Earth

A team of international researchers led by Colorado State University is calling for a new approach to understanding environmental risks in the Anthropocene, the current geological age in which humans are a dominant force of change on the planet.

Patrick Keys, a research scientist in the School of Global Environmental Sustainability at CSU, is the lead author of "Anthropocene risk," a perspective paper published July 22 in Nature Sustainability that suggests adopting a holistic approach to understanding environmental risks. Keys said the team hopes that the article is "productively provocative."

"The Anthropocene is a time of rapid global change - socially, environmentally, and geophysically," he said. "Typical notions of neatly and cleanly delineating complex environmental risks are changing in unexpected ways. It's becoming clear that a more holistic perspective, including social history, power relations, and environmental ethics may be important components of Anthropocene risks."

As an example, Keys said it's a common belief that the civil war in Syria has been driven by drought and climate change. While those two factors more than likely played a role in what led to the civil war, it also ignores other aspects such as incentives by Syrian government officials that kept farmers on agriculturally precarious land for decades. Keys said those incentives made it possible for drought and climate change to have such an impact.

"If we ignore the social and political economic factors that deliver us to this present, we will attribute an event to being caused by the environment when, in fact, that was just one cause or the icing on top of the cake. If we look at things only in the present, we will come up with solutions to a problem defined in the present, but we may not be defining the problem correctly."

This point of view stems from Guidance for Resilience in the Anthropocene: Investments for Development (GRAID), a program based at the Stockholm Resilience Centre, where five of the paper's co-authors currently work.

In the paper, the research team explores four different cases outside of Europe and North America to highlight this way of looking at environmental risks and underline why people studying such risks must take a broader approach.

"As the Anthropocene unfolds, navigating new and emerging risks will require considering changes that happen over years, decades, centuries, or even millennia." Keys said. "In this increasingly interconnected and accelerating world, it's on us to really educate ourselves about how to interact intelligently and meaningfully to work toward a more sustainable world."

A study of newborn infants has identified a compound produced by gut bacteria that appears to predispose certain infants to allergies and asthma later in life.

"We have discovered a specific bacterial lipid in the neonatal gut that promotes immune dysfunction associated with allergic asthma and can be used to assess which babies are at risk of developing the disease in childhood" said study senior author Susan Lynch, PhD, a professor of medicine at UCSF. "This finding paves the way for early-life gut microbiome interventions to prevent these diseases from developing."

Lynch's lab has previously shown that one-month-old infants with unhealthy gut microbial ecosystems -- more like a weedy lot than a well-functioning garden -- are at increased risk of developing asthma later in childhood. They have also shown that a specific fatty molecule, or lipid, called 12,13-diHOME, found at high concentrations in the feces of these babies, reduced the number and activity of a key group of immune cells called regulatory T cells (Tregs) that normally suppress allergic inflammation.

In their newest study, published July 22, 2019 in Nature Microbiology, research led by MD/PHD candidate Sophia Levan set out to test whether this bacterial molecule might directly drive the risk of asthma and allergy in young infants. First, they showed that injecting 12,13-diHOME into the gut of mice reduced Treg cell numbers in the animals' lungs, and that this molecule alters Treg and other immune cell function at a molecular level.

To understand where this pro-inflammatory lipid was coming from, the researchers studied the microbial genes present in stool samples from 41 one-month old infants collected as part of the racially and ethnically diverse WHEALS (Wayne County Health, Environment, Allergy and Asthma Longitudinal Study) cohort in Detroit. They found that the number of copies of three bacterial genes for 12,13 DiHOME or the concentration of the lipid itself in the babies' stool samples predicted which infants went on to develop allergy by age two or asthma by age four. They then replicated this finding in the stool samples of an independent cohort of 50 one-month-olds based in San Francisco.

"While these findings need to be replicated in an even larger study group, the fact that these two cohorts collected in demographically different populations in very different cities showed the same results gives us confidence that the association between this bacterial lipid and childhood asthma and allergy risk may generalize to a broader population," Levan said.

The researchers emphasize that 12,13-diHOME is likely just one of many microbial-derived products that contribute to early-life immune dysfunction and susceptibility to childhood allergy and asthma.

"This is likely just one component of a complex microbiome-immune interaction in young infants that promotes allergy and asthma development in childhood," Lynch said. "But it is a first step towards a more mechanistic understanding of the suite of microbial products that increase susceptibility to allergies and asthma during childhood."

DURHAM, N.C. - Continuation of community-wide HIV testing and prompt initiation of treatment as delivered in the HPTN 071 (PopART) study in South Africa and Zambia could lead to substantial reductions in new HIV cases, be cost-effective, and help to achieve the UNAIDS 2030 targets, according to projections from mathematical modelling and cost-effectiveness analyses presented today at the 10th International AIDS Society Conference on HIV Science in Mexico City (IAS 2019).

"Our projections show the impact of a sustained PopART intervention builds up over time. We estimate by 2030 HIV incidence in the communities where the study was conducted could be half what it would be without adopting this intervention," said Dr. William Probert, infectious disease modelling researcher, Nuffield Department of Medicine, University of Oxford, U.K.

Recognizing the importance of estimating the implementation cost of this type of intervention, study researchers undertook a detailed cost and cost-effectiveness analysis.

"We found the PopART home-based intervention package costs between $5.10-$6.80 in Zambia and $6.40-$8.20 in South Africa per year and per person older than 14 years of age living in the study communities," said Dr. Katharina Hauck, health economist, School of Public Health, Imperial College, London. "If sustained until 2030, the cost per disability-adjusted life-year would range between $465-$847 in Zambia and $503-$922 in South Africa, which would fall within the range considered as cost-effective."

HPTN 071 (PopART) examined the impact of a package of HIV prevention interventions, including universal testing and treatment, on community-level HIV incidence amongst more than one million people living in 21 urban and peri-urban communities in Zambia and South Africa. Primary results were published in The New England Journal of Medicine on 18 July 2019 and showed delivery of an HIV prevention package that included offering in-home HIV testing to all household members, with immediate referral to HIV care and treatment for all people living with HIV, can substantially reduce new HIV transmissions.

