Culture

Like many around the world, the lab of Professor Mriganka Sur in The Picower Institute for Learning and Memory at MIT has embraced the young technology of cerebral organoids, or "minibrains," for studying human brain development in health and disease. By making a surprising finding about a common practice in the process of growing the complex tissue cultures, the lab has produced both new guidance that can make the technology better, and also new insight into the important roles a prevalent enzyme takes in natural brain development.

To make organoids, scientists take skin cells from a donor, induce them to become stem cells and then culture those in a bioreactor, guiding their development with the addition of growth factors and other chemicals. Over the course of weeks, the stem cells become progenitor cells that multiply and then go on to become, or "differentiate" into, neurons or other brain cell types. Along the way the cells also migrate within the growing blob to take their places forming basic brain structures and circuits.

A beauty of organoids, therefore, is that as the cells in the culture grow and develop together, they simulate many of the basic processes that occur when real brains take shape. When cell donors have genes that cause disease, the organoid grown from their cells will reproduce underlying disease characteristics. The Sur lab uses organoids to study the abnormal brain development in Rett Syndrome, a devastating autism-like condition with a genetic underpinning.

A common practice among labs growing organoids is to improve the viability of the cells by adding a small molecule chemical called CHIR 99021 to inhibit the activity of a ubiquitous natural enzyme called GSK3-beta. In the new study in PLOS ONE the team led by Picower Fellow Chloé Delépine, confirmed that while different doses of CHIR 99021 can indeed keep cells alive, they have opposite effects on organoid growth - low doses promote growth but high doses constrain it and very high doses will stop it altogether. That information alone has obvious implications for labs using varying doses of CHIR 99021, but because Delépine's team investigated how these growth effects occur, it also helps to clarify what GSK3-beta activity affects during brain development.

It's an important question. Other research groups, for instance, have shown that perturbations in a signaling pathway involving GSK3-beta in the brain are associated with schizophrenia and autism. The new findings model how varying levels of inhibition may affect development.

"It's is not just increasing the viability of the cells, it is also changing other cellular processes such as division, differentiation and migration," Delépine said. "Our idea was to test the effects of different doses and to better understand these mechanisms we observed."

Eight organoids are shown in three columns. They appear as irregularly shaped white blobs. A scale marker suggests they are about 3mm in width.

Organoids showed different degrees of growth based on the dose of CHIR 99021. Controls are on the left. The ones in the middle received a low dose. The ones on the right received a high dose.

Different doses, opposite effects

To conduct the study, Delépine's team cultured organoids and, from day 15 through 35 of their development, treated them with doses of either an inert control, or 1, 10 or 50 micromolar of CHIR 99021. They then tracked various properties of cells by staining for different molecular markers of those properties.

Straight away, she noticed major differences in organoid size depending on the dose received. Low dose (1 micromolar) organoids were 1.6 times bigger than controls, but high dose (10 micromolar) organoids were 1.8 times smaller and very high dose (50 micromolar) organoids simply stopped growing at all early into treatment.

The growth differences were not because of cell death. As expected given that labs use CHIR 99021 to improve cell survival, adding CHIR 99021 enhanced cell viability and the effect was stronger for high dose than low dose treatments. But when the lab stained for markers of proliferation, or cell division, they found that high-dose organoids exhibited less while low-dose organoids exhibited more than controls.

When the team looked at another cellular activity that could affect growth they found a similar pattern. In high-dose organoids fewer cells differentiated into neural progenitor cells needed to produce new neurons while in low-dose organoids proliferation increased. As a result, high-dose organoids had fewer neurons.

Additionally, the low dose of CHIR 99021 resulted in more migration of newborn neurons to places needed for structural development of the organoid than control treatment did, suggesting that slight inhibition of GSK3 beta contributes to increased migration.

Delépine noted that the growth-promoting effects of low doses or the growth-limiting effects of high doses are not "good" or "bad." They are just levels of control of the culture. The new study provides more insight into how to use CHIR 99021 to achieve the desired end.

"It really depends on the goal of the organoid research that you are doing," she said. "Depending on what you want, different doses of this molecule can help you achieve a different phenotype."

And in natural brains, the study suggests, GSK3-beta likely plays a key role in the proliferation of progenitor cells, their differentiation into mature brain cells, and the propensity of those cells to migrate.

In addition to Delépine and Sur, the paper's other authors are Vincent Pham and Hayley Tsang.

The National Institutes of Health, The Simons Foundation Autism Research Initiative and the JPB Foundation supported the research.

Duluth, Minnesota - A new paper in the May issue of Nature Communications demonstrates why keeping local lakes and other waterbodies clean produces cost-effective benefits locally and globally.

A single season of a lake or water body with a harmful algal bloom that results in public do-not-drink orders, damages to fishing activity, lost recreational opportunities, decreased property values and increased likelihood of low birth weight among infants born to mothers exposed to polluted water bodies are but just a handful of reasons why clean water is important.

Most everyone wants their local lake or stream to be clean and useable for drinking, fishing, swimming and recreation. But previous cost-benefit studies showed the costs of protecting local water sources often exceeded the benefits.

Not so fast say the authors. One of the reasons past studies showed costs exceeding benefits is that not all benefits, especially global ones, were analyzed by economists.

New research, led by University of Minnesota Sea Grant Director John A. Downing, found that adding up global financial benefits of clean water shows that keeping water clean can help slow climate change, saving trillions of dollars. Using one Lake Erie case study as an example, the authors also found that the global climate change value of protecting and preventing this Great Lake from algae blooms was ten times greater than the value of beach use or sport fishing.

