Culture

Research sheds light on how silver ions kill bacteria

image: This is Yong Wang, assistant professor of physics, University of Arkansas.

Image: 
Russell Cothren

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.

Credit: 
University of Arkansas

Alarming abusive head trauma revealed in computational simulation impact study

image: 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.

Image: 
Milan Toma

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.

Credit: 
New York Institute of Technology

Ménière's disease: New clinical practice guideline

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.

Credit: 
American Academy of Otolaryngology - Head and Neck Surgery

Hidden army: How starfish could build up numbers to attack coral reefs

image: Researchers Ms Dione Decker (left) and Professor Maria Byrne with an adult crown of thorns starfish on the Great Barrier Reef.

Image: 
The University of Sydney

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.

Credit: 
University of Sydney

Newborns infected with COVID-19 in China experienced mild symptoms

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."

Credit: 
European Respiratory Society

Higher levels of coronavirus 'entry point' enzyme in lungs of COPD patients and smokers

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."

Credit: 
European Respiratory Society

An experimental study demonstrates the effectiveness of online learning

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.

Credit: 
National Research University Higher School of Economics

The Lancet Gasteroenterology & Hepatology: First clinical trial finds probiotic treatment with dead bacteria is better than placebo at alleviating symptoms of irritable bowel syndrome

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."

Credit: 
The Lancet

The Lancet: Modelling study estimates impact of relaxing control measures on possible second wave of COVID-19 in China

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."

Credit: 
The Lancet

Public policies push schools to prioritize creating better test-takers over better people

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."

Credit: 
University at Buffalo

COVID-19 in humanitarian settings and lessons learned from past epidemics

April 8, 2020 -- "COVID-19 in Humanitarian Settings and Lessons Learned from Past Epidemics" published in Nature Medicine, invokes a global response to protect the most vulnerable during the COVID-19 pandemic. The authors make the point that displaced populations, including refugees and migrants, are often the first to be stigmatized and unjustly blamed for the spread of disease, yet they are also among the most vulnerable people during a pandemic--to both the virus itself and the measures enacted to control it. The paper draws on the collective field experience of Columbia Mailman School of Public Health faculty in the Program on Forced Migration and Health who are currently deployed in the field engaged in the humanitarian response and health systems strengthening.

The authors, who comprise a multi-disciplinary group of academics and practitioners, including physicians, epidemiologists and lawyers, aim to share some of the lessons learned from past epidemics to inform a more effective, inclusive COVID-19 response that addresses the needs of the most vulnerable.

Credit: 
Columbia University's Mailman School of Public Health

Off-the-shelf artificial cardiac patch repairs heart attack damage in rats, pigs

image: An artificial cardiac patch promotes cardiac repair after injury.

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NC State University

Researchers from North Carolina State University have developed an "off-the-shelf" artificial cardiac patch that can deliver cardiac cell-derived healing factors directly to the site of heart attack injury. In a rat model of heart attack, the freezable, cell-free patch improved recovery. The researchers also found similar effects in a pilot study involving a pig model of heart attack.

Cardiac patches are being studied as a promising future option for delivering cell therapy directly to the site of heart attack injury. However, current cardiac patches are fragile, costly, time-consuming to prepare and, since they use live cellular material, increase risks of tumor formation and arrhythmia.

"We have developed an artificial cardiac patch that can potentially solve the problems associated with using live cells, yet still deliver effective cell therapy to the site of injury," says Ke Cheng, Randall B. Terry, Jr. Distinguished Professor in Regenerative Medicine at NC State's College of Veterinary Medicine and professor in the NC State/UNC Joint Department of Biomedical Engineering.

Cheng and colleagues from NC State and UNC-Chapel Hill built the patch by first creating a scaffolding matrix from decellularized pig cardiac tissue. Synthetic cardiac stromal cells - made of a biodegradable polymer containing cardiac stromal cell-derived repair factors - were embedded in the matrix. The resulting patch contained all of the therapeutics secreted by the cells, without live cells that could trigger a patient's immune response.

In a rat model of heart attack, treatment with the artificial cardiac patch resulted in ~50% improvement of cardiac function over a three-week period compared to non-treatment, as well as a ~30% reduction in scarring at the injury site.

