Culture

Mosquitoes push northern limits with time-capsule eggs to survive winters

image: Overwintering sites and sample locations for experimental populations. Range-core locations in white, range-edge locations in red, and field overwintering sites indicated by red box. A climate-based distribution model (sensu Medley 2010) indicates the predicted range for Ae. albopictus at the time of this study, where darker shading indicates a higher probability of occurrence.

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Journal of Applied Ecology

When the Asian tiger mosquito (Aedes albopictus) arrived in the United States in the 1980s, it took the invasive blood-sucker only one year to spread from Houston to St. Louis. New research from Washington University in St. Louis shows that the mosquitoes at the northern limit of their current range are successfully using time-capsule-like eggs to survive conditions that are colder than those in its native territory.

The northern mosquitoes have adapted to colder winters, compared to their southern counterparts. This new evidence of rapid local adaptation could have implications for efforts to control the spread of this invasive species, which is considered a "competent vector" of numerous pathogens that are relevant to humans, including Zika, chikungunya and dengue viruses. The work is published in the Aug. 21 issue of the Journal of Applied Ecology.

"This all happened within a period of 30 years," said biologist Kim Medley, director of Tyson Research Center and first author of the new study. "This disease vector has evolved rapidly to adapt to the United States. The fact that this has occurred at a range limit may suggest that there is potential for the species to continue to creep farther northward."

Mosquitoes respond to the shortening days signaling winter's onset by laying diapause eggs --  literally, delayed development eggs. These special eggs contain a fertilized embryo that's in a state of almost-hibernation and has a very slow metabolism. The result is almost like a mosquito time capsule.

The ability to produce eggs that can wait to hatch is not something new. This technique helps mosquitoes survive the winter cold, but it works for dry conditions as well. All mosquitoes lay their eggs in or near standing water, and the larvae need to hatch into standing water. But they can survive getting dried out in between.

Still, diapause eggs are different from regular eggs. Previous research had showed that northern mosquitoes lay more diapause eggs than their southern cousins. What researchers didn't know was how these eggs actually perform in the conditions in which they're prepped to perform.

For this new field experiment, Medley and her team, including Katie M. Westby, postdoctoral research associate at Tyson Research Center, collected live mosquito eggs and larvae from cities near the center of the habitat they've invaded (Huntsville, Ala.; Macon, Ga.; Beaufort, S.C.) and also from the approximate northern edge of their U.S. range (Peoria, Ill.; Columbus, Ohio; and Harrisburg, Pa.) The researchers hatched and raised these mosquitoes and their subsequent generations in batches in the laboratory.

Then it was time to get cold. The researchers exposed the mosquitoes to shortened periods of light to signal the onset of winter. They collected the diapause eggs that the mosquitoes produced, then dispatched batches of eggs to endure real winters in four different locations: in field sites at the northern edge and core of their current range; in a climate-controlled laboratory site that represented the "optimal" winter conditions in the mosquitoes' home territory in Japan; and in a far-north site in Wisconsin, clearly outside of the mosquitoes' current established range.

After that real winter passed, the researchers brought the eggs back into the lab and hatched them out.

"We counted all of the eggs to see how many survived the winter in all of these locations," Medley said. "What we learned was that the northern mosquitoes' diapause eggs survived northern winters significantly better than the southern mosquitoes' eggs did.

"Everybody did OK in the southern range winter," she said. "They performed about the same." The same was true for those in the chamber with the optimal conditions. As for Wisconsin? Well ...

"Nobody survived that Wisconsin winter," Medley said.

While the Wisconsin conditions are too harsh for these mosquitoes -- at least for now -- Medley is particularly interested in the changes that she is observing at the very edge of what is survivable.

"These northern mosquitoes are producing a lot more diapause eggs," Medley said. "Now we know that these eggs also do a lot better in the winter."

What Medley and her team learned is important not just for this species but for ecologists studying how animals adapt to new conditions and push the boundaries of their historic ranges.

"Based on theory, we expect that populations at range limits will be small, they will be fragmented and that they will be low in genetic diversity," she said. "It's thought that these populations will not have the demographic and genetic robustness to adapt, so they remain at this state of maladaptation.

"That may not be the case with this species," Medley said.

Credit: 
Washington University in St. Louis

Family history of diabetes linked to increased bone mineral density

CLEVELAND, Ohio (August 21, 2019)--The association between type 2 diabetes and increased fracture risk is well documented. However, little was known about the possible effect of family history of diabetes on bone mineral density (BMD). A study from China now confirms that a history of first-degree family members with diabetes is linked to increased BMD as well as to insulin resistance. Results are published online in Menopause, the journal of The North American Menopause Society (NAMS).

Because patients with type 2 diabetes are at an increased risk of fracture, understanding the early pathophysiology of altered BMD could be critical in the development of preventive strategies for diabetic osteoporosis. Although strong evidence has revealed normal to high BMD in most patients with type 2 diabetes, no data have been published, to date, that demonstrate whether BMD is altered in persons with a first-degree family history of diabetes.

In this new study involving nearly 900 normoglycemic postmenopausal women, it was found that the BMD of the lumbar spine and femoral neck was significantly higher in participants with a first-degree family history of diabetes than in those without such history, even in women with normal blood glucose levels. These same participants additionally showed increased insulin resistance and hyperinsulinemia.

Findings were published in the article "Association of bone mineral density with a first-degree family history of diabetes in normoglycemic postmenopausal women."

"This study shows an association between a family history of diabetes and increased bone density in postmenopausal women. This finding may be related to higher insulin levels in these women with a hereditary predisposition to diabetes, because insulin has a bone-building effect. Although this sounds like good news, these women are at increased risk for developing diabetes, which is associated with skeletal fragility and increased fracture risk," says Dr. Stephanie Faubion, NAMS medical director.