"Surface water is one of the Earth's most important resources," said Downing, who is also a lake scientist at the University of Minnesota Duluth Large Lake Observatory. "Yet people have mistakenly assumed that it costs more to protect our water than it is worth. Our research demonstrates that there is significant local and global value to protecting local water quality."

One reason for this, said the authors, is that scientists and economists have previously considered only a narrow range of local benefits when calculating the outcomes of good water quality. Downing and co-authors sought to calculate the potential global benefits.

Locally, cleaning or keeping a local lake or waterbody free of unwanted nutrients- what scientists call eutrophication - is obviously good for people who use or want to access that particular water body. Globally, it's also good for reducing the amount of the greenhouse gas methane that is released into the atmosphere from that eutrophic water body.

Methane is a stronger greenhouse gas than carbon dioxide because it has a much higher heat-trapping ability and has about 21 times the global warming potential of carbon dioxide. Less methane in the atmosphere can help slow global warming.

The authors sought to answer the question: is keeping a local water body clean worth the cost?

The cost of climate change comes from health-care costs, damages to urban infrastructure, agricultural damages, catastrophic storm damage, negative impacts on recreation, forestry, fisheries, energy systems, water systems, construction, and coastal infrastructure. 

"We calculated the global climate damages from methane emissions from eutrophic lakes and calculated the damages that would be avoided damages by preventing increased emissions from 2015 to 2050," said Downing. "If we could hold methane emissions at current levels rather than the expected 20-100% increase by 2050, the value of avoiding the resulting damages could be as much as $24 trillion." The authors estimated the costs of global climate change due to eutrophication from 2015 to 2050 to be as much as $81 trillion.

The authors' analysis shows that local water quality protection has global economic implications. The substantial emissions they document from lakes and reservoirs and the potential for increased emissions suggest that there is considerable value to be gained by improving water quality in lakes and reservoirs and in preventing further deterioration.

"It's not possible to avoid all emissions from lakes and reservoirs, but with concerted effort it may be possible to prevent increased emissions or even reverse it," said Downing.

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

Majority of COVID-19 patients receiving home-based hospital care did not require care escalation to traditional hospital setting
Free full text: https://www.acpjournals.org/doi/10.7326/M21-0409

A retrospective, single-center study found that the majority of COVID-19 patients receiving home-based hospital care did not require care escalation to a traditional hospital setting, even if the patients were older or obese. The findings are published in Annals of Internal Medicine.

The COVID-19 pandemic has challenged health care systems to rapidly transform care to address resource demands. Early in the pandemic, a large integrated health system implemented a hospital-at-home program to deliver home-based, hospital-level care to patients with COVID-19 and increase the health system's bed capacity.

Researchers from Atrium Health studied 391 adults 18 or older who met evidence-informed inclusion criteria and received treatment for COVID-19 in their program between March and November 2020 to determine which hospital-at-home patients were at increased risk for care escalation to traditional brick-and-mortar facilities. The researchers found that most patients did not require care escalation, with approximately 1 in 5 admitted within 14 days. More severe respiratory involvement was observed among transferred patients, particularly those requiring immediate care escalation. In addition, overall comorbidity burden was associated with transfer. The researchers expressed surprise that they did not observe independent associations between older age or obesity and transfer and speculate that this could be due to physician hesitation to enroll such patients with additional risk factors into the program.

According to the authors, this study is important because it provides practical initial evidence to help inform patient selection guidelines for hospital-at-home care as it becomes a standard care delivery option.

One of the most basic structural aspects of relativistic spacetime is the description of how time and distances are altered by motion. The theory of special relativity describes a spacetime framework for linear constant motion in which time dilates and lengths contract in response to motion. This framework is described by the Lorentz transformation, which encompasses mathematical formulas that describe how time and distance are altered between moving reference frames. The Lorentz transformation also describes how a stationary observer views time in the moving frame to be offset with distance. The offsetting of time with distance between reference frames generates differential simultaneity, in which events that are simultaneous for one observer will not be simultaneous for a second observer moving relative to the first observer.

The nature of spacetime in rotating frames has not been established at the most fundamental level of defining the transformation that accurately describes the relativistic effects and the simultaneity framework. There are four distinct rotational relativistic transformations in the literature: the Langevin metric; Post transformation; Franklin transformation; and the absolute Lorentz transformation (ALT) in its rotational form. Determining which transformation accurately describes experimental data would indicate the spacetime framework that is present in real-world rotating frames. Understanding this fundamental information has wide applicability because the majority of visible matter in the Universe is in rotational motion, including the rotating Earth.

The most widely-cited rotational transformation is the Langevin metric, which was first described in 1921. Over the decades, the Langevin metric has been used to describe relativity in rotating frames in hundreds of textbooks and research papers. However, the Langevin metric has never been assessed with experimental data that has sufficient resolution to distinguish it from the other major rotational transformations.

A transformation's combination of relativistic effects and simultaneity framework affects how light propagates. The four transformations have different predictions for the rotating-frame one-way speeds of light, two-way speed of light, and the Sagnac effect. This study derives the optical predictions for each transformation directly from their transformation equations, with several of the predictions not previously reported in the literature. The predictions are then compared to recent high-resolution optical experimental data.

