Culture

Boston, MA - A new study led by the Harvard Pilgrim Health Care Institute examines the benefits and barriers of Prescription Drug List coverage for preventive asthma medications. The study, "Preventive Drug Lists as Tools for Managing Asthma Medication Costs", appears in the February edition of The American Journal of Managed Care.

As drug manufacturers replace affordable generics with higher-cost name-brand drugs, U.S. families affected by asthma have seen a dramatic rise in the cost of medications. To reduce the financial burden of preventive medications and promote adherence, many insurance companies have introduced Preventive Drug Lists (PDLs). A type of value-based insurance design, PDLs are meant to supplement Health Savings Account-eligible high-deductible health plans (HDHPs) by allowing members to receive selected preventive medications for chronic conditions at low or no cost before meeting their deductible, but little is known about consumer experiences using PDLs.

Researchers conducted a qualitative study to explore PDLs from the perspective of families affected by asthma. The study team interviewed 22 U.S. adults enrolled in HDHPs with PDLs who either had asthma, had a child with asthma, or both. Study results showed that while some members reported financial benefit and increased medication adherence as a result of utilizing PDLs, many experienced barriers to PDL use. Barriers included lack of awareness of the PDL benefit; the exclusion or limitation of certain medications from the PDL; and inconsistency or shifting of PDL benefits.

Overall, researchers found that lack of awareness of members' access to PDLs impedes members' ability to seek out the lowest-cost medications. Employers serve as a source of information about PDLs, but greater outreach by health plans is needed to supplement member education and help facilitate use to maximize benefit.

"Our findings offer reasons to be optimistic that PDLs can help families manage asthma care costs and address disparities in asthma medication adherence," says senior author Alison Galbraith, MD, MPH, Associate Professor of Population Medicine at the Harvard Pilgrim Health Care Institute and Harvard Medical School.

Regarding future directions, lead author, Melissa Gilkey, PhD, Assistant Professor, Gillings School of Global Public Health, University of North Carolina, adds, "Our results suggest that additional research is needed to improve PDL design and to ensure that families are aware of --and make full use of--this benefit."

How are wild animals managed in European national parks and what factors influence management decisions? The team of Suzanne van Beeck Calkoen and associate professor Dr. Marco Heurich of the Department of Wildlife Ecology and Management at the University of Freiburg has examined differences in national policies for wild animal management in European national parks. Due to major variations in wild animal management policies in Europe, the researchers are calling for a uniform legal framework in order to improve the protection of wildlife in national parks. The researchers have published their latest results in the scientific publication the "Journal of Environmental Management."

The team has demonstrated that many of the European national parks fail to meet the targets set for the management of protected areas as defined by the International Union for Conservation of Nature (IUCN). "In contrast to the United States and Canada, in Europe there are no standard regulations for handling ungulates such as roe and red deer within the national parks," explains van Beeck Calkoen. According to the researchers, the absence of common policies and differences between species communities, hunting traditions, and cultural or political contexts have led to major differences in wildlife management in European countries. In order to achieve the aims of the national parks and continue to further the development of strategies for handling wild animals, van Beeck Calkoen and other researchers are calling for uniform, European policies on conserving wild animals that correspond to the IUCN guidelines. "A framework is needed that provides a common definition of national parks with clearly specified laws, requirements, and policies," says van Beeck Calkoen. The scientists emphasize that the parks require an integrated, adaptive management system that takes into account all ecosystem processes, local traditions, and socio-political contexts, and a network of national park authorities that promotes the sharing of knowledge and development of the management system.

Among the primary aims of national parks are the protection of natural processes and species conservation. If these goals are in conflict with one another, then park administrations decide over which measures should be taken while taking into consideration the protected assets of the national parks. In order to analyze whether the measures were in accordance with the defined goals, van Beeck Calkoen and her team evaluated the state of management of ungulates in European national parks on the basis of authenticity and other variables that could influence management. To do this, the team collected data from 209 European national parks in 29 countries.

"In more than two-thirds of the national parks, ungulate populations were regulated through culling, hunting, or both," explains Heurich, who led the study. What is more, only 28.5 percent of the parks are in compliance with international standards because they have spaces that are excluded from human intervention which account for at least three-quarters of their total surface area.

Immune system must strike a balance between reacting to a threat without overreacting

New research shows that immune cells 'count' how many of them have gathered to determine how much the system should react

Information could be used to design improved cancer immunotherapies or treatments for autoimmune diseases

EVANSTON, Ill. -- Many people consult their friends and neighbors before making a big decision. It turns out that cells also are consulting their neighbors in the human body.

Scientists and physicians have long known that immune cells migrate to the site of an infection, which individuals experience as inflammation -- swelling, redness and pain. Now, Northwestern University and University of Washington researchers have uncovered new evidence that this gathering is not just a consequence of immune activation. Immune cells count their neighbors before deciding whether or not the immune system should kick into high gear.

Understanding how to influence inflammation and activate an immune response could lead to new therapies to treat chronic autoimmune diseases or to mobilize the immune system to help fight cancer.

