Culture

Health claims on packaging for many foods marketed to UK kids are 'confusing'

The health claims made on the product packaging for a large proportion of foods marketed to children in the UK are 'confusing', and could be contributing to rising rates of childhood obesity, suggests research published online in the Archives of Disease in Childhood.

Stricter regulations are needed for food labelling and product content to lessen this risk, urge the researchers

Child-focused marketing techniques, using cartoon characters, toys, games and promotions (cards and vouchers), have long been an advertising staple. But the use of health and nutrition claims for particular foodstuffs is a more recent trend, note the researchers.

And the evidence suggests that when such claims are made, they create a positive impression, a phenomenon known as the 'health halo effect'.

While steps have been taken to control the advertising to children of products high in fat and sugar, such as sweets, chocolates and sugar sweetened drinks, rather less attention has been paid to other foods carrying product packaging claims suggesting that they contribute to good health/nutrition, say the researchers.

To try and address this, they scrutinised the energy, fat, sugar, and salt content of foods marketed to children above the age of 1, and widely available in various large food retail outlets in the UK.

The researchers focused on products with child-focused imagery and health and nutrition claims on the product packaging, including terms such as "one of 5 a day," in reference to the UK government's push to get everyone to eat five portions of fruit/vegetables every day.

In all, 332 different products, including breakfast cereals, fruit snacks, fruit-based drinks, dairy products, such as yogurts, and ready meals were assessed, using the broadcast regulator's tool (Ofcom NPM) to identify so-called 'healthy' food .

This uses a scoring system, made up of seven elements--energy; total sugars; saturated fat; salt; fruit/vegetables/nuts; fibre; protein--from the product labelling information, to classify the nutritional quality of foods.

The calculations showed that a large proportion of the products, including those commonly perceived as 'healthy' (41%), were classified as 'less healthy,' by the tool scoring system.

Cereal bars had the highest energy and saturated fat content, while cereals had the highest salt content.

Fruit snacks had the highest sugar content, averaging 48 g/100 g, but still made the 5-a day claim, in many cases--something which is likely to be confusing for parents, suggest the researchers.

One in three products contained concentrated fruit juice as an added ingredient while one in four used pureed fruit.

Nearly a quarter of the products, most of which were fruit based drinks and snacks, made 'no added sugars' claims. But half had concentrated juice or fruit puree as the added ingredients.

"Processed fruits are perceived by the public as a healthy natural alternative to added sugars, but because of the breakdown of the cellular structure they potentially have the same negative effect on weight gain as other forms of sugar, which is why they have recently been classified as free sugars in the UK," write the researchers.

Many products (over 41%) made 5-a day claims, most of which were fruit drinks, ready meals, and fruit snacks. Processed fruit, concentrated fruit juice, or puree appeared as ingredients in nearly half (just over 44%) of these products.

But despite most (82%) of them claiming to contain one portion of fruit or vegetables, three out of four didn't contain the recommended 80 g portion size. And half of the products making 5-a day claims didn't specify whether these were adult or child size portions.

The serving size for most (nearly 95%) fruit-based drinks exceeded the recommended 150 ml limit for fruit juice, yet the fruit and vegetable portions for most products were below the recommended portion size.

The researchers caution that while they tried to include as representative a sample of products as possible, some may have been missed, and they were obliged to estimate the content of some products in the absence of adequate ingredient information on the packaging.

But the findings indicate that "health and nutrition claims used on product packaging are currently confusing," they say.

"Prepacked foods targeted to children can be consumed as part of a 'balanced and healthy' diet, yet their health and nutrition claims remain questionable. Given the current rising rates of childhood obesity, the consumption of less healthy foods may have long term negative implications on child health." write the researchers.

"Stricter regulations on product composition, food labelling, and marketing techniques are required to discourage the promotion of foods which might be considered obesogenic," they conclude.

Credit: 
BMJ Group

Peptide keeps predatory nematodes from eating their kin

A small peptide produced in the skin of predatory nematodes prevents them from cannibalizing their immediate family members, while they feed upon their close relatives, a new study finds. The ability to recognize self is an important trait and regulates many crucial biological processes. While it's observed in a wide variety of organisms, the molecular mechanisms that underlie self-recognition systems are not well understood. This is particularly true for nematodes - one of the most well-studied organisms on the planet - in which the ability to discriminate self from other organisms has not yet been described. Previous research has shown that the predatory Pristionchus nematodes will feed on the larvae of other species of nematodes; however, it is unknown if this cannibalistic nature is due to their ability to discriminate amongst their own kin versus other species. James Lightfoot and colleagues investigated the prey interactions between Pristionchus, their kin and other nematode species and revealed a self-recognition system that enables Pristionchus nematodes to recognize their offspring. Over a series of experiments, predatory Pristionchus nematodes were observed killing and eating the larvae of other species, including closely related Pristionchus pacificus strains. However, the authors found that in each case, the killing and eating of self-progeny was avoided (see video). By mapping and comparing the genomes of two P. pacificus strains including after amino acid manipulations done with CRISPR/Cas9 to explore specific molecular drivers of self-recognition, Lightfoot et al. identified a peptide responsible - hypervariable small peptide SELF-1. Alterations to the self-1 gene resulted in elimination of self-recognition and individuals who lost the related peptide were promptly cannibalized by their own strains. According to the authors, the results demonstrate a likely molecular system P. pacificus use to prevent cannibalism.

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American Association for the Advancement of Science (AAAS)

Mass drug administration reduces scabies cases by 90% in Solomon Islands' communities

Mass drug administration (MDA) of two antibiotics can be highly effective at reducing cases of scabies and the bacterial infection impetigo, according to new research published in Lancet Infectious Diseases.