Optical resonator data on the two-way speed of light is among the highest resolution scientific measurements, with resolutions of 10-18. This high resolution is required to distinguish between the predictions of the transformations. The study reveals that ALT and the Franklin transformation prediction of the constant two-way speed of light, c, matches the optical resonator data, while the Langevin metric and Post transformation predictions are invalidated by the data. The failure of the Langevin metric and Post transformation to match optical resonator data is shown to be due to their exhibiting no (or no net) length contraction in the rotating frame. In contrast, the ALT and Franklin transformations exhibit length contraction, which allows their accurate predictions for the two-way speed of light.

Data on the Sagnac effect, which has lower resolutions of 10-8, is compatible with the Sagnac effect predictions of the Langevin metric, Post, and ALT transformations, but is incompatible with the Franklin transformation, which predicts no Sagnac effect. The failure of the Franklin transformation to generate an overt Sagnac effect is shown to be due to its incorporation of differential simultaneity. In contrast, the other three transformations incorporate absolute simultaneity in which time is not offset with distance, which allows overt Sagnac effects. Thus, ALT is the only transformation that accurately describes the full range of relativistic optical data.

Multiple publications have proposed mechanisms to incorporate differential simultaneity into rotating frames to allow the generation of an overt Sagnac effect. However, these mechanisms generate alternate Sagnac effect equations. The study shows that these alternate Sagnac effect equations imply two-way speeds of light that are invalidated by the high-resolution optical resonator data. In contrast, ALT predicts the conventional Sagnac effect, which implies the constant two-way speed of light, c.

The study demonstrates that the ALT rotational transformation accurately predicts both high-resolution optical data and non-optical rotating-frame relativistic observations. This analysis implies that the ALT rotational transformation describes the basic framework of spacetime in rotating frames. This clarifies that rotating-frame spacetime is characterized by the relativistic effects of time dilation and length contraction within an absolute simultaneity framework in which time is not offset with distance.

A new study from the University of Portsmouth calls for further government oversight to curb potential illegal activity through these zones.

This study demonstrates the attractive trading advantages offered by freeports to enable enterprise and innovation. Eight new freeports in England are due to enter operation in late 2021, which are hoped to drive investment, economic opportunities and growth to those regions.

However, researchers also advise that stronger regulation is needed to prevent Freeports being abused for money-laundering and tax-evasion purposes. The study, published today in the Journal of Money Laundering Control, raises justifiable concerns over the misuse of Freeports.

In early 2020, and with Brexit looming on the horizon, the UK government published a consultation into proposals to create Freeports across the country. The idea was to stimulate the economy following the departure from the EU.

Report lead author Paul Gilmour, from the University's Institute of Criminal Justice Studies, explains the role of freeports. He says: "In their basic form they are warehouses located within free-trade zones that lie within a country's geographical border but are designated by that country's government to be outside its normal customs regime.

"The companies based within these zones enjoy several concessions, such as cheaper import duties, suspended custom obligations, and reduced bureaucratic checks intended to streamline cross-border trade. They effectively act as offshore jurisdictions that offer attractive trading advantages which enable enterprise and innovation."

The research examined existing freeports around the world and found they are often used as tactical depots: intended as spaces to temporarily house valuable assets, such as artwork, precious metals and gems, wine collections and antiques.

Researchers say that many art dealers now commonly exploit the beneficial goods-in-transit position of freeports, to house assets on a more permanent basis. This means, as long as the dealers' goods remain within the freeports storage facility, those dealers are unaccountable for any duties (such as value-added taxes [VAT] or capital gains taxes) which would normally be applied upon export.

Gilmour explains: "The growth in freeports may have originally evolved from a desire to stimulate global investment by deregulating financial markets. However, there is an argument that permanent storage spaces within freeports only act to stifle capital mobility. Nonetheless, freeports do seem to provide innovative trading advantages to enable businesses to thrive in today's competitive global market."

The study warns that freeports can be abused for money-laundering and tax-evasion purposes because of a lack of transparency. It says they can help to obscure the true beneficial owners of assets through secretive corporate practices that thwart efforts by authorities to trace illicit profits and recoup government taxes.

"There is also evidence that these zones enable trade-based money laundering by the falsifying of trade invoices to deceive authorities," says Gilmour. "The many international transactions occurring through freeports, coupled with a lack of regulatory supervision, poses notable challenges for government officials."

The study suggests that banks that facilitate numerous international trade transactions need to be more alert to illicit trading and should be responsible for carrying out proper due diligence around freeport trade. It says that although governments have recognised the threat that freeports present by ensuring they fall within the scope of anti-money laundering control, there is still opportunity for freeports to operate without transparency.

In recent decades, Spain has undergone rapid social changes in terms of gender equality, despite, as a result of the Franco dictatorship, starting from a more backward position than most European countries. This process is hampered by the economic downturn that began in 2008, underlining the importance of the economic context in the development of gender inequality levels. Little attention has been paid in academia to how this gender revolution is associated with factors related to individual wellbeing.

A study by Jordi Gumà, a researcher at the Department of Political and Social Sciences and member of the UPF Sociodemography Research Group (DEMOSOC), together with Bruno Arpino, a researcher at the University of Florence (Italy), explores the association between the subjective level of satisfaction with life and the degree of relative participation by women and men in terms of providing financial resources to the household and performing domestic chores among the partnered adult Spanish population.

"When no financial difficulties are reported, it seems that gender behaviour in the home environment has less influence on individuals' levels of life satisfaction, whether men or women, than in homes with financial problems".