The researchers also conducted a seven-day pilot study of heart attack in a pig model, and saw ~30% reduction in scarring in some regions of the pig hearts, as well as stabilized heart function, compared to non-treatment.

Additional experiments demonstrated that artificial patches that had been frozen were equally potent to freshly created patches.

"The patch can be frozen and safely stored for at least 30 days, and since there are no live cells involved, it will not trigger a patient's immune system to reject it," Cheng says. "It is a first step toward a truly off-the-shelf solution to cardiac patch therapy."

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North Carolina State University

STEM students learn as well online as in classrooms

ITHACA, N.Y. - Students learned just as much in online STEM college courses as they did in traditional classroom settings, and at a fraction of the cost, according to a first-of-its-kind study.

The study tracked more than 300 students in Russia, where top universities standardize online classes for use by institutions with fewer resources. It has important implications for the teaching of science, technology, engineering and math - skills that are in high demand by the international workforce, said Rene Kizilcec, assistant professor of information science at Cornell University.

"Demand for higher education is surging in the digital economy we now live in, but the price of a college education has ballooned and we don't have enough people to teach these courses, especially in more rural areas," said Kizilcec, co-author of "Online Education Platforms Scale College STEM Instruction With Equivalent Outcomes at Lower Cost," which published April 8 in Science Advances. "This new study offers the best available evidence to judge whether online learning can address issues of cost and instructor shortages, showing that it can deliver the same learning outcomes that we're used to, but at a much lower cost."

These online courses cost institutions 80% less per student than in-person classes, the study found, while blended classes combining online lectures with in-person discussions lowered the per-student cost by nearly 20%.

"Online education platforms have a big potential to expand access to quality STEM education worldwide," said Igor Chirikov, the project's principal investigator, director of the Student Experience in Research Consortium and a senior researcher at the Center for Studies in Higher Education at the University of California, Berkeley.

"They could also strengthen the instructional resilience of colleges when in-person delivery is not an option, such as right now, when most universities are closed to mitigate the COVID-19 outbreak," Chirikov said.

A shortage of highly skilled professionals in STEM fields is slowing down the global economy, according to previous research. But at the same time, many colleges and universities struggle with the costs of attracting qualified instructors. To address this problem, countries including Russia, China and India have introduced national online educational platforms, in which leading universities create online courses that other institutions can integrate into their own curricula for a small fee.

In this study, the researchers developed a controlled, randomized trial to test whether students in Russia learned as much in these online classes, known as OpenEdu, as they did in traditional in-person classes. For two courses during the 2017-18 academic year, the researchers randomly assigned 325 students to one of three versions: the online version through OpenEdu; the in-person class offered by their local university; or a blended version that combined online lectures with in-person discussion groups.

They found that final exam scores did not differ significantly among the three versions. In their in-course assessments, students in the all-online course scored 7.2 percentage points higher, probably because they were allowed to make three attempts on weekly assignments. Online students, however, were slightly less satisfied with their course experience than students in in-person and blended classes.

"Satisfaction might be lower, but learning outcomes are the same," Kizilcec said. "This is a reminder that what students say about instruction quality in course evaluations at the end of the semester might not be so predictive of what students are actually learning."

Though online classes save money in the long run, they have significant startup costs, the study said, which could potentially be covered by states or consortiums of universities. Coordinating course requirements and academic calendars across institutions or states could also improve the effectiveness of this kind of model, according to the researchers.

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Cornell University

COVID-19 news from Annals of Internal Medicine

Below please find link(s) of new coronavirus-related content published today in Annals of Internal Medicine. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

Chest Computed Tomography for Detection of Coronavirus Disease 2019 (COVID-19): Don't Rush the Science

In this Ideas and Opinions piece from the University of California, San Francisco and San Francisco Veterans Affairs Medical Center, the authors discuss the findings of early studies that addressed the use of chest computed tomography for the detection of COVID-19. The authors urge caution in rushing science and overinterpreting preliminary or flawed data. Read the full text here: http://annals.org/aim/article/doi/10.7326/M20-1382.

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American College of Physicians

Wallflowers could lead to new drugs

image: Erysimum baeticum, a wallflower from the Sierra Nevada mountains in Spain, with visible damage to its leaves caused by local insects.