The study was conducted by the London School of Hygiene & Tropical Medicine (LSHTM), Murdoch Children's Research Institute (MCRI), the Kirby Institute at UNSW Sydney and the Solomon Islands Ministry of Health and Medical Services.

It saw the entire population of Choiseul Province of the Solomon Islands (26,000 people), in the Pacific, given one round of the antibiotics ivermectin and azithromycin together. The prevalence of scabies and impetigo in residents of 10 randomly selected villages before and after Mass Drug Administration (MDA) by the Solomon Islands Ministry of Health and Medical Services was then compared.

The strategy reduced scabies cases from 19% to 2% (90% reduction), and impetigo cases from about 25% to about 6% (75% reduction), in one year.

The study is the largest evaluation of ivermectin-based mass drug administration for the control of scabies, and supports large-scale implementation of this strategy for control of scabies in locations where the condition is identified as a public health priority.

Dr Michael Marks from LSHTM and co-author of the study, said: "We know that treating individual cases of scabies is not effective, however treatment of entire communities has been shown in small community-based trials to substantially reduce cases. Our study demonstrates this can be an effective approach when delivered at a larger scale."

Scabies is a parasitic skin disease that affects an estimated 200 million people worldwide. The disease causes skin inflammation with itch that is frequently severe, and often associated with bacterial skin infection caused by Staphylococcus aureus and Streptococcus pyogenes (impetigo). This can in turn lead to severe complications including septicaemia and post-streptococcal glomerulonephritis. In 2017, growing awareness of the burden of disease due to scabies led the World Health Organization to recognise it as a neglected tropical disease.

Dr Lucia Romani from the Kirby Institute and lead author on the paper, said: "Scabies is too common in many tropical developing countries, especially in rural and remote communities where people share small living and sleeping spaces access to treatment is limited."

This new study was conducted in Choiseul Province of the Solomon Islands where a very high number of scabies cases have been reported. 1,399 people had their skin examined at the start of the MDA in 2015, with 261 (one in five) having scabies and 347 having impetigo. Twelve months on, 1,261 people were examined with only 29 people with scabies and 81 with impetigo. Additionally, there was also almost 6,000 less people presenting to outpatient clinics, a drop of 36.1% cent, in the three-months after MDA. Presentations for skin sores, boils and abscesses also fell by 50.9%.

MCRI Professor and study PI Andrew Steer said: "Treatment is highly effective at reducing both scabies and impetigo and we saw significant reductions in outpatient presentations, especially those needing treatment for skin sores, boils and skin abscesses."

Oliver Sokana, from the Solomon Islands Ministry of Health, said: "Both diseases were most common in children aged between five and nine years old."

The safety and feasibility of large-scale mass co-administration of ivermectin and azithromycin in Choiseul Province was reported in a recent study.

Dr Marks said: "Scabies is extremely common, and is a major risk factor for dangerous bacterial skin infection. Our study provides crucial evidence for the global strategy of scabies control being developed."

The authors acknowledge limitations of their study including that is was non-randomised so they are unable to say with certainty that factors other than the intervention did not influence the outcome. Further research is needed to assess durability and scalability of mass drug administration in larger, non-island populations, and to assess its effect on the severe bacterial complications of scabies.

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London School of Hygiene & Tropical Medicine

Federal subsidies for US commercial fisheries should be rejected

DURHAM, N.C. -- In late 2018, the U.S. National Marine Fisheries Service proposed a rule change that would reverse current policy and allow the agency to use public funds to underwrite low-interest, fixed-term loans for the construction of new commercial fishing vessels.

The proposed change, which is still pending final approval, lacks scientific merit and should be rejected, according to a new analysis by a Duke University economist.

"We just spent millions buying out a bunch of fishing vessels to reduce overcapacity in our federal fisheries. Now we want to spend millions more to put them back in. That's a total waste of taxpayer dollars," said Martin D. Smith, George M. Woodwell Distinguished Professor of Environmental Economics at Duke's Nicholas School of the Environment.

"The notion that the government should subsidize commercial fishing beyond what the market deems profitable is a turn away from a market economy," he said. "For an administration that rails against socialism, it's bizarre that it would place more faith in big government to price vessel loans than in the private banking industry."

Smith published his peer-reviewed policy analysis April 5 in Science.

Aside from being fiscally unwise, the proposed rule change undercuts long-term sustainability objectives in U.S. fisheries, Smith argues. It also ignores the most current science on fisheries' interconnectivity and is unfair to taxpayers, other industries and future fishers, who will face a sharp disadvantage competing for available loans, he said.

If the proposed rule change is approved and finalized, it could also undermine global efforts to reduce illegal, unreported and unregulated fishing, and increase harmful impacts on habitats and non-targeted by-catch species, he argues, because boats and crews go where the fish are.

"The latest science teaches us that fisheries are interconnected and leakage from one to the others is a real thing. If there are too many boats in one fishery, there's little to stop fishers from seeking better opportunities by moving to another fishery," Smith explained.

As more and more fishers do this, the problems linked to excess capacity can spread to other fisheries -- including fisheries that currently are well-managed. These problems include overfishing, weak economic performance, increased by-catch and habitat impacts and unsafe working conditions on fishing vessels. The policy might also lead to an increased risk of the "race to fish" in which fishers ratchet up the number and power of their fishing vessels early each season to catch as much of the fisheries' limited supply of fish as possible before their competitors can.

The issues can also spread to unregulated fisheries or those in the high seas, beyond U.S. jurisdiction.

"It becomes like a giant game of Whack-a-Mole," Smith said. "You whack a problem back in one fishery, and it pops up again somewhere else."