"This is a previously unrecognized aspect of immune function," said Northwestern's Joshua Leonard, who co-led the study. "The cells make a coordinated decision. They don't uniformly activate but instead collectively decide how many cells will activate, so that together, the system can fend off a threat without dangerously overreacting."

"A key part of this work relied on the development of new computational models to interpret our experiments and elucidate how cells perform calculations to make coherent decisions," said University of Washington's Neda Bagheri, who co-led the work with Leonard.

The research will be published on Feb. 13 in the journal Nature Communications.

Leonard is an associate professor of chemical and biological engineering at Northwestern's McCormick School of Engineering and a member of Northwestern's Center for Synthetic Biology. Bagheri is an associate adjunct professor of chemical and biological engineering at McCormick and an assistant professor of chemical engineering and biology and a Distinguished Washington Research Foundation Investigator at the University of Washington. The paper's first author is Joseph Muldoon, a graduate student in Northwestern's Interdisciplinary Biological Sciences Graduate Program, who is co-advised by Leonard and Bagheri.

The body's immune system is constantly working to maintain a delicate balance. When a threat is introduced, the system needs to respond strongly enough to fight off infection or disease but not so strongly that it causes harm.

"When it comes to immune responses, it's the difference between life and death," Leonard said. "If your body over-responds to a bacterial infection, then you could die from septic shock. If your body doesn't respond enough, then you could die from rampant infection. Staying healthy requires the body to strike a balance between these extremes."

Leonard, Bagheri and their teams wanted to better understand how the immune system makes these types of decisions.

"It's especially interesting because the immune system is decentralized," Muldoon said. "Immune cells are individual agents that need to work together, and nature has come up with a solution for how they can get on the same page. Cells arrive at different activation states, but in such a way that, on the whole, the population response is calibrated."

To explore this phenomenon, the researchers examined macrophages, a type of immune cell that is part of the first line of defense for combatting infection and disease. They observed how macrophages responded to a chemical produced by bacteria -- a red flag that alerts the body to the presence of infection -- using techniques that enabled the researchers to watch individual cells' responses over time. They then used computational models to help interpret and explain these observations.

"Over time, the cells observe their surroundings to get a sense of their neighbors," Muldoon said. "Each cell becomes poised to respond as a high activator or not. Now that we know there's this additional layer controlling the immune system, it opens up a whole avenue to study whether there are new targets for immunomodulation."

The researchers believe this information could be used to help design better drugs as well as to guide the engineering of advanced cell-based therapies.

"Biology has evolved so many fascinating and surprising ways to control complex processes," Leonard said. "As synthetic biologists, we work to engineer cells to perform customized therapeutic functions, such as activating the immune system locally at a tumor site but not throughout the patient. Understanding nature's innovations helps us to come up with new designs and enables us to be better engineers."

COLUMBUS, Ohio -- Researchers -- and parents -- have long known that babies learn to speak by mimicking the words they hear. But a new study shows that babies also might try to imitate the singing they hear in songs.

As part of the study, scientists captured audio of a 15-month-old boy making sounds similar to the beginning of the song "Happy Birthday," hours after he heard the song played on a toy. An analysis of the sounds showed the boy hitting the first six notes of "Happy Birthday" almost spot-on, in G major.

"We know that throughout the first year of life babies become sophisticated music listeners -- they learn a lot about the patterns of pitches and rhythms in music," said Lucia Benetti, a doctoral student at The Ohio State University School of Music and lead author of the study, which was recently published in the Journal of Research in Music Education. "And infants become better at doing this spontaneously. But we don't know much about how exactly this happens."

The study is among the first to measure an infant's attempt to recreate music by following him for an entire day.

"And what we learned is that in this one case at least, the baby is trying to sing along to songs he's hearing," Benetti said.

For the study, Benetti recorded one infant, a 15-month-old boy named James, through one 16-hour period. James wore a small, light recording device throughout the day, which captured every sound he heard and made. Benetti and her adviser, Eugenia Costa-Giomi, a professor of music education at Ohio State, then analyzed that audio data using software designed to measure language -- things like the number of adult words the baby heard and tried to say. Benetti also listened to the recording and transcribed the music he heard and the music he made, searching for patterns or places where the child seemed to mimic what he heard happening around him.

That technology has primarily been used in previous research studies to collect data that shows how babies develop language, not to understand how they might begin to learn about music.

James' parents also logged his primary activities that day -- things like napping and meals.

In the morning, James spent about 10 minutes with a toy that played the melody of "Happy Birthday." Later that evening, the device recorded James making about 10 sounds, lasting about four seconds, that resembled the beginning of "Happy Birthday."

The researchers shared the recordings with people who didn't know James and didn't know what the researchers were studying. Those listeners reported that James was trying to sing "Happy Birthday."

Shortly after James ate lunch, his mom sang the song "Rain Rain" to him twice. (You know how it goes -- "Rain, rain, go away, come again some other day.") Six hours later, James was playing with his father and started singing a version of "Rain Rain." (The research notes that he sang it for seven seconds in the key of A-flat major.)

