Tech

Couples considering medically assisted reproduction (MAR) because they have difficulties conceiving naturally, have feared that they could do harm to their baby by opting for medical intervention. Doctors may warn that MAR raises the risk of preterm birth (less than 37 weeks of pregnancy) and low birth weight (less than 2.5 kilograms).

It's a hard decision for couples with an unmet desire for children. Low birth weight children have more respiratory, cognitive and neurological problems than those born with normal weight. Preterm babies have elevated risks of heart defects, lung disorders, brain damage, and delayed development.

The truth is that risks of preterm birth and low birth weight actually don't increase with MAR. This is the finding of a new study that has just been published in the medical journal The Lancet.

Scientists of the Max Planck Institute for Demographic Research (MPIDR) together with researchers from the London School of Economics and Helsinki University analyzed a large number of Finnish siblings and did not find elevated risks. This is in contrast to a number of previous studies by other researchers who did find a rise in risks.

Decision for fertility treatment freed from feelings of guilt

"Couples with an unmet desire for children don't have to decide against MAR anymore, because they might allegedly increase the health risks for their child," says Mikko Myrskylä, author of the study and MPIDR director.

However, the demographer points out that children born after MAR nevertheless have a higher risk for preterm birth and low birth weight than babies that have been conceived naturally. But these elevated risks have nothing to do with the medical intervention. Couples with conception difficulties always have this problem, regardless of their choice for or against fertility treatment.

Why they have these increased risks is not yet fully understood by scientists. "The physiology of reduced fertility itself probably plays an important role," says Alice Goisis, another MPIDR author of the study. She stresses that although the already elevated risk is a burden for couples, the finding of The Lancet study would still make a big difference for them. "When deciding for medically assisted reproduction nobody has to have the feeling anymore that she or he is deliberately putting her or his child at extra risk," says the MPIDR researcher.

Emotionally it plays an important role for affected couples if they have to deal with elevated health risks for their baby that they cannot change anyway, or if they increase threats knowingly, Goisis says. The latter is not the case when choosing MAR, as The Lancet Study shows.
Considering for or against fertility treatment can now happen free from feelings of guilt and bad conscience. This is a relief for many, says Alice Goisis. To date more than five million children have been born thanks to medically assisted reproduction globally.

Comparing siblings gives unambiguous results

In the past, several studies had already tried to determine the true risk of medically assisted reproduction. However, their results differed strongly and were highly uncertain because they had often been calculated with biased methods and based on only a small number of births. Some studies did claim strongly increased birth risks through MAR.

Myrskylä and his colleagues used a larger number of births for their study than any previous study. Out of over 65,000 children born in Finland between 1995 and 2000, they chose 1,245 siblings of whom at least one was conceived naturally and one using medical treatment.
Since parents hardly change from one birth to another, comparing siblings allows the possibility to distinguish health risks between medically assisted reproduction and natural conception because the method of conception was the only relevant difference between births. With this comparison, the additional risks for preterm birth and low birth weight through MAR vanished.

Excluding single causes often impossible due to lack of suitable data

The siblings' method applied in The Lancet paper is known to be a technique which can reliably confirm or rule out single health risks. For the most part, data on a sufficiently large number of siblings is not available. However, Finland's national registries are one of the rare exceptions. They provide not only data on the date of the birth and information about the parents and siblings for researchers, but also the birth weight and duration of pregnancy. In most countries such linked datasets are not available and The Lancet study would not have been possible anywhere else.

Canada should invest in a single national electronic health record for primary care to improve the health of Canadians, argues an editorial in CMAJ (Canadian Medical Association Journal).

"Although switching will be painful, one primary care electronic health record will make apparently insolvable problems solvable," writes Dr. Nav Persaud, a scientist at the Li Ka Shing Knowledge Institute of St. Michael's Hospital and the University of Toronto, Toronto, Ontario. "Sharing records among primary care sites would become easier and the creation of similar data sets for research purposes would be an added benefit."

The current patchwork system of electronic health records used in individual clinics, hospitals, laboratories and pharmacies means that, while electronic, most records cannot connect and share information with one another. As well, fax machines are still used for communication between health care providers.

A single primary care electronic health record will improve primary care and patient care in hospitals and specialty clinics by allowing them to connect with, and update, patient records for timely information exchange.

Canada Health Infoway, the organization responsible for promoting digital health solutions, should be mandated to select and adapt, with the help of physicians and patients, the single electronic health record for primary care in Canada.

Other health systems that have successfully done this, such as the US Department of Veteran Affairs and SingHealth in Singapore, can serve as models.

"If we are truly committed to improving the health of Canadians, a bold move such as this is needed," writes Dr. Persaud.

Levels of C-reactive protein (CRP), a chemical associated with inflammation and stress, may be linked to housing type and tenure in the UK, suggests research published online in the Journal of Epidemiology & Community Health.

While observational, the findings nevertheless lend weight to the inclusion of health outcomes in housing policies, say the researchers.

The link between damp and cold indoor temperature--one of the 'hard' physical characteristics that have a direct impact on health--is well known. But attention is now being paid to the potential role of 'soft' factors, such as housing affordability.

And although there's extensive evidence for the links between housing and health outcomes, most of it draws on subjective measures of health.

The researchers wanted to look at a more objective and reproducible measure of health, so they opted for C-reactive protein, a chemical in the body that is associated with stress and inflammation.

They drew on data from the UK Household Longitudinal Study (UKHLS), an annual survey covering around 40,000 households in the UK. The data included extensive information from individuals and households, including housing tenure and type.

Blood samples were collected around five months after the main survey interview for 13,107 adults to assess CRP levels.

The final analysis was restricted to 9593 participants to include those aged over 21-to capture people less likely to still be in education and living with their parents-and those with CRP levels below 10 mg/l, as levels this high are indicative of recent infection.