"Modelling the HPTN 071 (PopART) effects into the future provides evidence that achieving high coverage with HIV testing and treatment can be part of a pathway towards achieving epidemic control," said Dr. Wafaa El-Sadr, HPTN co-principal investigator and professor of epidemiology and medicine at Columbia University, New York. "Many implementation insights can be gained from the study on how to accomplish the scale-up of these interventions."

The research team was led by Dr. Richard Hayes, professor of epidemiology and international health at the London School of Hygiene and Tropical Medicine and Dr. Sarah Fidler, clinical professor of HIV medicine at Imperial College, London. The research team in Zambia was led by Dr. Helen Ayles, director of research, Zambart, Lusaka, Zambia. The research team in South Africa was led by Dr. Nulda Beyers and Dr. Peter Bock, research clinicians, Desmond Tutu TB Centre at Stellenbosch University, Cape Town, South Africa.

"The HPTN 071 study adds to compelling evidence that HIV testing and rapid initiation of treatment is important not just for personal health, but also to reduce the number of new HIV infections in sub-Saharan Africa," said Dr. Myron Cohen, HPTN co-principal investigator and director of the Institute for Global Health at the University of North Carolina at Chapel Hill, N.C.

HPTN 071 (PopART) was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, with primary funding from the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), which is administered by the Office of the U.S. Global AIDS Coordinator and Health Diplomacy in the U.S. Department of State. Additional funding was provided by the International Initiative for Impact Evaluation (3ie) with support from the Bill & Melinda Gates Foundation, as well as by three NIH institutes: NIAID, the National Institute on Drug Abuse (NIDA) and the National Institute of Mental Health (NIMH).

Cells assemble dynamically: their components are continuously exchanging and being replaced. This enables the structures to adapt easily to different situations, and by rearranging the components to respond to stimuli faster, to renew or to form just on demand. The microtubules, a scaffold structure made of protein fibers that can be found in the cytoplasm of the cells of algae, plants, fungi, animals and humans, are one such dynamic mesh. Because of their self-organizing structure, these fibers constantly form and degrade at the same time, thereby actively supporting the cell in complex tasks such as cell division or locomotion. The fibers require energy to form and maintain such dynamic states. Now, for the first time, Prof. Dr. Andreas Walther and Dr. Laura Heinen from the Institute for Macromolecular Chemistry and the Center of Interactive Materials and Bioinspired Technologies (FIT) at the University of Freiburg have succeeded in programming the dynamics of such dissipative, i.e. energy-consuming, structures in an artificial chemical system on the basis of DNA components. The researchers present their results in the latest edition of the journal Science Advances.

The difficulty of programmable structural dynamics in synthetic dissipative systems is the synchronization of the energetic deactivation and activation with the structural build-up and degradation of the components. The Freiburg researchers were able to solve the problem by using an energy-driven, dynamic covalent bond, that is responsible for the firm cohesion of atoms, in the backbone of the DNA sequences. The covalent bond is herein formed through the catalytic activity of the enzyme T4 DNA ligase, and simultaneously split at the very same site by a restriction enzyme, which can recognize and cut DNA at specific positions. This newly-formed system is reversible and results directly in structural dynamics, which distinguishes it from previous artificially-generated dissipative structures.

The study, which took place with the aid of Walther's ERC Starting Grant "TimeProSAMat", uses the dynamic synthesis of a polymer of DNA fragments, to show scientists how the lifetime, exchange frequency, or relative bond fraction of the DNA polymers can be controlled in dependence of the chemical fuel adenosine triphosphate and the enzyme concentrations. The Freiburg researchers were able to sustain these dynamic steady states for several days. The chemical modifications of DNA to use it as a construction material are versatile and there are also many available restriction enzymes, explains Heinen, "So our concept enables wide-ranging access to innovative functional materials, which act outside thermodynamic equilibrium. And it does so with so far unique programming possibilities in its dynamic structural characteristics."

Think twice before adding that extra kick of chili sauce or chopped jalapeno to your meal. New research involving the University of South Australia shows a spicy diet could be linked to dementia.

A 15-year study of 4582 Chinese adults aged over 55 found evidence of faster cognitive decline in those who consistently ate more than 50 grams of chili a day. Memory decline was even more significant if the chili lovers were slim.

The study, led by Dr Zumin Shi from Qatar University, showed that those who consumed in excess of 50 grams of chili a day had almost double the risk of memory decline and poor cognition.

"Chili consumption was found to be beneficial for body weight and blood pressure in our previous studies. However, in this study, we found adverse effects on cognition among older adults," Dr Zumin says.

UniSA epidemiologist Dr Ming Li, one of five researchers involved in the study, says chili intake included both fresh and dried chili peppers but not sweet capsicum or black pepper.

"Chili is one of the most commonly used spices in the world and particularly popular in Asia compared to European countries," Dr Li says. "In certain regions of China, such as Sichuan and Hunan, almost one in three adults consume spicy food every day."

Capsaicin is the active component in chili which reportedly speeds up metabolism, fat loss and inhibits vascular disorders but this is the first longitudinal study to investigate the association between chili intake and cognitive function.

Those who ate a lot of chili had a lower income and body mass index (BMI) and were more physically active compared to non-consumers. Researchers say people of normal body weight may be more sensitive to chili intake than overweight people, hence the impact on memory and weight. Education levels may also play a role in cognitive decline and this link requires further research.

A new paper offers fresh insight into the forces causing the world's largest ice shelf to melt.

The Ross Ice Shelf, a part of the Antarctic Ice Sheet that is floating on the ocean, measures several hundred meters thick and sits over 480,000 square kilometers, approximately the size of Spain. Its magnitude, and the fact that thinning of the ice shelf will speed up the flow of Antarctica's ice sheets into the ocean, mean that it carries significant sea level rise potential if it were to melt. Melting ice shelves like the Ross could cause seas to rise by several feet over the next few centuries.

