicals, including silver ions.

The National Science Foundation-funded study validated the idea of investigating the dynamics of single proteins in live bacteria, said Wang, an approach that could help researchers understand the real-time responses of bacteria to silver nanoparticles, which have been proposed for fighting against so-called "superbugs" that are resistant to commonly prescribed antibiotics.

"What we want to do eventually is to use the new knowledge generated from this project to make better antibiotics based on silver nanoparticles," said Wang.

Abusive head trauma (AHT), like that of Shaken Baby Syndrome, is the leading cause of fatal brain injuries in children under two. While children can suffer permanent neurological damage, developmental delay, and disability, the long-term effects of AHT are difficult to diagnose and predict. Now, researchers at New York Institute of Technology have developed computational simulations to help clinicians and caregivers better understand the impact of these injuries.

Similar to whiplash, shaking produces an accelerated force that causes a baby's head to undergo multiple cycles of hyperextension and hyperflexion--snapping backward and rebounding to its original position. During head injury, the cerebrospinal fluid (CSF), found in the central cavities and space surrounding the brain and spinal cord, cushions the brain and protects it from hitting the skull. Despite this protection, one in four shaken babies dies and 80 percent of survivors suffer permanent brain damage.

Computational simulations can help physicians visualize the true impact of AHT and assist them in making a prognosis. However, existing simulations are insufficient, as they portray the fluid as an elastic solid and fail to replicate intricate brain anatomy and the interaction between the CSF and the brain. These deficiencies are addressed, as reported in Journal of Pediatric Neurology, thanks to more precise simulations that reveal that the fluid's protection may last for only a single shake. The study was developed by researchers at New York Institute of Technology's College of Engineering and Computing Sciences.

"One instance of abusive head trauma could include as many as 80 shakes. Our findings demonstrate that the cerebrospinal fluid is only 'designed' to protect the brain for the first shake," said lead author Milan Toma, Ph.D., assistant professor of mechanical engineering. "By considering simulations like these, clinicians can better predict the short- and long-term effects of abusive head trauma and more accurately assess the victim's health."

The researchers replicated the fluid's cushioning effect for multiple cycles. In the first shake, CSF traveled to the sites of hyperextension and hyperflexion, providing the anticipated cushioning effect. However, during hyperflexion on the second shake, the fluid did not have enough time to reach the affected areas. In other words, following the first shake, the CSF was unable to prevent the brain from colliding with the skull, suggesting that the fluid offers no protection at repeated frequencies.

"Even when a baby is shaken at the lowest frequency, one shake is already too many," said Alfonso Dehesa Baeza, an undergraduate mechanical engineering student at New York Tech and Toma's co-investigator. "We hope that these surprising revelations help raise awareness among clinicians and caregivers, and prevent future incidents of abusive head trauma."

"The known incidence of AHT in children less than a year old is approximately 35 cases per 100,000. Unfortunately, AHT is not only often misdiagnosed, it is also under-diagnosed. This simulation allows a glimpse into the mechanism through which AHT occurs. Better knowledge of the brain and its response to trauma can help us to tailor treatment and possibly mitigate damage," said Rosalyn Chan-Akeley, M.D., M.P.H, OB/GYN research program manager at New York-Presbyterian Queens Lang Research Center, who was also an author on the study.

In continuing their work, New York Tech researchers aim to acquire pediatric data to refine their AHT models and also plan to add data on brain vasculature. Toma and his team of student researchers will also use their simulations to replicate nearly any head injury, test the effectiveness of protective helmets and replicate high-risk head injuries from automobile accidents and contact sports, including lacrosse, baseball, football, and ice hockey. Toma has also received a grant from the New York Thoroughbred Horsemen's Association to perform similar research on the efficacy of jockey helmets.

ALEXANDRIA, VA - The American Academy of Otolaryngology-Head and Neck Surgery Foundation published the Clinical Practice Guideline: Ménière's Disease today in Otolaryngology-Head and Neck Surgery. Ménière's disease is a disorder of the inner ear that includes episodes of vertigo with possible hearing loss, ringing or buzzing in the ear, or ear pressure.

"Ménière's disease has a lot of factors and can be mimicked by other illnesses. To add to that, it is an episodic disease that can take months, or even years, to diagnose," says Gregory J. Basura, MD, PhD, Chair of the Guideline Development Group. "We hope that this guideline will help support more accurate diagnoses and thereby improve patients' quality of life."