Around one in five (just over 22%) of participants had a raised CRP level above 3 mg/l--a threshold associated with cardiovascular disease.

After taking account of potentially influential factors, certain housing types and tenure were associated with raised CRP, the findings showed.

Renters in the private sector had significantly higher CRP levels than home owners with a mortgage. And those living in semi-detached and terraced houses and flats had higher CRP than those living in detached properties.

Surprisingly, those with below average incomes who spent more than a third of it on housing had lower CRP.

But this might be because higher proportional expenditure on housing secures better quality accommodation, the health benefits of which might outweigh any financial strain, suggest the researchers.

This is an observational study, and as such, can't establish cause. And the researchers were unable to obtain any information on housing conditions, such as damp/mould, which might have influenced the findings.

But the observations found do back up other research linking housing type and health, they say.

"It may be that access to gardens/green space, which likely varies according to housing type, may partially explain this result, but this could not be tested with the current data," they explain.

"The significant findings for housing type and tenure point to an influence of autonomy and control," they add. "Where control is low, [the sense of] security is reduced, which may affect health through chronic stress responses."

And they conclude that their findings support "arguments for greater consideration of the negative effects of the current private rented sector in the UK, characterised by greater insecurity, higher cost and lower quality than is typically found in other tenures."

In a paper to be published in the September/December 2019 issue of TECHNOLOGY, a team of researchers from the Department of Biomedical Engineering at Illinois Institute of Technology, Chicago has developed a novel microfluidic device for measuring in real-time the cholesterol secreted from liver tissue-chip containing human hepatocytes. Their innovation lies not merely in the development of the first on-chip real-time assay for cholesterol detection but also in adapting the assay chemistry which is common in the conventional well-plate based enzymatic assay for cholesterol to microfluidic format and localizing it on the microscopic beads. This innovation can help researchers employing microfluidic cultures to study the effects of drugs such as statins on lowering cholesterol in real-time.

Tissue-chips are an important tool in developing drugs which treat different health conditions as well as to understand the underlying mechanisms of different tissues. However, there is a general challenge in utilizing the tissue-chips for broad applications as due to the small sample volumes, on-chip assessment of cellular function is often quite limited. Abhinav Bhushan, Ph.D., Assistant Professor at Illinois Institute of Technology (IIT), Chicago, who is the principal investigator of this research says

"Perfusion based microfluidic cell cultures produce low sample volumes which cannot be used for analysis using conventional biochemical assays. Our bead-based enzymatic assay for cholesterol measurement is the first reported assay which can quantify cholesterol secreted by human hepatocytes in real-time on-chip. This method is novel as this is the first reported use of a bead-based enzyme immobilized system in combination with visual detection for quantifying cholesterol in real-time and we envision our assay can pave way for enabling studies that use perfusion in microfluidics which produces low sample volumes."

The bead-based enzymatic cholesterol detection system uses horseradish peroxidase that is immobilized on polystyrene beads; the entire oxidation reaction of cholesterol takes place on the bead. This oxidation reaction generates fluorescent signal by forming resorufin, making the beads appear fluorescent. Each bead can be imaged as a series of images, where the intensity of fluorescence is directly proportional to the amount of cholesterol in the sample. The simple chemistry and detection used in this assay makes the assay more adaptable to a lab setting.

"While the application of detection systems for biomolecules such as electrophoresis, mass spectroscopy, electrospray ionization, and fluorometric detection using a photomultiplier tube have been carried out in the past, this is the first time a non-protein molecule has been quantified in real-time and on-chip using immobilized enzyme beads. It's the simplicity of the assay chemistry and its potential for adaptation that makes our microfluidic assay unique", says Sonali Karnik, Ph.D. who is the lead author of the article.

The next step for them, the team says, is to multiplex their enzymatic assay with a different assay chemistry for simultaneous detection of multiple molecules.

Researchers from the Department of Chemistry, Veer Narmad South Gujarat University, India have designed and synthesized azole scaffolds (a series of A series of (E)-5-(4-((Z)-4-substitutedbenzylidene-2-thienylmethylene-5-oxo- 2-phenyl-4,5-dihydro-1H-imidazol-1-yl) benzylidene)thiazolidine-2,4-diones). Analysis of ligand-protein interactions was also conducted using molecular docking studies with (InhA) Enoyl-ACP reductase of the type II fatty acid synthase (FAS-II) system along with an investigation of the ADME properties of the scaffolds for use in oral medicine.

In vitro antimycobacterial activity was carried out against the M. tuberculosis H37Rv strain using Lowenstein-Jensen medium and antimicrobial activity against two gram-positive bacteria (S. aureus, S. pyogenes), two gram-negative bacteria (E. coli, P. aeruginosa) and three fungal species (C. albicans, A. niger, A. clavatus) using the broth microdilution method. In silico molecular docking studies were carried out using Glide (grid-based ligand docking) program incorporated in the Schrödinger molecular modeling package by Maestro 11.0 and ADME properties of synthesized compounds was performed using DruLito software.

Patel et al's investigations revealed 6 compounds that exhibited promising antimicrobial activity and 1 compound (labelled 3n) which showed very good antimycobacterial activity along with Gilde docking score (-8.864) and with the one violation in Lipinski's rule of five.

The researchers note that this is a preliminary result which gives directions for improving pharmaceutical derivatives for the treatment of tuberculosis.

City lifestyle has been criticised for being an important reason for children being disconnected from nature. This has led to an unhealthy lifestyle in regards to active play and eating habits. Even worse, many young children do not feel well psychologically - they are often stressed and depressed. 16 per cent of pre-schoolers in Hong Kong and up to 22% in China show signs of mental health problems (Kwok SY, Gu M, Cheung AP, 2017; Zhu J, et al. 2017).

