Culture

The introduction of standardised packaging for cigarettes in the UK, combined with stricter taxation measures on cheaper cigarettes, has led to a significant fall in sales for cigarettes, according to new analysis from researchers at the University of Bath.

By analysing sales data over three years from May 2015 to April 2018, the researchers from the Tobacco Control Research Group found that pre-legislation, cigarette sales (calculated by individual cigarettes) declined on average by 12 million a month; after legislation, this decrease accelerated sharply to 20 million a month.

The team behind the new study, published today (Monday 13 July) in the BMJ journal Tobacco Control, suggest their findings demonstrate the public health benefits that standardised packaging coupled with taxation can bring in reducing tobacco consumption. They hope their findings can provide important evidence to policymakers around the world of the effectiveness of standardised packaging.

The UK was the second country in the world to implement standardised packaging for cigarettes and the first where comprehensive sales data are available to analyse the impact. At the point when standardised packaging was fully implemented, May 2017, a new tax on cheaper cigarettes (the minimum excise tax - MET) was also introduced.

Principal Investigator and Director of the Tobacco Control Research Group, Professor Anna Gilmore explains: "The combination of tax increases and standardised packaging has led to a significant decline in tobacco sales. The underlying rate of decline in tobacco sales almost doubled after these policies were implemented."

Study findings also suggest that the tobacco industry's net revenue (which is an indication of profits once taxes have been paid) fell by 13% after implementation, from £231M to £198M per month.

Professor Gilmore comments: "Governments around the world considering plain packaging can be reassured that this policy works and that the real reason the industry opposes this legislation so vehemently is because it threatens its profitability. With coronavirus already posing a threat to tobacco company sales, and plain packaging of tobacco taking off in other jurisdictions, our findings are more bad news for tobacco companies."

Previous research from the group showed that prices of the cheapest cigarette brands rose around May 2017 as the tobacco industry adjusted to manage the incoming MET. This latest analysis suggests that as these cheapest brands increased in price, they became less appealing and growing sales ended.

Lead researcher on the new study, Dr Rosemary Hiscock also from the Tobacco Control Research Group at the University, adds: "Falling tobacco industry revenues suggest the new legislation has played a role in stopping formerly lucrative brand differentiation. For many years, the tobacco industry had used packaging to signal the difference between premium and cheap cigarette brands, with smokers often willing to pay markedly more for premium brands.

"This allowed the tobacco industry to make enough profit on premium brands to subsidise its cheap brands, keeping them cheap enough for young people to afford to start smoking and to prevent price conscious smokers from being incentivised to quit. Standardised packaging has weakened the appeal of premium brands, on which the tobacco companies made more profits, and the MET has forced cheap brands to become more expensive. This implies that the legislation should play a role in reducing the prevalence of smoking and its consequences (illness and premature death)."

Additional findings from the study suggest that sales of roll-your-own (RYO) tobacco have been growing steadily but this growth was not enough to compensate for the decline in cigarette sales.

In view of the continuing imbalance between taxes on cigarettes and roll-your-own tobacco, economist, tobacco tax expert and author on the study, Dr Rob Branston, adds: "Now that the MET has addressed cheaper factory-made cigarettes, the government also needs to increase RYO taxes. Currently, price-sensitive smokers can still switch to using cheap RYO cigarettes instead of quitting. These are just as deadly as factory-made cigarettes but are currently taxed at a significantly lower rate. There is no evidence that the resulting higher prices would cause RYO smokers to turn to illicit products."

Sarah Bullock, Policy Advisor for Cancer Research UK said: "Smoking continues to be the leading preventable cause of cancer in the world. This study suggests that increasing tobacco taxes and introducing standardised "plain" packaging has helped to reduce the number of cigarettes smoked in the UK. Measures like these, which reduce the use of this deadly product and ultimately save lives, should be a priority for all governments."

Strategies for the safe reopening of low and middle-income countries (LMICs) from months of strict social distancing in response to the ongoing COVID-19 pandemic must recognise that preserving people's health is as important as reviving the economy, argue an international team of researchers.

The team also say that strategies need to be based on local epidemic growth rate at the time, social and economic costs, existing health systems capabilities and detailed plans to implement and sustain the strategy.

The COVID-19 pandemic has been responsible for over half a million deaths globally. Many LMICs responded to the pandemic by introducing a number of measures from physical distancing to strict social distancing.

These measures have proved relatively successful in containing the disease and limiting the number of deaths in places where the risk of transmission is high, public health systems and usage are suboptimal and awareness of disease prevention practices is low. However, they have often come with tremendous negative social, economic and psychological effects.

To prevent further negative impacts of lockdown, many countries are now looking to 'reopen', risking population health, especially given shortcomings in surveillance infrastructure and poor diagnostic capabilities.

In a paper published in the European Journal of Epidemiology, a team of epidemiologists from the University of Cambridge, the University of Bern, BRAC University and the National Heart Foundation in Bangladesh, have examined three community-based exit strategies, and recommend their scopes, limitations and the appropriate application in the LMICs.

Dr Rajiv Chowdhury from the University of Cambridge, lead author of the paper, said: "Successfully re-opening a country requires consideration of both the economic and social costs. Governments should approach these options with a mind-set that health and economy both are equally important to protect - reviving the economy should not take priority over preserving people's health."

The three approaches considered are:

*Sustained mitigation

Sustained 'mitigation-only' approaches such as those adopted in the United Kingdom, Switzerland and other European countries, involve basic prevention measures such as mask wearing, physical distancing and the isolation of positive cases after testing.

However, the researchers point out that the relative success and ease of implementation of these approaches in high-income settings was aided by a number of factors. For example, high-income countries have the capacity to implement mass testing, population surveillance and case isolation to contain the epidemic, in addition to a high number of trained contact tracers operating in a relatively small and sparse population and high levels of adherence to the measures, including home quarantine and hygiene advice.