Ménière's disease is defined by spontaneous vertigo attacks, each lasting 20 minutes to 12 hours, with low- to mid- frequency sensorineural hearing loss in the affected ear before, during, or after one of the episodes of vertigo. The clinical practice guideline (CPG) defines vertigo as the feeling of spinning or moving when one is not moving. This is different from dizziness, which can mean feeling lightheaded or feeling like passing out.

Ménière's disease is almost exclusively reported in adults, with less than three percent of cases estimated to occur in children younger than 18 years old. The disease is most prevalent between ages 40 to 60 years, with peak onset in the 40s and 50s. In many patients, the most detrimental decline in hearing and balance function occurs within the first decade of diagnosis, yet patients continue to have longstanding deficits that make Ménière's disease a chronic disease. It is important to evaluate and document the hearing in both ears as a subset of patients will eventually experience Ménière's disease bilaterally.

The guideline discusses the background on possible causes of Ménière's disease, disorders that present similarly to it, and the ways in which the disease can progress. "The guideline aims to reduce the subjectivity of diagnosis and treatment for Ménière's disease and to provide some objective standards based on the literature available today," said Dr. Basura. "This new CPG gives providers some optimal tools with which to make their clinical decisions."

The CPG is intended for all healthcare providers in any setting who are likely to encounter, diagnose, treat, and/or monitor patients with suspected Ménière's disease. This includes emergency medicine, primary care, otolaryngology, neurology, audiology, and physical/vestibular therapy. The target patient for the guideline is anyone 18 years of age or older who has a suspected diagnosis of definite or probable Ménière's disease.

The coral-eating crown of thorns starfish that devastate tropical reefs can lie in wait as harmless young herbivores for more than six years while coral populations recover from previous attacks or coral bleaching, new research has shown.

The diet of the juvenile starfish is algae. Juveniles remain on this vegetarian diet for at least four months and then, if there is an abundance of coral, the starfish typically switch to a coral diet.

Research published today in Biology Letters led by Dione Deaker, a PhD student at the University of Sydney, and her adviser Professor Maria Byrne, has shown that juvenile starfish can delay their diet shift to coral for at least 6.5 years.

"This Peter Pan effect means that populations of juvenile crown of thorns starfish can build up on reefs in the absence of coral," Ms Deaker said. "They could become a hidden army waiting to consume reefs as the reefs recover."

As adults they grow to nearly a full metre in diameter and have a voracious appetite for coral, devastating critical reef habitats on the Great Barrier Reef and across the Indo-Pacific.

Professor Byrne from the Sydney Environment Institute said: "Despite the notoriety of the large adult starfish and their propensity for coral prey, the juveniles eat algae. For outbreaks to arise, these algal-eating juveniles must transition into coral predators."

How and when the juveniles switch to being coral predators remains something of a mystery to researchers but trying to understand the process is a crucial part in the fight to protect reef habitats from the starfish.

In this study Ms Deaker and Professor Byrne, along with colleagues at the National Marine Science Centre, Coffs Harbour, showed that in response to coral scarcity, crown of thorns starfish can remain as herbivores for at least 6.5 years.

The team reared two groups of starfish on algae for 10 months and 6.5 years. Both cohorts grew to the same maximum size - 16 to 18 millimetres. Despite restricted growth on a vegetarian diet, there was no impact on the ability of the 6.5-year-olds to eat corals. After provision of coral prey, the one-year-old and 6.5-year-old juveniles had the same growth pattern.

"Suppression of the switch to a coral diet due to scarcity of prey might occur after coral bleaching events," Ms Deaker said. "The remarkable resilience of juvenile starfish to coral scarcity complicates our ability to age them and indicates the potential for reserves of juveniles to accumulate on the reef to seed outbreaks when favourable conditions arise."

The research shows that starfish modelling needs to account for the possibility that an extended herbivorous phase of crown of thorns starfish has the potential to allow the formation of a reserve population in reef habitats.

Professor Byrne said: "Another important implication of our findings is the possibility that the current adult starfish killing programs used to manage crown of thorns starfish might, in fact, trigger a feedback mechanism in the starfishes' transition to coral predator as juveniles are released from adult competition."

The researchers say that armed with findings from this study, scientists need to study how the juvenile starfish respond in the wild to coral scarcity to see if it does trigger a population growth of this cohort.

Researchers have identified a total of four cases of newborn babies with COVID-19 infection in China. In all cases the babies experienced only mild symptoms with none requiring intensive care or mechanical ventilation according to research published in in the European Respiratory Journal today (Thursday). [2]

The study was carried out by Dr Zhi-Jiang Zhang and colleagues at Wuhan University in China. The team report that all four babies were born to mothers with COVID-19 and all were delivered by caesarean section. Three were separated from their mothers at birth.