Credit: 
The Menopause Society

Optimizing fertilizer source and rate to avoid root death

image: Canola is a crop from which seeds are commonly harvested to create canola oil and meal. Canola is in the family of Brassica plants.

Image: 
Meghnath Pokharel

Fertilizer is used worldwide in farming. It's used to give plants a boost, increasing yield and ultimately farmers' profits.

But, as the old adage goes: the dose makes the poison. Similar effects are seen in over-the-counter medicines. They need to take the right dose, at the right intervals, to be safe and effective. Fertilizer works the same way.

In particular, the rate and source of the fertilizer can make the difference, especially in a method called banding. It's a method where the fertilizer is placed in a band in the soil below the seed. While banding has many advantages, it can also cause damage to the plant roots if used incorrectly.

"While banding below and to the side is the recommended practice, banding directly below the seed continues to be a common practice used in dryland systems," says Isaac Madsen. "It can reduce the number of passes across the field required in a growing season. Banding also allows you to put on all or most of your fertilizer at one time. This generally causes less disturbance in a minimum or no-till system." Madsen is a postdoctoral research associate at Washington State University.

Researchers like Madsen are trying to find the ideal rate and source that will help the plants without damaging the roots. Madsen and his team studied canola in particular. New imaging and analysis techniques allowed them to see canola roots interacting with fertilizer in a way never previously done.

"In this study, we imaged canola roots growing into a fertilizer band and measured the damage to the canola tap root," Madsen explains. "Using scanner-based rhizoboxes (glass boxes filled with soil), we were able to collect a series of root images over time. This allowed us to look at the effect of fertilizer rate and source on the seedling root systems."

The reason the root damage is of such concern in canola is because it has a long tap root. These larger roots are especially affected by fertilizer. If the tap root is damaged, the plant can't properly take up nutrients and water.

The team's end goal was to determine what is called a dose-response curve. This will help farmers better apply their fertilizer and know if it will harm their crops' roots or not. They used the data they collected from the root images to develop these curves for the different fertilizer sources.

"A dose-response curve helps determine the amount or dose of a substance that will result in a specific response," Madsen says. "In this instance we modeled tap root survival, depth, and distance from fertilizer band."

They used three sources of nitrogen fertilizer in their study: urea, ammonium sulfate, and urea ammonium nitrate. Each one reacts differently in the soil, and the researchers thought they would cause different amounts of damage to the roots.

Madsen says their results show that banding urea ammonium nitrate rather than urea, along with keeping the rates low, is the best option for canola. He adds that this research is important for canola growers in the Pacific Northwest area. It helps establish guidelines for them to apply nitrogen fertilizers.

"I think banding is, indeed, frequently the best practice," says Madsen. "But we need to be careful with our rates and sources. Banding of fertilizers will not cause problems as long as the rates used are low enough and the sources used are safe enough. My research goal is to develop rate and source guidelines that growers can use to minimize damage and maximize fertility."

Madsen says the imaging techniques used in this study were unique and very useful. Getting a glimpse at the roots can be valuable. It allows something usually hidden beneath the soil and important for plant health to be studied in real time.

"I really like taking pictures and making videos of roots," Madsen adds. "There is something immensely satisfying about making videos of phenomena which have not been imaged before."

Credit: 
American Society of Agronomy

Electronic dance music party-goers at increased risk for drug-related emergencies

People who frequent electronic dance music (EDM) parties often use multiple drugs simultaneously and experience adverse effects with some ending up in the emergency department, say researchers at New York University School of Medicine and Rutgers University.

The study, published in the International Journal of Drug Policy, is the first to survey adverse effects associated with use of dozens of different drugs and could improve treatment for drug-related emergencies.

The researchers surveyed 1,029 people ages 18 to 40 as they entered EDM parties in New York City in 2018. They were asked about their use of drugs -- including opioids, alcohol, marijuana and other common illegal drugs -- over the past year, whether they had experienced adverse effects after using the drugs, and if they sought medical care. Adverse effects were defined as harmful or very unpleasant effects in which users were concerned about their immediate safety.

The study estimates that one-third of people at these events, commonly held at nightclubs and large outdoor dance festivals, have experienced a drug-related adverse effect over the past year. Of these, 40 percent experienced an adverse effect on more than one occasion and 5 percent experienced adverse effects on four or more occasions. Also, the more frequently people attended these parties, the more likely they were to experience an adverse drug reaction. The study also found that two-thirds of adverse effects involved alcohol, more than one-third involved marijuana, and 15 percent involved Ecstasy, commonly referred to as "Molly" when in powder or crystal form.

"Alcohol use was associated with the greatest number of adverse outcomes, perhaps due to its ubiquitous nature and its impact on judgment," said study co-author Lewis Nelson, a professor of emergency medicine at Rutgers New Jersey Medical School.

"Our findings suggest that drug use is not only prevalent among people who attend electronic dance music parties, but that there's also a substantial amount of drug-related harm," said lead author Joseph Palamar, an associate professor at the NYU School of Medicine.

About 37 percent of adverse effects occurred after marijuana use and more than one-third of these ate edible marijuana. "This may be the result of consuming too many edibles to accelerate the high or to experience a more intense or prolonged high. The increasing, and unpredictable, potency of cannabis also contributes to the difficulty in controlling the dose consumed" Nelson said.

One-fifth of those using Ecstasy or Molly reported an adverse effect. Of these, 14 percent felt the need to visit an emergency department, and one-half of those people did seek such help. Prescription opioids were used less than other drugs; however, 41 percent of nonmedical users had experienced an adverse reaction, with 14 percent making a trip to an emergency department. "Opioids are a high-risk group of drugs, particularly when used in combination with alcohol or other drugs," said Nelson.

Although infrequently used, synthetic cathinones - also known as "bath salts" -- were most likely to result in a hospital visit. "Our finding about 'bath salt' use leading to emergency room visits is particularly alarming because we've been finding that a lot of people who think they're using Molly are often using 'bath salts' without realizing it," Palamar added.