James' dad immediately picked up on what his son was trying to do, and sang the song back to him. James repeated it.

(James' dad also made up funny lyrics -- "Scrambled eggs, scrambled eggs, makes big muscles in my legs." James didn't repeat those.)

The study shows that it's possible for babies to learn melodies from the music they hear around them, Benetti said. She said future work could examine a larger group of babies, with more data, to see whether James' response was typical.

"We could try to do it systematically to really start to understand how this learning occurs," she said. "From this study, we at least know that it happens."

The takeaway for parents? It can't hurt to sing to your kids.

"The social aspect of music is important -- if a baby sees their mother singing, they know she's engaging with that song, that she's enjoying it, and they know it must be important," Benetti said.

"I think that social context is important. It's engaging and it's socially relevant, and for them, that's enough."

A new study of molecular interactions central to the functioning of biological clocks explains how certain mutations can shorten clock timing, making some people extreme "morning larks" because their internal clocks operate on a 20-hour cycle instead of being synchronized with the 24-hour cycle of day and night.

The study, published February 11 in eLife, shows that the same molecular switch mechanism affected by these mutations is at work in animals ranging from fruit flies to people.

"Many people with sleep phase disorders have changes in their clock proteins," said Carrie Partch, associate professor of chemistry and biochemistry at UC Santa Cruz and a corresponding author of the paper. "Generally, mutations that make the clock run shorter have a morning lark effect, and those that make the clock run longer have a pronounced night owl effect."

In the new study, researchers focused on mutations in an enzyme called casein kinase 1 (CK1), which regulates a core clock protein called PERIOD (or PER). Clock-altering mutations in CK1 had been known for years, but it was unclear how they changed the timing of the clock.

CK1 and other kinase enzymes carry out a reaction called phosphorylation, adding a phosphate to another protein. It turns out that CK1 can phosphorylate either of two sites on the PER protein. Modifying one site stabilizes PER, while the other modification triggers its degradation. Partch and her colleagues showed how mutations in either CK1 or PER itself can alter the balance, favoring degradation over stabilization.

PER proteins are part of a complex feedback loop in which changes in their abundance set the timing of circadian rhythms, so mutations that increase the rate of PER degradation throw off the clock.

"What we discovered is this neat molecular switch that controls the abundance of the PER proteins. When it's working right, it generates a beautiful 24-hour oscillation," Partch said.

Partch's lab performed structural and biochemical analyses of the CK1 and PER proteins that suggested how the switch works. To confirm that the interactions observed in the test tube matched the behavior of the proteins in living cells, they worked with researchers at the Duke-NUS Medical School in Singapore. Other collaborators at UC San Diego performed simulations of the molecular dynamics of the switch showing how the CK1 protein switches between two conformations, and how mutations cause it favor one conformation over another.

The switch involves a section of the CK1 protein called the activation loop. One conformation of this loop favors binding of CK1 to the "degron" region of PER, where phosphorylation leads to the protein's degradation. The clock-changing mutations in CK1 cause it to favor this degron-binding conformation.

The other conformation favors binding to a site on the PER protein known as the FASP region, because mutations in this region lead to an inherited sleep disorder called Familial Advanced Sleep Phase Syndrome. The stabilization of PER can be disrupted by either the FASP mutations, which interfere with the binding of CK1 to this region, or by the mutations in CK1 that favor the alternate conformation of the activation loop.

The new findings also suggest why binding of CK1 to the FASP region stabilizes PER. With phosphorylation of the FASP region, that region then acts to bind and inhibit CK1, preventing it from adopting the other conformation and phosphorylating the degron region.

"It binds and locks the kinase down, so it's like a pause button that prevents the PERIOD protein from being degraded too soon," Partch said. "This stabilizing region builds a delay into the clock to make it align with Earth's 24-hour day."

Partch noted that it is important to understand how these clock proteins regulate our circadian rhythms, because those rhythms affect not only the sleep cycle but almost every aspect of our physiology. Understanding these molecular mechanisms may enable scientists to develop therapies for intervening in the clock to alleviate disruptions, whether they are caused by inherited conditions or by shift work or jet lag.

"There might be ways to mitigate some of those effects," she said.

CK1 is also interesting because it seems to be the most ancient component of biological clocks. The whole feedback loop involving CK1, PERIOD, and other core clock proteins is found in all animals from insects to humans. CK1, however, is also found in every other organism with eukaryotic (nonbacterial) cells, including single-celled green algae in which it has been implicated in circadian rhythms.

"Our results provide a mechanistic foundation to understand the essentially universal role of CK1 as a regulator of eukaryotic circadian clocks," Partch said.

The scent of a romantic partner can improve sleep, suggests new psychology research from the University of British Columbia.

The researchers found that study participants who were exposed to their partner's scent overnight experienced better sleep quality, even though their partner was not physically present.

"Our findings provide new evidence that merely sleeping with a partner's scent improves sleep efficiency. Our participants had an average sleep efficiency improvement of more than two per cent," said Marlise Hofer, the study's lead author and a graduate student in the UBC department of psychology. "We saw an effect similar in size to what has been reported from taking oral melatonin supplements - often used as a sleep aid."