The use of subsidies for new vessel loans has been prohibited under U.S. policy since the 2007 reauthorization of the Magnuson-Stevens Fishery Conservation and Management Act. In the ensuing years, fishery managers have made substantial progress in reducing overfishing and rebuilding fisheries by adopting scientifically sound management practices, such as catch shares, to address overcapacity. Smith said the amount of money the U.S. now spends on "bad subsidies" that encourage overfishing or excess capacity is very small by global standards.

"If the new rule allowing taxpayer money to be spent on vessel loans is finalized, it could undo this progress and undermine our country's global leadership on reducing subsidies and maintaining a consistent commitment to fight illegal, unreported and unregulated fishing," Smith said.

No date has been publicly announced for when the proposed rule change might be finalized, but many experts expect it will be this spring.

"Rejecting the rule change would signal a commitment to fairness and foresight," Smith said. "It would mark a step away from outdated management approaches that ignore the fact that fish stocks are connected ecologically, fishing vessels can range across the water, and the ownership of vessels and other fishing capital can cross political boundaries," he said.

"These are the realities, and our policy should reflect them."

Credit: 
Duke University

Improving 3D-printed prosthetics and integrating electronic sensors

image: The mold of local teen Josie Fraticelli's hand that was scanned during the development of a personalized prosthetic. Photo by Logan Wallace.

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Virginia Tech

With the growth of 3D printing, it's entirely possible to 3D print your own prosthetic from models found in open-source databases.

But those models lack personalized electronic user interfaces like those found in costly, state-of-the-art prosthetics.

Now, a Virginia Tech professor and his interdisciplinary team of undergraduate student researchers have made inroads in integrating electronic sensors with personalized 3D-printed prosthetics -- a development that could one day lead to more affordable electric-powered prosthetics.

This newly published research out of the lab of Blake Johnson, a Virginia Tech assistant professor in industrial and systems engineering, took a step forward in improving the functionalities of 3D-printed personalized wearable systems.

By integrating electronic sensors at the intersection between a prosthetic and the wearer's tissue, the researchers can gather information related to prosthetic function and comfort, such as the pressure across wearer's tissue, that can help improve further iterations of the these types of prosthetics.

The integration of materials within form-fitting regions of 3D-printed prosthetics via a conformal 3D printing technique, instead of manual integration after printing, could also pave the way for unique opportunities in matching the hardness of the wearer's tissue and and integrating sensors at different locations across the form-fitting interface. Unlike traditional 3D printing that involves depositing material in a layer-by-layer fashion on a flat surface, conformal 3D printing allows for deposition of materials on curved surfaces and objects.

According to Yuxin Tong, an industrial and systems engineering graduate student and first author of the published study, the ultimate goal is to create engineering practices and processes that can reach as many people as possible, starting with an effort to help develop a prosthetic for one local teen.

"Hopefully, every parent could follow the description from the paper we published and develop a low-cost personalized prosthetic hand for his or her child," Tong said.

To develop the prosthetics integrated with electronic sensors, the researchers started with 3D scanning data, which is similar to taking pictures at various angles to get the full form of an object -- in this case, a mold of the teenager's limb.

They then used 3D scanning data to guide the integration of sensors into the form-fitting cavity of the prosthetic using a conformal 3D printing technique.

The process developed by the research team will lend itself to further applications in personalized medicine and design of wearable systems.

"Personalizing and modifying the properties and functionalities of wearable system interfaces using 3D scanning and 3D printing opens the door to the design and manufacture of new technologies for human assistance and health care as well as examining fundamental questions associated with the function and comfort of wearable systems," Johnson said.

Johnson's research into prosthetic hands was inspired when he learned about his colleague's daughter, Josie Fraticelli, then 12-years old, who had been born with amniotic band syndrome. While in utero, the development of her hand stopped. String-like amniotic bands restricted blood flow and affected the development of right hand, causing a lack of formation beyond the knuckles.

Johnson used his related research expertise in additive biomanufacturing and a team of interdisciplinary undergraduate researchers to 3D print the bionic hand for Fraticelli that would become the basis of the now-published research.

As they worked with Fraticelli, they continued tweaking the prototype prosthetic by developing new additive manufacturing techniques that would allow for a better fit to Fraticelli's palm, creating a more comfortable, form-fitting prosthetic device.

They validated that the personalization of the prosthetic increased the contact between Fraticelli's tissue and the prosthesis by nearly fourfold as compared to non-personalized devices. This increased contact area helped them pinpoint where to deploy sensing electrode arrays to test the pressure distribution, which helped them to further improve the design.

Sensing experiments were conducted using two personalized prosthetics with and without sensing electrode arrays. By running these experiments with Fraticelli, they found that the pressure distribution was different when she relaxed her hand versus holding her hand in a flexed posture.

"The mismatch between the soft skin and the rigid interface is still a problem that will reduce the conformity," said Tong. "The sensing electrode arrays may open another new area to improve the prosthetics design from the perspective of distributing a better balance of pressure."

Overall, Fraticelli does feel that the new personalized prosthetic improves her comfort level. Since her hand is soft and changeable under different postures and the prosthetic material is rigid and fixed, the level of conformity may continue to change.

Personalized prosthetics still have space for improvements, and Johnson's team will continue to research and develop new techniques in additive manufacturing to make improvements on wearable bionic devices.

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Virginia Tech

Multiple mechanisms behind disease associated with unexpected heart attacks

image: Research on three mutations associated with hypertrophic cardiomyopathy -- a disease best known for revealing itself as an unexpected, fatal heart attack during strenuous exercise -- found separate mechanisms at work at the molecular level.

