Culture

Cancer research is a field that has been especially dependent on public funding. The National Cancer Institute (NCI), an independent institute of the National Institutes of Health (NIH), was established in 1937 to provide for, foster and coordinate research relating to cancer. As the largest funder of cancer research in the world, it has spent an estimate of more than USD 100 billion on research and treatment. New screening, diagnosis, and treatment methods in consonance with groundbreaking pathogenetic discoveries in the oncologic field, mainly in the form of oncogene and cancer metabolism research, have led to an overall decrease of the cancer death rate by a quarter since 1975. Concerns have come to light in the past ten years surrounding the current funding system of the NIH. Criticisms encompass systematic disincentivizing of funding for transformative research, the grant mechanism's lack of predictive ability, and gender and racial biases.

Raphael Zingg, Assistant Professor at Waseda University, analyzed a set of 100,000 cancer-related patents aggregated by the US Patent and Trademark Office within the framework of the Cancer Moonshot Task Force. The study shows that the direct impact of the NIH on cancer-related inventions shifted over the years. A decline in number and share of federally funded inventions is followed by a decrease in the technological impact of those patents. These various pieces of the puzzle mirror a conservative funding strategy, rather than a high-risks high-rewards one.

Configuring grant review criteria might be a first step to strengthen the impact of funded research. Should the NIH lower its barriers for risky projects by specifying that is seeks to encourage research with potential practical impact in its criteria, reviewers might factor in the higher likelihood of failure of such ventures. Translating biological discoveries into clinical applications can further be strengthened by reinforcing targeted initiatives at the National Cancer Institute and National Institutes of Health level. In order to re-engineer translational science, a flagship initiative of the NIH was to launch Clinical and Translational Science Awards in 2005. Establishing translational cancer research as a field attractive for private investments can also be a way to complement public funds, and to help to close the gap from bench-to-bedside.

According to a new study by researchers from the Finnish National Institute for Health and Welfare, poor men's future outlooks are much shorter that poor women's. Poor men also experience more profound worthlessness than women do.

The researchers concluded that even when men are poor and unemployed, their recognition and role is tied to work, money, and markets. Women, however, have more means to attain a sense of worth outside the economic realm.

In the study, the researchers analyzed 50 written autobiographical accounts of poverty by 25 Finnish women and 25 Finnish men aged 28-57 years submitted to a writing competition. The participants were informed that their texts would be used also for research purposes.

"Male respondents tended to think that being active generated value. Women's futures were generally defined by waiting for something better and raising children," says researcher Reetta Siukola from the Finnish National Institute for Health and Welfare.

According to the accounts, motherhood brings with it an acknowledged position in society. Therefore, women respondents did not see unemployment as detrimental to them, as men seemed to do.

The analysed texts cover retrospective stories about childhood as well as descriptions of current poverty.

"The worst thing about living on a low income is that you feel your dignity diminishing with every penny you do not have in contrast with those who have them in abundance. The most important concern is finding your way and maintaining a healthy state of mind, where you can be as you are, whatever your financial situation," one respondent wrote.

In the stories, hopeful future expectations and recognition often emerged together, and hopeless future expectations and experiences of unrecognition were likewise paired.

The researchers also found that the social security bureaucracy, that the Finnish welfare state leans heavily on, was often described as a source of worthlessness.

"Professionals and officials often turned a deaf ear to people's experiences, even though the writers felt they would have been able to express sympathy for people in subjectively unfair situations. The writers' accounts described experiences of being left voiceless and unrecognized," says researcher Minna Kukkonen from the Finnish National Institute for Health and Welfare.

Social security practices and public attitudes combined with financial shortage eroded experiences of dignity for both men and women, and left respondents prone to exclusion. To avoid stigma and shame, many respondents reported withdrawing from social relations.

Findings from outside the social security system, however, revealed that loneliness was heavily reported by male respondents.

"Men may feel left alone if they are not able to perform the sole permitted gender contract of a salaried worker and a family supporter. Meanwhile women have more room to move between social motherhood and the working woman," says research manager Anna-Maria Isola.

Have you ever tried to stay away from fast food, but found hard-to-ignore signals that represent its availability - like neon lights and ads - are everywhere?

If you're stressed, tired or otherwise straining your brain power, you may find it harder to ignore cues in the environment that signal something rewarding.

That's what a UNSW Sydney experiment by a group of psychologists - published today in high-impact journal Psychological Science - has shown.

"We knew already that participants find it hard to ignore cues that signal a large reward," says study lead Dr Poppy Watson at UNSW.

But this experiment showed - for the first time - that ignoring these cues became harder as soon as participants had to perform a task while also holding other information in their memory.

"We have a set of control resources that are guiding us and helping us suppress these unwanted signals of reward. But when those resources are taxed, these become more and more difficult to ignore."

Up until now, researchers didn't know whether people's general inability to ignore reward cues is just something we have no control over or whether we do use our executive control processes to constantly work against distractions. But now it's become clear that the latter is the case - although unfortunately this resource is limited.

Executive control is a term for all cognitive processes that allow us to pay attention, organise our life, focus, and regulate our emotions.

"Now that we have evidence that executive control processes are playing an important role in suppressing attention towards unwanted signals of reward, we can begin to look at the possibility of strengthening executive control as a possible treatment avenue for situations like addiction," says Dr Watson.

In the experiment, participants looked at a screen that contained various shapes including a colourful circle. They were told they could earn money if they successfully located and looked at the diamond shape, but that if they looked at the coloured circle - the distractor - they would not receive the money.

They were also told that the presence of a blue circle meant they'd gain a higher amount of money (if they completed the diamond task) than the presence of an orange circle. The scientists then used eye tracking to measure where on the screen participants were looking.

"To manipulate the ability of participants to control their attention resources, we asked them to do this task under conditions of both high memory load and low memory load," Dr Watson says.

In the high-memory load version of the experiment, participants were asked to memorise a sequence of numbers in addition to locating the diamond, meaning they had fewer attention resources available to focus on the diamond task.

"Study participants found it really difficult to stop themselves from looking at cues that represented the level of reward - the coloured circles - even though they were paid to try and ignore them," Dr Watson says.

"Crucially, the circles became harder to ignore when people were asked to also memorise numbers: under high memory load, participants looked at the coloured circle associated with the high reward around 50% of the time, even though this was entirely counterproductive."

Limited resources

The findings demonstrate that people need full access to cognitive control processes to try and suppress unwanted signals of reward in the environment.

"This is especially relevant for circumstances where people are trying to ignore cues and improve their behaviour, e.g. consuming less alcohol or fast food," says Dr Watson.