Following their research, published in Revista Internacional de Sociología, the researchers (who separate the analysis of the public and the private spheres to capture the effects differentially) conclude that the level of satisfaction with life is marked largely by household financial capacity: "When no financial difficulties are reported, it seems that gender behaviour in the home environment has less influence on individuals' levels of life satisfaction, whether men or women, than in homes with financial problems", the researchers assert.

Furthermore, the results reveal that there would be a situation of tension between the social context and inherited values (with an imbalance between gender values, far more egalitarian, and the end practices observed) would affect the levels of individual wellbeing.

The research methodology analyses Spanish samples from the European Social Survey (ESS) of 2004 and 2010 together, in which questions about family, work and wellbeing were introduced. The various analyses have been carried out independently according to sex, in order to identify possible differences between men and women. The sample was restricted to partnered individuals, within the 25-59 years age bracket.

The researchers state that the relative contribution to household income and the performance of household chores "has a significant effect on life satisfaction in the specific case of people with financial difficulties". This effect shows that the gender profile in households that report having financial difficulties is far closer to the traditional one. However, significant differences were found between men and women.

The overall situation of the household determines women's satisfaction

With regard to women, the researchers found that "their satisfaction with life is defined mainly by the overall situation of the household, beyond their own situation in terms of their relative contribution to income and relative time spent on household tasks". That is, it is their position within the private sphere that has the greatest impact on the values of life satisfaction in respect of women in Spain.

The position of women within the private sphere has the greatest impact on the values of life satisfaction in respect of women in Spain.

Among women who report not having financial difficulties (reaching the end of the month adequately or comfortably), the authors observe a positive relationship between their levels of satisfaction and time spent on household tasks: the greater their dedication, the higher their level of satisfaction. This pattern is exactly the opposite in the case of women who report having financial difficulties, whereby the greater their dedication to household tasks, the lower their satisfaction.

According to the researchers, one possible explanation is that more solvent households would be more able to hire paid services to perform household chores, so that although these women spend more time on household tasks than their partners, the actual number of hours allocated may be less than those who report having financial difficulties, and neither does this mean that there is parity with men. In fact, if we look at the average number of hours spent on such tasks, the figure is significantly lower among women with greater economic power.

Men's satisfaction with life is marked by their individual situation

In the case of men, the authors found significant differences in the level of satisfaction with regard to their relative contribution to the family budget. In the context of households with financial difficulties, men who report contributing more to total family income display higher levels of satisfaction than those who report contributing less than their partners.

According to the researchers, "being the main provider of material resources to the household is associated with values of satisfaction in the group of men in households with financial difficulties, while among men who report not having financial difficulties, being the main contributor does not seem to give them an extra boost to their levels of satisfaction".

In the context of households with financial difficulties, men who report contributing more to total family income display higher levels of satisfaction than those who report contributing less than their partners.

The same applies in the case of participation in household tasks, where significant differences were only observed, again, in men with financial difficulties, who reveal that devoting less time than their partners to household tasks is a situation associated with higher levels of satisfaction.

In consequence, according to the researchers, unlike the case of women, Spanish men's life satisfaction is determined to a greater extent by their individual situation, beyond the characteristics of the household as a whole. This suggests that, in this particular group of men, their position within the public sphere continues to set their perception of satisfaction with life.

It was commonly assumed that wildlife products are exported from low-income countries to meet the demand of consumers in wealthy economies, and therefore, a widening wealth gap may drive up the volume of global trade and endanger wildlife.

Recently, a research team co-led by Research Division for Ecology and Biodiversity (E&B), Faculty of Science, the University of Hong Kong (HKU) and the Science Unit (SU) of Lingnan University (LU) corroborated this premise by analysing global wildlife trade databases. The research team includes Dr Jia Huan LIEW, Research Assistant Professor of SU, and Emeritus Professor David DUDGEON from E&B, HKU. Their findings are published in Science Advances.

Wealthier countries take the vast part of the responsibility

A major take-home message of the study was that wealthy countries are responsible for most of the world's wildlife trade. The top three importers of wild animals were the United States, France, and Italy, while in Asia, wealthier nations including China, Singapore, and Japan were all net importers of wildlife products. On the supply-end of the trade, countries with better logistics capabilities (e.g., Indonesia) also exported more wildlife products.

Hong Kong has long been a global hub of the legal wildlife trade, importing approximately 13 million individual animals between 1998 and 2018. In particular, the city was a major destination for fishes, sharks, and rays.

The researchers looked at 20 years of legal wildlife trade data, ranging from live corals for hobbyist, to wild-caught sturgeons for aquaculture, and seahorses for traditional remedies. During this period, an estimated 421 million individual animals were traded globally, and the market was more extensive when there was greater wealth inequality between countries.

The study's findings may have important implications in a post-pandemic world, where issues surrounding the wildlife trade is once again in the spotlight. The COVID-19 virus is believed to have spread to humans via the wildlife trade, leading notably, to a ban on the consumption of wild terrestrial animals in China. While increased regulation may suppress trade in the short term, the pandemic's impact on the global economy will likely exacerbate wealth inequality between nations by disproportionately impacting some parts of the world. This, according to research findings that show a positive correlation between wealth inequality and the extent of the global wildlife market, could encourage more international trade in wildlife products.

There were marked inequalities between exporters and importers of wildlife products, and importers were generally better off in all measures of socioeconomic well-being. For example, the largest trade partnership the study recorded was between the USA (importer) and Indonesia (exporter), where the per capita GDP of the US was 20 times that of Indonesia. Other prominent trade flows include exports from Jamaica to France (importer per capita GDP 8 times higher) and exports from Indonesia to Singapore (importer per capita GDP 17 times higher).