Recent research shows that spending time in nature may bring many health benefits, and many environmental programmes around the world are trying to decrease 'nature-deficit' and 'child-nature disconnectedness' in order to improve children's health. For example, the WHO, in order to monitor implementation of the Parma Declaration commitment to providing every child with access to "green spaces to play and undertake physical activity", has set a 300-meter target. Interestingly, 90 per cent of the Hong Kong population lives within 400 metres of such areas. However, despite the extensive, adjacent greenness, families are not using these areas.

"We noticed a tendency where parents are avoiding nature. They perceive it as dirty and dangerous, and their children unfortunately pick up these attitudes. In addition, the green areas are often unwelcoming with signs like "Keep off the grass", said Dr Tanja Sobko from the School of Biological Sciences of the University of Hong Kong. Until now, it has not been possible to measure connectedness to nature in preschool children, mostly due to the fact that they are too young to answer for themselves.

A new 16-item parent questionnaire (CNI-PPC) to measure "connectedness to nature' in very young children has been developed by Dr Sobko and her collaborator Prof Gavin Brown, Director of the Quantitative Data Analysis and Research Unit at the University of Auckland. The questionnaire identified four areas that reflect the child-nature relationship: enjoyment of nature, empathy for nature, responsibility towards nature, and awareness of nature.

The study consisted of two parts: the initial interviews with the families and the subsequent development of the questionnaire. Altogether, 493 families with children aged between 2 and 5 have participated in the study. Finally the new questionnaire was tested against the Strengths and Difficulties Questionnaire, a well-established measurement of psychological well-being and children's behaviour problems. The results revealed that parents who saw their child had a closer connection with nature had less distress, less hyperactivity, & fewer behavioural and emotional difficulties, and improved pro-social behaviour. Interestingly, children who took greater responsibility towards the nature had fewer peer difficulties. The results give a new possibility for investigating the link between the outdoor environment and well-being in pre-school children.

The study is part of Dr Sobko's research-based programme Play&Grow, which is the first in Hong Kong to promote healthy eating and active playtime with preschool children by connecting them to nature. Launched 2016, it has so far included almost 1000 families from all over Hong Kong. (https://foodnaturelab.org/page/).

The findings have been published in multidisciplinary Open Access journal, PLOS ONE. The new scale has already attracted international attention and is being adopted by universities worldwide including Western Australia and Deakin Universities. In addition, the HKU-developed 'Play&Grow' programme is also on track to be conducted in Australia.

The next step is to further fine-tune future health promotion/disease prevention interventions, which Dr Sobko and the team are committed to. "We are grateful for the recognition of the Government, which has recently granted significant financial support to this important project", said Dr Sobko. The new exciting extension of this work is to test the effect of the exposing children to nature and changes in their gut microbiota.

Chiral molecules are defined as molecules that are non-superimposable on their mirror image, much like that of left and right human hand bone structure. There are many examples of chiral molecules in nature, including proteins and deoxyribonucleic acid (DNA). The dynamic processes of these chiral molecules is highly significant to understanding their biological activity. Indeed, protein aggregation is associated with many pathological conditions, including Alzheimer's disease which is caused by the build-up of beta-amyloid fragments within the brain over time. Thus, it is important to understand and observe such (chiral) molecular aggregation and conformation over time.

Currently available options for analysing molecular conformation include electron microscopy and nuclear magnetic resonance (NMR) spectroscopy. Both methods require sample extraction under harsh conditions, a time-consuming process that can damage the molecular conformation of the sample. The second limitation to these methods is that the ultimate result will only provide the conformation of the compound at a specific point in time.

This new method involves aggregation-annihilation circular dichroism (AACD) effect and a well-studied chiral molecule called 1,1'-binapthyl derivatives (BN). It was observed that the CD signals of the BN were annihilated after BN aggregates were formed, likely due to the conformational change of the 1,1'-binapthyl group during the aggregation process.

In their work, four BN-based chiral molecules (P-1 to P-4 respectively) were synthesized through simple Suzuki coupling reactions. Polymers with the "open" BN units showed clear signs of aggregation-annihilated chiral dichroism (AACD). When the BN units were locked, the annihilation is restrained. The polymers were first dissolved in an organic solvent, tetrahydrofuran (THF). The second step involved adding water, a poor solvent for the polymers, was gradually added to the solution, which led to aggregate formation. CD spectra of the different polymers were taken at different water fractions and analysed. This methodology allowed researchers to analyse the molecular aggregation process in real time.

A molecular dynamics (MD) simulation of the polymers was performed in THF and water to further examine the relationship between CD annihilation and conformational change. This model indicated that open P-1 showed a broad distribution of dihedral angle ? but locked P-3 showed a narrow distribution. From solution to aggregate, the ? in open polymers (P-1 and P-2) becomes more negative and part of the conformers relax from cisoid to transoid. The ? in locked polymers (P-3 and P-4) increases slightly and cisoid conformation is preserved throughout the aggregation process.

"The combination of MD simulation and analysis on the change of CD couplet intensity and wavelength splitting during the aggregation process is thus an appealing method of in-situ and real-time monitoring of the conformational change," said HKUST's Prof. Ben-Zhong TANG, who led this research.

"This is a far cheaper, simpler method of monitoring conformational changes in chiral macromolecules means that we can apply this method to understanding many biological processes more easily," said Dr. Haoke ZHANG, a co-author of the paper.

Influenza is highly contagious and easily spreads as people move about and travel, making tracking and forecasting flu activity a challenge. While the CDC continuously monitors patient visits for flu-like illness in the U.S., this information can lag up to two weeks behind real time. A new study, led by the Computational Health Informatics Program (CHIP) at Boston Children's Hospital, combines two forecasting methods with machine learning (artificial intelligence) to estimate local flu activity. Results are published today in Nature Communications.