"There's this strong known link between where your attention is and what you eventually do, so if you find it hard to focus your attention away from reward cues, it's even harder to act accordingly.

Stress

That also explains why people might find it harder to focus on dieting or beating an addiction if they are under a lot of stress.

"Constant worrying or stress is the equivalent to the high-memory load scenario of our experiment, impacting on people's ability to use their executive control resources in a way that's helping them manage unwanted cues in the environment."

Dr Watson advises people to try and be strategic about exposure to cues.

"If you are under a lot of cognitive pressure (stress, or tiredness) you should really try and avoid situations where you'll be tempted by signals. You need to be in the right frame of mind to be in a situation where you can stop yourself from getting distracted and going down a path where you don't want to go," she says.

Treatment

The researchers now want to look at how executive control can be strengthened - and if that presents an opportunity for situations like drug rehab.

"Our research suggests that if you strengthen executive control you should have better outcomes. Some studies have already demonstrated that training executive control can reduce the likelihood that you will eat chocolate or drink alcohol.

"And in the clinic, training attentional focus away from pictures of alcohol towards soft drinks has been shown to reduce relapse in alcoholic patients," Dr Watson says.

"However, the exact mechanisms of how this works are still unclear and we need more research to figure out how exactly we can use executive control to our advantage."

High in the Andes Mountains, dagger-shaped ice spires house thriving microbial communities, offering an oasis for life in one of Earth's harshest environments as well as a possible analogue for life on other planets.

The distinctive icy blade formations known as nieves penitentes (or, "penitent ones") are named for their resemblance to praying monks in white robes and form in cold, dry conditions at elevations above 13,000 feet. The penitentes, which can range from a few inches to 15 feet high, are found in some of the most hostile conditions on Earth, with extreme winds, temperature fluctuations and high UV radiation exposure due to the thin atmosphere.

And yet, as a recently published study led by University of Colorado Boulder student researchers finds, these spires offer shelter for microbes by providing a water source in an otherwise arid, nutrient-poor environment.

In March 2016, CU Boulder students and faculty members traveled to Volcán Llullaillaco in Chile, the world's second-highest volcano. The two-week expedition into the arid landscape, planned in collaboration with their Chilean colleagues, was no easy feat.

"This is a very remote area that's difficult to access," said Steve Schmidt, a professor in CU Boulder's Department of Ecology and Evolutionary Biology (EBIO) and a co-author of the study. "The entire back of one of our pickup trucks had to be filled with barrels of drinking water. It's no trivial thing to go out there, and that's one of the reasons these formations haven't been studied much."

After reaching the penitente fields at 16,000 feet above sea level, the scientists noticed patches of red coloration, a telltale sign of microbial activity that has been previously observed in other snow and ice formations around the world.

Upon bringing back samples for analysis, the researchers confirmed the presence of algal species Chlamydomonas and Chloromonas in the ice, the first documentation of snow algae or any other life forms in the penitentes.

"Snow algae have been commonly found throughout the cryosphere on both ice and snow patches, but our finding demonstrated their presence for the first time at the extreme elevation of a hyper-arid site," said Lara Vimercati, lead author of the study and a doctoral researcher in EBIO. "Interestingly, most of the snow algae found at this site are closely related to other known snow algae from alpine and polar environments."

The new findings add to scientists' understanding of the limits of life on Earth, but may also have implications for the search for alien life. Penitente-like formations have recently been discovered on Pluto and are speculated to exist on Europa, one of Jupiter's moons. The Atacama region in Chile is also considered to be the best Earth analogue for the soils of Mars.

"We're generally interested in the adaptations of organisms to extreme environments," Schmidt said. "This could be a good place to look for upper limits of life."

"Our study shows how no matter how challenging the environmental conditions, life finds a way when there is availability of liquid water," Vimercati said.

Quitting alcohol may improve health-related quality of life for women, especially their mental well-being, according to a study from Hong Kong published in CMAJ (Canadian Medical Association Journal).

"More evidence suggests caution in recommending moderate drinking as part of a healthy diet," says Dr. Michael Ni, School of Public Health and The State Key Laboratory of Brain and Cognitive Science, University of Hong Kong (HKU).

The study carried out by Dr. Xiaoxin Yao, Dr. Michael Ni, Dr. Herbert Pang and colleagues at HKU included 10 386 people from the FAMILY Cohort in Hong Kong who were nondrinkers or moderate drinkers (14 drinks or less per week for men and 7 drinks or less per week for women) between 2009 and 2013. The researchers compared their findings with data from the National Epidemiologic Survey on Alcohol and Related Conditions, a representative survey of 31 079 people conducted by the National Institute on Alcohol Abuse and Alcoholism in the United States.

The mean age of participants in the FAMILY Cohort was 49 years and 56% were women. About 64% of men were nondrinkers (abstainers and former drinkers) and almost 88% of women were nondrinkers. Men and women who were lifetime abstainers had the highest level of mental well-being at the start of the study (baseline). For women who were moderate drinkers and quit drinking, quitting was linked to a favourable change in mental well-being in both Chinese and American study populations. These results were apparent after adjusting for sociodemographic characteristics, body mass index, smoking status, and other factors.

"Global alcohol consumption is expected to continue to increase unless effective strategies are employed," says Dr. Ni. "Our findings suggest caution in recommendations that moderate drinking could improve health-related quality of life. Instead, quitting drinking may be associated with a more favourable change in mental well-being, approaching the level of lifetime abstainers."

"Change in moderate alcohol consumption and quality of life: evidence from 2 population-based cohorts" is published July 8, 2019.

Passenger and pedestrian confidence and acceptance will be key to the future and development of autonomous vehicles so researchers at WMG at the University of Warwick have just conducted and reported an experiment to see which autonomous vehicles driving style engendered the highest levels of confidence among autonomous vehicles passengers - driving with full machine efficiency, or driving in a way that emulates average human driving. The surprising result was that neither was optimal but that a blend of both might be best.

The researchers took 43 volunteers into a large warehouse designed to resemble a pedestrianised area in a town centre with a series of routes that included a range of junctions. Half were given 4 journeys around the route in an autonomous vehicle driving with full machine efficiency using all its capabilities to drive in as safe and efficient manner as possible while the others were given 4 journeys around the route in autonomous vehicles that tried to closely emulate average human driving patterns. They then scored the level of trust in the autonomous vehicles. The result has have just been published in the journal Information (2019, 10, 219; doi:10.3390/info10060219).

The overall result was that there was only a marginal difference in trust between the two driving methods. The efficient machine method was slightly favoured but even that small gap between the two driving styles narrowed over the four runs. What was noticeable for both the "machine" and "human" driving styles is that confidence in both grew with each new round suggesting that simple familiarity and growing accustomed to the experience will be one of the most effective ways of quickly building trust and acceptance of autonomous vehicles once their use becomes more widespread.