Urge for reduction of demands for animal products

Inequalities in the wildlife market and the dominant role of wealthy countries highlights the importance of efforts to reduce the demand for wildlife products via awareness campaigns or product substitution, among others. "One message is that it is evidently demand from richer countries that is fueling the capture and trade of wildlife from poor/low-income countries. That means that it is the responsibility of affluent consumers in rich countries to do something to limit their demands and greed for animal products," says Emeritus Professor Dudgeon.

This may also be a more socially equitable approach than blanket bans on wildlife harvesting that could impact vulnerable communities reliant on the trade. "Globally, we need to manage the trade in wildlife in a way which does not endanger their populations and the communities that rely on it for a source of protein or important source of livelihood," says Dr Janice LEE, Assistant Professor at the Asian School of the Environment.

YouTube channels run by zoos focus on entertainment over education, according to a new study.

The videos also focus disproportionately on mammals, rather than reflecting the diversity of zoos' animals.

Conservation was the focus of just 3% of zoo videos in the study - but it found that conservation content in videos is gradually increasing.

The study evaluated the most recent and most-viewed videos, so the findings partly reflect the public's preference for certain species and content.

Of the animals that appeared in zoos' most-viewed videos, the top nine were mammals - with giant pandas top of the list - and the only non-mammals were penguins in tenth place.

"They key question is: what are zoos using YouTube for?" said Dr Paul Rose, of the University of Exeter.

"If the aim is to get people to visit the zoo, then a focus on entertainment and popular species might make sense.

"This way, education about wildlife and conservation can be done once people get to the zoo, where they will spend much more time than they would watching a YouTube video.

"However, some zoos have large YouTube audiences, so they should carefully consider how they represent different classes of animal, and how they can create educational material in interesting and accessible forms.

"If an animal is in a zoo's collection, there should be a way for it to be promoted."

Dr Rose said he was encouraged to see an increased focus on conservation in zoo videos.

For example, videos about animals of conservation concern on the IUCN Red List have featured more often in recent years.

Lead author Thomas Llewellyn, a graduate from UWE's Science Communication Unit, said: "It is important that zoos produce a variety of conservation-focused content for a range of different animals.

"Whilst it is reassuring to see YouTube channels upload more conservation-focused videos in recent times, this research is especially important to the conservation projects associated with those 'favoured animals'.

"There is no doubt that YouTube has the potential to become an effective and efficient tool for global conservation education, but more research is needed to be done."

The study's information was gathered before the COVID pandemic, and the content posted on many zoo YouTube channels has changed dramatically since then.

"I've seen a lot more zoos doing live videos during lockdown to explain the significance of their animal collections," Dr Rose said.

"With zoo admissions essentially being non-existent this year, the pandemic has only emphasised the importance of social media for this type of online outreach", added Llewellyn.

The researchers evaluated the content of 1,000 videos from 20 zoological organisations (50 most-viewed videos from each channel) from 2006 to 2019. More than 75% of these videos focussed on mammals.

Separately, educational content in a subsample of 300 of the most viewed and most recent videos from three zoo YouTube channels was catalogued and evaluated for the period 2016 to 2019.

A new paper in the Journal of the European Economic Association, published by Oxford University Press, indicates that distrust generated by a 2011 CIA-led vaccination campaign ruse designed to catch Osama Bin Laden resulted in a significant vaccination rate decline in Pakistan.

Using a local doctor, the US Central Intelligence Organization planned an immunization plan in Pakistan to obtain DNA samples of children living in a compound in Abbottabad where American authorities suspected Bin Laden was hiding in order to obtain proof of Bin Laden's location (because the presence of close relatives would be a likely indication of Bin Laden's presence). Without consent from the Pakistani health authorities, the doctor began to administer hepatitis B vaccines to children in Abbottabad. The Guardian published an article revealing the vaccine project shortly after a United States military special operations unit killed Bin Laden on May 2, 2011.

Even prior to this campaign extremist groups in Pakistan have worked to discredit formal medicine and vaccines. By discrediting such services (which are provided by the state) extremist groups may increase the credibility of non-state actors such as the Taliban.

The Taliban increased propaganda efforts against vaccines in the aftermath of the publication of the Guardian article. In particular, the Taliban issued several religious edicts linking vaccination campaigns to CIA espionage activities and later used violent action against vaccination workers.

Using data from the Pakistan Social and Living Standards Measurement on children born between January 2010 and July 2012, researchers have investigated the effects of the disclosure of this vaccination ruse on the extent to which children in Pakistan received doses of the polio, DPT, or measles vaccine. Their estimates indicate that the vaccination rate declined between 23% and 39% in districts with higher levels of electoral support for an alliance of parties espousing political extremism relative to districts with lower levels of electoral support for such groups. The researchers' investigation also revealed that the decline in girls' vaccination rates is larger than the decline in the vaccination rate of boys.

"The empirical evidence highlights that events which cast doubt on the integrity of health workers or vaccines can have severe consequences for the acceptance of health products such as vaccines," said Andreas Stegmann, one of the paper's authors. "This seems particularly relevant today as public acceptance of the new vaccines against Covid-19 is crucial to address the pandemic."