When the approach, called ARGONet, was applied to flu seasons from September 2014 to May 2017, it made more accurate predictions than the team's earlier high-performing forecasting approach, ARGO, in more than 75 percent of the states studied. This suggests that ARGONet produces the most accurate estimates of influenza activity available to date, a week ahead of traditional healthcare-based reports, at the state level across the U.S.

"Timely and reliable methodologies for tracking influenza activity across locations can help public health officials mitigate epidemic outbreaks and may improve communication with the public to raise awareness of potential risks," says Mauricio Santillana, PhD, a CHIP faculty member and the paper' senior author.

Learning about localized flu patterns

The ARGONet approach uses machine learning and two robust flu detection models. The first model, ARGO (AutoRegression with General Online information), leverages information from electronic health records, flu-related Google searches and historical flu activity in a given location. In the study, ARGO alone outperformed Google Flu Trends, the previous forecasting system that operated from 2008 to 2015.

To improve accuracy, ARGONet adds a second model, which draws on spatial-temporal patterns of flu spread in neighboring areas. "It exploits the fact that the presence of flu in nearby locations may increase the risk of experiencing a disease outbreak at a given location," explains Santillana, who is also an assistant professor at Harvard Medical School.

The machine learning system was "trained" by feeding it flu predictions from both models as well as actual flu data, helping to reduce errors in the predictions. "The system continuously evaluates the predictive power of each independent method and recalibrates how this information should be used to produce improved flu estimates," says Santillana.

Precision public health

The investigators believe their approach will set a foundation for "precision public health" in infectious diseases.

"We think our models will become more accurate over time as more online search volumes are collected and as more healthcare providers incorporate cloud-based electronic health records," says Fred Lu, a CHIP investigator and first author on the paper.

What does the blue whale have in common with the Bengal tiger and the green turtle? They share the risk of extinction and are classified as endangered species. There are multiple reasons for species to die out, and climate changes is among the main reasons.

The risk of extinction varies from species to species depending on how individuals in its populations reproduce and how long each animal survives. Understanding the dynamics of survival and reproduction can support management actions to improve a specie's chances of surviving.

Mathematical and statistical models have become powerful tools to help explain these dynamics. However, the quality of the information we use to construct such models is crucial to improve our chances of accurately predicting the fate of populations in nature.

"A model that over-simplifies survival and reproduction can give the illusion that a population is thriving when in reality it will go extinct.", says associate professor Fernando Colchero, author of new paper published in Ecology Letters.

Colchero's research focuses on mathematically recreating the population dynamics by better understanding the species's demography. He works on constructing and exploring stochastic population models that predict how a certain population (for example an endangered species) will change over time.

These models include mathematical factors to describe how the species' environment, survival rates and reproduction determine to the population's size and growth. For practical reasons some assumptions are necessary.

Two commonly accepted assumptions are that survival and reproduction are constant with age, and that high survival in the species goes hand in hand with reproduction across all age groups within a species. Colchero challenged these assumptions by accounting for age-specific survival and reproduction, and for trade-offs between survival and reproduction. This is, that sometimes conditions that favor survival will be unfavorable for reproduction, and vice versa.

For his work Colchero used statistics, mathematical derivations, and computer simulations with data from wild populations of 24 species of vertebrates. The outcome was a significantly improved model that had more accurate predictions for a species' population growth.

Despite the technical nature of Fernando's work, this type of model can have very practical implications as they provide qualified explanations for the underlying reasons for the extinction. This can be used to take management actions and may help prevent extinction of endangered species.

Living in extreme conditions requires creative adaptations. For certain species of bacteria that exist in oxygen-deprived environments, this means finding a way to breathe that doesn't involve oxygen. These hardy microbes, which can be found deep within mines, at the bottom of lakes, and even in the human gut, have evolved a unique form of breathing that involves excreting and pumping out electrons. In other words, these microbes can actually produce electricity.

Scientists and engineers are exploring ways to harness these microbial power plants to run fuel cells and purify sewage water, among other uses. But pinning down a microbe's electrical properties has been a challenge: The cells are much smaller than mammalian cells and extremely difficult to grow in laboratory conditions.

Now MIT engineers have developed a microfluidic technique that can quickly process small samples of bacteria and gauge a specific property that's highly correlated with bacteria's ability to produce electricity. They say that this property, known as polarizability, can be used to assess a bacteria's electrochemical activity in a safer, more efficient manner compared to current techniques.

"The vision is to pick out those strongest candidates to do the desirable tasks that humans want the cells to do," says Qianru Wang, a postdoc in MIT's Department of Mechanical Engineering.

"There is recent work suggesting there might be a much broader range of bacteria that have [electricity-producing] properties," adds Cullen Buie, associate professor of mechanical engineering at MIT. "Thus, a tool that allows you to probe those organisms could be much more important than we thought. It's not just a small handful of microbes that can do this."

Buie and Wang have published their results today in Science Advances.

Just between frogs

Bacteria that produce electricity do so by generating electrons within their cells, then transferring those electrons across their cell membranes via tiny channels formed by surface proteins, in a process known as extracellular electron transfer, or EET.

Existing techniques for probing bacteria's electrochemical activity involve growing large batches of cells and measuring the activity of EET proteins -- a meticulous, time-consuming process. Other techniques require rupturing a cell in order to purify and probe the proteins. Buie looked for a faster, less destructive method to assess bacteria's electrical function.

For the past 10 years, his group has been building microfluidic chips etched with small channels, through which they flow microliter-samples of bacteria. Each channel is pinched in the middle to form an hourglass configuration. When a voltage is applied across a channel, the pinched section -- about 100 times smaller than the rest of the channel -- puts a squeeze on the electric field, making it 100 times stronger than the surrounding field. The gradient of the electric field creates a phenomenon known as dielectrophoresis, or a force that pushes the cell against its motion induced by the electric field. As a result, dielectrophoresis can repel a particle or stop it in its tracks at different applied voltages, depending on that particle's surface properties.