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Mean scores of trust
Human
Machine

First Run
59.30
63.19

Second Run
59.55
66.33

Third Run
65.85
68.29

Fourth Run
67.20
69.38

Dr Luis Oliveira from WMG at the University of Warwick and the lead author on the paper said:

"The overall trust in both driving methods grew with every run. In the machine-like driving style this was steady upwards curve throughout the four journeys but in human-like behaviour there was a particularly steep change upwards in the scores between runs 2 and 3. The passengers in the experiment also acknowledged that future generations may be more comfortable with AVs and its features, as they learn to live with the new technology."

The researchers also asked the participants to give some narrative about their experience and this showed that there were advantages on both modes of driving that may therefore need to be blended together in any future final package. The researchers' literature review and warehouse experiment made clear that there re were two particularly clear lessons to be learned:

Smooth speed change - Past studies had already shown that Human drivers' tendency is to break most at the start of any manoeuvre that requires deceleration whilst the totally automated driving programmes applied speed changes more gradually and efficiently. Human passengers preferred the comfort of the smoother changes of acceleration and deceleration provided by the machine driving methods.

Sharp turns - A common complaint was a feeling that the vehicles were performing uncomfortable and worrying sharp turns. This feeling was actually expressed by both those in the machine and Human style driving set ups but it was much more noticeable in the machine-like driving style condition. One typical negative comment was "what you'd expect from a driver is a bit of a gradual turn....there were moments where it was accelerating around corners, I think it catches you unaware".

WMG's Dr Luis Oliveira said "this shows that the challenge is that the speed and trajectory of autonomous vehicles should be finely controlled, but at the same time the vehicle should be assertive to provide the benefits of automated driving.

However it was the AVs' behaviours at junctions in the WMG University of Warwick warehouse test that produced the most diverse and surprising reactions.

The machine driven AVs were left to make use of all of their sensors and ability to communicate with vehicles that may out of line of sight to decide whether to enter a junction. If their sensors said it was safe and their communications with other vehicles indicated no approaching threats they would simply enter the junction without stopping. If however they detected a vehicle that they believed should have right of way - even if it was not yet visible to the human passenger they would stop and let that vehicle pass. In contrast The AV's emulating human driving would always stop at a junction and would even edge into the junction as if the peek at what the oncoming traffic might be.

The reactions to those two different approaches were very varied and surprising.

Some liked the human approach with one saying that the AV was "...probably trying to inspire confidence in the passenger, I'm guessing, in terms of like the way it behaved, kind of quite similar to a human, it's only ever going to inspire confidence I think it's because that's what we're used to".

Some also liked the machine driving approach of stopping at junctions even though there was no visible issue but because it was in communication with another out of sight vehicle that it perceived had right of way. One passage said: "it stopped at a junction, because I assume it knew that something was coming, as opposed to it reacting to seeing something coming".

Equally there was dislike for both the human and machine driving methods of handling a junction.

Some perceived problems with the machine approach of just entering the junction if it believed it to be clear to do so with one saying that they were concerned about vulnerable road users. "..such as pedestrians or cyclists that could have been there that don't communicate with the pod. That may be a safer way of doing it rather than flying around the corner".

However others were greatly surprised at the "human" driving method AV stopping at every junction as they saw it not just as waste of the machines capabilities to scan and communicate ahead to understand traffic. They were frustrated that the vehicle was not "more assertive" One passenger saying "sometimes I didn't expect it to stop, because I thought the other pod was a bit further away but then it did, so I guess it's cautious...if I was driving I'd probably have gone". Another passenger said "If I was in an autonomous pod with sensors giving a 360-degree view at all times, I'd expect the vehicle to instantaneously know whether it was safe or not, and not need to edge out".

A further passenger who tested the human-like version, commented that a machine driving like a human and trying to look around the corners seemed ironically unnatural saying: "I think it was a bit unexpected because my expectation with the pods is that that there would be some un-naturalism to it rather than a human driver".

Despite this seeming mass of contradictions in views about how AVs should handle junctions the research team do think there are valuable lessons to be learned even here. In particular:

There is clearly a need to give the general public the details of the driving systems, for example, the recent technological features such as vehicle to vehicle communication

For passengers in a vehicle consideration should be given to having a display and/or audio information that shares some of the information the vehicle is using so users can understand that the system is aware of hazards beyond the field of view

There may be some merit in presenting the full benefits of the most efficient methods of machine based driving progressively when mass use is first introduced, so that passengers can build confidence over time

Philadelphia, July 8, 2019 - In the United States, both children and adults eat too few fruits and vegetables, which puts them at risk for poor diet quality and adverse health consequences. A new study in the Journal of Nutrition Education and Behavior, published by Elsevier, found new parents increased their spending on produce in middle- and high-income households.

"Although adult food preferences are considered relatively stable, major life events such as becoming parents may serve as a cue to behavior change," said lead author Betsy Q. Cliff, a doctoral candidate in the Department of Health Management and Policy, University of Michigan School of Public Health, Ann Arbor, MI, USA. "This creates opportunities for nutrition education programs aimed at increasing produce consumption."

This study used data available through the Nielsen Homescan Consumer Panel dataset. The panel, which is ongoing, includes over 40,000 participants who volunteer to have their retail purchases tracked. Panelists use in-home scanners to record all purchases. Categories of purchases include dry groceries, dairy, frozen food, and fresh produce. Nielsen also collects demographic information from participants such as number of children, employment status, education, etc.

The authors used demographic data from 2007 to 2015 to determine that 508 households in the panel became parents during the study period. The grocery budgets for these families were tracked to determine overall produce, fruits, vegetables, fresh produce, canned produce, frozen produce, and produce with another storage type. Gaining a child prompted an increase in the percent of a household's grocery budget spent on produce; on average pre-parenthood households spent 10 percent of their budget on produce, which increased to 12 percent once the household included kids. However, the increase was only apparent in households with an income greater than 185 percent of the US federal poverty level (about $39,000 for a family of 3 in 2019). Among families with an income lower than 185 percent of the federal poverty level, there was no detectable change in fresh produce purchases. Although both fruit and vegetable purchases increased, fresh fruit had the greater increase. There was no detectable change in purchases of canned, frozen, or other storage types of produce.

While increased spending was identified, the factors that resulted in increased spending were not explored in this study. It is unknown if parents' change in spending resulted from an increase in quality versus quantity of produce. Other limitations of the data include that they do not include food eaten outside of the home, it is possible that all purchases were not scanned, and the price of produce does not reflect any discount due to vouchers or coupons.