About 42% of rural school districts in the U.S. offered fully in-person instruction as of February, compared with only 17% for urban districts, according to a new RAND Corporation survey of school district leaders. The opposite pattern held for fully remote learning: 29% of urban districts offered fully remote instruction compared with 10% of rural districts and 18% of suburban districts.

The choice of in-person versus remote learning has important implications. Over a third of all U.S. school districts offering some form of remote instruction in early 2021 had shortened the school day, and a quarter had reduced instructional minutes.

"This survey shows how the choice of remote instruction has ramifications that extend beyond longstanding concerns about the lower quality of remote instruction.," said Heather Schwartz, lead author of the report and director of the Pre-K to 12 educational systems program at RAND, a nonprofit research organization. "Rural districts - which were primarily fully in-person or hybrid - did not decrease instructional minutes as often as urban districts, which means that urban students of color have likely lost more instructional time this school year than their white counterparts in rural districts."

To offset pandemic learning challenges, many districts added services. More than half of districts overall, and about seven in 10 urban districts, offered tutoring in 2020-2021 and increased social and emotional learning minutes or programming.

The survey found that about eight in 10 districts have not cut spending in 2020-2021, and most foresee spending the same or more next academic year. Similarly, many more districts have hired rather than fired school staff this academic year, and the prospect for next year looks the same.

Two-thirds of districts lost some enrollment this academic year from the year before, with an average decline of 5%. This is twice as many districts, and twice as large a decline, as the year before.

Looking forward, district leaders have great concern about a shortage of substitute teachers, bus drivers and teachers in several historically difficult-to-staff subject areas for 2021-2022.

RAND fielded the survey to the American School District Panel (ASDP) Jan. 21 through March 5. The report is based on responses from 434 district leaders from 48 states and the District of Columbia.

The ASDP is the first-of-its-kind nationally representative, longitudinal panel of school districts across the U.S., providing opportunities for district and charter management organization leaders to inform policy and practice.

The other authors of "Urban and Rural Districts Show a Strong Divide During the COVID-19 Pandemic: Results from the Second American School District Panel Survey" are Melissa Kay Diliberti, Lisa Berdie, David Grant, Gerald P. Hunter and Claude Messan Setodji.

RAND Education and Labor, a division of RAND, is dedicated to improving education and expanding economic opportunities for all through research and analysis. Its researchers address key policy issues in U.S. and international education systems and labor markets, from pre-kindergarten to retirement planning.

In some countries of the WHO European Region, 1 in 3 children aged 6 to 9 years is living with overweight or obesity. Mediterranean countries have the highest rates of obesity, but the situation there is starting to improve.

These are some of the findings of a new WHO European Childhood Obesity Surveillance Initiative (COSI) report on the fourth round of data collection (2015-2017), presented at this week's European Congress on Obesity (held online this year). The report gives the latest data available on 6- to 9-year-olds in 36 countries in the region. A questionnaire collecting data from 2021 on the impact of the pandemic will follow from some countries.

"COVID-19 could potentially amplify one of the most worrying trends in the WHO European Region - growing childhood obesity," said Dr Hans Henri P. Kluge, WHO Regional Director for Europe.

"Overweight and obesity are directly associated with life-threatening noncommunicable diseases such as cardiovascular diseases, diabetes and cancer. What we must do to brighten the future of coming generations is implement science- and data-based policies that can help reduce childhood obesity, while promoting healthier diets and physical activity," Dr Kluge added.

Effect of the COVID-19 pandemic on childhood obesity

COVID-19 is likely to negatively impact childhood obesity levels in the WHO European Region, and hence the results of the next rounds of the COSI survey. School closures and lockdowns can impact access to school meals and physical activity times for children, widening inequalities. Childhood obesity prevention strategies should therefore remain a priority during the pandemic.

Policies having a positive effect in hardest-hit countries

Overweight and obesity stabilized or declined in some of the 13 European countries where it was possible to examine trends over time. Greece, Italy, Portugal and Spain, which all have the highest rates of obesity, as well as Slovenia showed a decreasing trend for both overweight and obesity. The reduction of the overweight prevalence ranged from 4 to 12 percentage points for boys and from 3 to 7 for girls.

In the last years, some of these countries implemented WHO-recommended measures to help tackle obesity rates, such as imposing taxes on sweetened beverages, food marketing restrictions and physical education classes.

"The COSI data show a decreasing trend in childhood obesity in the countries which have the highest rates of obesity. They have heard the alarm from the previous studies and implemented the policies we know work. It is heartening to see that when countries act it has a measurable effect," said Dr Nino Berdzuli, Director of the Division of Country Health Programmes at the WHO Regional Office for Europe.

Comprehensive data

The latest COSI data come from 36 countries that participated in the survey during the 2015-2016 and 2016-2017 school years, measuring around 250 000 primary school-aged children. The COSI report holds the most comprehensive data for boys and girls on overweight, physical activity and dietary patterns.

Key findings

Overall, the prevalence of overweight (including obesity) was 29% in boys and 27% in girls aged 6 to 9 years; the prevalence of obesity was 13% in boys and 9% in girls. These figures hide wide variations between countries. For more data on overweight and obesity among boys and girls in 36 countries, please see the figure at the end of this press release.

The highest proportions of childhood overweight and obesity were observed in Mediterranean countries such as Cyprus, Greece, Italy and Spain, where over 40% of boys and girls were living with overweight, and 19% to 24% of boys and 14% to 19% of girls were living with obesity.