For the study, the researchers analyzed sleep data from 155 participants who were given two identical-looking t-shirts to use as pillowcases - one had been previously worn by their romantic partner, and the other had either been previously worn by a stranger or was clean.

To capture body odour on the t-shirts, the participants' partners were given a clean t-shirt to wear for 24 hours, and were asked to refrain from using deodorant and scented body products, smoking, exercising and eating certain foods that could affect their body odour. The t-shirts were then frozen to preserve their scent.

Each participant was then given two shirts to place over their pillows, without being told which one was which. They spent two consecutive nights sleeping with each t-shirt. Each morning, they completed a survey about how well-rested they felt. Their sleep quality was also objectively measured using an actigraphy sleep watch that monitored their movements throughout the night. At the end of the study, participants guessed if the shirts they had been sleeping with had previously been worn by their partner.

Participants reported feeling more well-rested on the nights when they believed they were sleeping with their partner's scent. Moreover, regardless of their beliefs about scent exposure, data from the sleep watches indicated that objective sleep improved when participants were actually exposed to their partner's scent.

"One of the most surprising findings is how a romantic partner's scent can improve sleep quality even outside of our conscious awareness," said Frances Chen, the study's senior author and associate professor in the UBC department of psychology. "The sleep watch data showed that participants experienced less tossing and turning when exposed to their partners' scent, even if they weren't aware of whose scent they were smelling."

The researchers say the physical presence of a long-term romantic partner is associated with positive health outcomes such as a sense of safety, calm and relaxation, which in turn leads to better sleep. By signalling recent physical proximity, the mere scent of a partner may have similar benefits.

Hofer says the research could pave the way for future work examining the efficacy of simple and effective methods of improving sleep, such as bringing a partner's shirt the next time you travel alone.

The researchers are currently recruiting participants for a pilot study to investigate whether the scent of parents can improve their infant's sleep quality.

Researchers at the University of Technology Sydney (UTS) have developed a cost-effective and practical method to protect pipelines and keep them operating during significant fault rupture incidents and large ground movements.

Australia's pipeline length of 50,000 km has a critical role in transporting water, gas and oil products, and transferring sewage to treatment plants.

UTS Associate Professor Behzad Fatahi (Head of Geotechnical and Transportation Discipline) supported by Habib Rasouli (PhD Candidate) at the School of Civil and Environmental Engineering developed an advanced three-dimensional computer model to assess the mechanical performance of a pipeline protected by proposed polymer blocks under a strike-slip (horizontal) fault rupture.

While Australia is a relatively stable continental region with low to moderate magnitude earthquakes expected, there are numerous active fault lines such as the Darling fault, extending over 1000 km in the west where most oil products - including 71% of crude oil and condensate - are produced.

"Polymeric geofoam blocks as an inexpensive and light material can offer a safer and cost-effective solution to the challenges faced by Australia engineers passing pipelines through fault lines, increasing Australian competitiveness in international market as well as safety and reliability," said Dr Fatahi.

His findings prove pipes protected with geofoam blocks have a superior performance and remain operational under different strike-slip fault rupture scenarios, while the conventional buried pipelines suffer catastrophic damage. This proposed solution can save lives and reduce the potential environmental disaster due to content leakage.

"We can see how conventional pipelines buried in soil could be severely damaged under a strike-slip fault rupture due to excessive longitudinal compressive and tensile strains in the pipeline, or how the pipe section could be flattened due to bending of the pipeline," he said.

The unacceptable performance of buried water mains, sewage network, and oil and gas pipelines could all lead to environmental disasters due to content leakage.

Researchers led by Tokyo Medical and Dental University find that neuronal necrosis occurs much earlier in Alzheimer's disease progression than originally thought, and uncover a novel target for future treatment strategies

Tokyo, Japan - Alzheimer's remains the leading cause of dementia in Western societies, with some estimates suggesting that as many as 24 million people worldwide are living with the disease. Alzheimer's is characterized by a progressive decline in cognitive ability that eventually affects even basic functions such as walking and swallowing. The exact cause of Alzheimer's is unknown, but pathological changes in the brain, including neuron loss and an accumulation of protein aggregates called beta-amyloid plaques, are a diagnostic hallmark of Alzheimer's disease.

Mild cognitive impairment (MCI) describes the slight but measurable changes in cognitive function that are often a precursor to Alzheimer's disease. However, despite the importance of MCI, very little is known about the changes that occur in the brain during the progression from MCI to Alzheimer's.

In a recent study published in Nature Communications, researchers led by Tokyo Medical and Dental University have now discovered that preventing pathological changes in the brain at the MCI stage could eliminate Alzheimer's disease altogether.

"Neuronal death, is obviously very important in the development of Alzheimer's, but is notoriously difficult to detect in real time because dying cells cannot be stained using chemical or immunohistological methods," says lead author of the study Hikari Tanaka. "Because of this, we used a new biomarker called pSer46-MARCKS to detect degenerative neurites surrounding dying neurons, allowing us to quantify levels of necrosis, a prototype of neuronal death, at different stages of disease."