Betsy Cliff emphasized, "Increased purchasing by higher income households suggests further support is needed to help low-income new parents increase produce as a part of their families' diet."

The positive effects of a rich home learning environment during a child's early years continue into adolescence and help improve test scores later in life, according to a new study published in School Effectiveness and School Improvement.

This research shows pre-schoolers whose parents regularly read and talked about books with them scored better on math tests at age 12. The study, lead by Dr Simone Lehrl of the University of Bamberg, is one of the first to provide detail on the importance of early years home learning on children's development up to early adolescence.

Researchers studied 229 German children from age three until secondary school and participants' literacy and numeracy skills were tested annually in their three years of preschool (ages 3-5), and again when they were 12 or 13 years old.

They found that children gained from home stimulation in their preschool years in literacy, language and arithmetic skills which, in turn, led to higher outcomes in reading and mathematical skills in secondary school, regardless of the home learning environment then.

Dr Lehrl said: "Our results underline the great importance of exposing children to books for development not just in literacy but numeracy too: early language skills not only improve a child's reading but also boost mathematical ability.

"Encouraging caregivers to engage with their children in direct literacy activities, shared book reading and advanced verbal interactions during reading, and to include language and mathematical content during these activities, should promote children's reading and mathematical abilities in secondary school. Such experiences lay a strong foundation for later school success."

Formal literacy activities not only boosted language skills and reading comprehension but also improved numerical skills. Book exposure and the quality of verbal interactions regarding mathematical content during shared book reading (for example, talking about numbers and counting) when children were of preschool age were also associated with better math outcomes at age 12. The effect also worked the other way with the quality of parent-child interaction regarding mathematics also improving children's language skills.

Aspects of the children's home learning environment - formal literacy and numeracy activities, book exposure (parents owning books and reading to the child), and the quality of verbal parent-child interactions regarding language and mathematics - were also assessed and researchers ensured they accounted for background variables, such as gender, maternal education and socio-economic status, which affect the home learning environment in the results.

Barcelona, Spain, 6 July 2019 - New data have shown for the first time that a combination of targeted therapies can improve survival in patients with advanced bowel cancer. Results of the BEACON CRC Phase III trial have shown that triple therapy targeting BRAF mutations in progressive metastatic colorectal tumours significantly improved overall survival and objective response compared to standard care. (1)

The data, reported at the ESMO World Congress on Gastrointestinal Cancer 2019, (2) suggest that the three-drug combination, encorafenib, binimetinib and cetuximab, should replace chemotherapy for the one in seven patients with metastatic colorectal cancer who have a BRAF mutation.

"These are very exciting results because we've been trying to target BRAF-mutant colorectal cancer for many years. It's encouraging to see such a significant improvement in overall survival and response in patients with such aggressive tumour biology. Hopefully, this will soon lead to increased access to this treatment for pa-tients where there is currently such a large unmet need," said study author Dr Scott Kopetz, from the UT MD Anderson Cancer Center, Houston, USA.

Kopetz explained that the three-drug combination builds on growing understanding of the activation of cancer genes such as BRAF and the effects of targeted therapies. "Colorectal cancer does not respond to BRAF therapy alone because tumour cells adapt through other mechanisms after initial treatment. With this triple targeted therapy, we are using a very scientifically logical combination to inhibit BRAF and these other mechanisms," he pointed out.

Commenting on the relevance of the new data, Prof. Andres Cervantes from the Biomedical Research Institute INCLIVA, University of Valencia, Spain, stressed that it will be important for all patients with colorec-tal cancer to be tested for BRAF mutations in the light of the BEACON CRC findings. "We now have a specif-ic treatment that can change the natural course of the disease in patients with BRAF mutations and is better than previous therapy, so it is essential that patients are routinely tested."

He also highlighted the chemotherapy-free nature of the targeted combination used in the study. "In many other types of cancer, and particularly in colorectal cancer, it is common for biological targeted therapies to be used in combination with chemotherapy. The fact that we can give this targeted combination without the need for chemotherapy is very good news for patients, not least because of the side effects that they typically experience with chemotherapy," he added.

"At present, targeted therapy should probably be limited to the patient group treated in the BEACON CRC trial who had progressed after one or two previous lines of chemotherapy. However, it is important that we investigate its use in other settings where more patients with BRAF mutations may also benefit, including those with less advanced metastatic disease and possibly in the adjuvant setting after primary surgery with curative intent," concluded Cervantes.

Study results

In the global BEACON CRC study (NCT02928224), 665 patients with BRAF V600E-mutant colorectal cancer who had progressed after one or two prior regimens in the metastatic setting were randomised to receive triplet therapy, doublet therapy (encorafenib and cetuximab) or the investigator's choice of irinotecan or folinic acid, fluoruracil and irinotecan (FOLFIRI) and cetuximab.

Median overall survival was 9 months (95% confidence interval [CI]: 8, 11,4) for the triplet targeted therapy compared to 5.4 months (95% CI: 4.8, 6.6) for standard therapy (hazard ratio [HR] 0.52; 95% CI: 0.39, 0.7, p

Confirmed objective response rate by blinded central review for the triplet targeted therapy was 26% (95% CI: 18, 35) compared to 2% (95% CI: 0,7, p

Median overall survival for the doublet combination was 8.4 months (95% CI: 7.5, 11) compared to standard therapy (HR 0.6; 95% CI: 0.45, 0.79, p

BRAF V600E targeted treatment was well tolerated, with Grade 3 or higher adverse events seen in 58% of patients on triplet treatment, 50% of those in the doublet group and 61% of those in the standard therapy group.

An ongoing study (ANCHOR-CRC) is investigating the effects of triplet therapy as first line treatment for patients with metastatic BRAF V600E-mutant colorectal cancer.

BARCELONA -- The three-drug combination of encorafenib, binimetinib and cetuximab significantly improved overall survival (OS) in patients with BRAF-mutated metastatic colorectal cancer (mCRC), according to results of the BEACON CRC Phase III clinical trial led by researchers at The University of Texas MD Anderson Cancer Center.

The treatment combination resulted in median OS of 9 months for the combination therapy compared to 5.4 months for current standard-of-care treatment. Objective response rate (ORR) for the triplet-targeted therapy was 26 percent compared to just two percent for standard therapy.

BEACON CRC is the first and only Phase III trial designed to test BRAF/MEK combination targeted therapies in patients with mCRC and the BRAF V600E mutation. BRAF mutations are estimated to occur in up to 15 percent of patients with mCRC, with V600E being the most common BRAF mutation and representing a poor prognosis for these patients.