"While we couldn't deduce to what extent adverse effects occurred at these parties, these are high-risk venues due to a combination of drug use and environmental factors," he continued. "Dancing for hours, hot temperatures, and dehydration appear to exacerbate the risk for adverse effects among those who use drugs."

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Rutgers University

Speed identified as the best predictor of car crashes

Speeding is the riskiest kind of aggressive driving, according to a unique analysis of data from on-board devices in vehicles.

Researchers at the University of Waterloo examined data from 28 million trips for possible links between four bad driving behaviours - speeding, hard braking, hard acceleration and hard cornering - and the likelihood of crashes.

Speeding is the riskiest kind of aggressive driving, according to a unique analysis of data from on-board devices in vehicles.

Researchers at the University of Waterloo examined data from 28 million trips for possible links between four bad driving behaviours - speeding, hard braking, hard acceleration and hard cornering - and the likelihood of crashes.

Their analysis revealed speeding is a strong predictor of crashes, while statistically significant links for the other kinds of aggressive driving couldn't be established.

"For insurance companies using this telematics data to assess who is a good risk and who isn't, our suggestion based on the data is to look at speed, at people driving too fast," said Stefan Steiner, a statistics professor in Waterloo's Faculty of Mathematics.

Data for the study came from insurance companies in Ontario and Texas with clients who had on-board diagnostic devices installed in their vehicles.

In the first study of its kind, researchers initially analyzed the data to identify 28 crashes based on indicators such as rapid deceleration.

Each vehicle in those crashes was then matched with 20 control vehicles that had not been in crashes, but were similar in terms of other characteristics, including geographic location and driving distance.

When the crash cases were compared to the control cases using a sophisticated penalty system for the four kinds of bad driving, speeding emerged as the key difference between them.

"Some of the results are no surprise, but prior to this we had a whole industry based on intuition," said Allaa (Ella) Hilal, an adjunct professor of electrical and computer engineering. "Now it is formulated - we know aggressive driving has an impact."

Steiner cautioned that the study was limited by several unknowns, such as different drivers using the same vehicle, and more research is needed to verify the results.

But he said the analysis of telematics data could eventually revolutionize the insurance industry by enabling fairer, personalized premiums based on actual driving behaviour, not age, gender or location.

Hilal believes the data could also make roads safer by giving drivers both tangible evidence and financial incentives to change.

"Having this information exposed and understood allows people to wrap their minds around their true risks and improve their driving behaviours," she said. "We are super pumped about its potential."

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University of Waterloo

Fake news can lead to false memories

Voters may form false memories after seeing fabricated news stories, especially if those stories align with their political beliefs, according to research in Psychological Science, a journal of the Association for Psychological Science.

The research was conducted in the week preceding the 2018 referendum on legalizing abortion in Ireland, but the researchers suggest that fake news is likely to have similar effects in other political contexts, including the U.S. presidential race in 2020.

"In highly emotional, partisan political contests, such as the 2020 US Presidential election, voters may 'remember' entirely fabricated news stories," says lead author Gillian Murphy of University College Cork. "In particular, they are likely to 'remember' scandals that reflect poorly on the opposing candidate.'

The study is novel because it examines misinformation and false memories in relation to a real-world referendum, Murphy explains.

She and her colleagues, including leading memory researcher Elizabeth Loftus of the University of California, Irvine, recruited 3,140 eligible voters online and asked them whether and how they planned to vote in the referendum.

Next, the experimenters presented each participant with six news reports, two of which were made-up stories that depicted campaigners on either side of the issue engaging in illegal or inflammatory behavior. After reading each story, participants were asked if they had heard about the event depicted in the story previously; if so, they reported whether they had specific memories about it.

The researchers then informed the eligible voters that some of the stories they read had been fabricated, and invited the participants to identify any of the reports they believed to be fake. Finally, the participants completed a cognitive test.

Nearly half of the respondents reported a memory for at least one of the made-up events; many of them recalled rich details about a fabricated news story. The individuals in favor of legalizing abortion were more likely to remember a falsehood about the referendum opponents; those against legalization were more likely to remember a falsehood about the proponents. Many participants failed to reconsider their memory even after learning that some of the information could be fictitious. And several participants recounted details that the false news reports did not include.

"This demonstrates the ease with which we can plant these entirely fabricated memories, despite this voter suspicion and even despite an explicit warning that they may have been shown fake news," Murphy says.

Participants who scored lower on the cognitive test were no more prone to forming false memories than were higher scorers, but low scorers were more likely to remember false stories that aligned with their opinions. This finding suggests that people with higher cognitive ability may be more likely to question their personal biases and their news sources, the researchers say.

Other collaborators on the project include Rebecca Hofstein Grady and Linda J. Levine at UC Irvine and Ciara Greene of University College Dublin. The researchers say they plan to expand on this study by investigating the influence of false memories related to the Brexit referendum and the "#MeToo movement."

Loftus says understanding the psychological effects of fake news is critical given that sophisticated technology is making it easier to create not only phony news reports and images, but fake video, as well.

"People will act on their fake memories, and it is often hard to convince them that fake news is fake," Loftus says. "With the growing ability to make news incredibly convincing, how are we going to help people avoid being misled? It's a problem that psychological scientists may be uniquely qualified to work on."

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Association for Psychological Science

What drives inflammation in type 2 diabetes? Not glucose, says new research

image: Research led by Barbara Nikolajczyk, Ph.D., disproved the conventional wisdom that glucose was the primary driver of chronic inflammation in type 2 diabetes.

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University of Kentucky Office of Research Communications

LEXINGTON, Ky. (Aug. 21, 2019) -- To date, the underlying causes of inflammation in obesity and type 2 diabetes mellitus (T2DM) have been poorly understood, which has hampered efforts to develop treatments to prevent complications from a disease that is the third leading cause of death in the United States.