Surprisingly, the researchers found that neuronal death occurred much earlier than originally thought, with higher levels of necrosis seen in patients with MCI than in patients with full-blown Alzheimer's disease.

The researchers also observed a significant decrease in the levels of a protein known as YAP in Alzheimer's disease model mice and human patients with MCI. YAP positively affects the activity of a second protein called TEAD, a deficiency of which leads to neuronal necrosis. Microscopic examination revealed that the missing YAP was sequestered within beta-amyloid plaques, which have also been linked to neuronal toxicity.

By directly injecting a gene therapy vector expressing YAP analog into the cerebral spinal fluid of mice that were genetically engineered to provide a model of Alzheimer's, the researchers were able to prevent early-stage neuron loss, restore cognitive function, and prevent the development of beta-amyloid plaques.

"Confirming that neuronal necrosis was dependent on YAP was really the pivotal moment for us, but observing the almost transformative effects of YAP supplementation was hugely exciting," says senior author of the study Hitoshi Okazawa. "By showing that neuronal necrosis is YAP-dependent and begins prior to the onset of most symptoms, we predict that novel Alzheimer's disease therapies will be developed to prevent the initiation of Alzheimer's disease."

"Another important issue is that the necrosis of neurons accumulating intracellular beta-amyloid occurs before formation of beta-amyloid plaques," continues Professor Okazawa. "Residual beta-amyloid after neuronal necrosis seems to be the seed for beta-amyloid plaques outside of neurons. This discovery might change the amyloid hypothesis considering that extracellular beta-amyloid plaque is the top of pathological cascade of Alzheimer's disease."

Dr Rebecca Monk and Professor Derek Heim carried out a computer-based study in bars and pubs local to the University's Ormskirk campus, by asking participants to respond to stimuli while ignoring photos of attractive and unattractive faces.

The findings of the study - published this week in Psychology of Addictive Behaviors - showed that while sober participants were distracted more by attractive faces, the attention of those who were intoxicated was diverted equally by both attractive and unattractive faces.

"Previous research into the beer goggles phenomena yielded inconsistent findings and has been largely limited to asking people directly about how attractive they find others" said Dr Monk, the lead author of the study. "By using an indirect measure of attention, our research was able to overcome some of these limitations.

"We know that attractive faces can pull attention away from the task at hand, but our research suggests that alcohol has the capacity to lessen this effect; to level the playing field."

More than 120 participants - both sober and intoxicated - were asked to indicate on a laptop whether the letter 'T' was the correct way around or inverted, while being told to ignore the series of faces that were shown on the screen at the same time.

Professor Derek Heim added: "Most people have heard of the 'beer goggles' effect, and our research adds to the body of evidence showing that there is some truth to this anecdotal wisdom.

"It's remarkable that in our study participants were only mildly intoxicated, suggesting that it doesn't take much alcohol at all for people to 'put on their beer goggles'."

WASHINGTON D.C. -- Average employer-sponsored insurance (ESI) spending rose to $5,892 per person in 2018, according to the Health Care Cost Institute's annual Health Care Cost and Utilization Report, which analyzes 2.5 billion medical claims to inform the public about trends affecting approximately 160 million U.S. individuals with employer-sponsored insurance. This spending growth outpaced 2017's growth due to continued price growth combined with an uptick in utilization.

"Prices, spending, and out-of-pocket costs continue to rise for the 160 million Americans with employer-sponsored health insurance," said Niall Brennan, president and CEO of HCCI. "Higher prices for medical services continue to drive most spending increases, but in 2018 we also saw an uptick in utilization for the first time in several years. If these price and utilization trends continue, we expect spending growth to stay on an upward trajectory in the coming years."

Despite recent increases in utilization, rising prices were the primary driver of spending growth over the 5-year study period. After adjusting for inflation, spending rose by $610 per person between 2014 and 2018. "Higher prices for medical services were responsible for about three-quarters of overall spending increases between 2014 and 2018, after inflation," said Jean Fuglesten Biniek, report co- author and senior researcher at HCCI.

While utilization changes accounted for a smaller share of spending growth after inflation, about one- fifth, most of the increase in use occurred over just one year. The increase in utilization in 2018 had a greater effect on costs than a similar increase would have had earlier in the period because of price growth between 2014 and 2017.

The report examines four groups of health care services and dozens of sub-categories. Of the four major categories, outpatient visits and procedures saw the highest 2018 spending increase (5.5%).

Other notable trends include:

Inpatient services.

Per-person spending on inpatient admissions rose 11.4% between 2014 and 2018.

Within each sub-category of inpatient admissions, average prices grew steadily between 2014 and 2018 while utilization trends varied. However, the 2.0% price increase in 2018 was lower than the near 4% annual increases from 2014 to 2017.

Outpatient services.

Increases in prices and use led to a 16% increase in spending from 2014 to 2018.

Over that period, ER visit spending increased 32% and spending on observation stays
went up 29%.