The researchers say the rapid spread of the infection may mean there are other cases of newborns with COVID-19 that they were not able to track down.

Dr Zhang said: "COVID-19 is highly contagious and our study suggests that intrauterine transmission cannot be ruled out, but that the prognosis is good for both pregnant women and newborn babies."

Professor Tobias Welte is an infections expert from the European Respiratory Society and is a coordinator for the national German COVID-19 task force and was not involved in the study. He said: "It's important to protect pregnant women and newborn babies against infection. It's also important that any cases of COVID-19 in newborns are picked up, monitored and treated quickly and carefully. At this stage we still do not know whether there are any longer-term consequences of infection."

People with chronic obstructive pulmonary disease (COPD) and people who currently smoke may have higher levels of a molecule, called angiotensin converting enzyme II (ACE-2), in their lungs according to a study published in the European Respiratory Journal today (Thursday). [1]

Previous research shows that ACE-2, which sits on the surface of lung cells, is the 'entry point' that allows coronavirus to get into the cells of the lungs and cause an infection.

The new study also shows that levels of ACE-2 in former smokers is lower than in current smokers.

The research was led by Dr Janice Leung at the University of British Columbia and St. Paul's Hospital, Vancouver, Canada. She said: "The data emerging from China suggested that patients with COPD were at higher risk of having worse outcomes from COVID-19. We hypothesised that this could be because the levels of ACE-2 in their airways might be increased compared to people without COPD, which could possibly make it easier for the virus to infect the airway."

The team studied samples taken from the lungs of 21 COPD patients and 21 people who did not have COPD. They tested the samples to gauge the level of ACE-2 and compared this with other factors, such whether they were from people who never smoked, were current smokers or former smokers. Not only did they find higher levels of ACE-2 in COPD patients, they also found higher levels in people who were smokers.

The researchers then checked their new findings against two existing study groups, which together contain data on a further 249 people - some non-smokers, some current smokers and some former smokers. Again, they found levels of ACE-2 were higher in current smokers but lower in non-smokers and in those who were former smokers.

Dr Leung said: "We found that patients with COPD and people who are still smoking have higher levels of ACE-2 in their airways, which might put them at an increased risk of developing severe COVID-19 infections. Patients with COPD should be counselled to strictly abide by social distancing and proper hand hygiene to prevent infection.

"We also found that former smokers had similar levels of ACE-2 to people who had never smoked. This suggests that there has never been a better time to quit smoking to protect yourself from COVID-19."

Professor Tobias Welte is an infections expert from the European Respiratory Society and is a coordinator for the national German COVID-19 task force and was not involved in the study. He said: "This study gives some interesting insight into why some people may be at risk of more severe COVID-19 symptoms than others. What it does not tell us is whether it's possible to manipulate ACE-2 levels to improve survival in patients infected with COVID-19 or whether this would make a difference in COPD patients who contract the infection."

High-quality online courses are no less effective than traditional classes when it comes to student learning outcomes. Online courses provide an opportunity to expand access to high-quality education without increasing costs: the number of students that universities will be able to enroll increases by 15-18%. The results of a study carried out jointly by HSE University researchers and US researchers have been published in Science Advances.

The experiment involved 325 second-year engineering students from resource-constrained universities. Students took two courses hosted by the national Open Education platform. Before the start of the course, they were randomly divided into three groups. The first group studied in person with the instructor at their university, the second group watched online lectures and attended in-person discussion sections (i.e., a blended modality), and the third group took the entire course online and communicated with instructors at the course's forum.

Researchers then compared groups' performance in three areas: the level of subject knowledge (final exam score), grades for assignments during the course, and satisfaction with the course. The results demonstrated that the average level of knowledge acquired in the course was the same in all three groups. The average grade for in-course assessments of online students was slightly higher, while satisfaction with the studies, on the contrary, was a little lower compared with students who studied in person.

According to the research team, the lower student satisfaction is primarily associated with a lack of experience and relevant learning skills in an online environment, for example, time management skills. It is important to provide students with extra support in this area.

With equivalent learning outcomes, the cost of instruction per one student in blended modality is 15-19% lower, and in the online modality, it is 79-81% lower, depending on the course. These estimates take into account the costs of developing and maintaining online courses. According to the authors of the study, with online courses universities will be able to teach 15-18% more students at the same cost.