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Rensselaer

TROY, N.Y. --Hypertrophic cardiomyopathy is best known for revealing itself in one certain way: as an unexpected, fatal heart attack during strenuous exercise. But researchers suspect as many as 300 mutations can individually cause enlargement of the heart that renders it vulnerable to strain. Recent studies examining three of those mutations at the molecular level found separate mechanisms at work, said Rensselaer Polytechnic Institute muscle protein and contraction expert Doug Swank, whose most recent paper on the topic was published today in the Journal of Physiology.

"Our work suggests that a simple one-size-fits-all hypothesis about how these mutations lead to an enlarged heart and to the disease is not likely to be the case. It's likely to be multiple mechanisms, perhaps depending on where the mutation is found in the protein or what it does to the protein," said Swank, a professor of biological sciences and member of the Rensselaer Center for Biotechnology and Interdisciplinary Studies.

Swank's research on hypertrophic cardiomyopathy is being conducted in collaboration with researchers at San Diego State University and Johns Hopkins University, with support from the National Institutes of Health.

The current paper and a previous study published in eLife in 2018 examine two mutations in myosin, a lever-shaped muscle protein that generates force to contract heart muscle tissue. Like all proteins, muscle proteins are chains of amino acids twisted into a three-dimensional shape that determines their function. But mutations slightly alter the composition of the amino acid chain, which also changes the shape of the protein and its performance.

Swanks' lab expresses the mutation in the wing muscle of a fruit fly, making it possible to examine how the mutations impact mechanical properties like force production, work and power. The eLife study looked at a mutation in myosin known as K146N (the mutation name is derived from the name of the affected amino acid residue and how it is altered in myosin). Examinations of fruit fly muscles with this mutation supported the "increased contractility hypothesis," which proposes that the heart is spending more time in a contracted state than in a relaxed state.

Ordinarily, as filaments of the myosin protein absorb energy, they bind to filaments of the protein actin and bend back upon themselves, pulling on the actin filaments and contracting the muscle.

"Our results for K146N indicated that the myosin bound longer to actin than it normally does," said Swank. "Considering that hundreds of these myosin molecules are doing this all the time, if they stay bound longer, at any given time you're going to have more myosin heads bound and pulling together than you otherwise would. So that gives you more force."

But the newly released Journal of Physiology study looked at an R249Q mutation and found a nearly opposite result. Fruit fly muscle with a R249Q mutation, which typically produces a less severe form of the disease, generated less force, less work, and less power. Swank said this result suggests that, in the heart, such a mutation is unlikely to be causing increased contractility - and yet it yields a similar outcome.

A third study to be published in the near future describes a mechanism for a mutation in another heart protein.

"Our hope is that, as we continue to understand how these mutations affect muscle contraction, a few general mechanisms will emerge which will make it possible to devise a group of treatments to address the disease," said Swank.

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Rensselaer Polytechnic Institute

People with autism have an altered sense of self

New research has indicated that people with autism have an altered sense of self, which may explain some of the differences shown in social functioning.

The study, which was carried out by scientists at Anglia Ruskin University and published in the journal Autism, involved a group of 51 adults, half with and half without autism.

It is the first time that responses to the self-altering 'full body illusion', which simulates an out of body experience, have been measured in people with autism.

The research found that, unlike neurotypical participants, people with autism do not experience the 'full body illusion'. This is a test that causes people to experience their self as being located outside of their body and to identify with their own virtual 'avatar' viewed through virtual reality goggles.

The scientists also measured the size of the participants' peripersonal space. This is the area of space directly around our body which the brain treats in a special way as it enables us to interact with the external world. They found that this area of space, that defines the boundaries of self, is smaller in people with autism.

A smaller peripersonal space may explain certain behaviours sometimes seen in individuals with autism, such as approaching others more closely than social norms prescribe, or having difficulty considering communications coming from outside their personal space as being directed towards them.

First author, PhD student Cari-lene Mul, said: "For a long time autism has been considered a disorder of the self as some people with autism have difficulties accessing memories about themselves and using personal pronouns such as 'me' and 'I'.

"We wanted to find out whether arguably more fundamental aspects of the self - the feeling that your body belongs to you and that your self is located within it - might be altered in people with autism."

Senior author of the study Dr Jane Aspell, Senior Lecturer in Psychology at Anglia Ruskin University, added: "The findings of our study show that the 'bodily' self is less flexible in people with autism and their brains may combine sensory information about their bodies in a different way.

"These differences in self may relate to, and partly explain, differences in self processing and problems with social functioning, including the ability to empathise with others."

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Anglia Ruskin University

Government and NHS leaders could do more to encourage collaborative relationships between healthcare

The Nuffield Council on Bioethics has published a briefing note outlining the factors that can contribute to disagreements between parents and healthcare staff about the care and treatment of critically ill babies and young children. It concludes that the Government and NHS leaders could do more to foster good, collaborative relationships between parents and healthcare staff across the UK.

The care and treatment of critically ill children often involves complexity and uncertainty. Disagreements can arise between parents and healthcare staff about the best course of action, and sometimes these become entrenched. Recent high-profile court cases in the UK have highlighted the damaging effects that these kinds of disagreements can have on everyone involved.

The reasons why disagreements develop are wide ranging, but include poor communication - such as conflicting messages being given to families by different members of staff, or the use of insensitive language - and delays in seeking resolution interventions, such as mediation.

The Nuffield Council has highlighted areas of action for healthcare policy-makers and NHS leaders that could help to prevent prolonged and damaging disagreements developing in future, or to resolve them more quickly. Overall, the aim should be:

good communication between families and staff and an understanding of differing perspectives

appropriate involvement of parents in discussions and decisions about the care and treatment of their child

timely use of resolution interventions, such as mediation, in cases of disagreement

attention to the profound psychological effects that disagreements can have for families and staff.