A study just published in the Journal of Geophysical Research: Oceans helps to reveal the local factors that influence the Ross Ice Shelf's stability, refining predictions of how it will change and influence sea rise in the future.

Prior studies on ice shelf melt have focused on warming global waters. Yet three years of Rosetta data show that the Ross Ice Shelf is melting due to local surface waters, and that the melt is happening on an unanticipated part of the shelf. These discoveries were released in a Rosetta paper published in May; the new study details the source of this strange activity.

The study comes out of the Rosetta-Ice project, a three-year-long collection of geologic, oceanographic, and glaciological data in Antarctica. The project is immense in scope, involving a multi-institutional, interdisciplinary team with specialized instrumentation to collect first-of-its kind Antarctic data.

A new approach

The Rosetta team needed data on ocean temperature, salinity, depth, and circulation around the ice shelf. Traditionally, this oceanographic data is obtained in two ways: research cruises and deep moorings. Because the Ross Sea is covered by sea ice for most of the year, ship-based measurements are restricted to a short period in high Austral summer. Moored sensors, on the other hand, can collect data for several years; however, they are generally deployed no higher than 200 meters below the water's surface, to avoid passing icebergs, so they provide a less complete picture of what's happening around the ice shelf.

The Rosetta scientists took a new approach to gather data from the Ross Sea. They deployed six profiling floats called Air-Launched Autonomous Micro Observer, or ALAMO, floats. They fastened parachutes to the floats and launched them out of a New York Air National Guard airplane from 2,500 feet above the icy waters below. The instruments were programmed to avoid sea ice that could damage their external sensors and antennae. In addition, the team took a novel approach by "parking" the floats on the sea floor between profiling so as to limit their drifting on ocean currents.

The floats gathered temperature and salinity data from the seabed to the surface, sending data back to the team by satellite every day. Seven other floats, deployed from a ship three years earlier, provided records of ocean conditions further north, away from the ice shelf.

Local effects

"In other places in Antarctica, the ice shelves are being melted by flows of global warm water from the deep ocean to the coast," explained Dave Porter, the Lamont-Doherty Earth Observatory scientist who led the new study. "But changing melt rates for the Ross are caused mainly by a local buildup of heat in the surface layer. The question is: What dictates how much heat we build up in the summer? And the answer is that it's mostly caused by local weather processes along the ice front."

The team found that the main source of ocean heat causing the ice shelf to melt was sunlight warming the upper ocean after the region's sea ice disappeared in summertime; sea ice normally reflects sunlight, whereas darker sea water absorbs it. The team also measured large amounts of fresh water coming into the Ross Sea from rapidly melting ice shelves in the Amundsen Sea to the east of the Ross Sea. Once this extra fresh water reaches the ice front, it changes how heat mixes down from the surface to the base of the ice shelf, where melting occurs, leading the team to conclude that future Ross Ice Shelf stability depends on changing coastal conditions in both the Amundsen Sea and close to the ice shelf front.

The scientists noted that increased ocean heating and ice-shelf melting could occur if the summer season, during which the sea is free of ice, becomes longer -- for example, if changing local winds pushing the sea ice away from the ice shelf, or a decrease in summer cloudiness allowing more sunlight to reach the ocean surface.

Co-author Scott Springer of Earth & Space Research in Seattle said that "this new approach to collecting data from remote Antarctica's continental shelves provides a new way to check the reliability of numerical models that we use to understand how the Antarctic Ice Sheet will respond to future changes in the oceans around Antarctica."

The importance of local conditions near the ice front also shows that researchers must find a way to include these smaller-scale processes in global climate models, which scientists use to simulate climate impacts over the coming centuries. Testing and refining the global models will be critical in narrowing the range of predictions regarding how much ice Antarctica will lose in future climates, and how high seas will rise.

To co-author Helen Amanda Fricker of the Scripps Institution of Oceanography at the University of California San Diego the study also shows how important it is to study relatively stable areas such as the Ross ice shelf. "Many current field programs are focused on parts of Antarctica that are known to be changing, but we must also collect observations in regions that are not changing to understand how the ice sheet works as a whole," she said. "This is critical because there remains a large range across predictions of Antarctica's contribution to sea level in future climates."

The incidence of colorectal cancer in adults younger than 50 years of age has increased in the United States since 1970. A new study published early online in CANCER, a peer-reviewed journal of the American Cancer Society, found that the proportion of adults diagnosed with colorectal cancer under age 50 in the United States has continued to increase over the past decade, and younger adults are diagnosed with more advanced disease.

To determine recent trends in colorectal cancer rates, Boone Goodgame, MD, of The University of Texas at Austin, and his colleagues examined information from the National Cancer Database registry, which includes more than 70 percent of new cancer cases in the United States. From 2004 to 2015 (the most recent year included in the database), 130,165 patients under age 50 and 1,055,598 patients over age 50 were diagnosed with colorectal cancer.

Among the major findings:

The proportion of patients diagnosed with colorectal cancer under the age of 50 rose from 10 percent in 2004 to 12.2 percent in 2015.

The proportion of young onset disease was higher in African American and Hispanic populations than non-Hispanic whites throughout 2004 to 2015.

51.6 percent of younger adults were diagnosed with more advanced stages of cancer (stage III/IV) versus 40 percent in those older than 50 years.

Diagnoses in men under the age of 50 years rose only in non-Hispanic whites, while in women, Hispanic and non-Hispanic whites had an increase in younger diagnoses over time.

Rates of colorectal cancer diagnosis in young adults increased over time regardless of income level. The highest proportion of young adult diagnoses occurred in the top income category.

The proportion of colorectal cancers diagnosed in younger individuals rose in urban areas, but not in rural areas.

"Several studies have shown that the rates of colorectal cancer in younger adults have risen slowly in the US since the 1970s, but for practicing physicians, it feels like we are seeing more and more young people with colorectal cancer now than we were even 10 years ago," said Dr. Goodgame. "Until just last year, guidelines recommended colon cancer screening beginning at 50. Now many guidelines do recommend screening at age 45, but most physicians and patients don't appear to be following those recommendations."