The lowest proportions of childhood overweight and obesity were observed in central Asian countries such as Kyrgyzstan, Tajikistan and Turkmenistan, where 5% to 12% of boys and girls were living with overweight and less than 5% were living with obesity.

Dietary habits

On average, almost 80% of children had breakfast every day, around 45% ate fruit daily, and around 25% consumed vegetables daily. However, country-level figures for these healthy habits varied widely: daily consumption ranged from 49% to 96% for breakfast, from 18% to 81% for fruit, and from 9% to 74% for vegetables.

Frequent consumption of sweet snacks (27% of children overall) was more widespread than consumption of savoury snacks (14%). The percentage of children eating these unhealthy foods more than 3 days a week also varied greatly between countries - from 5% to 62% for sweet snacks and from less than 1% to 35% for savoury snacks.

Physical activity

On average, 1 in 2 children used active transport (walking or cycling) to and from school. In all countries, most children spent at least 1 hour per day playing outside (ranging from 62% to 98% in different countries).

Children with more educated parents were more likely to engage in sports/dancing in most countries. The difference between children of parents with high and low levels of education exceeded 20 percentage points in 7 countries. On the contrary, children of less educated parents were more likely to walk or cycle to and from school.

Lack of data for children under 5 years

COSI provides the Region with a large dataset on the prevalence of overweight and obesity and the determinants of childhood obesity for primary school-aged children. Unfortunately, no such large dataset exists for children under 5. The need to strengthen surveillance initiatives for this younger age group with the support of all governments and other stakeholders is urgent.

New Curtin University research has found a bias among scientists toward colourful and visually striking plants, means they are more likely to be chosen for scientific study and benefit from subsequent conservation efforts, regardless of their ecological importance.

Co-author John Curtin Distinguished Professor Kingsley Dixon from Curtin's School of Molecular and Life Sciences was part of an international team that looked for evidence of an aesthetic bias among scientists by analysing 113 plant species found in global biodiversity hotspot the Southwestern Alps and mentioned in 280 research papers published between 1975 and 2020.

Professor Dixon said the study tested whether there was a relationship between research focus on plant species and characteristics such as the colour, shape and prominence of species.

"We found flowers that were accessible and conspicuous were among those that were most studied, while colour also played a big role," Professor Dixon said.

"Blue plants, which are relatively rare, received the most research attention and white, red and pink flowers were more likely to feature in research literature than green and brown plants.

"Stem height, which determines a plant's ability to stand out among others, was also a contributing factor, while the rarity of a plant did not significantly influence research attention."

Professor Dixon said plant traits such as colour and prominence were not indicators of their ecological significance, and so the 'attractiveness bias' could divert important research attention away from more deserving species.

"This bias may have the negative consequence of steering conservation efforts away from plants that, while less visually pleasing, are more important to the health of overall ecosystems," Professor Dixon said.

"Our study shows the need to take aesthetic biases more explicitly into consideration in experimental design and choice of species studied, to ensure the best conservation and ecological outcomes."

The full paper, 'Plant scientists research attention is skewed towards colorful, conspicuous, and broadly distributed flowers' was published in Nature Plants.

Analysis of The Autopsy, Toxicological, and Psychiatric Reports of Portugal's First Major Forensic Case: Part III
https://doi.org/10.1080/20961790.2021.1898079

Announcing a new article publication for Forensic Sciences Research journal. In this review article the author Ricardo Jorge Dinis-Oliveira of the University Institute of Health Sciences (IUCS)-CESPU, Gandra, Portugal continues a three-part investigation of the "Crime of Flores Street" one of the most famous cases of poisoning which occurred in Portugal in the late 19th century. The case demonstrated the weaknesses of the Portuguese medicolegal system and attests to the importance of toxicological analysis. The first article retold the case which gave birth to forensic toxicology studies in Portugal and informed present day Portuguese medicolegal procedures. The second article analysed all the relevant and contradictory testimonial evidence of the prosecution and defence witnesses.

In this latest publication the author analyses the forensic evidence, particularly from the autopsy, toxicological, and psychiatric forensic reports. Today, it would be easy to perform irrefutable toxicological analysis, but in those times, the circumstantially produced evidence, together with the toxicological expert reports, allowed the court to produce a damning judgment. The author suggests, that with current knowledge, it is now possible to add further insights if the burial location of at least one victim could be identified. In late 2020 one of the victims was finally located. Permission for a new autopsy for samples collection was obtained and has been performed more than 130 years after the first major autopsy was executed in Portugal. Future research will include correlation of the identity of the victim by DNA analysis and comparison with relatives and toxicological analyses.

Most people who are infected with SARS-CoV-2 develop no or only mild symptoms. However, some patients suffer severe life-threatening cases of COVID-19 and require intensive medical care and a ventilator to help them breathe. Many of these patients eventually succumb to the disease or suffer significant long-term health consequences. To identify and treat these patients at an early stage, a kind of "measuring stick" is needed - predictive biomarkers that can recognize those who are at risk of developing severe COVID-19.

First biomarker to predict severity of disease

A team led by Professor Burkhard Becher at the Institute of Experimental Immunology at the University of Zurich, working with researchers from Tübingen, Toulouse and Nantes, has now discovered such a biomarker - the number of natural killer T cells in the blood. These cells are a type of white blood cell and part of the early immune response. "The number of natural killer T cells in the blood can be used to predict severe cases of COVID-19 with a high degree of certainty - even on a patient's first day in hospital," says Burkhard Becher.