But new research at the University of Kentucky shows that changes to mitochondria--the powerhouse of cells--drive chronic inflammation from cells exposed to certain types of fats, shattering the prevailing assumption that glucose was the culprit.

Chronic inflammation fuels many of the devastating complications of type 2 diabetes, including cardiovascular, kidney, and periodontal diseases, and is thus one of the key targets for therapy development. This new data may enlighten the conversation about tight glycemic control as the dominant treatment goal for people with diabetes.

The research was recently published in Cell Metabolism by a team led by Barbara Nikolajczyk (UK Barnstable Brown Diabetes Center, Department of Pharmacology and Nutritional Sciences) and Douglas Lauffenberger (MIT Department of Biological Engineering).

Nikolajczyk and Lauffenberger didn't set out to disprove the glucose-inflammation causation theory. Based on the importance of glycolysis--a 10-reaction sequence that produces energy--in other types of inflammation, the team hypothesized that immune cells from patients with type 2 diabetes would produce energy by burning glucose. "We were wrong," Nikolajczyk said.

"We exclusively used immune cells from human subjects for all of the work, " Nikolajczyk explained, noting that humans, but not animal models of type 2 diabetes, have the specific pro-inflammatory T cell profile her team had identified in earlier research.

The team was surprised to find that glycolysis wasn't driving chronic inflammation. Instead, a combination of defects in mitochondria and elevated fat derivatives were responsible.

Nikolajczyk said she sees applications for this research in both basic and clinical sciences. She hopes to precisely define pro-inflammatory lipid types and explore associations between circulating and/or tissue-associated lipids and insulin resistance, one key feature of Type 2 diabetes. She is also interested in contributing to the development of new analytical approaches, spearheaded by Dr. Lauffenburger's team, that leverage ongoing lipid-related findings into a new understanding of pathology in type 2 diabetes.

"Aggressive blood glucose control to lower the risk of diabetic complications has been the goal for most people with Type 2 Diabetes for decades," Nikolajczyk said. "Our data provide an explanation for why people with tight glucose control can nonetheless have disease progression."

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University of Kentucky

New study highlights sociodemographic disparities in oral cancer screening rates

Oral cancer accounts for 2 percent of reported malignancies and 1.2 percent of cancer-related deaths in the United States. Oral cancer screening (OCS), recommended by the American Dental Association since 2010, can help to diagnose the cancer early, and this can significantly improve survival rates. If caught early, the five-year survival rate of oral cancer is 82.8 percent, but once the cancer metastasizes, that rate drops to 28 percent. Researchers at Brigham and Women's Hospital led a study to examine OCS rates among those who had been to the dentist within two years, looking at whether sociodemographic factors such as income or race predicted differences in these rates. The team found that a significantly higher proportion of minority and low-income individuals reported that they had not received an OCS exam despite a recent dental visit. The results of this study are published in The American Journal of Preventive Medicine.

"We wanted to look specifically at the population that has access to dental care and report having access to a dentist," said first author Avni Gupta, a research scientist at the Brigham's Center for Surgery and Public Health. "Our results indicate that the selection of patients for screening isn't based on the high-risk profile for oral cancer, but on sociodemographic characteristics. This is not appropriate. All patients should be receiving oral cancer screenings, but providers aren't screening these groups, and this may be why they are presenting with more advanced cancer."

The study looked at civilian, non-institutionalized individuals, aged 30-and-over, that had visited a dentist in the last two years. In three data cycles, from 2011 to 2016, patients self-reported if they had ever had an intra-oral or extra-oral exam, noninvasive procedures that can easily and safely be performed in an out-patient setting by a qualified health professional.

The intra-oral exam, in which a health professional pulls on the tongue and feels around the mouth to detect any premalignant lesions, was the primary outcome of the study. The extra-oral exam, in which the health professional feels the patient's neck, was a secondary outcome. The patient survey described the intra-oral exam and extra-oral exam in detail so that a patient could easily identify the two types of screenings.

The team found that only 37.6 percent of people who had seen a dental professional reported receiving an intra-oral cancer screening exam while only 31.3 percent reported receiving an extra-oral exam. Adjusting for different risk factors, the team found that OCS rates were much lower among racial minorities, lower-income groups, and those who were uninsured or publicly insured. These disparities were independent of the two major risk factors for oral cancer, smoking and alcohol consumption.

The largest limitation of the study was the use of self-reported data that is subject to recall bias. However, this would only impact the study if these biases had greater influence on some sociodemographic groups than others.

Gupta said that while the previous studies have indicated disparities in access to dental care, she hopes that this study shows that providing access is not enough to get rid of the gaps in OCS rates between different sociodemographic groups.

"Just providing access is not enough - it matters what type of care patients are able to access," Gupta said. "We talk a lot about disparities in medical care, but the quality of dental care services is important, too. We need to better understand the barriers that dental care providers face in order to ensure that patients get the same level and quality of care regardless of sociodemographic factors."

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Brigham and Women's Hospital

Omega-3 fats have little or no effect on type 2 diabetes

Increasing omega-3 fats in the diet has little or no effect on risk of type 2 diabetes, finds an evidence review published by The BMJ today.

As such, the researchers say omega-3 supplements should not be encouraged for diabetes prevention or treatment.

Type 2 diabetes is a leading cause of illness and death, with annual costs estimated at over US $800 billion worldwide. The rise in type 2 diabetes is mainly due to increased body fatness and inactivity so diet and body weight are key in treating, preventing, and delaying its onset.

Previous studies have suggested that polyunsaturated fatty acids (PUFAs) derived from oily fish (long-chain omega-3) and from plants (alpha-linolenic acid and omega-6) may have beneficial effects on the body that could help protect against type 2 diabetes but results are inconclusive.

Many countries also recommend a diet high in polyunsaturated fats for a range of conditions, including diabetes.