Dr. Goodgame noted that the cause of increasing rates of colorectal cancer in younger patients is unclear, but emerging research suggests that it may be a combination of increases in body weight and changes in gastrointestinal bacteria.

In an accompanying editorial, Chyke Doubeni, MD, MPH, of the University of Pennsylvania, pointed to the need for additional research. "Because the number of colorectal cancer cases from inherited causes are much higher in younger individuals, it is unknown whether screening for sporadic cases in a group with such low disease rate can result in a favorable balance of harms and benefits," he wrote. "It is therefore imperative that the various hypotheses for increasing colorectal cancer incidence among people younger than 50 be rigorously tested to determine if changing the current screening age in people who are not at increased familial risk represents the most appropriate public health response."

The American Cancer Society's guideline for colorectal cancer screening recommends that average-risk adults aged 45 years and older undergo regular screening, either with colonoscopy or with alternatives such as fecal immunochemical tests and fecal occult blood tests.

Preschoolers with symptoms of attention-deficit hyperactivity disorder are much less likely than other children their age to be ready for school, new research from the Stanford University School of Medicine has found.

The study, which will be published online July 21 in Pediatrics, is among the first to comprehensively examine school readiness in young children with ADHD. Several previous studies have addressed academic difficulties in school-aged children with ADHD, but few studies have investigated whether these children start school behind their peers.

"We were pretty surprised at the proportion of kids within the ADHD group who were not school-ready," said the study's senior author, Irene Loe, MD, assistant professor of pediatrics. Seventy-nine percent of children with ADHD had impaired school readiness compared with 13 percent of children in a control group, the study found. "It's a really high number," Loe said.

The study's lead author is Hannah Perrin, MD, who was a fellow in developmental and behavioral pediatrics at Stanford when the research was done.

The main symptoms of ADHD -- inattention, hyperactivity and impulsivity -- can be normal in toddlers, and these behaviors sometimes persist into the preschool years even in children who will not ultimately meet the diagnostic criteria for ADHD. This makes the disorder difficult to diagnose in preschoolers. "A lot of these kids are not identified until they're really having a lot of trouble in the school setting," Loe said.

The study included 93 children, all of whom were 4 or 5 years old. Nearly all had attended or were currently enrolled in preschool, and some were enrolled in kindergarten. The ADHD group included 45 children who previously had been diagnosed with the disorder or were identified by their parents as having significant levels of ADHD symptoms. The comparison group consisted of 48 children without ADHD. The researchers tested all the children to confirm their levels of ADHD symptoms.

The researchers conducted tests and administered parent questionnaires to measure five areas of the children's functioning: physical well-being and motor development; social and emotional development; approaches to learning; language development; and cognition and general knowledge. "Approaches to learning" included measures of executive function, which is a person's ability to prioritize actions and tasks and exercise self-control to regulate behavior and meet long-term goals.

Children were considered impaired in an area of functioning if their assessment scores in that area were more than one standard deviation worse than the mean score for their age. They were considered unready for school if they were impaired in two or more of the five areas of functioning measured in the study.

Struggling in 4 of 5 areas

Children with ADHD were no more likely than their peers to show impairment in the area of cognition and general knowledge, the study found. This area includes IQ and, importantly, knowledge people traditionally associate with kindergarten readiness, such as being able to identify letters, numbers, shapes and colors.

But children with ADHD were much more likely than their peers to struggle in all four other areas measured. They were 73 times more likely than children without ADHD to be impaired in approaches to learning; more than seven times as likely to have impaired social and emotional development; six times as likely to have impaired language development; and three times as likely to have impaired physical well-being and motor development.

The assessment was broader than other school-readiness measures researchers have used in the past, Loe said. "We looked at many aspects of the child more comprehensively," she said, adding that approaches to learning or executive function as a component of school readiness has been especially under-studied.

The findings suggest that identifying and helping preschoolers with significant levels of ADHD symptoms could reduce their struggles in elementary school.

"We need to help general pediatricians figure out how they can flag kids who might be at risk for school failure," Loe said. Families also need better access to behavioral therapy for preschoolers with ADHD, which is not always available or covered by insurance, even though it is recommended as the first-line ADHD treatment for this age group, she added.

"Thinking about how we can provide services for young children with ADHD or who are at high risk for the diagnosis is really important," she said.

Loe is a member of the Stanford Maternal & Child Health Research Institute. Nicole Heller, a former clinical research coordinator at Stanford, is also a co-author of the research.

ANN ARBOR, Mich. -- Something most parents don't want to hear from their teenager: I am not prepared to be an adult, and it's your fault.

Nearly all parents (97%) in a new national poll say they are helping their teen become more independent by using strategies like allowing them to make more choices (86%), pushing them to handle things themselves (74%) and no longer doing things for them (65%).

Despite this, one quarter of parents surveyed say they are the main barrier to their teen's independence by not taking the time or effort to give their teen more responsibility, according to the C.S. Mott Children's Hospital National Poll on Children's Health at the University of Michigan.

"As children become teenagers, the role of parents shifts to helping them gain the knowledge and experience they will need for being independent adults," says poll co-director Sarah Clark, M.P.H.

"This process of transitioning from childhood to adulthood includes everything from preparing for work and financial responsibility, to taking care of one's health and well-being. Our poll suggests that parents aren't letting go of the reins as often as they could be to help teens successfully make that transition."

The report is based on responses from a nationally-representative sample of 877 parents of at least one child 14-18 years old.

Sixty percent of parents polled say their teen's characteristics are barriers to becoming more independent, such as not being mature enough (24%), not having time (22%) or not knowing enough (14%) to take on more responsibility.

In contrast, one quarter of parents admit their own role in impeding their teen's independence, saying it's quicker and less hassle to do things themselves (19%) or they don't think about how to give teens more responsibility (7%).

Parents gave the lowest rating of teen independence for tasks related to health care. When it comes to their teen's health, parents may feel responsible for ensuring that appropriate care is received and medical advice is followed, Clark says.