By contrast, in LMICs, a sustained mitigation-only approach may be unfeasible due to poor or absent nationwide population surveillance, contact tracing, testing infrastructure and critical care. For example, LMICs generally have limited supply of ventilators (around 48,000 for India's 1.3 billion people), personal protective equipment, trained healthcare personnel and safe working conditions, compromising the healthcare system's effectiveness.

*Zonal lockdowns

Zonal lockdowns involve identifying and 'cordoning off' new outbreak clusters with a high number of cases, keeping contact between zones low and containing the disease within a small geographic area.

However, the authors point out that any successful implementation of zonal lockdown requires regular data feedback operations in real time to identify hotspots, including information on newly confirmed cases, updated region-specific reproduction and growth rates, and deaths by age. This may be especially difficult to introduce in LMICs due to the absence of widespread population surveillance on random selections of the population and poor reporting and testing capabilities - for example, Pakistan conducts only 0.09 tests daily per 1,000 individuals compared to 0.52 in France.

Additionally, control of transmission within zones may be an enormous undertaking. In India, where this approach has been employed, the infection size within a cordoned zone can be as high as 100-200 times that outside the zone.

Countries seeking to introduce such measures should establish within the lockdown zone public health measures, including house-to-house surveillance and case-referral systems, and emergency services. They should also create buffer zones to reduce the rates of transmission from outside the zone. Such measures may only be effective when overall population transmission is relatively low and reducing.

*Rolling lockdowns

Intermittent rolling lockdowns are now advocated by the World Health Organization in various LMICs. These involve implementing strict social distancing for a set number of days before a period of relaxation. Rolling lockdowns may be particularly useful in LMICs with dense populations, where this is a high potential for contact, weak health systems and poor contact tracing.

A modelling study published by the team in May showed that a system involving 50 days of strict lockdown followed by 30 days of relaxation, enabling the economy to 'breathe' and recuperate, could reduce the reproduction number to 0.5, reduce the strain on health systems and considerably reduce the number of deaths compared to a situation with no lockdown.

Professor Oscar Franco, of the University of Bern and senior author of the paper, said: "Rolling lockdowns need be flexible and tailored to the specific country. The frequency and duration of the lockdowns or relaxed periods should be determined by the country based on local circumstances. They don't necessarily need to be nationwide - they can also involve a large zone or province with very high incidence of COVID-19."

Dr Shammi Luhar of the University of Cambridge and co-author of the paper, added: "These three strategies should not be considered as one or the other. A country should further adapt and could combine them as needed."

For the first time, physicians can examine the systemic burden of inflammatory arthritis simultaneously across all joints and organ systems, using the high-sensitivity, high-resolution uEXPLORER total-body positron emission tomography/computed tomography (TB-PET/CT) scanner. Results of the first in-human TB-PET/CT scans conducted in the arthritic population were presented at the Society of Nuclear Medicine and Molecular Imaging 2020 Virtual Annual Meeting.

Inflammatory arthritic conditions, such as rheumatoid arthritis or psoriatic arthritis, are considered systemic disorders, affecting the whole body. Yet current evaluation--mostly via anatomical imaging, such as x-ray or CT imaging--is conducted for only a few joints of the body, such as those of the wrist and hand. In the past, 18F-FDG PET scans have been used infrequently in this population due to spatial resolution and sensitivity limitations as well as radiation dose concerns.

The total-body coverage, high resolution and high sensitivity of the TB-PET/CT scanner, however, offers new imaging options for inflammatory arthritis. "In our research, we sought to examine the feasibility of assessing glucose metabolism both in normal and diseased joint tissues across the body as a means for quantifying systemic inflammatory burden for these conditions," stated Yasser Abdelhafez, MBBCh, MSc, MD, FEBNM, a postdoctoral researcher in Abhijit Chaudhari's laboratory at the University of California, Davis, in Sacramento, California.

The ongoing, prospective study enrolled 14 participants with established rheumatoid arthritis, psoriatic arthritis or osteoarthritis who underwent a single-timepoint TB-PET/CT scan for 20 minutes. The participants received an injection of 75.5 MBq of 18F-FDG, which is approximately 20 percent of the conventional 18F-FDG dose. Qualitative findings and different patterns for the three conditions were analyzed.

Participants with rheumatoid arthritis showed multiple, rather symmetric joint involvement, most commonly in the hands; joints of the feet appeared to be less frequently affected. Other notable features of this group included radiotracer uptake patterns consistent with inflammation of the joint synovium. All participants with psoriatic arthritis had positive findings in large joints and demonstrated multiple sites of enthesitis (inflammation where a tendon or ligament attached to a bone), which affected the tendons of the hand and fingers, including the nail beds. Osteoarthritic participants showed unilateral enhanced FDG uptake in at least one large joint (shoulder, elbow or knee), and occasionally in a few small joints of the hand and feet and the quadriceps femoris tendon.

"Systemic joint evaluation of patients with inflammatory arthritis is indeed feasible with this TB-PET/CT scanner, and feasible with low radiation dose," stated Abdelhafez. "The evaluation of arthritic disease activity at all joints of the body could have direct implications for disease staging, risk stratification, treatment selection and monitoring of treatment response. Furthermore, the impact of arthritis on other tissues of the body can be studied to better understand systemic disease burden."

He continued, "Total-body molecular imaging could provide currently unavailable, systemic, objective biomarkers that could help address the significant clinical challenges in managing inflammatory arthritic populations. These biomarkers may also have clear potential to accelerate arthritic drug discovery and development."

This work was supported by the National Institutes of Health (grants R01 AR076088 and R01 CA206187) and the National Psoriasis Foundation.

