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Laboratory animals such as mice are an important part of chemical safety tests, say researchers

by Jeff Tollefson

The US Environmental Protection Agency (EPA) is trying to sharply reduce its use of animals in toxicity tests. Many scientists and environmentalists say the move is premature and could undermine chemical regulation.

In a memo to staff, EPA administrator Andrew Wheeler said that the agency would make use of “cutting-edge, ethically sound science” that does not rely on animal testing.

Wheeler signed a directive on 10 September that commits the EPA to reduce its funding request for animal studies by 30% by 2025, and to phase them out entirely by 2035. After 2035, any tests or funds for studies involving animals such as mice would require the approval of the EPA administrator. The plan, which will affect research by EPA scientists and industry, has been in the works for more than a year. Agency officials have said that the shift away from animal experiments won’t limit chemical regulation or reduce public safety.

Wheeler also said that EPA had awarded US$4.25 million in grants to universities for research into alternative toxicity testing methods. The grant recipients are Johns Hopkins University in Baltimore, Maryland; Vanderbilt University in Nashville, Tennessee; Oregon State University in Corvallis; and the University of California, Riverside.

“I don’t think anyone would be saddened by reducing animal research,” says Laura Vandenberg, an environmental health scientist at the University of Massachusetts Amherst. But she fears that the EPA is effectively tying its own hands.

Uncertain outcomes

Scientists can and do use advanced screening tools to study the potential effects of chemicals at the cellular and biochemical level, Vandenberg says. But to regulate a chemical, the EPA must show that there are adverse effects in living organisms, she says. “There is no adverse effect in a Petri dish.”

And just because researchers don’t see negative effects of chemicals on cells in the lab, it doesn’t mean that they aren’t there, Vandenberg adds. “We are going to get caught in a position where we won’t really be able to regulate chemicals in the US.”

The Humane Society of the United States, an animal-advocacy group in Washington DC, praised the EPA’s decision. “We applaud the agency and urge industry and other stakeholders to continue this momentum and move away from animal testing,” said chief executive officer Kitty Block in a statement.

Not everyone is so sanguine about EPA’s decision. The move represents an “unholy alliance” between the chemical industry and animal-rights groups that are pushing to halt animal tests, says Jennifer Sass, a senior scientist at the Natural Resources Defense Council, an environmental advocacy group in New York City.

Sass says that the EPA has reduced its reliance on animal testing in certain areas. For instance, tests to see whether a chemical is corrosive to the skin can now be done on skin that is grown in a Petri dish. But without tests on animals such as mice or rabbits, the only way for companies to study chemical interactions in the body is to use computer models, she says. And those models are often proprietary, which makes it hard to assess their accuracy.

“A chemical goes into a black box, and out comes an answer that is very hard for people to understand and independently review,” Sass says.

https://www.nature.com/articles/d41586-019-02715-0?utm_source=Nature+Briefing&utm_campaign=c98b98c2f6-briefing-dy-20190910_COPY_01&utm_medium=email&utm_term=0_c9dfd39373-c98b98c2f6-44039353

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by Madison Mahoney

Experiences during medical school can systematically shape biases and attitudes against gay and lesbian individuals, according to a study published by researchers from Yale, Oregon Health & Science University, Syracuse University and the Mayo Clinic.

The study, published on Aug. 5 in the journal Social Science & Medicine, is part of a large long-term research project called the Medical Student Cognitive Habits and Growth Evaluation Study, more commonly known by the title CHANGES. CHANGES, a longitudinal study of medical students, seeks to understand the “culture of medicine” that promotes or inhibits physician expression of biases, according to a 2015 study report published in the Journal of General Internal Medicine.

“Bias can influence physicians’ medical decision-making, as well as their behavior toward patients,” said Natalie Wittlin GRD ’21, lead author of the study. “The goal of this research was to understand experiences during medical training that may contribute to or mitigate physician bias against lesbian and gay individuals — and ultimately health disparities.”

In this component of the CHANGES project, researchers sought to understand the influence of medical school on physician biases against sexual minorities. According to the study, these biases can impede the delivery of high-quality health care and contribute to the prevalence of poor health outcomes within these populations.

“Social psychologists have given more attention recently to sexual orientation biases than ever before, but they still remain underexamined relative to certain highly prototypical forms of race and gender bias,” said Sara Burke, one of the authors of the study and an assistant professor of psychology at Syracuse University.

In the CHANGES project, the researchers collected data from 2,940 medical students across a number of U.S. medical schools at three time points: their first semester of medical school in the fall of 2010, their last semester in the spring of 2014 and their second year of medical residency in the spring of 2016.