"We did not ask about life-or-death health care matters. But we did ask parents whether their teens could independently handle very basic tasks, such as taking care of minor injuries, figuring out the correct dose of a medication or calling to make a doctor's appointment," says Clark.

"It is crucial for teens to begin taking ownership of their health before they enter adulthood when they will face more complex, adult tasks."

"Parental over-involvement impedes teens from gaining experience and confidence to be independent in all aspects of their lives," Clark adds.

Parents are nearly universal in the belief that it is important for teens to make mistakes, but they also feel they should prevent teens from mistakes that are too serious.

"It is clear that parents recognize tension in helping teens move toward independence, and they agree that valuable learning experiences often result from a poor decision," Clark says.

Clark recommends parents to position themselves as a back-up resource, to be consulted only if the teen cannot handle the matter independently. Parents should also establish specific milestones and create opportunities to mentor their teens in gaining experience and confidence while reaching those goals.

"Some parents justify taking control over certain responsibilities because they don't believe their teen is 'mature enough.' But this type of logic inhibits their teen from actually becoming more mature," Clark says.

Clark adds: "Parents need to carve out more time for supporting teens in their transition to adulthood.

Testing for genetic weaknesses in repairing DNA could pick out men who may benefit from a new type of targeted nuclear medicine, a new study reports.

An emerging class of drugs are made up of a radioactive particle that can kill cells attached to a 'homing device' to seek out cancers by detecting the presence of a target molecule on their surface.

These new 'search-and-destroy' treatments are starting to show promise even in men with prostate cancer for whom targeted treatments and chemotherapies have stopped working - but not all patients respond.

In the new study, scientists at The Institute of Cancer Research, London, found that testing men for faults in DNA repair genes in their tumours could identify those most likely to respond to the new type of treatment.

The study is published in the journal European Urology today (Tuesday), and was funded by the Movember Foundation, Prostate Cancer UK, Cancer Research UK and the Prostate Cancer Foundation.

The researchers analysed tumour samples from men with advanced prostate cancer who had been treated at The Royal Marsden NHS Foundation Trust, in order to try to understand why the response to search-and-destroy treatment varied.

They found that the target for these new treatments - a protein molecule called prostate-specific membrane antigen, or PSMA - was present at higher levels on the surface of cancer cells in some patients than others. PSMA levels even varied substantially between different cancer sites in the same patient.

But crucially, the amount of PSMA on the surface of cancer cells was more than four times higher in tumours where there were also faults in DNA repair genes.

That means that testing for genetic faults in DNA repair genes could be used as a first-stage screen to select patients for PSMA-targeted treatment - followed by having tumours scanned using PSMA imaging technology.

The researchers believe that PSMA plays a key role in keeping the genome in cells stable - and could be produced by tumours as a survival mechanism where they are defective in repairing their DNA. This could explain the link between DNA repair faults and high levels of PSMA.

These findings also suggest that combination therapy with other drugs that increase genetic instability could make prostate tumours more likely to respond to PSMA-targeting treatments.

Next, the researchers aim to assess whether testing for DNA repair faults can effectively target search-and-destroy treatment as part of clinical trials, and to explore combination strategies to see if the response to these treatments could be heightened.

Precise targeting of cancer cells and use of drug combinations are among a range of strategies being pursued at The Institute of Cancer Research (ICR) through its new Centre for Cancer Drug Discovery.

The ICR - a charity and research institute - is raising the final £15 million of a £75 million investment in the Centre for Cancer Drug Discovery, to create new 'anti-evolution' treatments that can overcome drug resistance.

Professor Johann de Bono, Regius Professor of Cancer Research at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said:

"Our new study helps to explain why some patients respond to search-and-destroy treatments and others don't. Understanding the biology of response to these new treatments is critical to getting them into use in the clinic as soon as possible.

"We found that testing for DNA repair defects was a good indication of which tumours had high levels of PSMA - and so would be expected to respond to these PSMA-targeted therapies. We will need to further assess the use of DNA tests to target these treatments effectively in routine care, but we can already now start to take into account DNA repair faults in our design of clinical trials."

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

"PSMA-targeting drugs are an exciting new wave of treatments coming through for prostate cancer. They combine a potent nuclear medicine with a 'homing signal' that searches out prostate cancer cells.

"To get these new drugs into the clinic, we need a good understanding of the biology of the treatment response and how to spot those patients who will most benefit. This new study gives us an important handle on how to select men for treatment.

"Innovative new treatment strategies such as PSMA-targeting drugs are one of the ways in which we can start to overcome the challenge of cancer evolution and drug resistance - which will be the focus of the pioneering work in our new Centre for Cancer Drug Discovery."

Preliminary data from multi-country randomised trial find that half of patients in Cambodia, Thailand, and Vietnam not cured by first-line malaria treatment

Authors call for widely used drug combination to be abandoned in the affected countries in southeast Asia and for accelerated malaria elimination to prevent further development of multidrug resistant malaria, which would jeopardise malaria control and could spread, causing a global health emergency

Multidrug-resistant forms of Plasmodium falciparum parasites, the most lethal species causing human malaria, have evolved even higher levels of resistance to antimalarial drugs and spread rapidly since 2015, becoming firmly established in multiple regions of Cambodia, Laos, Thailand, and Vietnam, where they are causing alarmingly high treatment failure rates to a widely used frontline malaria drug combination.

The findings of two studies, published in The Lancet Infectious Diseases journal, reveal that by 2016-2018 malaria parasites resistant to both artemisinin and its widely used partner drug piperaquine represented more than 80% of the parasites circulating in northeast Thailand and Vietnam, despite having only emerged in western Cambodia in 2008.

These rapidly spreading parasites have also acquired new resistance mutations linked with even higher rates of treatment failure, causing failures to one of the newest and most powerful frontline drug combinations (dihydroartemisinin-piperaquine;DHA-PPQ) in half of cases in western and northeastern Cambodia, northeastern Thailand, and southwestern Vietnam in 2015-2018, further compromising efforts to eliminate the disease.