Abstract 331. "Total-body 18F-FDG PET/CT in patients with inflammatory arthritis: initial findings using the uEXPLORER system," Yasser Abdelhafez, Nuclear Medicine Unit, South Egypt Cancer Institute, Assiut University, Assiut, Egypt, and Radiology, University of California, Davis, Sacramento, California; Heather Hunt, Mike Nguyen, Denise Caudle, Lorenzo Nardo, Ramsey Badawi and Abhijit Chaudhari, Radiology, University of California, Davis, Sacramento, California; Soumajyoti Sarkar, Internal Medicine, University of California Davis, Sacramento, California; Simon Cherry, Biomedical Engineering and Radiology, University of California, Davis, Davis, California; and Siba Raychaudhuri, Internal Medicine, University of California, Davis, Sacramento, California and Sacramento Veterans Affairs Medical Center, Mather, California. SNMMI's 67th Annual Meeting, July 11-14, 2020.

A team of researchers from Kazan Federal University, Russia, led by Dr. Igor Sedov, reported an application of capillary differential scanning calorimetry technique for the study of the binding of albumin, a plasma transport protein, with different drug ligands.

The processes of binding of various biologically active ligands to proteins can be quantitatively characterized by the values of thermodynamic binding constants, which determine the ratio between the concentrations of free and bound ligand. Accurate determination of these quantities is not an easy task. Presently, a fairly sensitive and robust isothermal titration calorimetry method is most commonly used; however, it does not allow to study the processes with very high binding constants or separate binding steps.

The differentl scanning calorimetry (DSC) method, based on monitoring changes in the heat capacity of a heated sample, is widely used to study protein denaturation. A shift of the denaturation peak to higher temperatures in the presence of a ligand is a sign of protein-ligand binding. However, the relationship between the shift magnitude and the binding constant cannot be described by a simple mathematical formula. Therefore, only a few attempts were made to use DSC thermograms for the quantitative ligand binding studies. The authors of the paper developed a program that takes into account the denaturation and ligand binding equilibria and allows one to predict the DSC curve from the known binding constants and protein and ligand concentrations. Then the values of the constants can be optimized to provide the best fit of the calculated curves to the experimental ones.

The application of this approach to albumin is complicated by the mechanism of denaturation of this protein, which is usually considered to be two-stage. However, the authors showed that the two-state model of protein denaturation used in the program gives the results consistent with other experimental methods. Moreover, the analysis of DSC thermograms helps measure very high binding constants, as well as weak binding constants with the second molecule of a ligand, and the stoichiometry of a complex at the large excess of ligand, when simultaneous binding to several centers, including those with low affinity, occurs.

Albumin is the main transport protein in blood plasma and can bind to a wide variety of molecules. Albumin has a two-domain structure with at least two high-affinity and several low-affinity binding sites. The binding affinity of drugs to plasma proteins influences the fraction of the free drug in plasma, which, in turn, is one of the major factors governing drug permeability through physiological barriers. Only unbound drugs can cross these barriers. As an example, the studied strong albumin binders - naproxen and ibuprofen - have limited brain bioavailability due to low permeability through the blood-brain barrier. On the other hand, slowly metabolized drugs with weak plasma binding have increased clearance, which may result in lower efficacy. The binding constant values can give the idea about the fraction of an unbound drug in blood plasma, while the knowledge of sequential binding constants is important for the studies of competition between drugs and other substrates or between two different drugs for albumin binding centers. In the case when the strongest binding center is occupied by another molecule, the unbound fraction of the drug will be determined by its affinity to the other binding sites. The interest in albumin binding also arises from the prospective use of drug delivery systems based on albumin nanoparticles.

The DSC-based method has potential applications to a wide range of proteins and bioactive ligands and can be useful in drug development and protein science.

This work was supported by the Russian Science Foundation (grant 19-73-00209).

Venus flytraps catch spiders and insects by snapping their trap leaves. This mechanism is activated when unsuspecting prey touch highly sensitive trigger hairs twice within 30 seconds. A study led by researchers at the University of Zurich has now shown that a single slow touch also triggers trap closure - probably to catch slow-moving larvae and snails.

The Venus flytrap (Dionaea muscipula) is perhaps the most well-known carnivorous plant. It catches its prey, mostly spiders and insects, using a sophisticated trapping mechanism. Its distinct leaves have three highly sensitive trigger hairs on each lobe. These hairs react to even the slightest touches - e.g. when a fly crawls along the leaf - by sending out an electrical signal, which quickly spreads across the entire leaf. If two signals are triggered in a short time, the trap snaps within milliseconds.

New trigger for trapping mechanism

The physiological reactions on which this trapping mechanism is based have been studied for over 200 years. The consensus has been that every sufficiently strong touch of a trigger hair causes an electrical signal, and that two signals within 30 seconds result in the closing of the trap. A new study from the University of Zurich (UZH) and ETH Zurich has now found another triggering mechanism. "Contrary to popular belief, slowly touching a trigger hair only once can also cause two signals and thus lead to the snapping of the trap," says co-last author Ueli Grossniklaus, director of the Department of Plant and Microbial Biology at UZH.

First, the interdisciplinary team of researchers determined the forces needed to trigger the plant's trapping mechanism. They did this by using highly sensitive sensors and high-precision microrobotic systems developed by the team of co-last author Bradley J. Nelson at the Institute of Robotics and Intelligent Systems at ETH Zurich. This enabled the scientists to deflect the trigger hairs to a precise angle at a pre-defined speed in order to measure the relevant forces. These experiments confirmed the previous theory. If the chosen parameters approximate the touch of regular prey, it takes two touches for the trap to snap.