Professional services.

Spending increased 16% and growth accelerated over the 5-year period, driven by office visits and administered drugs.

Psychiatry also saw strikingly high spending growth of 43% from 2014 to 2018, which was driven mostly by increased use.

Prescription drugs.

Generic drugs accounted for 88% of all prescriptions.

Out-of-pocket payments for prescriptions for generic drugs was less than one-fifth of out-of-pocket payments on brand drugs.

Out-of-pocket spending grew in each year of the 5-year period. "People with job-based insurance saw their out-of-pocket costs rise 14.5%, or $114, between 2014 and 2018," said John Hargraves, senior researcher and co-author of the report. Study authors stressed that the analysis covers out-of-pocket costs paid for services, such as copays, coinsurance, or deductible payments, but does not include other payments related to health care like insurance premiums.

Methodology. Since 2011, HCCI has tracked, independently analyzed, and reported health care spending, utilization, and prices each year in its Health Care Cost and Utilization Report, using de- identified claims data of people up to age 65 with employer-sponsored health insurance. Data come from four of the largest health insurance providers in the U.S. -- Aetna, Humana, Kaiser Permanente and UnitedHealthcare -- representing about 26 percent of the employer-sponsored insured population. For this year's report utilization and price measures for three of the four service categories (the exception being prescription drugs) were adjusted to account for changes in the mix of services provided in each category, and therefore, facilitate comparisons across years. Further, measures of drug spending reflect discounts negotiated from the wholesale price of drugs but do not include manufacturer rebates that are provided through separate transactions. Thus, drug prices reflect the point-of-sale prices.

The cost of smoking in the UK has risen since the advent of 'plain packs' for cigarettes in 2017, countering claims made by the tobacco industry at the time that the public health measure would lead to discount pricing.

Authors of the new study from the University of Bath's Tobacco Control Research Group (TCRG), argue their findings provide important evidence to policymakers in the UK and around the world of the effectiveness of standardised packaging.

The new paper, published in the journal PLOS One (embargoed 2pm ET / 7pm GMT, Thursday 13 February 2020), highlights the impact of standardised packaging, comparing prices pre- and post-implementation from 2015-18.

During consultation on the introduction of plain packaging for cigarettes in the UK, major tobacco companies claimed smokers would refuse to pay high prices for premium cigarettes in plain packs so the policy would lead to falling prices, which in turn would increase smoking rates.

By analysing tobacco sales data, the researchers from Bath found the reverse: prices were higher one year after standardised packaging legislation was fully adopted, when compared to prices in 2015 when branding was still permitted (by 20p per pack of 20; 60p per RYO 30g pouch).

Principal Investigator and Director of the Tobacco Control Research Group, Professor Anna Gilmore explains: "Like many tobacco industry predictions, their claims did not withstand scrutiny. In fact, we found that prices in most market segments rose faster after the policy than before."

Through their latest analysis, the researchers argue this was achieved partly through the introduction of new requirements under a minimum excise tax (MET). Introduced to coincide with the introduction of plain packs, the MET's objective was to make it harder for the tobacco industry to keep factory made cigarettes cheap.

Cheap tobacco makes it easier for young people to start smoking and harder for smokers to stop. The TCRG's previous work had shown that tobacco companies were gaming the tobacco tax system by over-shifting taxes on their premium products (to maximise profits) and using this to offset minimal revenue on their cheapest products where they absorbed the tax increases to keep these products as cheap as possible.

The MET aims to stops tobacco companies from doing this by forcing them to pay at least £5.88 (currently) to the government every time a pack of 20 cigarettes is sold - it works like a minimum price, but one tobacco companies have to pay in tax.

As the new MET duty was introduced in 2017, prices of the cheapest cigarette brands rose towards the prices of other brands and tax increases were passed on more consistently and quickly to smokers.

Professor Gilmore added: "In short, the MET addressed the industry's cheapest cigarette pricing and reduced its ability to manipulate prices. There is an important message to policymakers around the world here: standardised packaging when introduced within a setting of tax increases, does not appear to result in long term price falls."

Kruti Shrotri, Cancer Research UK's tobacco control manager, said: "Smoking is the biggest cause of health inequalities and raising taxes on tobacco is one of the most effective ways to reduce smoking. "The government should use the next budget to increase taxes above inflation for the sake of public health, and make sure that Stop Smoking Services are properly funded so that people who smoke can get support to quit."

The authors hope these findings can be used in jurisdictions around the world when debating the effectiveness of standardised packaging and to counter tobacco industry claims.

While standardised packs has increased the average price of a pack of RYO tobacco, due to the introduction of a 30g minimum pack size, they suggest more needs to be done. Separate studies from the team, published in recent years suggest HM Treasury officials need to re-evaluate taxation on RYO. Their results from 2018 suggested prices for the most popular brand of RYO should almost double.

Economist and tax expert within the research team at the University of Bath, Dr Rob Branston explained: "Higher taxes need to be levied on Roll Your Own tobacco so that it is on a par with factory made cigarettes when it comes to price. Currently there is a price gap which is encouraging RYO purchasing by smokers - in particular poorer ones - and this measure could help them quit this deadly product."