"These worrying findings indicate that the problem of multidrug resistance in P falciparum has substantially worsened in southeast Asia since 2015", says Professor Olivo Miotto from the Wellcome Sanger Institute and University of Oxford, UK who co-led the genomic epidemiology study. "This highly successful resistant parasite strain is capable of invading new territories and acquiring new genetic properties, raising the terrifying prospect that it could spread to Africa where most malaria cases occur, as resistance to chloroquine did in the 1980s, contributing to millions of deaths." [1]

With DHA-PPQ now providing ineffective treatment and promoting the spread of resistance, the authors of a multi-country randomised trial led by Professor Arjen Dondorp from the Mahidol Oxford Tropical Medical Research Unit in Thailand, call for this commonly used frontline combination therapy to be abandoned in the eastern Greater Mekong Subregion (Cambodia, southern China, Laos, Myanmar, Thailand, and Vietnam), even in areas where resistance has only just started to emerge.

"With the spread and intensification of resistance, our findings highlight the urgent need to adopt alternative first-line treatments", says Professor Tran Tinh Hien from the Oxford University Clinical Research Unit in Vietnam co-author on the clinical study. "One option is to switch the partner drug piperaquine to a drug that is currently effective such as mefloquine or pyronaridine--as Cambodia and Thailand have already done. But there is a possibility that in the presence of artemisinin resistance, resistance to these partner drugs might develop rapidly as well. Another option is to use triple ACTs, in which an artemisinin is combined with two partner drugs instead of one."[1]

According to Professor Mallika Imwong from Mahidol University in Thailand co-author on the genomic epidemiology study: "To stay one step ahead, continued surveillance, including genetic surveillance, is needed to map the spread of resistance in real time, so other countries can act quickly and switch drugs if needed." [1]

More than 200 million people are infected with the malaria parasite P falciparum, which is responsible for 9 out of 10 deaths from malaria. Worldwide, antimalarial efforts are mainly dependent on artemisinin combination therapies (ACTs) that pair artemisinin with one of six partner drugs to complete parasite clearance. Introduced in Cambodia in 2008, DHA-PPQ was initially effective, but by 2013, malaria parasites had become resistant to both drugs in western Cambodia. Since then, these resistant strains have spread to other parts of Cambodia, Thailand, Vietnam, Myanmar, and Laos.

In 2018, a genetic study published in The Lancet Infectious Diseases journal tracked the emergence and spread of a multidrug resistant strain named KEL1/PLA1 across Cambodia between 2007 and 2013 [2]. KEL1 indicates a specific origin of an artemisinin resistance mutation in the kelch13 gene, while PLA1 describes a specific origin of the amplification (multiple copies) of the plasmepsin-2 and plasmepsin-3 genes, which is a marker of piperaquine resistance. KEL1/PLA1 parasites carry both of these gene variants, and therefore are resistant to both components of DHA-PPQ treatment. At the time, KEL1/PLA1 had only spread within the borders of Cambodia.

In a new genomic epidemiology study, an international team of scientists investigated the evolution and spread of KEL1/PLA1 from 2007 up to 2018. By analysing the genomes of 1,673 P falciparum samples from 19 provinces across Cambodia, Laos, northeast Thailand, and Vietnam, they found that KEL1/PLA1 had spread rapidly from Cambodia across all the surveyed countries, with prevalence rising to higher than 50% in all regions apart from Laos (figure 1B).

These KEL1/PLA1 parasites maintained a high level of genetic relatedness reflecting their common origin. Importantly, several genetic KEL1/PLA1 subgroups have recently emerged that carry mutations in the chloroquine resistance transporter (crt) gene, which increase the parasites' ability to resist piperaquine--causing a proliferation of biologically fitter and increasingly resistant parasites.

These findings are supported by interim evidence from a multi-country randomised trial evaluating the efficacy, safety, and tolerability of triple ACTs (artemisinin plus two partner drugs) compared with current ACTs (artemisinin plus one partner drug) in areas with multidrug-resistant falciparum malaria [3]. The Tracking Resistance to Artemisinin Collaboration (TRACII) reports preliminary data for 140 patients (aged 2 to 65 years) with uncomplicated falciparum malaria from 7 sites in Cambodia, Vietnam, and Thailand treated with a standard 3-day course of DHA-PPQ between 2015 and 2018.

Results suggest that the failure rate for DHA-PPQ has now reached 27% in northeastern Cambodia, whilst in western Cambodia it is 62%; and reached 53% southwestern Vietnam, and 87% in northeastern Thailand (table 3; figure 1).

The researchers also noted substantial increases in the frequency of genetic markers of artemisinin and piperaquine resistance across the region over the past decade. In particular, they found a rapid increase in the newly described crt mutations that contribute to piperaquine resistance and have an additive effect on treatment failure with DHA-PPQ. In 2015-2018, 74% (272/375) of resistant parasite samples from Cambodia, Thailand, and Vietnam carried crt mutations associated with piperaquine resistance, compared with 5% (20/368) in 2011-2013 when these mutations were only present in western Cambodia.

"These results suggest that the P falciparum co-lineage resistant to DHA-PPQ has now acquired crt mutations linked with even higher rates of treatment failure. These have immediate public health importance as they may continue to evolve, producing biologically fitter parasite strains more capable of surviving treatment", says Professor Dondorp. "Accelerated efforts to eliminate all P falciparum in the Greater Mekong Subregion are urgently needed to avoid further spread of these difficult-to-treat, highly resistant parasites, which have the potential to cause health emergencies regionally, and possibly globally." [1]

The authors of the randomised trial note that overrepresentation of potential recurrent infections might have led to an underestimation of the efficacy of DHA-PPQ in primary infections. The authors of the genomic epidemiology study point out that the trends they describe rely on opportunistic sampling, combining data from multiple varied studies, resulting in temporal and geographical diversity, which may limit the conclusions that can be drawn. They add that longitudinal surveillance would benefit from systematic, comprehensive, and maintained sampling.