'The results of the study demonstrate that high-quality online courses can no longer be considered a mediocre instruction method. They advance students skills and knowledge the same way as in-person classes,' commented the study's principal investigator Igor Chirikov https://www.hse.ru/en/staff/ichirikov, SERU Consortium Director and Senior Researcher at UC Berkeley and Affiliated Researcher at the HSE Institute of Education.

He believes that in today's context it is essential to invest in advanced online platforms, interactive online learning content, and new teaching methods. This would allow to expand the access to high-quality education without considerable additional costs and would provide students with flexible educational trajectories. In addition, it would help universities prepare for various unpredictable situations, such as the novel coronavirus pandemic.

'We are seeing how universities that are more advanced in creating and using online courses have adapted to the transition to online format more quickly. The fact that Russia has a major national platform with online courses from leading universities has given the country a big advantage in switching to a remote instruction quickly,' he said.

'Now in Russia, as in other countries, we can see a real-time experiment unfolding with the use of remote instruction. Our study only focused on engineering courses, but the current mass transition to online learning will allow us to assess the extent to which online courses are effective for other types of studies, in particular the social sciences and humanities. This will be the real stress test,' adds Tatyana Semenova, co-author of the study and researcher at the Center for Sociology of Higher Education, HSE University.

Probiotic bacteria that have been killed by heat can significantly improve symptoms of irritable bowel syndrome (IBS) compared to placebo, and are not associated with any safety risk, according to a new 12-week, randomised, double-blind, placebo-controlled clinical trial with 443 patients published in The Lancet Gastroenterology & Hepatology journal.

Although they do not know the exact way this potential treatment works, the researchers suggest that these dead bacterial cells are able to stick to cells lining the stomach in the same way that live probiotics do. This may help to strengthen the gut's barrier against harmful bacteria and toxins, which otherwise may contribute to the symptoms of IBS. They also observed a strong placebo effect, which is common in IBS studies, but the probiotic treatment was still significantly better than placebo.

Previous trials with probiotics to alleviate IBS symptoms have focused on live bacterial strains, with a few having a significant clinical effect, including Bifidobacterium bifidum MIMBb75 [1]. This bacterium is particularly good at sticking to cells in the gut wall, which could explain its effects. The use of live probiotics is considered safe, but they have a limited shelf life. Some bacteria die in storage, so it is not known how many are still alive when people take them. On rare occasions, live probiotics have also been reported to cause severe infections, particularly in people with severe illnesses or compromised immune systems. Non-viable probiotics could therefore be an even safer alternative, with the added advantage of a longer shelf life, even in countries with warm climates.

"To our knowledge, no other dead bacterial strain has been found to significantly improve IBS and its symptoms, but the probiotic we used in this first clinical trial appears to reach or even surpass the effects of the live form," says Professor Peter Layer from University of Hamburg Teaching Hospital, Germany, who led the research. [2]

Symptoms of IBS include recurrent episodes of abdominal pain, flatulence, a swollen stomach, feeling uncomfortably bloated, pain while defecating, diarrhoea, and constipation. The symptoms can harm patients' quality of life, and according to previous studies, the effect on quality of life can be even worse in people with chronic diseases [3]. The causes of IBS are not fully known, but the internal lining of the gut is thought to be more permeable in patients with symptoms.

All patients in the new study experienced chronic abdominal pain or discomfort on at least three days in the past three months, with symptoms having started at least six months previously (in accordance with Rome III diagnostic criteria). In addition, the researchers only included patients who experienced abdominal pain on at least two days in the two weeks prior to the start of the study.

They randomly assigned 443 patients to take either two capsules of heat-inactivated Bifidobacterium bifidum MIMBb75, or two placebo capsules, twice daily, for eight weeks. They measured whether abdominal pain improved by at least 30% over eight weeks of treatment, from when they took the first capsule of treatment, and whether all IBS symptoms were significantly relieved at least 50% of the time while the capsules were being taken.

Out of 221 patients who received the probiotic, 74 (34%) experienced an improvement in abdominal pain by at least 30% and a significant alleviation of IBS symptoms at least 50% of the time, compared to 43 (19%) of the 222 patients who received the placebo. This translates to 1.7 times greater treatment success in the probiotic group.

There was no difference in side effects between the groups, and none of the side effects were severe. The most common side effect reported was abdominal pain, which was reported by less than 1% of patients in both groups. 200 (91%) of patients rated the tolerability of treatment as good or very good, compared to 191 (86%) in the placebo group.