Professor Ann Gallagher, member of the Nuffield Council on Bioethics, and Professor of Ethics and Care at the University of Surrey says:

"Disagreements about the care and treatment of critically ill children can be extremely distressing for parents and for everybody involved, particularly if the case is referred to the courts. Every situation is different, but we have tried to understand some of the common causes of disagreements by talking to parents, healthcare staff and range of other people with expertise in this area.

"We heard that problems can start early, with poor communication leading to a breakdown of trust, or parents feeling they are excluded from medical conversations about their child. Healthcare staff can feel they are not adequately supported to deal with conflict.

"Although there is a lot of good practice already out there, we think more could be done at a national level to support good, collaborative relationships between families and healthcare staff leading to shared decision-making. We want to prompt policy makers and NHS leaders to think carefully about how the damaging and protracted disagreements that we have seen in recent years can be avoided in future."

Areas of action

The Council suggests that, amongst other measures, those responsible for national policy making in relation to healthcare practice should consider:

supporting hospital trusts across the UK to develop processes for recognising and managing disagreements between parents and healthcare staff, such as introducing conflict management frameworks and increasing timely access to resolution interventions

making ethics, communication and conflict management training for paediatric healthcare staff more widely available, or even compulsory

improving access to and awareness of children's palliative care services.

Amongst other measures, those involved in leading NHS trusts and hospitals should consider:

providing parents with a trusted and appropriately trained healthcare professional as a central point of communication

exploring ways in which those parents who want to can be more involved in discussions and decisions about their critically ill child, including having access to their child's medical records

ensuring healthcare staff involved in disagreements are better supported by, for example, developing conflict management frameworks, providing more psychological support, and protecting them from abuse and intimidation.

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Nuffield Council on Bioethics

Making lead pipes safe

image: Briefly applying electricity to a lead pipe enables a safe coating to quickly form inside the pipe.

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Gabriel Lobo

ORLANDO, Fla., April 3, 2019 -- Lead leaching from pipes into the water supply is a serious public health concern. And if water sources or treatment regimens are changed, the new chemistry can cause water distribution systems that were previously safe to begin releasing toxic lead, as the crisis in Flint, Michigan, demonstrated a few years ago. Today, scientists will describe a cost-effective and quick method that could overcome these problems and make lead pipes safe for carrying drinking water.

The researchers will present their results today at the American Chemical Society (ACS) Spring 2019 National Meeting & Exposition. ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features nearly 13,000 presentations on a wide range of science topics.

A brand-new video on the research is available at http://bit.ly/HLS_Lead_Pipes.

"More than 18 million people in the U.S. are currently at risk of developing health problems from lead leaching from pipes in their water distribution systems," says Gabriel Lobo, a doctoral student who is presenting the work at the meeting. Lead poisoning in young children can cause a broad range of symptoms, including brain damage, learning difficulties, and slowed growth and development. Adult exposure can cause high blood pressure, memory difficulties, miscarriages and other conditions.

Historically, many municipalities installed iron water mains that were connected to individual buildings by lead water pipes. In a typical lead pipe, chemicals in the water cause the inside wall of the pipe to corrode, releasing lead ions into the water, Lobo explains. To address this problem, municipalities add corrosion inhibitors to the water. Over time, these added phosphates react with the lead ions to create compounds that deposit on the inside of the pipe. This coating, or "scale," blocks other lead ions from leaching from the pipe into the water, making the pipe safe for water distribution. However, in Flint, the drinking water source was changed to a source that had different water quality, and concurrently, the city of Flint stopped using corrosion control measures. The protective scale dissolved, and toxic lead ions leached into the water.

Lobo became involved in this issue when his adviser, Ashok Gadgil, Ph.D., began to focus on finding a solution for the lead problems in Flint. Gadgil's team is at the University of California, Berkeley, and Gadgil is also affiliated with Lawrence Berkeley National Laboratory.

After a few months of intense effort, Gadgil and his team came up with an electrochemical approach to the problem. They applied a small external voltage to a sample of pipe to speed up corrosion. As usual, the freed lead ions then reacted with phosphates in the water to form scale. The process took just a few hours, compared with a couple of years for the usual scaling method. Lobo hopes this process could quickly restore the protective coating in the pipes in Flint, where scale has still not recoated the pipes.

The researchers have tested their process in the laboratory but caution that they haven't yet conducted any trials on lead pipes in the ground. For real-world applications, Gadgil envisions attaching external connectors to a homeowner's pipe at the water meter and at other junctions in the pipes, and then threading another wire through the pipes to complete the circuit. "The idea is that we wouldn't have to dig the whole pipe out, so we could keep the cost low," Gadgil explains. "Replacing all the plumbing in one house would cost several thousand dollars, whereas our process would cost less than one tenth of that."

Currently, the group is working with experts from a local water utility in California to determine the practical parameters for a test under real-world conditions. They are also planning to conduct a test later this year at an Oakland school where normal scale buildup isn't happening in the pipes.

A press conference on this topic will be held Wednesday, April 3, at 10:30 a.m. Eastern time in the Orange County Convention Center. Reporters may check-in at the press center, Room W231B, or watch live on YouTube http://bit.ly/ACSLive_Orlando2019 ("ACSLive_Orlando2019" is case-sensitive). To ask questions online, sign in with a Google account.