Writing in a linked Comment, Dr Didier Ménard from the Institut Pasteur in France, says: "[These] two studies illustrate the accelerated pace at which P falciparum resistance to DHA-PPQ has evolved and spread across Southeast Asia, decimating its efficacy...[and] clearly highlight the urgent need for adopting new and effective treatments (such as triple ACTs or the ACT artesunate plus pyronaridine). They also evoke advantages of implementing a regional strategy rather than country-specific programs to address population movements and integrate region-wide clinical and genetic surveillance systems into a coordinated campaign whose goal is to achieve malaria elimination in Southeast Asia."]

Genomic surveillance has revealed that malaria resistance to two first-line antimalarial drugs has spread rapidly from Cambodia to neighbouring countries in Southeast Asia. Researchers from the Wellcome Sanger Institute, University of Oxford and Mahidol University, Bangkok, discovered that descendants of one multi-drug resistant malaria strain are replacing the local parasite populations in Vietnam, Laos and northeastern Thailand. They also found the resistant strain has picked up additional new genetic changes, which may be enhancing resistance even further.

The study, published in The Lancet Infectious Diseases today (22nd July), reveals the importance of ongoing genomic surveillance to inform public health malaria control strategies. Global efforts to eliminate malaria could be threatened by any delays in detecting and acting on the spread of resistance.

Malaria is caused by Plasmodium parasites which are spread through mosquito bites. The World Health Organization estimates that nearly 220 million people were infected in 2017, causing at least 400,000 deaths*, with children under the age of five in sub-Saharan Africa at most risk. Malaria can be treated when caught early enough, but the parasite is becoming resistant to antimalarial drugs in many areas, especially Southeast Asia, putting elimination efforts at risk.

Over the last decade, the first-line treatment for malaria in many areas of Asia has been a combination of two powerful antimalarial drugs - dihydroartemisinin and piperaquine - otherwise known as DHA-PPQ. However, a previous study identified a strain of malaria that had become resistant to this treatment. Researchers found that this resistant strain, named KEL1/PLA1 because of its combination of genetic mutations that cause resistance, had spread across Cambodia under the radar between 2007 and 2013.

This highlighted an urgent need to follow up and determine how far this resistance had then spread and if it had evolved further, and eventually understand which drugs would work against current malaria parasites in Southeast Asia.

In the most up-to-date and comprehensive whole genome study of malaria parasites in Southeast Asia, the team sequenced and analysed the DNA of 1,673 Plasmodium falciparum parasites, taken from the blood of malaria patients between 2008 and 2018. Their analysis, focusing on the KEL1 and PLA1 gene variants, revealed that the situation had got much worse after 2013. The multidrug resistant KEL1/PLA1 parasites had spread internationally, in some regions making up more than 80 per cent of the parasites analysed.

Dr Roberto Amato, joint first author from the Wellcome Sanger Institute, said: "We discovered that the multi-drug resistant KEL1/PLA1 malaria strain had spread aggressively, replacing local malaria parasites, and had become the dominant strain in Vietnam, Laos and northeastern Thailand. Our large-scale genomic approach demonstrates how surveillance can provide crucial information to malaria control programmes, supporting them in evaluating available treatment options."

The spread is likely to have occurred because resistant parasites had an evolutionary advantage, as DHA-PPQ was the first-line treatment in most of these areas. This killed other malaria strains but was less effective against KEL1/PLA1 malaria.

The researchers discovered that not only had this resistant strain spread geographically, but it had evolved and picked up new mutations in the chloroquine resistance transporter gene (crt). These parasites had then rapidly spread across borders. A related paper** on clinical outcomes published today in The Lancet Infectious Diseases revealed that these crt mutations were associated with complete treatment failure of DHA-PPQ. This supported the finding that the resistance had not only spread, but worsened as the parasite evolved under further drug pressure.

Professor Olivo Miotto, a senior author from the Wellcome Sanger Institute, Big Data Institute at University of Oxford and Mahidol University, Bangkok, said: "The speed at which these resistant malaria parasites have spread in Southeast Asia is very worrying. Other drugs may be effective at the moment but the situation is extremely fragile and this study highlights that urgent action is needed to eliminate the parasites from the Greater Mekong Subregion, to prevent them spreading and evolving further."

Dr Michael Chew, Infection and Immunobiology Portfolio Manager at Wellcome said: "This study clearly shows the rapid spread of multi-drug resistant malaria across Southeast Asia. Affecting millions globally, malaria is a devastating disease, especially when access to effective treatment is unavailable.

"The spread of drug-resistant strains as demonstrated by this important genetic surveillance, building upon previous research, provides a warning signal. It serves as a reminder that we must not show complacency with the response to malaria. It also shows we have the tools to effectively track drug resistance across borders, which can be used to inform co-ordinated elimination and control efforts."

Professor Dominic Kwiatkowski, a senior author on the paper from the Wellcome Sanger Institute and the Big Data Institute at University of Oxford, said: "Our study provides a clear picture of how malaria that is resistant to the first-line treatment is spreading, and demonstrates the importance of using genetics to detect patterns of resistance in each area. Active genomic surveillance is now vital to inform national malaria control programmes, to help reduce the risk of a major global outbreak."

A major new study has found children with Autism are more likely to be bullied by both their siblings and their peers, meaning that when they return from school, they have no respite from victimisation.

The researchers also found that children with Autism are more likely to be both the victims and perpetrators of sibling bullying compared to those without Autism.

The study used data from The Millennium Cohort Study to investigate sibling bullying in a sample of over 8,000 children, more than 231 of which had Autism.

The children were asked questions about how often they were picked on or hurt on purpose by their siblings and peers and how often they were the perpetrators of such acts.

The study revealed that, at the age of 11 years, two thirds of children with Autism reported being involved in some form of sibling bullying, compared to half of children without Autism.

While there was a decrease in bullying for children in both groups by the time they reached the age of 14 years, there were still differences in the specific types of involvement. Children with Autism were still more likely to be involved in two-way sibling bullying, as a victim and a perpetrator.