From the collected data, the researchers at the ETH Institute for Building Materials developed a mathematical model to determine the range of angular deflection and velocity thresholds that activate the snapping mechanism. "Interestingly, the model showed that at slower angular velocities one touch resulted in two electrical signals, such that the trap ought to snap," says Grossniklaus. The researchers were subsequently able to confirm the model's prediction in experiments.

Catching slow prey

When open, the lobes of the Venus flytrap's leaves are bent outwards and under strain - like a taut spring. The trigger signal leads to a minute change in the leaves' curvature, which makes the trap snap instantaneously. The electrical signals are generated by ion channels in the cell membrane, which transport atoms out of and into the cell. "We think that the ion channels stay open for as long as the membrane is mechanically stretched. If the deflection occurs slowly, the flow of ions is enough to trigger several signals, which causes the trap to close," explains co-first author Hannes Vogler, plant biologist at UZH. The newly discovered triggering mechanism could be a way for the Venus flytrap to catch slow-moving prey, such as larvae or snails.

A new single-cell RNA sequencing analysis of more than 59,000 cells from three different patient cohorts provides a detailed look at patients' immune responses to severe cases of COVID-19. The results suggest that patients with severe COVID-19 experience increased regulation of the type I interferon (IFN-I) inflammation-triggering pathway - a signature that the researchers also observed in patients hospitalized with severe cases of influenza. Their findings suggest that anti-inflammatory treatment strategies for COVID-19 should also be aimed toward the IFN-I signaling pathway, in addition to targeting inflammatory molecules such as TNF, IL-1?, and IL-6 that have been implicated in COVID-19. Seong Seok Lee and colleagues sequenced the RNA from a total of 59,572 blood cells obtained from four healthy donors, eight patients with mild or severe COVID-19, and five patients with severe influenza. Patients in both the mild and severe COVID-19 cohorts all showed increased regulation of the TNF/IL-1ß-driven inflammatory response, while patients with severe COVID-19 also exhibited an increased IFN-I response. By comparison, patients with severe flu showed increased expression of various IFN-stimulated genes, but did not experience TNF/IL-1ß responses as seen in COVID-19 patients. Unlike the flu cohort, patients in the severe COVID-19 cohort exhibited the IFN-I signature concurrently with TNF/IL-1ß-driven inflammation - a combination also not seen in patients with milder cases of COVID-19. Based on their results, the scientists propose that the IFN-I response exacerbates inflammation in patients with severe COVID-19. Their results, along with past mouse studies that highlight how the timing of IFN-I expression is critical to determining the outcome of SARS-CoV-2 infection, support targeting IFN-I as a potential treatment strategy for severe COVID-19.

In a pioneer study published in Cell Host & Microbe - Researchers at Osaka City University and The Institute for Medical Science, The University of Tokyo, reported intestinal bacterial and viral metagenome information from the fecal samples of 101 healthy Japanese individuals. This analysis, leveraging host bacteria-phage associations, detected phage-derived antibacterial enzymes that control pathobionts. As proof-of-concept, phage-derived endolysins are shown to regulate C. difficile infection in mice.

Abnormalities in human intestinal microflora, known as dysbiosis, are connected to various diseases. Altered microbial diversity impairs the beneficial effects of host intestinal microflora, which cause some symbiotic commensal bacteria to acquire virulence traits, proliferate, and become directly involved in the development of disease. These bacteria are referred to as "pathobionts", which are distinct from opportunistic pathogens.

C. difficile, which is a Gram-positive, spore-forming anaerobic bacterium, is a pathobiont and the representative cause of nosocomial diarrhea following antibiotic treatment. Since antibiotic usage has the risk of killing beneficial bacteria and promoting dysbiosis, the development of methods to specifically manipulate intestinal pathobionts is essential.

"Phages were sure to be applicable as a highly specific therapy for intestinal pathobiont elimination", believed Professor Satoshi Uematsu. The infectious associations between phages and bacteria in the human intestine is essential information for the development of phage therapies. Known as "viral dark matter" as it had yet to be understood, researchers obtained metagenome information about bacteria-phage associations from the fecal samples of 101 healthy individuals through the development of a virome analysis pipeline. Based on this information, researchers screened C. difficile-specific phages and identified novel antibacterial enzymes, both in vitro and in vivo.

"The accumulation of more metagenomic information on intestinal phages and bacteria will open up the possibility of developing treatments for a variety of dysbiosis-related diseases", say Dr. Kosuke Fujimoto and Prof. Seiya Imoto.

The most vulnerable residents of the nation's 10th most populous state say their health improved significantly after they enrolled in Michigan's expanded Medicaid program, a new study finds.

Michiganders with extremely low incomes, those who live with multiple chronic health problems, and those who are Black, got the biggest health boosts year over year among all those enrolled in the safety-net health coverage program, the study shows.

But participants of almost all ages, backgrounds and in all geographic regions reported improvements in health over time.

Writing in the new issue of JAMA Network Open, a team from the University of Michigan reports the results of a survey that asked more than 3,000 enrollees in the Healthy Michigan Plan about their health, at two time points a year apart.

The new paper adds to a growing body of evidence about the impacts of Michigan's Medicaid expansion, compiled by a team from the U-M Institute for Healthcare Policy and Innovation with funding from the Michigan Department of Health and Human Services.

The IHPI team just unveiled a summary of findings based on the final report from the first five years of their evaluation of the Healthy Michigan Plan. The new paper is the latest in a series of peer-reviewed, data-driven articles that the team has published in academic journals based on their evaluation work.

Michigan's experience might inform states where Medicaid has not yet been expanded, or is about to be - including Missouri which has a ballot proposal up for a vote in early August, Oklahoma, whose voters just approved expansion last week, and Nebraska, which is preparing to start its program this fall. Twelve other states have not expanded their Medicaid programs.