To explore this further, researchers at the University of East Anglia analysed the results of 83 randomised controlled trials involving 121,070 people with and without diabetes, all of at least six months duration.

Trials assessed the effects of increasing long-chain omega-3, alpha-linolenic acid, omega-6 or total PUFAs on new diabetes diagnoses or measures of glucose metabolism (how well the body processes sugars) taken either as supplements or via enriched or naturally rich foods. The quality of evidence for each trial was also measured.

The researchers found that increasing long-chain omega-3 fats (LCn3, from fish oils, by 2g per day LCn3 over a mean trial duration of 33 months) had little or no effect on likelihood of diabetes diagnosis or on glucose metabolism, and this did not change with longer duration.

Effects of alpha-linolenic acid (or ALA, another type of omega-3), omega-6 and total PUFAs on diabetes diagnosis were unclear (as the evidence was of very low-quality). Meta-analysis (combining the results of the trials) suggested little or no effect of these fats on measures of glucose metabolism.

There was a suggestion that high doses of long-chain omega-3 fats (more than 4.4g per day) may have negative effects on diabetes risk and glucose metabolism, but the researchers stress that this finding should be interpreted with caution.

The researchers point to some weaknesses, including missing data and risk of bias in some trials. Nevertheless, when they restricted their analyses to only include the highest quality trials (those at lowest risk of bias) there was still no effect on diabetes risk or glucose metabolism.

The researchers say this is the most extensive review to date assessing the effects of polyunsaturated fats on diabetes and glucose metabolism in long-term randomised controlled trials.

As such, they say "there is no convincing evidence to suggest that altering our LCn3, ALA, omega-6 or total PUFA intakes alters glucose metabolism or risk of diabetes." And they suggest that supplements "should not be encouraged for diabetes prevention or treatment.

Larger, high quality trials of at least 12 months duration looking at the effects of ALA, omega-6, oily fish and total PUFA on diabetes diagnosis and measures of glucose metabolism would be helpful, they conclude.

Credit: 
BMJ Group

US tuberculosis rates in young people are declining

Tuberculosis (TB) cases among children and adolescents in the USA have almost halved within a ten-year period, yet stark differences exist in the incidence rates between different ethnic, racial, and geographical communities, according to an observational study using national TB surveillance and census data from 2007-2017, published in The Lancet Public Health journal.

This study reports the first update of national estimates of TB in children and adolescents since 2010, analysing all the data from the National TB Surveillance System during 2007-17. It looks at trends by race and ethnicity, and, for the first time, in US territories (American Samoa, Guam, Northern Mariana Islands, Puerto Rico, and the Virgin Islands) and freely associated states (Federated States of Micronesia, Marshall Islands, and Palau), and by parental country of birth.

Although potentially fatal, TB in children and adolescents is preventable and curable. In the context of historically low TB incidence in the USA, information about groups at highest risk is useful to inform tuberculosis testing decisions.

Lead author of the study, Tori Cowger, Harvard T H Chan School of Public Health, USA, says: "These wide-ranging and pervasive disparities probably reflect structural inequalities that give rise to disproportionate exposure, vulnerability to infection and disease, and unequal access to prompt diagnosis and treatment. The findings suggest that TB care prevention strategies in the USA are succeeding in reducing overall burden among children and adolescents, but more attention and possibly new approaches are needed to address the inequalities." [1]

During 2007-17, one in every 100,000 young people was diagnosed with TB annually, and this rate almost halved over the decade (reduced by 48%, from 1.4 cases per 100,000 children and adolescents in 2007 to 0.8 cases per 100,000 in 2017).

Despite low rates of new cases overall in the USA, incidence rates among all other single racial or ethnic groups were at least 14 times higher than among non-Hispanic white children and adolescents between 2007-2017 - there were 0.1 new cases per 100,000 non-Hispanic white young people per year, compared with four, two and two cases per 100,000 for Asian, Black and Hispanic young people per year, respectively.

Rates were even higher in indigenous populations. Incidence rates in Native Hawaiian or Pacific Islanders were more than 100 times higher than their non-Hispanic white counterparts - 14.4 cases per 100,000 young people per year versus 0.1.

Geographic comparisons also showed disparities. Incidence rates were much higher in children living in US-affiliated islands, compared to those in US states --12 cases compared to one case per 100,000 young people per year, respectively. Despite the relatively small population size, cases occurring in US islands accounted for 15% (897 of 6,072) of overall cases, while 85% (5,175 out of 6,072) cases occurred in US states from 2010-17. Children and adolescents living in Marshall Islands and Federated States of Micronesia faced a particularly high burden, accounting for 11% (995 out of 9,276) of TB cases during 2007-17 and more than half of all TB deaths during 2010-17, despite representing less than 0.1% of the estimated population.

Incidence rates were higher for children born outside the USA themselves (7 new cases per 100,000 young people per year) or with parents born outside the USA, and risk increased depending on whether one or both parents were born outside the US (2 per 100,000 annually for US-born children with both parents born outside the US, and 1 per 100,000 annually for US-born children with one parent born outside the US). In contrast, the incidence rate was only 0.3 cases per 100,000 young people annually for US-born children with both parents born in the US.

Approximately two-thirds (66%, 2,565 of 3,896) of children aged younger than 15 years with TB in US states from 2010 to 2017 would have been recommended for TB testing under current targeted testing guidelines - 38% (1,465 of 3,896) were identified through contact tracing, and 21% (807 of 3,896), and 8% (294 of 3,896) were born or travelled outside the USA for at least two months, respectively.

An additional 21% (806 of 3,896) did not meet guidelines for testing but did have at least one parent born abroad. The remaining 13% (524 of 3,896) had none of these characteristics reported.