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Tobias Züst

Plant-derived chemicals called cardenolides have long been used to treat heart disease, and have shown potential as cancer therapies. But the compounds are very toxic, making it difficult for doctors to prescribe a dose that works without harming the patient.

For decades, researchers have longed to figure out how plants biosynthesize cardenolides, knowledge that could help them discover and develop safer versions of the drugs. Unfortunately, the cardenolides' best-known plant sources - foxglove and milkweed - are not amenable to experimental techniques for identifying the genes and enzymes that are involved in producing the chemicals.

In a new study published online in eLife on April 7, a multi-institution team led by Boyce Thompson Institute faculty member Georg Jander and Tobias Züst, a research associate at the University of Bern's Institute of Plant Sciences, showed that Erysimum cheiranthoides (wormseed wallflower) could be used as a model species to elucidate that information. Indeed, the team identified 95 candidate cardenolides, and has begun using the plant to investigate cardenolide biosynthesis.

"Twelve different plant families produce cardenolides, but nobody knows exactly how they make them," Jander said. "I was looking for the best plant to study this pathway and settled on wormseed wallflower." Jander is also an adjunct professor at Cornell University's School of Integrative Plant Science.

The species is a great model for genetic studies because it has a short life cycle and is readily inbred, he said. "We need a plant that reproduces and gives us seeds quickly, which E. cheiranthoides does in about 10 weeks."

The team's study builds on work done in the 1990s by Alan Renwick, who is currently an Emeritus Professor at BTI.

In this study, the team assembled the complete genome of the wormseed wallflower and sequenced more than 9,000 expressed genes from E. cheiranthoides and 47 other Erysimum species. The results provide a foundation for identifying the genes that encode enzymes involved in the biosynthesis of cardenolides. For example, the team discovered potential pathways by which Erysimum species modify a basic precursor cardenolide, digitoxigenin, into eight more structurally complex molecules.

To further enable the use of E. cheiranthoides as a model, the genome was assembled with long read data and Hi-C scaffolding, a method that can provide a more contiguous genome than previous approaches, said Susan Strickler. Strickler is the director of the BTI Computational Biology Center (BCBC) and senior research associate at BTI.

"A high quality reference genome makes it easier for us to find genes of interest and their locations, in this case genes for the biosynthesis of cardenolides," she said.

The team is now conducting mutagenesis studies in E. cheiranthoides to allow them to find the entire cardenolide biosynthetic pathway. "Ultimately the genes underlying the biosynthetic pathways could be inserted into bacteria or yeast, which would be used to manufacture heart and cancer medicines that are safer than what are currently available," said Jander.

Evolutionary insights

The study also revealed a wide diversity of cardenolides, both across the Erysimum genus as a whole and within individual species. "What was most surprising to me is the huge chemical diversity in the genus: nearly one hundred different cardenolides and 25 or so glucosinolates," said first author Züst.

Many plant species produce either cardenolides or glucosinolates as toxic defenses against herbivorous insects. In turn, many insects have evolved resistance to one or the other chemical class, depending on which occurs in the insects' food source. Erysimum is unusual in that it produces both types of chemicals.

The team's findings suggest the genus originally produced glucosinolates as an ancestral defense, then acquired the ability to produce cardenolides as recently as 2 to 4 million years ago as part of an "arms race" between plants and insects. This second line of defense gives Erysimum an advantage against its insect enemies because none have yet developed resistance to cardenolides.

"It has allowed Erysimum to escape herbivory," said Züst. "And it is a nice example of ongoing evolution."

Züst said it was also surprising to find no apparent cost to Erysimum, in terms of growth, reproduction or general fitness, in maintaining both defensive systems. "In all but one of the species we studied, both systems are expressed and we don't see any apparent tradeoffs."

However, he theorized that the cost of maintaining dual defenses might be reflected in the rarity of Erysimum species: they are not widely distributed and grow in small patches only in niche environments - such as cracks and roadsides - not colonized by other plant species.

The study was supported by funding from the Swiss National Science Foundation (grant PZ00P3-161472), the U.S. National Science Foundation (awards 1811965 and 1645256) and a grant from the Ithaca, NY-based Triad Foundation, which funds early work in new areas of research.

"This is a nice example of putting Triad funding to use in getting good preliminary data, which will help us apply for additional grants," Jander said.

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Boyce Thompson Institute