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American Chemical Society

Doing more with less in the study of plant chemical defense

Plants can't run away to avoid being eaten, so instead they employ a variety of chemical defenses to keep herbivores at bay. Understanding plant chemical defenses is critical for keeping crops healthy, and for answering a variety of more academic questions about ecology and evolution. However, current techniques for assessing plant chemical defenses are time consuming and require impractically large amounts of plant tissue. In research presented in a recent issue of Applications in Plant Sciences, Dr. Chandra Jack and colleagues devised a new technique for assessing plant chemical defenses that is less laborious and more practical for a variety of experimental applications.

Traditional methods of measuring defense compounds use light to measure different chemicals in leaves using an apparatus called a spectrophotometer. These methods require large tissue samples, meaning that multiple leaves must be pooled together, collapsing meaningful variation. The technique reported here, using a microplate reader, detected activity in samples smaller than 10 mg, or 2% of the traditional tissue sample weight.

"One of the biggest constraints is the amount of tissue that is needed for traditional spectrophotometer-based assays," said Dr. Jack, the lead author of the study. "Now, because researchers don't have to combine leaves from a single plant, they can better explore localized versus systemic responses, or monitor individual plant response over time... It allows us to measure population-level variation and to parse out the influence of environment on genes."

"The other constraint is the time needed to carry out these experiments," said Dr. Jack. The huge amounts of labor and time required to carry out assays using spectrophotometric methods put serious constraints on the number of samples that can be assessed. This limits feasible experimental designs, and consequently the types of questions one can hope to answer. Additionally, both the time and tissue demands of traditional methods make it more difficult to re-run a sample or reproduce a result. In this study, researchers were able to conduct a set of assays that would normally take 41 hours in only six hours.

Plant chemical defense is complex, involving the production of multiple compounds at once. While traditional techniques require separate extractions to assay each class of defense compounds, the technique presented here uses consolidated preparation buffers and protocols to extract multiple compounds at once. This makes it practical to measure a wider range of chemical responses, providing a more nuanced and higher-resolution picture of plant defense. "Plants produce so many secondary metabolites and enzymes in response to herbivore attack, that the story of plant defenses is not complete unless you assay multiple compounds," said Dr. Jack.

The method presented here, in which sample preparation buffers are consolidated and samples are run simultaneously on a microplate, vastly reduces the time and expense of assaying defense compounds. "For us it was a case of necessity being the mother of invention," said Dr. Jack. "I was planning to set up an experiment...and couldn't find high-throughput assays to accomplish what was needed." But in developing this technique, the authors opened up avenues of inquiry into plant defenses for others. Researchers can now investigate multiple defense compounds at once, look at localized and systemic responses, compare a larger sample of individuals, and replicate their findings much more feasibly than before.

"Originally, this wasn't going to be a stand-alone project," said Dr. Jack. "However, as we combed through the literature and invested so much time into the protocol, we realized that this would be useful for the scientific community and could impact so many different fields."

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Botanical Society of America

Ellen N. La Motte was Hemingway before Hemingway

Virtually everyone has heard of Ernest Hemingway. But you’d be hard-pressed to find someone who knows of Ellen N. La Motte.

People should.

She is the extraordinary World War I nurse who wrote like Hemingway before Hemingway. She was arguably the originator of his famous style – the first to write about World War I using spare, understated, declarative prose.

Is your melanoma hot enough for immunotherapy?

Melanomas tend to be "hot" or "cold" - if they're hot, immunotherapy lights melanoma tumors like beacons for elimination by the immune system; but 40-50 percent of melanomas are cold, making them invisible to the immune system, and patients with cold tumors tend to show little benefit from immunotherapies. The problem is that it's been impossible to distinguish a hot melanoma from a cold one - the solution has been to administer immunotherapy and hope for the best, often leading to wasted time and resources. Now a University of Colorado Cancer Center study presented at the American Association for Cancer Research (AACR) Annual Meeting 2019 identifies a possible way to predict which melanomas are hot and cold: Tumors with mutations in genes leading to over-activation of the NF-kB signaling pathway were more than three times as likely to respond to anti-PD1 immunotherapy compared with tumors in which these changes were absent.

"I want to do a little more examination, but we're pretty close to pinpointing high NF-kB as a predictor of response," says Carol Amato, MS, investigator at CU Cancer Center and senior professional research assistant.

One factor hypothesized to create a "hot" tumor is the overall tumor mutation burden - the total number of mutations a tumor holds - with the idea being that more mutations would create more differences between tumor and healthy tissue, leading to a higher likelihood that the immune system will recognize tumor tissue as foreign and work to eliminate it.

However, Amato and colleagues including William Robinson, MD, PhD, and first author Keith Wells, MD, show that while overall tumor mutation burden may increase the chance of important genetic changes, the immune system's ability to see tumor tissue may depend more on specific, important changes than on overall mutation burden.

To discover what these changes are, the group leveraged patient samples gathered over the course of a decade by the Robinson lab in the Colorado Skin Cancer Biorepository.

"Basically, a few years back, we decided to do whole-exome sequencing on our biorepository, about 500 melanoma samples in all. In this project, we asked which of these 400 patients had been treated with immunotherapy, and whether genetic or genomic features of their tumors could predict response to treatment," Amato says.

Of 52 patients treated with anti-PD1 immunotherapies, 21 responded favorably to therapy, and 31 showed little or no benefit. Sixty-seven percent of those responding favorably had alterations in genes associated with the NF-kB signaling pathway, compared with only 19 percent in patients whose tumors did not respond to immunotherapy.

"NF-kB is a complex pathway - sometimes it's bad and sometimes it's good. The cell context may be different than the treatment context," Amato says.

What she means is that, on one hand, over-active NF-kB signaling has been implicated in the development of many cancers ("sometimes it's bad"). But on the other hand, over-active NF-kB signaling may also allow immunotherapies to better target existing cancers ("sometimes it's good").