For the first time, researchers managed to make intact human organs transparent. Using microscopic imaging they could revealed underlying complex structures of the see-through organs at the cellular level. Resulting organ maps can serve as templates for 3D-bioprinting technologies. In the future, this could lead to the creation of on demand artificial organs for many patients in need. The findings published in Cell joined forces from Helmholtz Zentrum München, Ludwig Maximilians University Munich (LMU), and Technical University of Munich (TUM).

In biomedical research, seeing is believing. Deciphering the structural complexity of human organs has always been a major challenge due to the lack of technologies to image them at the cellular level. Recent developments in tissue clearing allowed researchers to obtain first cellular views of intact transparent mouse organs in 3D. These methods, however, were not applicable to human organs.

"We had to change our approach completely"

Human organs are particularly stiff due to accumulation of insoluble molecules including collagen in tissues that have grown for years or even decades. Thus, traditional detergents that are used for making mouse organs transparent do not work on human organs, particularly adult ones. "We had to change our approach completely and start from scratch to find new chemicals which can make human organs transparent," says Shan Zhao, PhD student at Helmholtz Zentrum München and first author of the study. After exhausting trials, the team discovered that a detergent called CHAPS could make small holes throughout the entire stiff human organs. CHAPS allows additional solutions to travel deep into centimeters-thick human organs and convert them into a transparent structure.

After making the human organs transparent, which were obtained post mortem from Prof. Ingo Bechmann's lab at the University of Leipzig, the team had to tackle additional challenges for both organ imaging and the analysis of the large amount of resulting data. First, they developed a new laser-scanning microscope with a large sample holding capacity called "Ultramicroscope Blaze" in collaboration with Miltenyi Biotec. This microscope enabled imaging of human organs as large as the kidney. Next, together with Prof. Bjoern Menze from TUM, the team developed deep learning algorithms to be able to analyze hundreds of millions of cells in 3D.

The researchers named this new technology SHANEL (Small-micelle-mediated Human orgAN Efficient clearing and Labeling). "SHANEL can develop into a key technology for mapping intact human organs in the near future. This would dramatically accelerate our understanding of organs such as the brain, their development and function in health and disease," explains Dr. Ali Ertürk, Director of the Institute for Tissue Engineering and Regenerative Medicine at Helmholtz Zentrum München and also Principal Investigator at the Institute for Stroke and Dementia Research at the hospital of LMU.

Final goal: 3D-bioprinting of artificial organs

Cellular maps of human organs could be used to engineer large scale human tissues and organs with emerging 3D-bioprinting technologies. Towards this goal, Ertürk and his team are currently working on mapping major human organs, starting with the pancreas, heart and kidney.

"There is a huge shortage of organ donors for hundreds of thousands of people," says Ertürk. "The waiting time for patients and the transplantation costs are a real burden. Detailed knowledge about the cellular structure of human organs brings us an important step closer to creating functional organs artificially on demand."

Researchers from the University of Illinois at Chicago have discovered that endothelial cells -- those that create the inner lining of blood vessels -- have unique genetic signatures based on their location in the body.

Their study, which is published in the journal eLife, used a genetic mouse model to compare endothelial cells in their natural organ environment. The researchers first looked at healthy mice and compared how genes were expressed in endothelial cells from heart, lung and brain tissues. Next, they studied the blood vessel endothelial cells of unhealthy mice -- those exposed to a bacterial toxin, which mimicked inflammation in the whole body.

Under both conditions, endothelial cells from various organs expressed distinct genetic signatures.

"One of the most surprising findings of this study is that blood vessel endothelial cells in the brain express genes that were previously thought to be primarily found in neurons -- such as the genes involved in the transport of neurotransmitters and synaptic vesicles," said Dr. Jalees Rehman, UIC professor of medicine, pharmacology and bioengineering at the College of Medicine.

Similar results were found for heart endothelial cells, which expressed the genes known to help heart muscle cells beat and pump blood.

"We have had anecdotal descriptions that blood vessel cells function differently in each organ for some time, but newer genetic tools allowed us to perform a global analysis of thousands of genes in the blood vessels of these vital organs," Rehman said.

Rehman said the results of this study can be used to inform the bioengineering of blood vessels that are specific to different organs and that the findings suggest there are untapped avenues for developing more targeted treatments.

"Our findings provide organ-specific blood vessel 'ZIP codes' for the potential delivery of drugs to specific tissues," Rehman said. "Right now, most treatments for vascular disease target all blood vessels regardless of where they are. Imagine if we could develop more effective treatments to uniquely improve the function of blood vessels in the heart or the brain?"

Rehman said that this research suggests that blood vessels may play previously unrecognized roles in some neurological diseases such as Alzheimer's disease and other forms of dementia because the brain's endothelial cells expressed genes involved in cognitive function.

ITHACA, N.Y. - After times of major conflict, such as the civil wars in Liberia from 1980 to 2003, peace often leaves a power vacuum, especially in remote areas not yet reached by a developing government.