The authors highlight the considerable placebo response as a potential limitation of the study, with 19% of patients recording an improvement in symptoms according to the study criteria. However, they point out that a strong placebo response is common in controlled IBS trials. For example, in some studies, over 40% of patients have reported an improvement in IBS symptoms when receiving only a placebo. [4]

"Our results show for the first time that dead or alive, it's possible to preserve the beneficial effects of some probiotic bacteria," says co-author Dr Viola Andresen, also from University of Hamburg teaching hospital. "They could be just as effective as live probiotics, as well as even safer, with the added commercial benefit of a longer shelf life." [2]

Writing in a linked Comment, lead author Nicholas Talley (who was not involved in the study) from the University of Newcastle, Australia, says: "A previous, smaller randomised controlled trial reported that viable B bifidum modestly improved IBS symptoms compared with placebo. Andresen and colleagues' trial reported a similar benefit of non-viable B bifidum to that observed with viable organisms in terms of effect size. A strength of the study was that all IBS subtypes were included in the analysis, and the inactivated bacterial therapy appeared to benefit the different subgroups."

New modelling research, published in The Lancet journal, suggests that China's aggressive control measures appear to have halted the first wave of COVID-19 in areas outside Hubei province, the epicentre of the epidemic. However, given the substantial risk of the virus being reintroduced from abroad, and with economic activity increasing, real-time monitoring of COVID-19 transmissibility and severity is needed to protect against a possible second wave of infection, researchers say.

The study estimates that in regions outside Hubei, the instantaneous reproductive number of COVID-19--the average number of cases generated by a single infected individual during the outbreak --fell substantially after lock down measures were introduced on January 23, 2020, and has remained below 1 since then--suggesting that the epidemic has shifted from one that is expanding rapidly to one that is slowly shrinking [1].

However, mathematical modelling to simulate the impact of relaxing current control measures, suggests that premature lifting of these interventions will likely lead to transmissibility exceeding 1 again, resulting in a second wave of infection.

The findings are critical to countries globally that are in the early phases of lock down because they warn against premature relaxation of strict control measures, researchers say. However, the study did not specifically examine the effect of each intervention, or which one was most effective in containing the spread of the virus.

"While these control measures appear to have reduced the number of infections to very low levels, without herd immunity against COVID-19, cases could easily resurge as businesses, factory operations, and schools gradually resume and increase social mixing, particularly given the increasing risk of imported cases from overseas as COVID-19 continues to spread globally", says Professor Joseph T Wu from the University of Hong Kong who co-led the research.

He continues, "Although control policies such as physical distancing and behavioural change are likely to be maintained for some time, proactively striking a balance between resuming economic activities and keeping the reproductive number below one is likely to be the best strategy until effective vaccines become widely available." [2]

Further analysis suggests that the confirmed case fatality risk (the probability of dying among confirmed cases of COVID-19 as officially reported) outside Hubei was 0.98%--which is almost six times lower than in Hubei (5.91%) - and varied substantially among different provinces, based on economic development and availability of health-care resources. Among the ten provinces with the largest number of confirmed cases, case fatality ranged from 0% in prosperous regions like Jiangsu to 1.76% in less developed provinces such as Henan (figure 4).

"Even in the most prosperous and well-resourced megacities like Beijing and Shanghai, health-care resources are finite, and services will struggle with a sudden increase in demand", says senior author Professor Gabriel M Leung from the University of Hong Kong. "Our findings highlight the importance of ensuring that local health-care systems have adequate staffing and resources to minimise COVID-related deaths." [2]

In December 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan city and spread across China. Stringent restrictions on the movement of people and goods were introduced nationwide on January 23. These measures have impacted on people's livelihood and personal liberties, as well as lost economic opportunity. Since February 17, restrictions have been progressively relaxed in several provinces, and factories and offices are gradually reopening.

In the study, researchers analysed local Health Commission data of confirmed COVID-19 cases between mid-January and 29 February, 2020, to estimate the transmissibility and severity of COVID-19 in four major cities--Beijing, Shanghai, Shenzhen, Wenzhou--and ten provinces outside Hubei with the highest number of confirmed COVID-19 cases [3]. The number of new daily imported and local cases were used to construct epidemic curves for each location by date of symptom onset, and reporting delays--time lags between the onset of a disease and the reporting of cases--were incorporated in the modelling to calculate weekly reproduction numbers (figure 2). The researchers also modelled the potential impact of relaxing control measures after the first wave of infection for different scenarios with rising reproduction numbers.