Researchers including Buie have used dielectrophoresis to quickly sort bacteria according to general properties, such as size and species. This time around, Buie wondered whether the technique could suss out bacteria's electrochemical activity -- a far more subtle property.

"Basically, people were using dielectrophoresis to separate bacteria that were as different as, say, a frog from a bird, whereas we're trying to distinguish between frog siblings -- tinier differences," Wang says.

An electric correlation

In their new study, the researchers used their microfluidic setup to compare various strains of bacteria, each with a different, known electrochemical activity. The strains included a "wild-type" or natural strain of bacteria that actively produces electricity in microbial fuel cells, and several strains that the researchers had genetically engineered. In general, the team aimed to see whether there was a correlation between a bacteria's electrical ability and how it behaves in a microfluidic device under a dielectrophoretic force.

The team flowed very small, microliter samples of each bacterial strain through the hourglass-shaped microfluidic channel and slowly amped up the voltage across the channel, one volt per second, from 0 to 80 volts. Through an imaging technique known as particle image velocimetry, they observed that the resulting electric field propelled bacterial cells through the channel until they approached the pinched section, where the much stronger field acted to push back on the bacteria via dielectrophoresis and trap them in place.

Some bacteria were trapped at lower applied voltages, and others at higher voltages. Wang took note of the "trapping voltage" for each bacterial cell, measured their cell sizes, and then used a computer simulation to calculate a cell's polarizability -- how easy it is for a cell to form electric dipoles in response to an external electric field.

From her calculations, Wang discovered that bacteria that were more electrochemically active tended to have a higher polarizability. She observed this correlation across all species of bacteria that the group tested.

"We have the necessary evidence to see that there's a strong correlation between polarizability and electrochemical activity," Wang says. "In fact, polarizability might be something we could use as a proxy to select microorganisms with high electrochemical activity."

Wang says that, at least for the strains they measured, researchers can gauge their electricity production by measuring their polarizability -- something that the group can easily, efficiently, and nondestructively track using their microfluidic technique.

Collaborators on the team are currently using the method to test new strains of bacteria that have recently been identified as potential electricity producers.

"If the same trend of correlation stands for those newer strains, then this technique can have a broader application, in clean energy generation, bioremediation, and biofuels production," Wang says.

EVANSTON, Ill. --- A Northwestern University-led international team is getting closer to understanding the mysteriously bright object that burst in the northern sky this summer.

On June 17, the ATLAS survey's twin telescopes in Hawaii found a spectacularly bright anomaly 200 million light years away in the Hercules constellation. Dubbed AT2018cow or "The Cow," the object quickly flared up, then vanished almost as quickly.

After combining several imaging sources, including hard X-rays and radiowaves, the multi-institutional team now speculates that the telescopes captured the exact moment a star collapsed to form a compact object, such as a black hole or neutron star. The stellar debris, approaching and swirling around the object's event horizon, caused the remarkably bright glow.

This rare event will help astronomers better understand the physics at play within the first moments of the creation of a black hole or neutron star. "We think that 'The Cow' is the formation of an accreting black hole or neutron star," said Northwestern's Raffaella Margutti, who led the research. "We know from theory that black holes and neutron stars form when a star dies, but we've never seen them right after they are born. Never."

Margutti will present her findings at the 233rd meeting of the American Astronomical Society at 2:15 p.m. PST on Jan. 10 in Seattle. (Reporters can join the session to watch, listen and ask questions via webcast.) The research will then be published in the Astrophysical Journal.

Margutti is an assistant professor of physics and astronomy in Northwestern's Weinberg College of Arts and Sciences and a member of CIERA (Center for Interdisciplinary Exploration and Research in Astrophysics), an endowed research center at Northwestern focused on advancing astrophysics studies with an emphasis on interdisciplinary connections.

The curious Cow

After it was first spotted, The Cow captured immediate international interest and left astronomers scratching their heads. "We thought it must be a supernova," Margutti said. "But what we observed challenged our current notions of stellar death."

For one, the anomaly was unnaturally bright -- 10 to 100 times brighter than a typical supernova. It also flared up and disappeared much faster than other known star explosions, with particles flying at 30,000 kilometers per second (or 10 percent of the speed of light). Within just 16 days, the object had already emitted most of its power. In a universe where some phenomena last for millions and billions of years, two weeks amounts to the blink of an eye.

"We knew right away that this source went from inactive to peak luminosity within just a few days," Margutti said. "That was enough to get everybody excited because it was so unusual and, by astronomical standards, it was very close by."

Using Northwestern's access to observational facilities at the W.M. Keck Observatory in Hawaii and the MMT Observatory in Arizona, as well as remote access to the SoAR telescope in Chile, Margutti took a closer look at the object's makeup. Margutti and her team examined The Cow's chemical composition, finding clear evidence of hydrogen and helium, which excluded models of compact objects merging -- like those that produce gravitational waves.

Comprehensive strategy

Astronomers have traditionally studied stellar deaths in the optical wavelength, which uses telescopes to capture visible light. Margutti's team, on the other hand, uses a more comprehensive approach. Her team viewed the object with X-rays, hard X-rays (which are 10 times more powerful than normal X-rays), radio waves and gamma rays. This enabled them to continue studying the anomaly long after its initial visible brightness faded.

After ATLAS spotted the object, Margutti's team quickly obtained follow-up observations of The Cow with NASA's Nuclear Spectroscopic Telescope Array (NuSTAR) and INTEGRAL hard X-ray laboratories, soft X-rays at XMM-Newton and radio antennae at the Very Large Array toward The Cow.