The trial results will be reported at the ESMO World Congress on Gastrointestinal Cancer 2019 by principal investigator Scott Kopetz, M.D., associate professor of Gastrointestinal Medical Oncology.

"This study builds on a decade of research into the tumor biology of BRAF-mutated colorectal cancer, and reflects a rationale combination to address the vulnerabilities unique to this tumor," said Kopetz. "We are encouraged to see a meaningful improvement in outcomes with this new regimen for our patients."

According to the American Cancer Society, colorectal cancer is the third leading cause of cancer-related deaths in men and in women, and the second most common cause of cancer deaths when men and women are combined. It is expected to cause about 51,020 deaths during 2019. BRAF mutations are estimated to occur in up to 15 percent of patients with mCRC, with V600 being the most common BRAF mutation and representing a poor prognosis for these patients.

The international study was a multi-institutional collaboration with over 200 centers worldwide. In the open label, three-arm randomized clinical trial, 665 patients with BRAF V600E-mutant mCRC who had progressed after one or two prior regimens in the metastatic setting were randomized to receive triplet therapy, doublet therapy (encorafenib and cetuximab) or the investigator's choice of irinotecan or folinic acid., fluoruracil and irinotecan (FOLFIRI) and cetuximab.

The triplet combination was generally well tolerated with no unexpected toxicities. Grade three or higher adverse events were seen in 58 percent of patients on triplet treatment, 50 percent of those in the doublet group and 61 percent of those in the standard therapy group.

In August 2018, the Food and Drug Administration granted Breakthrough Therapy Designation to encorafenib, in combination with binimetinib and cetuximab for the treatment of patients with BRAF V600E-mutant mCRC, after failure of one to two prior lines of therapy for metastatic disease.

Data from the BEACON CRC trial is being used to support regulatory approval of the triplet combination in metastatic BRAF V600E-mutant mCRC, and BRAF inhibitor based treatment has recently been included as a treatment option in National Comprehensive Cancer Network (NCCN) guidelines for colon and rectal cancers in the United States.

"This targeted therapy combination should be a new standard of care for this patient group," said Kopetz. "Further investigation is needed to determine if this combination may also benefit those with less advanced disease or as a first-line treatment."

The study was not intended to compare triplet and doublet therapies but future analyses will explore which patients are most likely to benefit from triplet versus doublet combinations. Additionally, an ongoing study (ANCHOR-CRC) is investigating the effects of triplet therapy as initial therapy for patients with metastatic BRAF V600E-mutant colorectal cancer.

Scientists have discovered that a special type of cell is much more prolific in generating a protective sheath covering nerve fibers than previously believed.

The revelation about Schwann cells raises the possibility of new avenues to treat nerve injuries and various forms of neuropathy. Further research could prove useful in promoting myelin repair in central nervous system disorders such as multiple sclerosis, where damage to myelin slows or blocks electric signals from the brain.

"This totally overturns the textbook definition of the way Schwann cells work," said senior author Kelly Monk, Ph.D., professor and co-director of the Vollum Institute at Oregon Health & Science University.

The research published today in the journal Nature Communications.

Two types of cells in the body produce myelin: oligodendrocytes in the brain and spinal cord, and Schwann cells in the rest of the body. Until now, scientists thought that only oligodendrocytes generated multiple myelin sheaths around axons, the slender projection of a nerve cell that carries electrical signals between cells.

The new research reveals that Schwann cells also are capable of spreading myelin across multiple axons.

Researchers made the discovery after conducting a genetic screen in zebrafish in the Monk laboratory. They discovered some fish had more myelin than expected, and those fish carried a mutation in a gene called fbxw7. When they knocked out the gene in genetically modified mice, they discovered an unexpected characteristic: individual Schwann cells began spreading myelin across many axons.

"It highlights a very plastic potential for these cells," Monk said.

In discovering how Schwann cells generate myelin at the molecular level, the discovery may lead to new gene-therapy techniques to repair damaged myelin in peripheral nervous system disorders such as Charcot-Marie-Tooth disease, a painful inherited form of neuropathy that affects 1 in 2,500 people in the United States.

Both Schwann cells and oligodendrocytes arose at the same point in evolutionary history, with the appearance of jaws in the vertebrate lineage. Invertebrates lack myelin, and some, like the modern squid, uses thick axons to quickly transmit signals between neurons.

"We could have evolved that way, but our spinal cord would be the diameter of a giant sequoia tree," Monk said.

Instead, vertebrate axons evolved myelin to protect axons and speed up signal transmission. To create myelin, Schwann cells evolved to produce it around a single axon in the peripheral nervous system. Oligodendrocytes, in turn, generated myelin along multiple axons within the more confined environment of the brain and spine - the central nervous system.

"The real estate is fundamentally different in the central nervous system than in the peripheral nervous system," Monk said.

Monk theorizes that Schwann cells evolved a mechanism to repair damaged myelin on a cell by cell basis, since it would have been common for injuries to occur without necessarily killing the entire organism. Those traits would have been passed down and strengthened through generations of evolution.

By contrast, remyelination in the central nervous system tended to be an evolutionary dead end since few would have survived a severe whack to the brain or spine.

"There's no selective pressure in repairing myelin damage in the central nervous system, because you're probably going to die," Monk said.

However, the discovery published today suggests a new opportunity to heal the brain and spine.

"Targeting the fbxw7 gene - or downstream pathway molecules - could be a powerful way to promote myelin repair in the central nervous system," Monk said.

Restoration of the Earth's forests is the world's most effective solution to climate change available today and has the potential to capture two thirds of man-made carbon emissions, finds landmark research by the Crowther Lab, published today in the journal Science.

The study is the first to quantify how many trees the Earth can support, where they could exist and how much carbon they could store. It finds that there is potential to increase the world's forest land by a third without affecting existing cities or agriculture, regrowing trees over an area the size of the United States or larger than Brazil.

Once mature, these new forests could store 205 billion tonnes of carbon, about two thirds of the 300 billion tonnes of extra carbon that exists in atmosphere as a result of human activity since the Industrial Revolution.

The study, led by Dr. Jean-Francois Bastin, also suggests that there is further potential to regrow trees in croplands and urban areas, highlighting the scope for agroforestry and city trees to play a major role in tackling climate change.

But the research paper, The global tree restoration potential, warns that the need for action is urgent: the climate is already changing and every year reduces the area of land that can support new forests. Even if global warming is limited to 1.5°C, the area available for forest restoration could be reduced by a fifth by 2050.