Targeted therapy thanks to precise immunopathogenesis

The new biomarker test helps clinicians decide which organizational and treatment measures need to be taken for patients with COVID-19, such as transfer to the ICU, frequency of oxygen measurements, type of therapy and treatment start. "Predictive biomarkers are very useful for making these decisions. They help clinicians provide patients suffering severe symptoms with the best care possible," says Stefanie Kreutmair, first author of the study. "Our findings also make it possible to investigate new therapies against COVID-19."

With the help of high-tech

The rapid deterioration in the health of COVID-19 patients is caused by an overreaction of the body's immune system. "The body produces small proteins called cytokines at a much higher rate, which leads to a 'cytokine storm' and triggers massive inflammation. Immune cells invade the lungs, where they disrupt gas exchange," explains Becher. To detect the immune cells and cytokines in patient samples, the UZH researchers used high-dimensional cytometry. This technology enables researchers to characterize many surface and intracellular proteins in millions of individual cells and process them using computer algorithms.

SARS-CoV-2-specific immune signature deciphered

Many other pathogens besides SARS-CoV-2 can cause pneumonia - and thus spark an immune response. The immune response triggered by COVID-19 has been studied extensively, but the exact nature of the immune response to SARS-CoV-2 has, to date, been unclear. To characterize this response, the researchers also analyzed blood samples of patients with severe pneumonia driven by a pathogen other than the novel coronavirus. By comparing the immune responses in COVID-19 patients with those of the control group, the researchers were able to determine the unique characteristics of the SARS-CoV-2 immune response.

"The immune responses to the various pneumonias are very similar and part of the body's general inflammatory response, as often observed in patients in intensive care. When it comes to COVID-19, however, T cells and natural killer cells display a unique behavior and describe a kind of pattern in the immune system - the immune signature specific to COVID-19," explains Becher.

Antibiotic resistance in E. coli has been steadily increasing since the early 2000s despite attempts to control it, a new study suggests. In the biggest genomic survey of E. coli to date, that took more than 16 years in Norway, researchers have successfully tracked the spread of antibiotic resistant genes and have shown that these genes are being transferred between E. coli strains.

Researchers from the Wellcome Sanger Institute and University of Oslo have tracked multidrug resistance in Norway and compared this to a previous study from the UK. They found that resistant strains developed around the same time, but increased more rapidly in the UK population.

The results, published today (10th May) in The Lancet Microbe show that tracking these resistant strains is important in the surveillance and control of drug resistant E. coli, which poses a significant issue in hospitals where it can cause severe infection and mortality. In addition, understanding how these genes are transferred between strains, and what has caused them to acquire drug resistance can help prevent the growth of antibiotic resistance strains.

The bacterium, Escherichia coli is a common cause of bloodstream infections world-wide*, which seem to be increasing over the last decade. E. coli is commonly found in the gut, where it does not cause harm, but if it gets into the bloodstream due to a weakened immune system it can cause severe and life threatening infections. As an added challenge for health care providers, multi-drug resistance (MDR) has become a frequent feature of such infections, and in a worrying number of cases the available treatment options are becoming limited.

In the largest study of its kind, and only the second systematic longitudinal genomic study of bacteremia E. coli, researchers from the Wellcome Sanger Institute and the University of Oslo processed a nation-wide catalogue of samples from more than 3,200 patients to track antibiotic resistance over 16 years. By harnessing the power of large-scale DNA sequencing, they tracked the emergence of drug resistance and compared this to a similar study conducted in the UK**.

The team found that MDR started to increase and show in more strains in the early 2000s due to antibiotic pressure, and now multiple MDR E. coli strains are present in Norway. However, MDR E. coli seems to be more widely present in the UK, despite similar policies in place around antibiotic use. The UK population however is considerably larger than Norway which could explain some of the differences. Further research is needed to allow for closer comparison and to identify the exact factors that cause rapid spread in some locations compared to others.

MDR is relatively rare in bacteria. However, this new study has identified that lineages that previously were not thought to have MDR have acquired drug-resistance genes, showing the increased ability of E. coli to share MDR genes that move horizontally between strains.

Professor Jukka Corander, co-author and Associate Faculty member at the Wellcome Sanger Institute, said: "The high number of samples from the Norwegian population and the level of genomic detail on the strains of bacteria enabled us to make much more far-reaching conclusions than were ever possible before. This study demonstrates the power arising from a systematic national surveillance of resistant organisms, which both collects and makes the data available for in-depth analyses. Without these in place, it would have been impossible to approach the central research questions formulated in the study and find answers to them."

The researchers hope to conduct similar research in the UK to build on previous studies and gain a full data set of 16 years in the UK in order to more closely track MDR resistant E. coli.

Dr Rebecca Gladstone, lead author of the study and Bioinformatician at the University of Oslo, Norway, said: "Being able to estimate the expansion timelines of the MDR clones of E. coli and to identify multiple occasions of novel acquisition of resistance genes is particularly exciting as this is the first time that this has been possible. Understanding and tracking the movement of these drug resistance genes and the strains that carry them are necessary for controlling the spread of drug-resistant bacteria, which is a huge issue in healthcare."

Professor Julian Parkhill, co-author and Professor in the Department of Veterinary Medicine at University of Cambridge, said: "Long-term studies such as this one provide in-depth understanding about the complex epidemiology underlying bloodstream infections. The next step would be further research to detail the factors determining the success of emerging pathogenic clones of these bacteria, to help find a way to control and possibly minimise the spread of multidrug resistance."