Margutti attributes The Cow's relative nakedness to potentially unraveling this intergalactic mystery. Although stars might collapse into black holes all the time, the large amount of material around newly born black holes blocks astronomers' vision. Fortunately, about 10 times less ejecta swirled around The Cow as compared to a typical stellar explosion. The lack of material allowed astronomers to peer straight through to the object's "central engine," which revealed itself as a probable black hole or neutron star.

"A 'lightbulb' was sitting deep inside the ejecta of the explosion," Margutti said. "It would have been hard to see this in a normal stellar explosion. But The Cow had very little ejecta mass, which allowed us to view the central engine's radiation directly."

Galactic neighbor

Margutti's team also benefited from the star's relative closeness to Earth. Even though it was nestled in the distant dwarf galaxy called CGCG 137-068, astronomers consider that to be "right around the corner."

"Two hundred million light years is close for us, by the way," Margutti said. "This is the closest transient object of this kind that we have ever found."

Margutti's team at Northwestern includes graduate student Aprajita Hajela, postdoctoral fellows Giacomo Terreran, Deanne Coppejans and Kate Alexander (who is a Hubble Fellow), and first-year undergraduate student Daniel Brethauer.

"Being given the opportunity to contribute to something as cutting edge and international as understanding AT2018cow as an undergrad is a surreal experience," Brethauer said. "To have helped the world's experts figure out what AT2018cow is even in the smallest way was beyond my wildest expectations at the beginning of the summer and something that I will remember for the rest of my life."

Funding by private foundations is inadvertently changing the international journalism it supports, according to a new study led by the University of East Anglia (UEA).

Researchers found that journalists change the ways they understand, value and carry out their work when supported by organisations such as the Bill and Melinda Gates Foundation, the Rockefeller Foundation and the Ford Foundation.

This is not because foundations deliberately try to influence editorial decision making at the news organisations they fund. Few do, and maintaining editorial independence is very important to both journalists and foundations. However, the nature of foundation funding does cause three important changes to international reporting.

First, in order to secure and retain foundation funding, journalists carry out new marketing and administrative tasks. This often takes a significant amount of time away from their editorial work, leading to a reduction in news output.

Second, foundations often require news outlets to provide evidence of the impact of their work. This incentivises journalists to produce longer-form, off-agenda content aimed at influencing specialist audiences, rather than shorter, timelier pieces for wider audiences.

Third, foundation funding usually supports coverage of specific thematic areas, such as Global Development. However, this encourages journalists to focus on a relatively narrow range of topics that broadly align with the priorities of the most active foundations.

Publishing their findings in the journal Journalism Studies, the researchers conclude that foundation funding unintentionally reshapes international journalism to favour outcome-oriented, explanatory reporting in a small number of niche subject areas.

Between 2011 and 2015, foundations awarded grants worth more than $US1.3 billion annually to media and journalism, according to Media Impact Funders. It has even been suggested that foundations may offer a partial solution to journalism's economic crisis.

The study was conducted by Dr Martin Scott of UEA's School of International Development, Dr Mel Bunce from City, University of London, and Dr Kate Wright at the University of Edinburgh.

Lead author Dr Scott said: "Foundations support a significant amount of important international journalism. Without it, very few of the non-profit news outlets we spoke to would survive. But we are concerned that the nature of this journalism - and the role that it plays in democracy - is inadvertently being shaped by a handful of foundations, rather than by journalists themselves.

"For journalists collaborating with foundations, one of the key implications of the study is to consider not just how to protect their independence, but also to reflect on what kinds of journalism they want to produce."

Maunakea, Hawaii - A Northwestern University-led international team of astronomers is getting closer to understanding the mysterious bright object that burst in the northern sky this summer, dubbed AT2018cow or 'The Cow.'

With the help of W. M. Keck Observatory on Maunakea, Hawaii and the University of Hawaii Institute for Astronomy's ATLAS twin telescopes, the multi-institutional team now has evidence that they likely captured the exact moment a star collapsed to form a compact object, such as a black hole or neutron star.

The stellar debris, approaching and swirling around the object's event horizon, caused the remarkably bright glow.
The research, which will be appearing in The Astrophysical Journal, was announced today during a press conference at the 233rd Meeting of the American Astronomical Society in Seattle.

This rare event will help astronomers better understand the physics at play within the first moments of the creation of a black hole or neutron star.

"Based on its X-ray and UV emission, 'The Cow' may appear to have been caused by a black hole devouring a white dwarf. But further observations of other wavelengths across the spectrum led to our interpretation that 'The Cow' is actually the formation of an accreting black hole or neutron star," said lead author Raffaella Margutti, assistant professor of physics and astronomy at Northwestern University and faculty member of Northwestern's CIERA (Center for Interdisciplinary Exploration and Research for Astrophysics). "We know from theory that black holes and neutron stars form when a star dies, but we've never seen them right after they are born. Never."

THE CURIOUS COW

The Cow was first spotted on June 16 after the ATLAS telescopes on Haleakala and Maunaloa captured a spectacularly bright anomaly 200 million light years away in the Hercules constellation. The object quickly flared up, then vanished almost as quickly.

The event captured immediate international interest and left astronomers scratching their heads. "We thought it must be a supernova," Margutti said. "But what we observed challenged our current notions of stellar death."

For one, the anomaly was unnaturally bright -- 10 to 100 times brighter than a typical supernova. It also flared up and disappeared much faster than other known star explosions, with particles flying at 30,000 kilometers per second (or 10 percent of the speed of light).

Within just 16 days, the object had already emitted most of its power. In a universe where some phenomena last for millions and billions of years, two weeks amounts to the blink of an eye.

"We knew right away that this source went from inactive to peak luminosity within just a few days," said co-author Ryan Chornock, assistant physics and astronomy professor at Ohio University. "That was enough to get everybody excited because it was so unusual and, by astronomical standards, it was very close by."