Lead author of the study, Dr Umar Toseeb from the Department of Education at the University of York, said: "Children with Autism experience difficulties with social interaction and communication, which may have implications for their relationships with siblings.

"From an evolutionary perspective, siblings may be considered competitors for parental resources such as affection, attention and material goods - children with Autism might get priority access to these limited parental resources leading to conflict and bullying between siblings."

The parents of the children involved in the study were asked questions about their children's emotional and behavioural difficulties, focusing on things like whether their child was unhappy, downhearted and restless.

According to the research, those children involved in sibling bullying, irrespective of whether they had Autism or not, were more likely to experience emotional and behavioural difficulties both in the long and short term.

Because sibling bullying disproportionately affects children with Autism, the researchers are calling for more resources to help children with Autism and their parents identify and deal with bullying behaviours in the home, particularly earlier in childhood.

Dr Toseeb added: "Parents should be aware of the potential long term consequences of sibling bullying on children's mental health and wellbeing.

"Persistent conflicts between siblings may be indicative of sibling bullying and this should not be viewed as a normal part of growing up."

DALLAS, July 19, 2019 -- Nearly 50 years after man's first steps on the moon, researchers have discovered a way that may help astronauts spending prolonged time in space come back to Earth on more stable footing, according to new research in the American Heart Association's journal Circulation.

"One of the biggest problems since the inception of the manned space program has been that astronauts have fainted when they came down to Earth. The longer the time in a gravity-free environment space, the greater the risk appeared," said Benjamin Levine, M.D., the study's senior author who is professor of Exercise Sciences at UT Southwestern Medical Center and director of the Institute for Exercise and Environmental Medicine at Texas Health Presbyterian Hospital in Dallas. "This problem has bedeviled the space program for a long time, but this condition is something ordinary people often experience as well."

Orthostatic hypotension is the technical term for a temporary drop in blood pressure when a person stands up after sitting or lying down because blood rushes to the feet, away from the brain. Dizziness or fainting due to changes in blood flow can occur after lengthy bed rest, among people with certain health disorders or, in the case of astronauts, being in a low-gravity environment.

The study included 12 astronauts (eight men and four women age 43-56) who spent about six months in space. All performed individualized endurance and resistance exercise training for up to two hours daily during space flight to prevent cardiovascular, bone and muscle deconditioning. They also received a saline infusion upon landing.

The astronauts' blood pressure was recorded with every heartbeat over each 24-hour period before, during and after their time in space. The researchers found that there was minimal impact on their blood pressure during all phases of measurement and none of the astronauts in the study experienced dizziness or fainting during routine activities 24 hours after landing.

This is the first study to demonstrate that astronauts do not experience dizziness or fainting during routine activity after landing, as long as they participate in certain types of exercise training while in flight and receive IV fluids when they return to earth, said Levine

"What surprised me the most was how well the astronauts did after spending six months in space. I thought there would be frequent episodes of fainting when they returned to Earth, but they didn't have any. It's compelling evidence of the effectiveness of the countermeasures--the exercise regimen and fluid replenishment," he said.

The researchers note that the sample size was small. Also, they could not clearly distinguish whether specific in-flight blood pressure readings occurred while the astronauts were awake or asleep, so the data were combined and examined over 24-hour periods. Since all the astronauts participated in the exercise regimen and received a saline fluid infusion upon landing, researchers do not know the blood pressure stabilization would have occurred without those measures.

Next, the researchers would like to study larger numbers of astronauts and those who spend longer than six months in space.

"Understanding the physiology of space flight can be helpful for understanding many conditions experienced by non-astronauts. For example, the exercise program our lab developed for the space program is already helping people with a fainting condition known as postural orthostatic tachycardia syndrome (POTS)," Levine said. "As we prepare to celebrate the 50th anniversary of the Apollo 11 moon landing, it's exciting to think of how our exploration in and of space can lead to important medical advances here on Earth."

A world-first study led by Monash University has discovered a technique and phenomenon that can be used for creating stronger, lightweight magnesium alloys that could improve structural integrity in the automobile and aerospace industries.

Published in the prestigious Nature Communications on Friday, 19 July, researchers from Monash University, CSIRO and Chongqing University discovered a pattern of alloying element segregation in twin boundaries by using atomic-resolution X-ray mapping at much lower electron voltage.

Engineers are constantly seeking strong, lightweight materials for use in cars, planes and in high-speed vehicles to improve fuel efficiency, aerodynamics, speed and weight load.

The finding is significant, as the deformation of lightweight magnesium during thermomechanical processes and applications prevents those alloys from being used more widely in place of steel. It also has implications for other light alloys such as aluminium and titanium.

"Lightweight magnesium has tremendous potential for energy-efficient and environmentally-friendly applications. But the segregation in these materials is prone to electron beam damage," lead author Professor Jian-Feng Nie, from Monash University's Department of Materials Science and Engineering, said.

"The electron beam damage is most severe when segregated solute atoms become a single atomic column. This impacts the formability, deformation behaviour and tension-compression strength of wrought magnesium products.

"We demonstrated that it's possible to solve this difficulty by using atomic-resolution X-ray mapping at a much lower accelerating voltage of electrons [120kV] instead of 300kV, which is commonly used.

"We further discovered that the new segregation pattern increases the boundary pinning effect by more than 30 times, and switches the migration mechanism of the twin boundary from the commonly accepted mode to a new one."

The researchers used a magnesium alloy comprising neodymium and silver as part of their study. This alloy contains superior mechanical properties at both ambient and elevated temperatures.

They found significant improvements in shear stress, by 33 times, and elastic strain limit occurred when the twin boundary was populated with neodymium and silver.

The increased charge density between silver and neodymium with the magnesium indicated a stronger bond and strengthening of the twin. As force is applied, the magnesium is pushed towards the neodymium and away from the silver - creating a stronger, lightweight alloy.

"Our work demonstrates that the atomic-scale analysis of the structure and chemistry of solute segregation in metallic alloys with complex compositions is now possible," Professor Nie said.