Professor Tom Crowther, senior author of the study said: "We all knew restoring forests could play a part in tackling climate change, but we had no scientific understanding of what impact this could make. Our study shows clearly that forest restoration is the best climate change solution available today and it provides hard evidence to justify investment. If we act now, this could cut carbon dioxide in the atmosphere by up to 25%, to levels last seen almost a century ago.

"However, it will take decades for new forests to mature and achieve this potential. It is vitally important that we protect the forests that exist today, pursue other climate solutions, and continue to phase out fossil fuels from our economies in order to avoid dangerous climate change."

The Crowther Lab is a group of multi-disciplinary scientists studying the ecological processes that influence climate change, based at ETH Zürich, the world's leading University in Earth and Environmental Sciences. Its study provides the first quantitative assessment of the feasibility of global forest restoration targets.

Research provides benchmark for a global action plan

Forests have always been considered an option for capturing atmospheric carbon, but it has never been clear what impact this could have at a global scale. This is because, until now, there has been no quantitative assessment of how much tree cover might be possible under current or future climate conditions.

The future scenarios proposed by the UN's Intergovernmental Panel on Climate Change propose that limiting climate change to 1.5°C will require up to an extra billion hectares of forest by 2050, even while radically reducing emissions from energy, transport and so on. The new study allows this claim to be evaluated for the first time, showing where these trees could be restored and how much carbon they can capture. It confirms that this scenario projection is "undoubtedly achievable under the current climate".

Currently there are 5.5 billion hectares of forest (defined by the UN Food and Agriculture Organisation as land with at least 10% tree cover and without human activity), with a total 2.8 billion hectares of tree canopy cover.

The Crowther Lab finds that forests could be regrown on 1.7-1.8 billion hectares of land in areas with low human activity that are not currently used as urban or agricultural land, adding 0.9 billion hectares of tree canopy. Importantly, these are not areas that would naturally be grasslands or wetlands, but degraded ecosystems that would naturally support some level of tree cover.

If cropland and urban areas were included the study finds that forests could be regrown on a further 1.4 billion hectares of land, adding 0.7 billion hectares of tree canopy.

Dr Jean-François Bastin, the lead author of the study, said: "Our study provides a benchmark for a global action plan, showing where new forests can be restored around the globe. Action is urgent and governments must now factor this into their national strategies to tackle climate change."

The study finds that more than half the potential to restore trees can be found in just six countries: Russia (151 million hectares); USA (103 million); Canada (78 million); Australia (58 million); Brazil (50 million); and China (40 million).

It also highlights major inconsistencies in the targets of several global restoration initiatives and warns that better country-level forest accounting is critical for developing effective forest management and restoration strategies.

At the start of 2019, 48 countries had signed up to the Bonn Challenge, which aims to restore 350 million hectares of forest by 2030. However, the study finds that over 43% of these countries have committed to restore less than half the area that can support new forests while 10% have committed to restoring considerably more land than is suitable for forest growth.

Climate models wrong in forecasting more tree cover in warming world

The study also warns that some existing climate models are wrong in expecting climate change to increase global tree cover. It finds that there is likely to be an increase in the area of Northern "Boreal" forests in regions such as Siberia, where tree cover averages 30-40%. However, this would be outweighed by losses in dense tropical forests, which typically have 90-100% tree cover.

Prof, Crowther added: "Although government action is essential to make the most of this opportunity, this is a climate solution we can all get involved in and make a tangible impact. You can grow trees yourself, donate to forest restoration organizations or just invest your money responsibly in businesses which are taking action on climate change."

René Castro, Assistant Director-General, FAO, commented on the paper: "Forests are one of our biggest allies in combatting climate change with measurable results. Deforestation not only contributes to an alarming loss of biodiversity, but limits our ability to store carbon in the trees, undergrowth and soil. We now have definitive evidence of the potential land area for re-growing forests, where they could exist and how much carbon they could store."

Ms. Christiana Figueres, Founding Partner, Global Optimism and Former Executive Secretary, UN Climate Convention, also commented: "Finally an authoritative assessment of how much land we can and should cover with trees without impinging on food production or living areas. A hugely important blueprint for governments and private sector".

Will Baldwin-Cantello, Global lead on Forests at WWF, said: "Our forests are the world's biggest natural ally in the fight against climate change but without them, we will lose the fight to keep global warming below 1.5 C. That's why it's crucial that we act to restore forests whilst drastically cutting our global carbon emissions. This new research demonstrates how much natural capacity our planet has to grow and sustain additional forest; now, the challenge is to understand how and where we can accelerate this implementation, whilst still feeding our growing global population.

"Tackling the climate crisis and restoring our forests requires unprecedented levels of co-operation and support at both a local and global level, supported by initiatives such as Trillion Trees that are accelerating delivery on the ground. We have the solutions at our fingertips; we just need the global political will to fight for our world."

A tool on the Crowther Lab website enables users to look at any point on the globe, and identify the areas for restoration and learn which native tree species exist there. It also offers lists of forest restoration organizations. Furthermore, Crowther Lab are supporting the creation of a global coalition that will bring targeted innovation to the opportunities and challenges identified by the Report.

Methodology

This is the first study to link direct tree measurements to environmental characteristics to provide quantitative, spatially explicit global estimates of potential tree cover. This was made possible because of a unique global dataset of forest observations and the free mapping software of Google Earth Engine.

Researchers analyzed tree cover in protected forest areas largely unaffected by human activity across the Earth's ecosystems, from arctic tundra to equatorial rainforest, studying nearly 80,000 high resolution satellite photographs. They used this to approximate the natural level of tree cover in each ecosystem.

In Google Earth Engine, they then used machine learning to identify 10 soil and climate variables that determine tree cover in each ecosystem and generate a predictive model to map potential tree cover worldwide under current environmental conditions in areas with minimal human activity.

They used three well-known climate models to update changes to the variables in order to project tree cover capacity for 2050.

A small chemical change — shifting the position of two hydrogen atoms — makes the difference between mice that are healthy and mice with insulin resistance and fatty liver, major risk factors for diabetes and heart disease. Making the change prevented the onset of these symptoms in mice fed a high-fat diet and reversed prediabetes in obese mice.

The scientists changed the trajectory of metabolic disease by deactivating an enzyme called dihydroceramide desaturase 1 (DES1). Doing so stopped the enzyme from removing the final hydrogens from a fatty lipid called ceramide, having an effect of lowering the total amount of ceramides in the body.

The finding highlights a role for ceramides in metabolic health and pinpoints DES1 as a “druggable” target that could be used to develop new therapies for metabolic disorders such as prediabetes, diabetes and heart disease — that affect the health of hundreds of millions of Americans. Scientists at University of Utah Health and Merck Research Laboratories led the research, published online in Science on July 4, 2019.