Using Northwestern's access to Keck Observatory's twin telescopes, Margutti's team took a closer look at the object's makeup with the Low Resolution Imaging Spectrometer (LRIS) on the Keck I telescope as well as the DEep Imaging and Multi-Object Spectrograph (DEIMOS) on Keck II.

"Keck was instrumental in determining the chemical composition and geometry of AT2018cow," said co-author Nathan Roth, a JSI postdoctoral fellow at the University of Maryland. "Keck's unique niche is its capability to monitor the late-time behavior of The Cow. This can be difficult; as more time passes after the event, the fainter it becomes. But with Keck's late time spectroscopy, we were able to pierce through the 'interiors' of the explosion. This revealed AT2018cow's red-shifted spectral features very nicely."

"The Cow is a great example of a type of observation that's becoming critical in astronomy: rapid response to transient events," says Keck Observatory Chief Scientist John O'Meara. "Looking forward, we are implementing new observational policies and telescope instrumentation that allow us to be as quick on the sky and to the science as we can." 

The team also obtained optical images from the MMT Observatory in Arizona, as well as the Southern Astrophysical Research SOAR Telescope in Chile.

When Margutti and her team examined The Cow's chemical composition, they found clear evidence of hydrogen and helium, which excluded models of compact objects merging -- like those that produce gravitational waves.

"It took us a while for us to realize what we were looking at, I would say months," said co-author Brian Metzger, associate physics professor at Columbia University. "We tried several possibilities and were forced to go back to the drawing board multiple times. We were finally able to interpret the results, thanks to the hard work of our incredibly dedicated team."

In addition to Chornock, Roth, and Metzger, Margutti's core team also includes Indrek Vurm, senior research fellow at Tartu Observatory, as well as Northwestern CIERA postdoctoral researchers Giacomo Terreran, Deanne Coppejans, and Kate Alexander.

COMPREHENSIVE STRATEGY

Astronomers have traditionally studied stellar deaths in the optical wavelength, which uses telescopes to capture visible light.

Margutti's team, on the other hand, used a more comprehensive approach. After ATLAS spotted the object, Margutti's team quickly conducted follow-up observations using multiple observatories to analyze The Cow in different wavelengths.

The researchers viewed the object in hard X-rays using NASA's Nuclear Spectroscopic Telescope Array (NuSTAR) and the European Space Agency's (ESA) INTErnational Gamma-Ray Astrophysics Laboratory (INTEGRAL), in soft X-rays (which are 10 times more powerful than normal X-rays) using ESA's X-ray Multi-Mirror Mission (XMM-Newton), and in radio waves using National Radio Astronomy Observatory's (NRAO) Very Large Array (VLA).

This enabled them to continue studying the anomaly long after its initial visible brightness faded.

Margutti attributes The Cow's relative nakedness to potentially unraveling this intergalactic mystery. Although stars might collapse into black holes all the time, the large amount of material around newly born black holes blocks astronomers' vision.

Fortunately, about 10 times less ejecta swirled around The Cow compared to a typical stellar explosion. The lack of material allowed astronomers to peer straight through to the object's "central engine," which revealed itself as a probable black hole or neutron star.

"A 'lightbulb' was sitting deep inside the ejecta of the explosion," Margutti said. "It would have been hard to see this in a normal stellar explosion. But The Cow had very little ejecta mass, which allowed us to view the central engine's radiation directly."

GALACTIC NEIGHBOR

Margutti's team also benefited from the star's relative closeness to Earth. Even though it was nestled in the distant dwarf galaxy called CGCG 137-068, astronomers consider that to be "right around the corner."

"Two hundred million light-years is close for us," Margutti said. "This is the closest transient object of this kind that we have ever found."

"Being given the opportunity to contribute to something as cutting edge and international as understanding AT2018cow as an undergrad is a surreal experience," said co-author Daniel Brethauer, a first-year undergraduate student at Northwestern. "To have helped the world's experts figure out what AT2018cow is even in the smallest way was beyond my wildest expectations at the beginning of the summer and something that I will remember for the rest of my life."

A new study by researchers at The Picower Institute for Learning and Memory at MIT finds that the protein CPG2 is significantly less abundant in the brains of people with bipolar disorder (BD) and shows how specific mutations in the SYNE1 gene that encodes the protein undermine its expression and its function in neurons.

Led by Elly Nedivi, professor in MIT's departments of Biology and Brain and Cognitive Sciences, and former postdoc Mette Rathje, the study goes beyond merely reporting associations between genetic variations and psychiatric disease. Instead, the team's analysis and experiments show how a set of genetic differences in patients with bipolar disorder can lead to specific physiological dysfunction for neural circuit connections, or synapses, in the brain.

The mechanistic detail and specificity of the findings provide new and potentially important information for developing novel treatment strategies and for improving diagnostics, Nedivi said.

"It's a rare situation where people have been able to link mutations genetically associated with increased risk of a mental health disorder to the underlying cellular dysfunction," said Nedivi, senior author of the study online in Molecular Psychiatry. "For bipolar disorder this might be the one and only."

The researchers are not suggesting that the CPG2-related variations in SYNE1 are "the cause" of bipolar disorder, but rather that they likely contribute significantly to susceptibility to the disease. Notably, they found that sometimes combinations of the variants, rather than single genetic differences, were required for significant dysfunction to become apparent in laboratory models.

"Our data fit a genetic architecture of BD, likely involving clusters of both regulatory and protein-coding variants, whose combined contribution to phenotype is an important piece of a puzzle containing other risk and protective factors influencing BD susceptibility," the authors wrote.

CPG2 in the bipolar brain

During years of fundamental studies of synapses, Nedivi discovered CPG2, a protein expressed in response to neural activity, that helps regulate the number of receptors for the neurotransmitter glutamate at excitatory synapses. Regulation of glutamate receptor numbers is a key mechanism for modulating the strength of connections in brain circuits. When genetic studies identified SYNE1 as a risk gene specific to bipolar disorder, Nedivi's team recognized the opportunity to shed light into the cellular mechanisms of this devastating neuropsychiatric disorder typified by recurring episodes of mania and depression.