The analyses suggest that in regions outside Hubei, control measures should be lifted gradually so that the resulting reproductive number does not exceed 1, or the number of cases will progressively rise over the relaxation period (figure 5). Moreover, the estimates suggest that once elevated, simply tightening control interventions again would not reduce the burden back to its original level, and would require extra effort to drive the reproductive number below 1 in order to revert to the pre-relaxation level--likely resulting in both higher health and economic loss.

"We are acutely aware that as economic activity increases across China in the coming weeks, local or imported infection could lead to a resurgence of transmission", says co-lead author Dr Kathy Leung from the University of Hong Kong. "Real-time monitoring of the effect of increased mobility and social mixing on COVID-19 transmissibility could allow policymakers to fine tune control measures to interrupt transmission and minimise the impact of a possible second wave of infections." [2]

Despite these important findings, the study has some limitations, including that the estimated reproductive numbers were based on the reported number of confirmed cases, and the time and dates of symptom onset were unavailable for some provinces and relied on data derived from Shenzhen. Finally, a limited number of simulations for relaxing control measures were done, and did not specify which interventions or public responses to the epidemic might correspond to each of these scenarios.

Writing in a linked Comment, lead author Dr Shunqing Xu (who was not involved in the study) from Huazhong University of Science and Technology in China says: "Case fatality rate (CFR) is one of the important unknowns of COVID-19...Leung and colleagues found the confirmed CFR was correlated with provincial per capita gross domestic product and the availability of hospital beds per 10,000. In Wuhan, the CFR was up to 5.08% by March 28, 2020. The remarkable difference in the CFR between these locations and Wuhan might be attributed to the difference in the degrees of health-care capacity. Therefore, consideration should be given to the variations in health-care capacity when implementing interventions."

BUFFALO, N.Y. -- Personal growth and job skills have taken a backseat to an increased focus on standardized test scores in schools across the nation, according to new University at Buffalo-led research.

The study, which analyzed the educational goals of principals at thousands of public, private and charter schools over two decades, found the shift in priorities is most pronounced in public schools.

The change in educational goals can be traced to the rise in test-based school accountability policies in the 1990s, which culminated with the No Child Left Behind Act (NCLB) of 2001 that mandated statewide testing in the United States, according to the research.

"The balanced development of both academic and soft skills is crucial, not only for well-rounded child development in schools, but also for career and life success," says Jaekyung Lee, PhD, lead researcher and professor of learning and instruction in the UB Graduate School of Education.

"Increasing concerns about poor student performance in the United States led states to adopt high-stakes testing policies," says Lee. "However, working under the constraints of limited resources, complex power dynamics and externally imposed policies, school principals are often faced with challenges in prioritizing educational goals. Forced to focus narrowly on academic skills measured by state tests, other equally important goals were deprioritized."

The study, published in March in Educational Administration Quarterly, is one of few studies to examine the influence of education policies on school principals' priorities, rather than on student achievement or teacher practices. A school leader's perception of educational goals guides, directs and motivates the daily operations and performance of school members, says Lee.

Using data from the Schools and Staffing Survey, the researchers compared the national trends of educational goal priorities between public and private schools from 1991-2012.

The surveys asked principals to choose their top three priorities among the following goals: basic literary and numerical skills, academic excellence, personal growth, job skills, work habits and discipline, human relations, moral values, and multicultural awareness.

Academic excellence experienced a significant rise in ranking among public school principals, with 83% choosing it as one of three top priorities in 2012, up from 60% in 1991. The percentage who selected development of basic literacy and numeracy skills also rose, increasing from 76% to 85%.

The shift, however, came at the expense of personal growth (self-esteem and self-awareness), which in 1991 was chosen by 62% of public school principals but only by 32% in 2012. The importance of job skills also declined, with the percentage of principals rating it as one of three top priorities falling from 13% to 9%.

Private school principals experienced a similar but less drastic shift in priorities. The results, says Lee, reflect the influence of educational policy discourse and media reports on private schools which, unlike public schools, are less exposed to government regulations on curriculum standards.

The study's findings about the NCLB policy impact on narrowing educational goals resonate with Lee's previous studies, including a recent report published by the Rockefeller Institute of Government that called for renewed education policy actions to improve children's socioemotional skills and well-being.

"School leaders can and should play an important role in envisioning and realizing educational goals," says Lee. "Principals need to develop strategies to accomplish the whole educational mission, encompassing academic, socioemotional, moral, multicultural and vocational learning to meet the diverse needs of their students as well as the larger society."