Cowger says: "Two-thirds of children with TB diagnosed in U.S. states had at least one risk-factor covered by current clinical practice guidelines. Nevertheless, a third of TB cases occurred outside of the groups currently identified for targeted testing, highlighting the need, to consider additional characteristics, such parental place of birth, in appropriate settings, to improve TB care and prevention." [1]

The authors suggest the underlying causes of the disparities they found in different racial, ethnic, and geographical groups, might be related to underlying inequities in social, economic and environmental conditions. A previous study suggested that socioeconomic status explained more than half of racial disparities in adult TB [2]. Other factors that might contribute to disparities in TB burden include food security and nutrition, poverty, residential segregation, exposure to second-hand smoke, air quality, lasting effects of historical trauma, and health-care policy. [3]

The authors note some limitations of their study. The birthplace of one or both of their parents was unknown for approximately 31% of children, so incidence rates on parental nativity may underestimate the numbers of children with TB who had at least one non-US-born parent. Additionally, data on parental place of birth and international travel had only started being collected in 2009 and only for children under 15, limiting the ability to draw conclusions on these trends.

Writing in a linked Comment, Professor Michael Lauzardo, from University of Florida, USA, comments on the findings: "These results have several important implications for
the control and eventual elimination of tuberculosis in the USA and other countries on the path towards elimination. The first is that this report is generally good news. Imagine the incidence of any other disease decreasing by almost half within a 10-year period. This trend should be encouraging to those working to eliminate tuberculosis and provide evidence that current strategies of control, including early initiation of therapy, screening of close contacts, and aggressive treatment of latent tuberculosis infection, are highly effective when applied consistently. However, these data are overshadowed by the most important finding of this report: the stark disparity between various subpopulations."

Peer-reviewed / Observational study / People

NOTES TO EDITORS

This study was funded by and conducted by researchers from the US Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US CDC.

The labels have been added to this press release as part of a project run by the Academy of Medical Sciences seeking to improve the communication of evidence. For more information, please see: http://www.sciencemediacentre.org/wp-content/uploads/2018/01/AMS-press-release-labelling-system-GUIDANCE.pdf if you have any questions or feedback, please contact The Lancet press office pressoffice@lancet.com

[1] Quote direct from author and cannot be found in the text of the Article.

[2] Current clinical guidelines recommend TB testing for people in contact with individuals with TB, as well as young people immigrating from, or who have travelled to, countries where TB is more common, but not those with foreign born parents.

[3] https://www.ncbi.nlm.nih.gov/pubmed/9563713

[4] https://www.cdc.gov/socialdeterminants/docs/SDH-White-Paper-2010.pdf

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The Lancet

Understanding the animal brain could help robots wash your dishes

image: Robot hand holding a virtual brain.

Image: 
Patra Kongsirimongkolchai/Pond5

Artificial intelligence (AI) still has a lot to learn from animal brains, says Cold Spring Harbor Laboratory (CSHL) neuroscientist Anthony Zador. Now, he's hoping that lessons from neuroscience can help the next generation of artificial intelligence overcome some particularly difficult barriers.

Anthony Zador, M.D., Ph.D., has spent his career working to describe, down to the individual neuron, the complex neural networks that make up a living brain. But he started his career studying artificial neural networks (ANNs). ANNs, which are the computing systems behind the recent AI revolution, are inspired by the branching networks of neurons in animal and human brains. However, this broad concept is usually where the inspiration ends.

In a perspective piece recently published in Nature Communications, Zador describes how improved learning algorithms are allowing AI systems to achieve superhuman performance on an increasing number of more complex problems like chess and poker. Yet, machines are still stumped by what we consider to be the simplest problems.

Solving this paradox may finally enable robots to learn how to do something as organic as stalking prey or building a nest, or even something as human and mundane as doing the dishes-a task that Google CEO Eric Schmidt once called "literally the number one request... but an extraordinarily difficult problem" for a robot.

"The things that we find hard, like abstract thought or chess playing, are actually not the hard thing for machines. The things that we find easy, like interacting with the physical world, that's what's hard," Zador explained. "The reason that we think it's easy is that we had half a billion years of evolution that has wired up our circuits so that we do it effortlessly."

That's why Zador writes that the secret to quick learning might not be a perfected general learning algorithm. Instead, he suggests that biological neural networks sculpted by evolution provide a kind of scaffolding to facilitate the quick and easy learning for specific kinds of tasks-usually those crucial for survival.

For an example, Zador points to your backyard.

"You have squirrels that can jump from tree to tree within a few weeks after birth, but we don't have mice learning the same thing. Why not?" Zador said. "It's because one is genetically predetermined to become a tree-dwelling creature."

Zador suggests that one result of this genetic predisposition is the innate circuitry that helps guide an animal's early learning. However, these scaffolding networks are far less generalized than the perceived panacea of machine learning that most AI experts are pursuing. If ANNs identified and adapted similar sets of circuitry, Zador argues, the future's household robots might just one day surprise us with clean dishes.

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Cold Spring Harbor Laboratory

Study explores barriers of access and acceptability for treatment of opioid use disorder

image: Assistant professor in the UMass Amherst School of Public Health and Health Sciences.

Image: 
UMass Amherst

In an effort to find ways to improve long-term outcomes for people with opioid use disorder, University of Massachusetts Amherst epidemiology researcher Elizabeth Evans set out to study the obstacles to treating this chronic condition with an effective medication, buprenorphine-naloxone.

"Very few people with opioid use disorder ever get treatment for it - 10 percent or less," says Evans, assistant professor in the School of Public Health and Health Sciences. "Of those who do, few remain in treatment long enough to really benefit from it."

In a newly published paper in the Journal of Substance Abuse Treatment, lead author Evans, along with researchers at UCLA and the Veterans Affairs Puget Sound Health Care System in Seattle, identify factors that inhibit the long-term use of buprenorphine, which was approved in 2002 by the FDA to treat opioid use disorder.

"Patients and families still have that expectation that short-term treatment is what they should get and want," Evans says. "But they need to have more realistic expectations and understand that long-term treatment is often necessary."