Reductions in poor health

The new paper's lead author is Minal Patel, Ph.D., M.P.H., an associate professor at the U-M School of Public Health who analyzed data from the longitudinal survey of participants who had been enrolled in the Healthy Michigan Plan for at least a year before the first time they were surveyed.

The percentage of respondents who called their health fair or poor dropped from nearly 31% in 2016 to 27% in 2017. Larger decreases were seen among those with the very lowest incomes, those who were Black, those who had two or more chronic conditions, and those who live in the Detroit metropolitan area.

Additional survey data contained in a new report showed that the percentage who said their health was fair or poor dropped further, to 25.6% by 2018.

The average number of days in the past month when the respondents said they had been in poor physical health dropped by more than a day in many groups, including those with two or more chronic health conditions. But there was no significant change in days of poor mental health or days when respondents said their health interfered with their usual activities.

Nearly one quarter of respondents who answered in 2016 were no longer enrolled in the program when surveyed in 2017.

Enrollees had incomes below or just above the federal poverty line, but 57% said they were employed or self-employed. Just over half had incomes less than 35% of the federal poverty level, which was $11,880 for a single adult in 2016.

"Our study showed that sub-groups who would benefit the most from greater access to care through Michigan's Medicaid expansion reported improved health over time," says Patel. "Better access is indeed translating to better health."

The emphasis that the Healthy Michigan Plan places on primary care and prevention, as well as the inclusion of dental and vision care that can address long-unmet needs, likely played a role, she adds.

"It is rare to find a change in health policy that actually improves health of a target population in merely one year," says Susan D. Goold, M.D., MHSA, M.A., study co-author and professor of internal medicine at U-M. "The Healthy Michigan Plan model of expansion, which emphasized both insurance coverage and primary care, built on what we have learned from health systems around the globe."

Five years in, some key findings

The economic effects of COVID-19 have likely led more Michiganders to seek coverage from the safety net of the Healthy Michigan Plan. As of this week, more than 751,000 people are enrolled in the plan, up from 675,000 in February before COVID-19 struck Michigan.

"This new study adds to the large body of evidence on Medicaid expansion that our team at the University of Michigan has developed over the past five years," says IHPI director and study co-author John Z. Ayanian, M.D., M.P.P.

Some other key findings documented in the five-year summary brief:

Before enrolling in the Healthy Michigan Plan, half of those surveyed said they had a doctor or clinic they could see for regular care. By 2018, that had climbed to 83%.

The percentage who said that emergency rooms were their usual source of care dropped from 12% to 3%.

85% of enrollees had seen a primary care provider in the last year, 84% had received a preventive medical service such as a cancer screening, and nearly half had seen a dentist.

40% of enrollees surveyed said their dental health had improved since enrolling

85% of enrollees said they had fewer problems paying medical bills since they enrolled

The percentage of enrollees who said they were employed or enrolled as a student grew to 61% in 2018, up from 55% in 2016.

43% of enrollees said they had completed a Health Risk Assessment, a special feature of the Healthy Michigan Plan. Of these, 91% said it motivated them to be more responsible for their health.

Enrollees with incomes above the poverty level pay a contribution of 2% of their household income for their Healthy Michigan Plan coverage. Some services have co-pays. 88% of enrollees said that the amount they pay for their coverage seems fair. Among those who were billed for contributions or copays, the average quarterly statement amount was $16.85.

The IHPI team continues to study the impacts of Medicaid expansion on Michigan's enrollees. Learn more about IHPI's Healthy Michigan Plan evaluation: https://ihpi.umich.edu/featured-work/healthy-michigan-plan-evaluation

The GRACE-FO (Gravity Recovery and Climate Experiment-Follow-On) satellites launched in May 2018 are able to quantify the water mass deficit in Central Europe. Relative to long-term climate development, the water mass deficits during the two consecutive summer droughts of 2018 and 2019 amounted to 112 Gt in 2018 and even 145 Gt in 2019, according to a research team from the German Research Centre for Geosciences GFZ and the University of Potsdam led by Eva Börgens. The deficits in 2018 and 2019 are thus 73 percent and 94 percent of the average fluctuation in seasonal water storage. In other words, compared with the average value, it would take about twice the increase in water over the winter to compensate for this deficit. The changes are so serious that a recovery within one year is not to be expected. The water shortage in the years 2018 and 2019 is thus the largest in the entire GRACE and GRACE-FO measurement campaign of almost 20 years. The results were published in the journal Geophysical Research Letters.

The GRACE-FO pair of satellites records the movement of water on Earth based on variations of the Earth's gravitational field triggered by this movement. These variations can be determined from high-precision distance measurements using microwave signals emitted by the two satellites flying behind each other. GRACE-FO is the successor project of GRACE. The two GRACE satellites had completed their mission in 2017 after 15 years of operation.

On the whole, the data show no offset between the two missions, which confirms the successful continuation of GRACE by GRACE-FO and thus the reliability of the observation of extreme events in Central Europe. According to the researchers, this allows a joint evaluation of the four Central European droughts in the years 2003, 2015, 2018 and 2019: Compared to 2003 and 2015, 2018 and 2019 were significantly drier. In 2019 the water shortage was so severe that a recovery of water supplies within one year is not expected, especially since the winter of 2019/2020 brought only a very slight recovery.

In order to be able to draw a comparison between GRACE and GRACE-FO drought observations and other parts of the water balance, such as soil moisture or surface water, the data were converted into drought indices. In contrast to other data sources, the data of GRACE-FO and GRACE allow to cover the entire water balance in lakes, rivers, soils and groundwater. Measurements on surface waters such as Lake Constance, on the other hand, can be strongly influenced by local or regional factors.