"What we show is that cancers with alterations that over-activate the NF-kB may better benefit from immunotherapy," Amato says.

Exactly why this is the case is complex and requires looking inside the NF-kB signaling pathway to a specific mutation in NFKBIE, a negative regulator of NF-kB. This mutation, G34E, found only in tumors that responded to immunotherapy, has an effect like removing a limiter on NF-kB, allowing increased activation of this pathway. Then, when especially activated, the transcription factor NF-kB was able to pass into the cell nucleus, where it magnified the expression of the gene CD83.

"And it's CD83 that we think is enhancing responsiveness of the tumor to immunotherapy," Amato says, explaining this action by suggesting that CD83 may be presenting antigens on the surface of tumor cells that make these cells more visible to the immune system.

When the group artificially increased NFKBIE G34E mutations, they saw increased NF-kB signaling. And this activity was independent of many of the genetic alterations commonly seen in melanoma, for example, BRAF and NRAS mutations.

"Even beyond tumor mutation burden, these specific changes could help doctors predict which melanoma patients will respond and which patients will not respond to anti-PD1 immunotherapies," Amato says.

Credit: 
University of Colorado Anschutz Medical Campus

Researchers advance in the development of 'papaya sugarcane'

image: Sugarcane root aerenchyma seen under a microscope. Description of genes involved in sugarcane root cell separation could lead to the development of varieties with softened cell walls similar to those of papaya, boosting the production of second-generation etanol.

Image: 
Débora Chaves Coelho Leite

During the period in which the papaya (Carica papaya) is ripening, its cell walls separate, making the tissue softer and more digestible because the cell contents become accessible and the sucrose in the fruit is more easily extracted.

Sugarcane roots have recently been found to undergo a similar process. Their cell walls are modified during development to form gas-filled intercellular spaces in a type of tissue known as aerenchyma.

"Aerenchyma is very common in crops grown in flooded fields, such as rice, since it supports them or enables them to float in water while also allowing the submerged parts of the plant to breathe in oxygen and breathe out carbon gas," said Marcos Buckeridge, a professor in the University of São Paulo's Bioscience Institute (IB-USP) in Brazil.

In recent years, Buckeridge and collaborators have focused on studying the genes involved in sugarcane root cell separation with the aim of developing transgenic varieties of sugarcane in which the process occurs in other parts of the plant, such as the stem, where biomass and sucrose accumulate. The cell walls in these varieties would be as soft as in a papaya - hence the nickname "papaya sugarcane" - and could more easily be degraded to produce second-generation bioethanol (obtained from biomass) on a large scale.

Researchers affiliated with Brazil's National Institute of Science and Technology of Bioethanol (INCT Bioethanol, one of several such research centers supported by São Paulo Research Foundation - FAPESP in São Paulo State in partnership with the National Council for Scientific and Technological Development (CNPq), have now taken an important step in this direction.

Partnering with colleagues from other universities and research institutions in Brazil and abroad, they described the first gene sequences involved in sugarcane root cell separation and elucidated their functions in this process. The results of the study were published, in the Journal of Experimental Botany.

"If we succeed in promoting cell wall separation in the sugarcane stem, it will be possible not only to reduce the amount of enzyme cocktails used for enzymatic hydrolysis [degradation of the carbohydrates in sugarcane trash and bagasse and their conversion into fermentable sugar] to obtain second-generation ethanol but also to increase sucrose extraction," Buckeridge, principal investigator for INCT Bioethanol, told.

The researchers sequenced two genes considered essential to the initial stages of aerenchyma development in sugarcane roots. The first was scRAV1, which encodes the RAV transcription factor that controls plant leaf aging. The second was scEPG1, which encodes endopolygalacturonase (EPG), an enzyme that degrades the pectin that keeps cells together, thereby contributing to cell separation and the softening of fruit tissue via aerenchyma formation.

Owing to the complexity of the sugarcane genome, which has several copies of each chromosome and numerous variants of each gene, the two genes were sequenced from 17 artificial bacterial chromosome clones containing genomic regions homologous to those of the R570 sugarcane variety.

The gene sequences were compared with those of the corresponding regions of Sorghum bicolor (the sorghum genome closely resembles the sugarcane genome). A similar sequence from each of the two genes was expressed in tobacco leaves for transactivation assays to see which other genes they activated.

"Tobacco is easy to transform genetically and serves as a model to demonstrate how mechanisms like this actually work," Buckeridge said.

Analysis of the genomic regions and the transactivation assays showed that scRAV1 controls early pectin degradation during sugarcane root aerenchyma formation and that the protein produced by scRAV1 binds to the scEPG1 promoter, blocking transcription of this gene.

"Our findings pave the way for using biotechnology for the genetic manipulation of sugarcane to boost the production of second-generation ethanol," Buckeridge said.
First step

The researchers developed a sugarcane variety with enhanced expression of scRAV1. They also discovered a microRNA (a molecule that regulates gene expression) capable of specifically inhibiting scRAV1 and stimulating the expression of scEPG1throughout the plant.

"In this genetically transformed variety, we're starting to see what seems to be a softening of the sugarcane cell wall, similar to the effect we want. The stems of some of the plants, for example, are unable to stay erect. This could be the first step toward the development of papaya sugarcane," Buckeridge said.

Credit: 
Fundação de Amparo à Pesquisa do Estado de São Paulo

'NarcoLogic' computer model shows unintended consequences of cocaine interdiction

CORVALLIS, Ore. - Efforts to curtail the flow of cocaine into the United States from South America have made drug trafficking operations more widespread and harder to eradicate, according to new research published this week in Proceedings of the National Academy of Sciences.