"We have identified a potential therapeutic strategy that is remarkably effective, and underscores how complex biological systems can be deeply affected by a subtle change in chemistry," says Scott Summers, Ph.D., chair of Nutrition and Integrative Physiology at U of U Health, who was co-senior author on the study with David Kelley, M.D., formerly of Merck Research Laboratories.

"Our work shows that ceramides have an influential role in metabolic health," says Summers. "We're thinking of ceramides as the next cholesterol."

This isn't the first time that Summers' group has found that lowering ceramides could reverse signs of diabetes and metabolic disease. However, techniques used in previous experiments caused severe side effects, showing the approach would not be suitable for therapeutic applications.

This time, rather than taking a sledgehammer to the problem, they developed a fine scalpel. They wondered whether making the smallest change possible and at a precise time and place might yield better results.

To lower ceramides, the investigators blocked the final step of ceramide synthesis in two ways. Summers' group genetically engineered mice in which the gene coding for DES1 could be switched off during adulthood and deactivated the gene from tissues throughout the body, or alternatively from either liver or fat cells. Kelley's group injected short hairpin RNA into the adult liver, a method that selectively lowered production of DES1 by destroying the RNA precursor.

The scientists tested the new approaches first by placing adult mice on a high-fat diet - one that resembled cookie dough with plenty of sugar and six times the fat of a normal rodent diet. The mice gained two times their body weight within three months. Along with obesity came a strain on their metabolic health. They developed insulin resistance and fat accumulated in the liver, both signs of metabolic disease.

Within weeks after lowering ceramides using either technique, there were significant changes. Mice remained obese but their metabolic health improved. Fat cleared from the liver and they responded to both insulin and glucose like a healthy, skinny mouse. In contrast to previous interventions, mice remained healthy during the two-month investigation. Long-term effects on health are currently under investigation.

"Their weight didn't change but the way they handled nutrients did," says Summers. "The mice were fat but they were happy and healthy."

In another paradigm, lowering ceramides before putting the mice on a high-fat diet prevented weight gain and insulin resistance.

Although the impact of lowering ceramides in humans is still unknown, there is evidence that ceramides are linked to metabolic disease, says Summers. He points out that clinics are already performing ceramide screening tests to gauge an individual's risk for developing heart disease.

Summers and Kelley are now developing drugs that inhibit DES1 with a goal of making new therapeutics. "This project provides substantial validation that this is a discreet and highly effective point of intervention," says Kelley.

When the Good Goes Bad

If ceramides cause poor health, why do we have them in the first place? Summers' group addressed the question by measuring how the lipid affects metabolism. They found that ceramides trigger a number of mechanisms that promote the storage of fat in cells. They also impair cells' ability to use glucose, a type of sugar, as fuel.

The evidence for these effects includes activation of a molecular pathway, Akt/PKB, that inhibits both the ability of cells to synthesize sugars and to take them up from the bloodstream. At the same time, ceramides slow the turnover of fatty acids in part by causing cells in the liver to increase fatty acid storage and adipose tissue to burn less fat.

The shift in how cells use fuel is an advantage in the short-term, says Summers. This is because ceramides have another role in stiffening the cell membrane. Further, promoting fat storage increases production of ceramides. These data lead to a model suggesting that one benefit of ceramides is that they protect the cell. When food is plentiful and cells store lots of fat, the increase in ceramide levels strengthen the cells' outer membrane, preventing ruptures.

"Serving in this role is usually good but it can potentially be bad," explains Trevor Tippetts, a graduate student in Summers' lab. He, U of U Health research assistant professor Bhagirath Chaurasia, Ph.D., and two of their Merck colleagues, Rafael Mayoral Moñibas, Ph.D., and Jinqi Liu, Ph.D., share lead authorship.

Tippetts explains that problems arise in times of chronic overabundance, such as during obesity, when there are persistently high levels of ceramides. Summers' team speculate that sustained impairment of metabolic homeostasis leads to insulin resistance and fatty liver disease.

The results hint at ceramide's normal role. "We think that ceramides evolved to become a nutritional sensor," says Chaurasia. He says that ceramides serve as a signal, helping the body to cope when the amount of fat that is coming into cells is exceeding its energetic needs, and its storage capacity.

These findings are leading to a deep understanding of how cells in the body assess nutrient status and adapt accordingly. "To me, that's the really exciting result," Chaurasia says.

13 young adults with tetraplegia are able to feed themselves, hold a drink, brush their teeth, and write as a result of a novel surgical technique which connects functioning nerves with injured nerves to restore power in paralysed muscles
Nerve transfer surgery has enabled 13 young adults with complete paralysis to regain movement and function in their elbows and hands, according to the largest case series of this technique in people with tetraplegia (paralysis of both the upper and lower limbs), published in The Lancet.

During the surgery, Australian surgeons attached functioning nerves above the spinal injury to paralysed nerves below the injury. Two years after surgery, and following intensive physical therapy, participants were able to reach their arm out in front of them and open their hand to pick up and manipulate objects. Restoring elbow extension improved their ability to propel their wheelchair and to transfer into bed or a car.

They can now perform everyday tasks independently such as feeding themselves, brushing teeth and hair, putting on make-up, writing, handling money and credit cards, and using tools and electronic devices.

The findings suggest that nerve transfers can achieve similar functional improvements to traditional tendon transfers, with the benefit of smaller incisions and shorter immobilisation times after surgery.

In 10 participants, nerve transfers were uniquely combined with tendon transfers allowing different styles of reconstruction to be performed in each hand, and enabling participants to benefit from the innate strengths of both tendon and nerve transfers. Nerve transfers restored more natural movement and finer motor control in one hand, and tendon transfers restored more power and heavy lifting ability in the other hand.

While only a small study, researchers say that nerve transfers are a major advance in the restoration of hand and arm function, and offer another safe, reliable surgical option for people living with tetraplegia.

Nevertheless, four nerve transfers failed in three participants and the authors conclude that more research will be needed to determine which people are the best candidates to select for nerve transfer surgery to minimise the incidence of failure.