"The study shows how important the long time series of observations from the GRACE and GRACE-FO missions are for classifying current climatic events," says study leader Eva Börgens. "Whether the drought years 2015, 2018 and 2019 are the first signs of longer-term change in Central Europe or merely statistical outliers will only be known in the future. However, initial data from 2020 suggest that the drought will continue."

PHYSICS The cold, famine and unrest in ancient Rome and Egypt after the assassination of Julius Caesar in 44 BCE has long been shrouded in mystery. Now, an international team, including researchers from the University of Copenhagen, has found evidence suggesting that the megaeruption of an Alaskan volcano may be to blame.

Dark times befell upon the Mediterranean around the time of Julius Caesar's assassination in 44 BCE. Written accounts describe the region as severely impacted by unusual cooling, failed harvests, famine and disease, all of which combined to contribute to the fall of the Roman Republic and Ptolemaic Kingdom. While researchers long suspected that a volcanic eruption was to blame, they were unable to pinpoint exactly where and when such an eruption might have occurred.

The brightness of the sun was darkened, the disc was pale for a year and the sun did not rise with its usual brilliance and force. It gave but slight heat. For this reason, the crops brought forth were so poor and immature that they rotted in the cold air.

Greek Roman philosopher Plutarch describing the weather in the wake of Julius Caesar's death

Now, an international team, including researchers from the University of Copenhagen's Niels Bohr Institute, the Desert Research Institute in Reno, Nevada and the University of Bern has analysed volcanic ash in Greenlandic ice core samples, which together with historical accounts, can be linked to an inexplicable cooling event in the Mediterranean region during this crux in the history of Western civilization.

The ash comes from the remote Okmok volcano in Alaska's Aleutian Island Chain. According to the ice core tests, the volcano experienced a two-year megaeruption that began in early 43 BCE, one that filled Earth's atmosphere with enough smoke and ash to significantly impact climate.

"The eruption is regarded as one of the largest volcanic eruptions of the past 2,500 years. Using the ice core samples, climate models and historical records, we are quite certain that the eruption is linked to the violent climatic changes noted around the Mediterranean and in Rome," says Jørgen Peder Steffensen, professor of ice, climate and geophysics at the Niels Bohr Institute and one of the researchers behind the discovery.

Coldest years in the Northern Hemisphere

In an extensive collaboration with historians and others, researchers collected prehistoric climate data from around the planet to confirm the likelihood that this particular eruption was responsible for widespread climate change. The sources of evidence include tree ring archives from Scandinavia, Austria and California and a Chinese cave formation.

The researchers' extensive analysis of climate during this ancient era demonstrates that the years after the Okmok eruption were some of the coldest in the northern hemisphere over the past 2,500 years. The researchers' climate models indicate that temperatures were roughly seven degrees Celsius below normal during the summer and autumn after the eruption in 43 BCE.

"Historical accounts describe how wet and extremely cold weather led to poorer harvests, as well as how the Nile overflowed its banks--destroying crops and leading to famine--all of which correlates with our results," says Jørgen Peder Steffensen.

While the researchers believe that a variety of factors contributed to the fall of the Roman Republic and Ptolemaic Kingdom, they maintain that Okmak's eruption played an unmistakably large role and that their discovery serves to fill in gaps which have been missing in history books dealing with the era.

The research was recently published in the journal Proceedings of the National Academy of Sciences (PNAS)

Facts:

The Niels Bohr Institute's Ice and Climate Group has been working on the "Caesar Volcano" since the 1980's. The group was the first in the world to systematically use the counting of annual layers in ice cores to date volcanic eruptions.

The group also invented the ECM-method (Electric Conductivity Method) to find volcanic ash in ice cores. ECM consists of placing two electrodes along fresh ice cores and measuring resistance. Sulphuric acid from volcanoes changes the resistance in the ice, making it quite easy to identify volcanic layers.

The new research article is the latest in more than 40 years of work on the volcano.

Consuming protein at night increases blood sugar level in the morning for healthy people, according to new research presented this week at The Physiological Society's virtual early career conference called Future Physiology 2020.

Having high blood sugar levels after eating is linked to health problems, such as diabetes, heart disease and obesity. Previous research has shown that a snack a few hours before a meal can help control blood sugar levels, which may partly explain why the first thing we eat each day (i.e. breakfast) tends to increase blood sugars more than other later meals.

This study investigated whether waking-up at night to consume some protein might keep blood sugars lower the next morning. Surprisingly, the blood sugar response to breakfast was higher when participants had consumed protein rather than plain water at 4 am.

These unexpected findings may be informative for people trying to improve their control of blood sugar levels.

One explanation for the result is that the body does not expect or need much food to be consumed during the night and so the protein itself was turned into sugar. This may result in the body having more carbohydrate already available upon waking such that the energy in the breakfast can less easily be used or stored, so it builds-up more in the blood.

The researchers at the University of Bath studied fifteen healthy young men and women (8 females and 7 males). The participants were woken up at 4 am to drink 300 ml of a water solution, either with or without 63 grams of whey protein.

They then went back to sleep and at 9 am were provided with a standard amount of porridge for breakfast, with blood samples collected for 2 hours afterwards to check the blood glucose response.

The participants then returned to the lab to do the same again a week or so later, but were provided with the other drink at night (4 am) so that we could compare the glucose response to the same breakfast in the same person and see the effects of the night-time protein.

Eleanor Smith, who presented the work, said:
"Future research will look at whether this applies to older and overweight people who tend to have more problems controlling their blood sugar levels. It would also be interesting to know to what extent our findings are due to eating at an unusual time or the type of protein consumed."

A team of researchers from Aarhus University have, for the first time ever, linked 40 years of productivity data from the construction industry with the actual work done. The results show that productivity in the construction industry has been declining since the 1970s. The results also explain the decline and how to achieve far more efficient construction in North America and Europe.