In one of the few studies looking at a two-year period of buprenorphine treatment, the researchers analyzed data from a long-term, follow-up study of participants in a multisite randomized clinical trial, called START (Starting Treatment with Agonist Replacement Therapy), which was funded by the National Institute on Drug Abuse. Evans directed the study while doing research at the UCLA Semel Institute for Neuroscience and Human Behavior.

Conducted from 2011 to 2014, the study included long-term, follow-up interviews with a cohort of 1,269 adults with opioid use disorder in five states who had participated in a clinical trial comparing the effects of buprenorphine and methadone on liver health. About 9.3-11.2 percent of study participants used buprenorphine treatment over the two-year follow-up period that Evans and colleagues studied. A key finding was that individuals who perceived buprenorphine to be unacceptable were least likely to use the medication during follow-up, regardless of the perceived access to the medication.

"This points to the need to address people's experiences and perceptions of the medication - why they never tried it and, if they did, why they stopped taking the medication," Evans says. "Increasing access is important, but we need to address why people find that medication to be unacceptable."

Some of the other findings:

51.9 percent of participants said they had a problem getting buprenorphine when needed because, most commonly, it either wasn't accessible or affordable.

Among those not willing to continue taking buprenorphine, 54.1 percent said they were not using any opioids, 44.3 percent preferred methadone and 38.3 percent said they did not like buprenorphine.

The most common reasons cited for disliking buprenorphine were: negative physical reaction (72.9 percent), side effects (47.1 percent), can't feel opioids when taking buprenorphine (41.4 percent), had to pick it up at the clinic every day (38.6 percent) and the medication was not strong enough (30.0 percent).

Evans says all these perceptions and concerns can and need to be addressed. In addition, public health efforts should focus on education so that people with the condition, as well as their families and the public, understand that opioid use disorder usually requires long-term, if not lifetime, treatment.

"That's a challenge we face in the field," says Evans, who is co-principal investigator for a $10 million grant included in the Justice Community Opioid Innovation Network (JCOIN) initiative, an ambitious effort to improve opioid addiction treatment in criminal justice settings. "We need to flip the narrative. We know this is a chronic health condition. The good news is that buprenorphine is effective, but only if patients take it. We need to help patients access and use medication that will help them avoid a return to opioid use."

Credit: 
University of Massachusetts Amherst

Health records pin broad set of health risks on genetic premutation

MADISON, Wis. -- It was long believed the FMR1 premutation -- an excessive number of trinucleotide repeats in the FMR1 gene -- had no direct effect on the people who carry it. Until recently, the only recognized effect on the carriers of the flawed gene was the risk of having offspring with fragile X syndrome, a rare but serious form of developmental disability.

In recent years, however, at least two clinical conditions have been well documented in the carriers themselves: an age-dependent neurodegenerative disorder and, in female carriers, early menopause.

Now, a team of researchers from the University of Wisconsin-Madison and Marshfield Clinic has found that there may be a much broader health risk to carriers, with potentially dozens of clinical conditions that can be ascribed directly to carrying the premutation. The researchers employed machine learning, a form of artificial intelligence, to mine decades of electronic health records of nearly 20,000 individuals.

In a study published Aug. 21 in Science Advances, a team led by Marsha Mailick, a researcher and professor at UW-Madison's Waisman Center, and UW-Madison graduate student Arezoo Movaghar provide a better understanding of the previously disputed relationship between this well-known genetic premutation and a wide range of clinical conditions. At the same time, the interdisciplinary study richly illustrates the power of data-driven discovery.

In the study, carriers were found to experience a much higher prevalence and severity of such conditions as depression, anxiety, mood disorders, sleep apnea, respiratory and stomach problems, bone fractures, incontinence, and a host of other conditions.

"Our extensive phenotyping shows that premutation carriers experience a clinical profile that is significantly different from controls, and that is evident throughout adulthood," the study's authors write.

"The research was especially challenging as not all carriers are affected and the specific conditions each may experience varies," explains Mailick. "Yet the overall pattern revealed in the electronic health record was striking."

The findings have important implications for the estimated 1 million people in the United States and many more in the rest of the world who carry premutations of the FMR1 gene. People are generally unaware they carry the altered gene unless a family member is found to have fragile X syndrome, which is rare.

The new study depended on the electronic health records of 19,996 adults collected over 40 years from Marshfield Clinic, a health system in central Wisconsin that was among the first in the nation to adopt electronic record keeping. In addition to their extensive, searchable medical histories, study subjects also contributed their DNA through the clinic's Personalized Medicine Research Project, enabling the study's authors to identify 98 patients who carry the FMR1 premutation.

A primary goal of the new study, according to Mailick, was to use electronic health records to set up a double-blind methodology -- where both clinicians and patients were blind to genotype -- to assess whether premutation carriers differed in their patterns of clinical diagnoses from those lacking the premutation.

The question is an important one as some clinical reports have suggested that premutation carriers were at greater risk for a wide range of health conditions, including autoimmune diseases, migraines, neuropathy, depression, infertility, fibromyalgia, anxiety and cognitive deficits, all with varying frequencies and emerging at different stages of life.

Such correlations, notes Mailick, are the stuff of biomedical controversy as nearly all of the studies associating those conditions with the premutation were the result of a family member being diagnosed with fragile X. Following diagnosis of fragile X, family members are offered genetic testing leading to the identification of relatives who carry the premutation. Awareness of that genetic status by patients and clinicians can confound prevalence estimates of symptoms. Frequently, carriers' medical conditions are blamed on the stress of care giving and having a family member with fragile X syndrome.

"This is a controversy," says Mailick, who has spent a career studying the life course trajectories of people with developmental disabilities as well as their families through UW-Madison's Waisman Center. "There wasn't unbiased data available before this study to inform the controversy. This study does so in a powerful way. The data validate the clinical experience."