The National Science Foundation supported the study, which included an Oregon State University geographer and was led by Nicholas Magliocca from University of Alabama. The collaboration also included researchers from The Ohio State University, Northern Arizona University, Arizona State University, Texas State University-San Marcos, the University of Wyoming and the U.S. Fish and Wildlife Service.

"It really is surprising how the model matches our observations," said David Wrathall of OSU's College of Earth, Ocean and Atmospheric Sciences. "Our team consists of researchers who worked in different parts of Central America during the 2000s and witnessed a massive surge of drugs into the region that coincided with a reinvigoration of the war on drugs. We asked ourselves: did drug interdiction push drug traffickers into these places?"

The findings are important because after five decades, the United States' war on drugs has yet to prove itself effective or cost-efficient for dealing with cocaine trafficking, the researchers note. The study comes at a time of increased attention on Central American migrants fleeing drug-related violence in their home countries.

The scientists developed a computer model named NarcoLogic that shows how drug traffickers respond to interdiction strategies and tactics. It differs from previous approaches because it models local- and network-level trafficking dynamics at the same time.

Interdiction efforts are linked to the spread and fragmentation of trafficking routes - a phenomenon known as the "balloon and cockroach effect." When interdiction efforts are focused in one location, drug traffickers simply relocate.

"Between 1996 and 2017, the Western Hemisphere transit zone grew from 2 million to 7 million square miles, making it more difficult and costly for law enforcement to track and disrupt trafficking networks," Wrathall said. "But as trafficking spread, it triggered a host of smuggling-related collateral damages: violence, corruption, proliferation of weapons, and extensive and rapid environmental destruction, which has been the focus of my work."

Since the Nixon Administration launched the war on drugs in 1971 and declared drug abuse to be "public enemy No. 1," the United States has spent an estimated $1 trillion on drug prevention and enforcement efforts.

That includes roughly $5 billion annually on cocaine interdiction, without having much effect on the drug's supply or its price, the researchers say.

"Wholesale cocaine prices in the United States have actually dropped significantly since 1980, deaths from cocaine overdose are rising, and counterdrug forces intercept cocaine shipments at a low rate. More cocaine entered the United States in 2015 than in any other year," Wrathall said. "And one thing people who support interdiction and those who don't can agree on is that change is needed. This model can help determine what that change should look like."

The researchers' main hypothesis, borne out by comparing NarcoLogic's predictions of where, when and how cocaine shipments were trafficked from2000-14 against the actual patterns recorded in interdiction databases, was that trafficking operations didn't become more widespread and resilient because of ineffective interdiction - but did so simply as a result of interdiction.

"The study is a victory for observation and theory. This model successfully recreates the dynamic our team had observed," Wrathall said. "It tells us that increased interdiction will continue to push traffickers into new areas, spreading networks, and allowing them to continue to move drugs north."

Credit: 
Oregon State University

Study identifies potential fix for hospital star rating program

image: David Nerenz, Ph.D., director emeritus of Henry Ford's Center for Policy and Health Services Research and the study's lead author.

Image: 
Henry Ford Health System

DETROIT - Allowing for more quality measures in the federal government's Quality Star Rating program would create a fairer and more equitable model for assessing the level of quality at U.S. acute-care hospitals, according to a Henry Ford Health System study.

Researchers found that recognizing four fundamental quality factors in the safety of care category and assigning more equal weights to the eight measures in that category would modify the rating system's current scoring methodology and produce more accurate and informative results.

"Since the star ratings introduction in 2016, the ratings have been met with skepticism because of the methodology," says David Nerenz, Ph.D., director emeritus of Henry Ford's Center for Policy and Health Services Research and the study's lead author. "In our study, we believe we've identified a simple and straightforward solution in the safety of care domain that would make these ratings more meaningful and unbiased."

The study is published online in the American Journal of Medical Quality.

Created by the Centers for Medicare & Medicaid Services (CMS), the rating system assigns a score of one to five stars - five being the highest - based on a set of 57 individual quality measures across seven categories: mortality, readmission, safety of care, patient experience, effectiveness of care, timeliness of care and efficient use of medical imaging.

The first four categories each account for 22 percent of a hospital's total score, while the last three each count for four percent. A complex weighting scheme is used to assign an importance to each measure in each category, and the scheme for the safety of care category makes only one of the eight measures really count.

For their study, Dr. Nerenz and his team of researchers sought to evaluate the current methodology and how an alternative approach might affect the ratings scoring. Researchers performed principal components analyses on a subset of 674 hospitals in the December 2017 national data set that reported on eight safety measures used at the time. Then they assigned equal weight to each of the measures instead of the model employed by CMS and considered the number of cases at a hospital and how it impacted the accuracy of each measure.

The effect of applying this alternative methodology was illustrated in a single hospital, whose safety category score was markedly different (+1.65) compared to CMS' current methodology (-2.35). That was enough difference to move the score from below average to above average. Assigning equal weight to each measure had a "pronounced effect," researchers wrote.

"A stated aim of the Hospital Star Ratings program is to effectively summarize available hospital performance measures on Hospital Compare into a single, summary rating," says Brian Waterman, Ph.D., MPH, vice president of Analytic Business Solutions for the Missouri Hospital Association and a study co-author. "Our study results indicate that the current form of the methodology employed by CMS likely leaves important information about safety of care effectively out of the mix."

Researchers say the designers of the ratings system were well intentioned in creating a system that would be both "simple and patient-friendly" for consumers. However, the methodology is so highly complex that it has led to confusion and "very significant consequences for the ratings of individual hospitals." Further refining the methodology, they say, would better summarize the quality measures and "offer greater upside for consumers and providers."

Credit: 
Henry Ford Health