"This is a clear and cut business case and a helping hand for decision-makers in the construction industry: If the country's contractors are to make more money, they need to optimise processes."

This is how Hasse Neve, carpenter, MSc in Engineering, PhD and researcher in construction industry productivity at the Department of Engineering at Aarhus University, introduces the new study that, for the first time ever, links national productivity statistics in the construction industry with the efficiency of the actual work done on construction sites.

As it turns out, there is a statistically significant correlation between the two.

"Since 1972, we've continuously gotten less and less out of every hour of work. Construction sites have simply become less and less efficient because more time is spent on non-value adding work. Ultimately, this means that we spend more and more working hours on a single construction job. Therefore, our contractors do not earn as much money on construction as they could," says Hasse Neve.

The study has just been published in Construction Engineering and Management, one of the world's leading scientific journals for construction management.

Hasse Neve emphasises that it is primarily the construction management and not the builders who are responsible for and can influence how a building site operates, and thus how efficiently work is carried out. In general, everybody wants a good workflow and no waste:

"But to achieve this, the construction management team will need to use the right tools and competences and dedicate themselves to the task," he says and continues:

"The construction management team have the greatest influence on efficiency, and thereby on how much money is earned. And the way to increase efficiency is to use methods, tools and knowledge that already exist. Lean Construction tools are basically all about eliminating waste. It is therefore crucial that the construction management are trained in Lean Construction and that extra resources are added to both implementation and support throughout the project."

In the study, the research team used national productivity statistics from the construction industry and so-called work-sampling studies (observational studies of the work performed) from the US and Canada. The studies were carried out between 1972 and 2010. The reason that no Danish or European data were used is simply because not enough work-sampling studies have been completed in Denmark and Europe.

"Since the construction industry in North America isn't too different from its European or Danish counterparts, there's good reason to take these results seriously. If we're going to change the productivity development of the Danish construction industry, we need to focus on efficiency on construction sites," says Hasse Neve.

To illustrate the value that the construction industry could generate if more time was spent on value-adding work, Hasse has calculated what just 36 more seconds per hour (for builders) spent on generating value could mean for the construction industry's gross domestic product in the US and Canada: 5.4 billion dollars annually (approx. DKK 36 billion).

"Although there is a degree of uncertainty, this shows what a society could earn by simply spending one percentage point more time on value-adding work on construction sites. But the vast majority of sites can be optimised even more, thus the numbers could be huge," he says and continues:

"The results are of course based on North American data, but there is no doubt that the potential for the Danish construction industry is also significant. And that's a really fantastic thought. We have lots of tools and knowledge that can make construction processes far more efficient, so why not use them? Fundamentally, construction is about generating value. A good final product for the client and users, and an efficient process for contractors, so they can earn money.

And if you are unsure about how to get started?

"Then just call me," says the researcher with a smile.

A new study has warned of the power of a type of behaviour dubbed the 'lone wolf' effect which could result in people 'opting out' of supporting organ donation.

A behavioural study led by researchers from the University of Nottingham's School of Psychology and Nanyang Technological University's Department of Economics found that initial co-operation, encouraged by an opt-out policy, can be undermined by members of the public observing the actions of 'lone wolves'.

The study revealed that lone wolves unilaterally defect and publicly display their decision to opt out leading others to follow suit and do the same. This effect of lone wolves is a stronger social force for change than people following 'good shepherds' who are observed to register under an opt-in policy. Their findings have been published in Scientific Reports.

It has long been recognised that when it comes to making an organ donation decision, not everyone wishes to or can donate. People also may wish to donate, but don't, simply because they never got around to signing up. To help overcome this inertia, and redress the shortage in organs, some countries, including Wales and most recently, England, have introduced a change in law, to move from an opt-in system (where everyone is assumed to be a non-donor and registers to be a donors) to an opt-out system (where everyone is assumed to be a donor, unless they opt out.)

The policy in England is a so-called "soft opt-out" policy. This means that all adults in England (unless they are in one of the excluded groups), will be considered to have agreed to be an organ donor when they die unless they have recorded a decision not to donate (either by registering their decision on the NHS Organ Donor Register or telling their family and friends.) The system is a "soft opt-out" as relatives will still be consulted, before organ donation goes ahead.

Professor Eamonn Ferguson from the University of Nottingham said: "The opt-out system relies on people accepting the default of their organs being donated, unless they take action to confirm their decision not to donate. However, our research uncovered a disruptor to this called the 'lone wolf'.

If people know that others have decided to opt out, they are very likely also to do the same. In a world dominated by social media and instant messaging, this can sets up a negative cascade that quickly spreads.

This is important as much of the evidence for moving to opt-out is derived from population studies that cover time periods prior to the social media explosion."

The researchers devised economic games to model the organ donor decision. 213 people participated in games where they indicated their decision to register as a donor under opt-in, or opt-out. They examined the effect the feedback from others (akin to social media updates) had on people's decisions.

Associate Professor Jonathan Tan of Nanyang explains: "In theory, under an opt-out system where feedback is available, people are better off cooperating if they cannot get away with free-riding since others can observe them and opt out too. In practice, however, so long as there are lone wolves who unconditionally free-ride, this default system will lose its strategic power."

Professor Ferguson adds: "The results showed that when people decide not to follow an opt-out default or request, the effect on causing others to follow suit is very strong and much stronger than following people who are acting in accordance with an opt-in policy and registering.

We know that people follow others behaviour, but it is interesting that when everyone is requested to cooperate and help, people has a strong tendency to follow the example of a negative uncooperative influence (or lone wolf). Many people may decide to opt-out simply because others do. This may be because they think that others know something they don't or they don't want to be left behind.