"For people with tetraplegia, improvement in hand function is the single most important goal. We believe that nerve transfer surgery offers an exciting new option, offering individuals with paralysis the possibility of regaining arm and hand functions to perform everyday tasks, and giving them greater independence and the ability to participate more easily in family and work life", says Dr Natasha van Zyl from Austin Health in Melbourne, Australia who led the research. [1]

"What's more, we have shown that nerve transfers can be successfully combined with traditional tendon transfer techniques to maximise benefits. When grasp and pinch was restored using nerve transfers in one hand and tendon transfers in the other, participants consistently reporting that they liked both hands for different reasons and would not choose to have two hands reconstructed in the same way." [1]

Traditionally, upper limb function has been reconstructed using tendon transfer surgery, during which muscles that still work, but are designed for another function, are surgically re-sited to do the work of muscles that are paralysed. In contrast, nerve transfers allow the direct reanimation of the paralysed muscle itself. Additionally, nerve transfers can re-animate more than one muscle at a time, have a shorter period of immobilisation after surgery (10 days in a sling vs 6-12 weeks in a brace for a nerve transfer for elbow extension), and avoid the technical problems associated with of tendon transfer surgery including tendon tensioning during surgery and mechanical failure (stretch or rupture) after surgery.

Previous single case reports and small retrospective studies have shown nerve transfer surgery to be feasible and safe in people with tetraplegia. But this is the first prospective study to use standardised functional outcome measures and combinations of multiple nerve and tendon transfer surgeries.

In total the study recruited 16 young adults (average age 27 years) with traumatic, early (less than 18 months post injury) spinal cord injury to the neck (C5-C7), who were referred to Austin Health in Melbourne for restoration of function in the upper limb. Most were the result of motor vehicle accidents or sports injuries.

Participants underwent single or multiple nerve transfers in one or both upper limbs to restore elbow extension, grasp, pinch, and hand opening. This involved taking working nerves to expendable muscles innervated above the spinal injury and attaching them to the nerves of paralysed muscles innervated below the injury to restore voluntary control and reanimate the paralysed muscle.

For example, the surgeons selected the nerve supplying the teres minor muscle in the shoulder as a donor nerve and attached it to the nerve supplying the triceps that activates the muscles that extend (straighten) the elbow. To restore grasp and pinch the nerve to a spare wrist extensor muscle was transferred to the anterior interosseous nerve (figure 1).

In total, 59 nerve transfers were completed in 16 participants (13 men and three women; 27 limbs). In 10 participants (12 limbs), nerve transfers were combined with tendon transfers to improve hand function.

Participants completed assessments on their level of independence related to activities of daily living (e.g., self-care, toilet, upper limb function, muscle power, grasp and pinch strength, and hand opening ability) before surgery, one year after surgery, and again two years later. Two participants were lost to follow up, and there was one death (unrelated to the surgery).

At 24 months, significant improvements were noted in the hands ability to pick up and release several objects within a specified time frame and independence. Prior to surgery, none of the participants were able to score on the grasp or pinch strength tests, but 2 years later pinch and grasp strength were high enough to perform most activities of daily living (table 4).

Three participants had four failed nerve transfers--two had a permanent decrease in sensation, and two had a temporary decrease in wrist strength that resolved by 1 year after surgery. Overall, surgery was well tolerated. Five serious adverse events were recorded (including a fall from a wheelchair with femur fracture), but none were related to the surgery.

Despite these achievements, nerve transfer surgery still has some limitations. For the best results nerve transfers should ideally be performed within 6-12 months of injury. Additionally, it can take months after nerve transfer for nerve regrowth into the paralysed muscle to occur and for new movement to be seen, and years until full strength is achieved. However, the authors note that one of the benefits of nerve transfers is that most movements not successfully restored by nerve transfers can still be restored using tendon transfers.

Discussing the implications of the findings in a linked comment, Dr Ida Fox from Washington University in the USA writes, "Stem cells and neuroprostheses could change the landscape of regenerative medicine in the future. For now, nerve transfers are a cost-effective way to harness the body's innate capability to restore movement in a paralysed limb. As nerve transfers are adopted and their uses adapted, careful ongoing outcomes research--including comparison of nerve versus tendon transfer outcomes, which nerve transfers produce the greatest functional improvements, and optimal timings for surgery after injury--is paramount to advancing the field. Detailed study of the reasons for nerve transfer failure is also required, as is improving our understanding of the effects of biopsychosocial factors (including access to information and care, psychological readiness, and social support) on patient decision making and outcomes."

Hundreds of sharks and rays have become tangled in plastic waste in the world's oceans, new research shows.

University of Exeter scientists scoured existing published studies and Twitter for shark and ray entanglements, and found reports of more than 1,000 entangled individuals.

And they say the true number is likely to be far higher, as few studies have focussed on plastic entanglement among shark and rays.

The study says such entanglement - mostly involving lost or discarded fishing gear - is a "far lesser threat" to sharks and rays than commercial fishing, but the suffering it causes is a major animal welfare concern.

"One example in the study is a shortfin mako shark with fishing rope wrapped tightly around it," said Kristian Parton, of the Centre for Ecology and Conservation on Exeter's Penryn Campus in Cornwall.

"The shark had clearly continued growing after becoming entangled, so the rope - which was covered in barnacles - had dug into its skin and damaged its spine.

"Although we don't think entanglement is a major threat to the future of sharks and rays, it's important to understand the range of threats facing these species, which are among the most threatened in the oceans.

"Additionally, there's a real animal welfare issue because entanglements can cause pain, suffering and even death."

Co-author Professor Brendan Godley, co-ordinator of the university's marine strategy, added: "Due to the threats of direct over-fishing of sharks and rays, and 'bycatch' (accidental catching while fishing for other species), the issue of entanglement has perhaps gone a little under the radar.

"We set out to remedy this. Our study was the first to use Twitter to gather such data, and our results from the social media site revealed entanglements of species - and in places - not recorded in the academic papers."

The review of academic papers found reports of 557 sharks and rays entangled in plastic, spanning 34 species in oceans including the Atlantic, Pacific and Indian. Almost 60% of these animals were either lesser spotted dogfish, spotted ratfish or spiny dogfish.

On Twitter, the researchers found 74 entanglement reports involving 559 individual sharks and rays from 26 species including whale sharks, great whites, tiger sharks and basking sharks.

Both data sources suggested "ghost" fishing gear (nets, lines and other equipment lost or abandoned) were by far the most common entangling objects. Other items included strapping bands used in packaging, polythene bags and rubber tyres.

The study identified factors that appear to put certain species more at risk:

Habitat - sharks and rays in the open ocean appear more likely to get entangled, as do those living on the sea floor, where materials such as nets loaded with dead fish sink and attract predators, which in turn get stuck.

Migration - species that cover long distances appear at more at risk of encountering plastic waste.

Body shape - sharks seem to be at greater risk than rays. Species with unusual features - such as manta rays, basking sharks and sawfish - are also at more risk.

The study says more research is needed, and the researchers have worked with the Shark Trust to create an online report form to gather data on entanglements: https://recording.sharktrust.org/entanglement/record

The paper, published in the journal Endangered Species Research, is entitled: "A global review of shark and ray entanglement in anthropogenic marine debris."