By scouring the medical histories of patients with the premutation, the Wisconsin researchers identified an astonishing range of health conditions and symptoms affecting FMR1 carriers later in life. For women, these include agoraphobia, social phobia, panic disorders, infertility, menstrual disorders, and falls and fractures, among others.

For men, clinical diagnoses commonly found in health records of FMR1 carriers include depression, diseases of the respiratory system, and urinary incontinence, as well as half a dozen other afflictions.

Movaghar and Mailick say some of the conditions associated with FMR1 carriers have long been suspected, but the number and range of health effects they found was a surprise: "We see conditions nobody ever associated with the premutation," Movaghar says.

To be included in the study data, subjects had to experience the diagnosis in at least two separate visits, helping weed out misdiagnoses or recording errors.

The approach used in this study, the Wisconsin researchers say, could also be applied to other genetic variants similarly believed to be innocuous but that potentially may have health effects.

Credit: 
University of Wisconsin-Madison

Earliest evidence of artificial cranial deformation in Croatia during 5th-6th century

image: CT scans of the so called circular-erect type cranial deformation.

Image: 
M Kavka

People in Croatia during the 5th to 6th centuries may have used cranial modifications to indicate their cultural affiliations, according to a study published August 21, 2019 in the open-access journal PLOS ONE led by Ron Pinhasi of the University of Vienna and Mario Novak of the Institute for Anthropological Research in Zagreb, Croatia.

The Hermanov vinograd archaeological site in Osijek Croatia has been known since the 1800s. A new pit excavated in 2013 contained three human skeletons dating to 415-560 CE, during the Great Migration Period, a time of significant movement and interaction of various European cultures. Two of the skeletons showed dramatically modified head shapes, one whose skull had been lengthened obliquely and another whose skull had been compressed and heightened. This is the oldest known incidence of Artificial Cranial Deformation (ACD) in Croatia.

ACD is the practice of modifying the skull from infancy to create a permanently altered shape, often to signify social status. In this study, genetic, isotopic and skeletal analysis of the bodies revealed that all were males between 12 and 16 years of age at death and that they all suffered from malnutrition. They are not obviously of different social status, but genetic analysis found that the two with cranial modifications exhibited very distinct ancestries, one from the Near East and the other from East Asia. The latter is the first individual from the Migration Period with a majority East Asian ancestry to be found in Europe.

The authors suggest the ACD observed here may have functioned to distinguish members of different cultural groups as these groups interacted closely during the Migration Period. From the evidence at hand, it is unclear if these individuals were associated with Huns, Ostrogoths, or another population. It is also unclear whether the use of ACD to signify cultural identity was a widespread practice or something peculiar to these individuals.

Dr Novak adds: "The most striking observation, based on nuclear ancient DNA, is that these individuals vary greatly in their genetic ancestries: the individual without artificial cranial deformation shows broadly West Eurasian associated-ancestry, the individual with the so-called circular-erect type cranial deformation has Near Eastern associated-ancestry, while the individual with the elongated skull has East Asian ancestry."

Credit: 
PLOS

New pharmaceutical target reverses osteoporosis in mice

image: Yu-Ru "Vernon" Shih, a research scientist at Duke University, takes a close look at the tissue integrity of vertebral sections of a mouse with osteoporosis that has been treated by targeting a cell receptor.

Image: 
Duke University

DURHAM, N.C. -- Biomedical engineers at Duke University have discovered a pharmaceutical target that, when activated, can reverse bone degradation caused by osteoporosis in mouse models of the disease.

"The most widely used drugs currently approved by the FDA to treat osteoporosis can prevent further bone loss, but they don't help rebuild the bone," said Shyni Varghese, professor of biomedical engineering, mechanical engineering and materials science, and orthopedics at Duke.

"We've discovered a biochemical receptor that, when activated, can do both," added Yu-Ru "Vernon" Shih, a research scientist in Varghese's lab and the study's first author.

The findings appear online August 21 in the journal Science Advances.

Despite its apparent rigidity, bone is living tissue constantly being broken down and replaced by the body. Osteoporosis occurs when old tissue is lost faster than new tissue can be created, causing the bone to become weak and brittle. The disease afflicts more than 40 million men and women in the United States alone and is most common in older women past menopause.

In 2014, Varghese was studying the role of popular biomedical devices made of calcium phosphate in promoting bone repair and regeneration. She discovered that the biochemical adenosine acting on the A2B receptor plays a particularly large role in promoting bone growth. It stood to reason that a lack of the chemical might play a role in the development of osteoporosis, so Varghese decided to find out.

In the study, Varghese and her research team studied mice that had had their ovaries removed to mimic post-menopause osteoporosis. They looked at the expression levels of two enzymes that help produce adenosine as well as the levels of adenosine traveling between cells. As predicted, they discovered that the mice's lack of estrogen was causing all three to plummet.

The researchers then tested to see if increasing the levels of adenosine in the mice would help reverse the damaging effects of the disease. But rather than pumping in adenosine itself, they injected a non-hormonal small molecule produced by Bayer that activates the A2B receptor.

"The mice that received the drug were completely cured," said Varghese. "Their bones were just as healthy as the control group without osteoporosis."

While the discovery of a pharmaceutical target capable of reversing osteoporosis is exciting, creating a small molecule drug that can activate it without side effects is a difficult task. Adenosine is created naturally throughout the entire body and has many roles such as modulating neurons and regulating blood flow to various organs. Researchers can't simply dump a bunch of it into the bloodstream to stop bone degradation without side effects.

But with the A2B receptor identified, Varghese and others can start looking for ways to deliver activators to bones without flooding other areas of the body. For example, one of Varghese's students is beginning to study ways of tethering adenosine-like molecules to carriers that target bone tissue. Her lab is also pursuing a sort of bandage that can deliver growth-supporting drugs directly to damaged or broken bones.

Credit: 
Duke University