"In areas of limited statehood, a country's central authority lacks the ability to implement and enforce rules and decisions," Sabrina Karim, assistant professor of government, wrote in new research published in the American Political Science Review.

The paper, "Relational State Building in Areas of Limited Statehood: Experimental Evidence on the Attitudes of the Police," is based on Karim's research in Liberia. She finds that personal contact between police officers and citizens encourages a positive attitude about the country's central authority because such relationships provide information and facilitate social bonds.

The state earns legitimacy when the public accepts state authority over other sources of authority, including traditional chiefs, criminal groups or external forces such as United Nations peacekeepers.

"As the state expands its enforcement capacity, and as individuals have positive experiences with new state agency personnel, citizens' attitudes toward state authority may change," Karim wrote.

To reach this conclusion, Karim coordinated a study with the Liberian National Police (LNP) to test whether household visits from a pair of police officers - either two male or two female - improved residents' attitudes toward police. Her study also measured whether police officers' gender influenced citizens' acceptance of them.

Building on relationships she's established in Liberia through years of work in the country, Karim collaborated with the LNP to conduct outreach into a rural area, Grand Kru County, as a part of the LNP's community policing expansion.

She prepared four Liberian police officers - teams of two females and two males - to go door to door in randomly selected villages, accompanied by Liberian enumerators. Both teams paid visits of 20-30 minutes each to 375 households; at the end of each visit, officers left a card with the police phone number.

Three weeks later, the 750 households were surveyed about a variety of topics, including perceptions of police. A third set of households, a control group, received no police visits.

The data showed that visits increased citizens' preferences for the police, over alternative sources of security, for a wide range of security issues.

"This could be due to social bonds created with the new state security actor," Karim said. "If citizens did not have personal relationships with a police officer before, the visit put a face to police officers and started a process of trust in the individual police officers who visited them. It led community members to prefer those specific officers to come back and respond if there is a dispute in the community."

There was, however, no added improvement in perceptions of the police among female residents who were visited by female police officers. Karim was surprised at this outcome, but sees it in a positive light.

"Female officers elicit the same response among local men and women as male police officers," she said. "It shows that local men and women are not put off by female police officers."

Based on this study, Karim suggests that building relationships may help a new government earn legitimacy in the eyes of citizens and could help prevent violence in the future.

"The most important kinds of reforms are ones that enable trust-building in the formation of real positive relationships between different groups of people," Karim said, "even more so in a post-conflict country because there's a deficit of trust overall."

Ichthyosaurs were fish-like reptiles that first appeared about 250 million years ago and quickly diversified into highly capable swimmers, filling a broad range of sizes and ecologies in the early Mesozoic oceans. However, this rapid pace didn't last long and an evolutionary bottleneck 200 million years ago, through which only one lineage of ichthyosaurs survived, led to much slower evolution in much of their long history.

Dr Ben Moon, who led the research, published in the journal Communications Biology, said: "Ichthyosaurs are a fascinating group of animals to work on because they evolved so many adaptations for living in water very quickly: a fish-like body and tail fin, giving birth to live young rather than laying eggs, and lots of different feeding styles.

"Because of this we expected to see a rapid evolution early after ichthyosaurs first appeared, but we were staggered by just how big this early burst was and how relatively short it was."

There are over 100 known species of ichthyosaur from between 250-90 million years ago in the Mesozoic Era, when the infamous dinosaurs ruled the land and the seas were full of marine reptiles, the top predators that filled comparable roles to dolphins, orcas, and sharks in modern seas.

The study used state-of-the-art computational methods and looked at two types of data, one covering skull size and the other including many features of ichthyosaurs' skeleton. All methods show an 'early burst' of evolution in ichthyosaurs, with high rates and rapid variation soon after the appearance of the group, that quickly diminishes later on.

Co-author Dr Tom Stubbs said: "Ichthyosaurs really dominated early in the Triassic (252-201 million years ago), rapidly evolving in an ocean with few predators soon after the largest known mass extinction in Earth's history. However, the seas quickly became more crowded and competitive, and ichthyosaurs lost their top position in the Jurassic (201-145 million years ago) to other marine reptiles like plesiosaurs and pliosaurs.

"It may well have been the ichthyosaurs' decreasing evolutionary rates which made them less able to adapt quickly, and therefore less diverse and competitive, allowing other marine reptiles to take over as the top predators."

Despite slower evolution and going through a bottleneck at the end of the Triassic period, ichthyosaurs remained a common group but had less variation between them. These are perhaps best known ichthyosaurs, found in several UK locations, including Lyme Regis in Dorset, and first collected by Mary and Joseph Anning.

Dr Ben Moon added: "Even though ichthyosaurs were evolving more slowly in their last 100 million years, they are still known from many species, but with less variety between them.

"It's possible that we might find more ichthyosaurs out there that buck this trend, but it seems that this lack of variety was eventually the cause of their extinction when global conditions became less favourable around 90 million years ago. Ichthyosaurs were simply unable to adapt."