For the new study, Rathje led the charge to investigate how CPG2 may be different in people with the disease. To do that, she collected samples of postmortem brain tissue from six brain banks. The samples included tissue from people who had been diagnosed with bipolar disorder, people who had neuropsychiatric disorders with comorbid symptoms such as depression or schizophrenia, and people who did not have any of those illnesses. Only in samples from people with bipolar disorder was CPG2 significantly lower. Other key synaptic proteins were not uniquely lower in bipolar patients.

"Our findings show a specific correlation between low CPG2 levels and incidence of BD that is not shared with schizophrenia or major depression patients," the authors wrote.

From there they used deep-sequencing techniques on the same brain samples to look for genetic variations in the SYNE1 regions of BD patients with reduced CPG2 levels. They specifically looked at ones located in regions of the gene that could regulate expression of CPG2 and therefore its abundance.

Meanwhile, they also combed through genomic databases to identify genetic variants in regions of the gene that code CPG2. Those mutations could adversely affect how the protein is built and functions.

Examining effects

The researchers then conducted a series of experiments to test the physiological consequences of both the regulatory and protein coding variants found in BD patients.

To test effects of non-coding variants on CPG2 expression, they cloned the CPG2 promoter regions from the human SYNE1 gene and attached them to a 'reporter' that would measure how effective they were in directing protein expression in cultured neurons. They then compared these to the same regions cloned from BD patients that contained specific variants individually or in combination. Some did not affect the neurons' ability to express CPG2 but some did profoundly. In two cases, pairs of variants (but neither of them individually), also reduced CPG2 expression.

Previously Nedivi's lab showed that human CPG2 can be used to replace rat CPG2 in culture neurons, and that it works the same way to regulate glutamate receptor levels. Using this assay they tested which of the coding variants might cause problems with CPG2's cellular function. They found specific culprits that either reduced the ability of CPG2 to locate in the "spines" that house excitatory synapses or that decreased the proper cycling of glutamate receptors within synapses.

The findings show how genetic variations associated with BD disrupt the levels and function of a protein crucial to synaptic activity and therefore the health of neural connections. It remains to be shown how these cellular deficits manifest as biopolar disorder.

Nedivi's lab plans further studies including assessing behavioral implications of difference-making variants in lab animals. Another is to take a deeper look at how variants affect glutamate receptor cycling and whether there are ways to fix it. Finally, she said, she wants to continue investigating human samples to gain a more comprehensive view of how specific combinations of CPG2-affecting variants relate to disease risk and manifestation.

More than half of people who take medical cannabis for chronic pain say they've driven under the influence of cannabis within two hours of using it, at least once in the last six months, according to a new study.

One in five of them said they'd driven while 'very high' in the past six months, researchers from the University of Michigan Addiction Center report in the journal Drug & Alcohol Dependence .

Lead author Erin E. Bonar, Ph.D., assistant professor of psychiatry and a practicing clinical psychologist at the U-M Addiction Treatment Services finds the results of a survey of 790 Michigan medical cannabis users troubling.

Hundreds of thousands of Americans have state approval to use medical marijuana, including nearly 270,000 in the state of Michigan, according to Statista, as of May 2018. Michigan is second only to California for the highest number of medical marijuana patients in a state.

Risky driving

Bonar says that when people drive under the influence of marijuana their reaction time and coordination may be slowed down and they could have a harder time reacting to the unexpected. If they are in a risky situation, they could be more likely to be involved in motor vehicle crash, because they would not be able to respond as quickly.

For the study, the team surveyed adults in Michigan who were seeking medical cannabis recertification or a new certification for chronic pain in 2014 and 2015. The researchers asked about respondents' driving habits for the past six months.

Fifty-six percent of participants reported driving within two hours of using cannabis, 51 percent reported they drove while a "little high", and 21 percent reported driving while "very high."

"There is a low perceived risk about driving after using marijuana, but we want people to know that they should ideally wait several hours to operate a vehicle after using cannabis, regardless of whether it is for medical use or not," Bonar said. "The safest strategy is to not drive at all on the day you used marijuana."

There is uncertainty about how marijuana could affect driving for chronic daily users, who might have even longer-lasting effects that linger in their system, Bonar added.

Uncharted territory

To add complexity to the issue, in November Michigan voters approved the use of recreational marijuana in the state. In early December, it became legal under state law for any Michigan resident over the age of 21 to use marijuana inside a private residence, and to grow up to 12 plants for personal use. Retail sales are only allowed for those with medical marijuana cards issued by the state. Marijuana use and possession remains illegal under federal law.

In light of this policy change, Bonar says, all cannabis users need a clear understanding of the side effects of this drug.

"When it comes to driving, we haven't yet figured out the best way to know how impaired marijuana users are at any given time," she says. "With alcohol, you can do some quick math based on the amount you drank, and take an educated guess at your blood alcohol level. For marijuana, an estimate like this would be complicated. It's hard to quantify because there is a lot of variation in marijuana dosing, THC potency, and route of administration. We also don't have specific guidelines yet about when exactly it would be safe to operate a vehicle."

Bonar says the goal of her team's study - conducted before the passage of the ballot question that resulted in the change in state law -- is to help medical marijuana users to be safer on the roads.

"We believe more research is needed to inform a larger public education effort that will help individuals understand the risks for themselves, and others, of driving while under the influence of cannabis," she says. "It is especially needed during this time of rapid policy change as many states are determining how to manage marijuana legalization. We also need clearer guidelines about marijuana dosing and side effects with an understanding of how individual differences in things like sex and body weight interact as well."