This also raises a very real risk that incorrect information about organ donation and the law change could lead large numbers of people to opt out. This is something that has not been documented before in academic research and we feel is important for the public to be aware, so they can be alert and on their guard for the influence of such information.

While we examined these effects in organ donation they have implications for other public health policies where defaults may be considered such as vaccinations, energy conservation and social distancing."

We would recommend harnessing the 'good shepherd' effect to help encourage registration as exemplified by recent evidence that posting about signing up to be a donor increased registration: the so called 'Facebook' effect.

If moving to an opt-out policy then strategies to ameliorate the 'lone wolf 'effect need to be considered. This could involve the use of moral norms to ameliorate the 'lone wolf 'as well as strategies to monitor social media and 'fake news' or negative stories about organ donation and ask people to question the validity of any information they see."

Medical researchers in the UK and Australia have identified a new marker which could support the search for novel preventative and therapeutic treatments for dementia.

In an innovative new study, coordinated by Flinders University and University of Aberdeen, the researchers investigated the role of asymmetric dimethylarginine (ADMA), a blood marker associated with atherosclerosis and cardiovascular disease in epidemiological studies, on temporal changes in cognition in an established cohort of human ageing (the 1936 Aberdeen Birth Cohort).

Unlike other human ageing study cohorts, the 1936 Aberdeen Birth Cohort participants also underwent childhood intelligence tests at age 11, a key predictor of intelligence and health in old age.

Research has primarily focused on a set of abnormalities found in diseased brains. However, observational studies and clinical trials targeting these alterations have been disappointing, suggesting the urgent need to better understand the causes of dementia and identify novel markers of disease.

In the first longitudinal study, ADMA levels measured in the year 2000 (at participants' age 63 years) was associated with decline in cognitive performance assessments after four years, says Flinders University Professor Arduino Mangoni.

"Therefore the results of this study suggest, that ADMA, an easily measurable marker of atherosclerosis and cardiovascular risk, could be an early indicator of cognitive decline in old age - and possibly dementia," says Professor Mangoni, Head of Clinical Pharmacology at Flinders University.

Alzheimer's disease (AD), a neurodegenerative disorder characterised by a rapid decline in cognition and significant disability in old age, currently affects more than 342,000 Australians. This number is expected to increase to 400,000 in less than a decade.

The causes of late onset AD are largely unknown and despite extensive research, there is still no clear consensus on robust biomarkers to predict disease onset and progression and the response to therapies.

UK researcher Dr Deborah Malden says the results of the new study should be approached with caution and need further extensive investigations.

"We should be cautious about emphasising the results with the 93 participants' results here," she says.

"We would know much more after repeating this study in a large-scale cohort, potentially tens of thousands of individuals, and perhaps a genetic MR (Mendelian randomization) study," Dr Malden says.

Nevertheless, if the initial study findings are verified in large-scale testing, researchers hope the findings could pave the way for population-wide dementia risk stratification and perhaps future development of therapeutic strategies to reduce ADMA levels and/or slow the progression of cognitive decline in old age.

Lopinavir is a drug against HIV, hydroxychloroquine is used to treat malaria and rheumatism. Until recently, both drugs were regarded as potential agents in the fight against the coronavirus SARS-CoV-2. A research group from the University of Basel and the University Hospital has now discovered that the concentration of the two drugs in the lungs of Covid-19 patients is not sufficient to fight the virus.

In February 2020, a Covid-19 patient cohort was established at the University and the University Hospital in Basel to prospectively monitor a range of diagnostic means and potential treatments for Covid-19, including the off-label use of hydroxychloroquine and lopinavir/ritonavir.

A research group prospectively monitored lopinavir plasma levels in Covid-19 patients. "Considering that substantial inflammation was observed in these patients, and previous studies have shown the inhibition of drug metabolism by systemic inflammation, we had the rationale to investigate the effect of inflammation on lopinavir and hydroxychloroquine plasma levels," states Professor Catia Marzolini, first author of the study and professor for experimental medicine at the University of Basel.

The authors included 92 patients in their study. Professor Parham Sendi, who is the co-leader of this study summarizes the main findings as follows: First, lopinavir plasma levels were more than two to threefold higher than typically observed in HIV patients. Hydroxychloroquine levels were with normal range. Second, there was a significant correlation between the inflammation marker levels in the blood and lopinavir plasma levels. Third, when the inflammation was blocked with the Interleukin-6 inhibitor Tocilizumab, lopinavir plasma levels were significantly lower than the ones in patients without Tozulizumab treatment.

These results clearly indicate that drug metabolism enzymes (cytochrome P450 3A) are inhibited by systemic inflammation. "Caution is advised when prescribing CYP3A4 substrates such as Lopinavir/ritonavir or any other drug with a narrow therapeutic index to Covid-19 patients because of the risk of elevated drug levels and related toxicities," the authors state.

Importantly, from the lopinavir and hydroxychloroquine concentrations in the plasma, the study group calculated the corresponding concentration in the lung compartment - the anatomic site of SARS-CoV-2 infection. The results strongly suggest that it is unlikely that both drugs reach sufficient concentrations to inhibit the virus replication in the lung.

WHO accepted the recommendation from the Solidarity Trial's International Steering Committee to discontinue the trial's hydroxychloroquine and lopinavir/ritonavir arms on 4 July 2020. Professor Manuel Battegay - co-leader of this study and head of the Division of Infectious Diseases and Hospital Epidemiology at the University Hospital in Basel - mentioned that the results provide important pharmacological and antiviral insights to the rationale of discontinuing the lopinavir/ritonavir arm. In fact, they add scientific reasoning why hydroxychloroquine and lopinavir are not effective against the SARS-CoV-2.