Through surveys taken at these time points, the researchers examined the relationship between experiences reported by heterosexual, cisgender medical students during medical school and explicit and implicit biases against lesbian and gay individuals during their residency. Explicit biases refer to overtly expressed attitudes towards a group of people, while implicit biases are defined as unconscious negative associations with a specific group of people.

The researchers found that students who had more contact and favorable interactions with LGBT individuals during medical school expressed less explicit and implicit bias towards sexual minorities during their residency. On the other hand, students who were exposed to “negative role modeling” during medical school expressed more explicit bias against sexual minorities.

According to Burke, the next iteration of the study will involve physicians evaluating hypothetical patients presenting different symptoms. She added that the researchers plan to continue contributing to the discussion on sexual orientation biases within medicine.

“We hope to participate in the larger conversation about how to structure medical training so as to maximize its beneficial consequences and minimize harmful side effects,” Burke said. “There is much more to be done.”

Wittlin added that the team will continue to follow up with the original cohort of medical students. The researchers will be able to observe how these biases change over time, as well as the long-lasting effects of experiences during medical training. She added that though the team has not tested any interventions, she expects that increasing diversity and inclusivity in medical schools could help to reduce bias against lesbian and gay individuals.

The CHANGES project is primarily funded by the National Institutes of Health, according to the project’s website.

Medical school experiences predict bias against LGBT individuals

by Lisa Rapaport

Kids who have more supportive experiences with family, friends, and people in their school and community may be less likely to have psychological or relationship troubles in adulthood, a new study suggests.

Adverse childhood experiences (ACEs) like abuse, neglect, violence, and parental absence have long been linked to lasting negative effects on physical and mental health, researchers note in JAMA Pediatrics. But less is known about whether positive experiences make it easier for kids to cope, or what happens with children whose lives have mix of negative and positive experiences

For the current study, researchers surveyed 6,118 adults about how often in childhood they felt able to talk to family and friends about feelings; felt their family stood by them during difficult times; enjoyed participating in community traditions; felt a sense of belonging in high school; felt supported by friends; had at least two nonparent adults who took an interest in them; and felt safe and protected by an adult in their home.

Overall, adults who reported six to seven of these positive childhood experiences were 72% less likely to have depression or at least 14 poor mental health days each month than adults who reported no more than two positive childhood experiences. Even three to five positive experiences were tied to a 50% lower likelihood of depression or poor mental health than two or fewer.

These associations held true even when respondents reported multiple adverse childhood experiences.

“The absence of the types of positive childhood experiences we assessed in our study is very stressful for a child,” said lead study author Christina Bethell of the Bloomberg School of Public Health at Johns Hopkins University in Baltimore.

“Without positive nurturance, children’s stress hormones can get stuck on high and this impacts how their brain develops in ways that can make it hard for them to experience safety, relaxation and to become open, curious and learn to have positive relationships with others,” Bethell said by email.

The association between positive life experiences and better adult mental health and relationships persisted even among people who experienced ACEs during childhood.

Compared to participants who reported no more than two positive childhood experiences, people who experienced six to seven positive childhood experiences were also more than three times more likely to report that as adults, they “always” got the social and emotional support they needed.

When people had no more than two positive childhood experiences, only about one-third reported always getting the social and emotional support they needed – even when they didn’t have a history of ACEs.

The study doesn’t prove that positive childhood experiences impact adult mental health or relationships.

“In fact, people with poor mental health might be less likely to view their childhood experiences as positive,” said Dr. Rebecca Dudovitz, a researcher at the David Geffen School of Medicine at the University of California Los Angeles.

“It might actually be that adults with depression remember their childhood differently than adults without depression,” Dudovitz, who wasn’t involved in the study, said by email.

Parents may not be able to prevent adverse childhood experiences, but they can help kids become resilient, said Dr. Angelica Robles, a developmental-behavioral pediatrician at Novant Health in Charlotte, North Carolina, who wasn’t involved in the study.

“Parents can accomplish this by simply talking about feelings with their children, standing by their children during difficult times, and showing interest in their daily lives,” Robles said by email. “The child will then feel safe, and it is in this sense of security in the face of stress that the child learns to flourish.”

https://www.reuters.com/article/us-health-childhood/positive-childhood-experiences-tied-to-better-adult-mental-health-idUSKCN1VU2CP

An ambitious research project aims to assess the state of mental-health resources and support for graduate students. The 22-month initiative is a joint venture of the Council of Graduate Schools (CGS) in Washington DC and the Jed Foundation, a non-profit organization in New York City that focuses on the mental health of young adults. The initiative will explore current schemes and programmes centred on student wellness at CGS member universities in the United States and Canada, and provide recommendations for future approaches to promote mental and emotional well-being in students.

“We want to create a road map for moving forward,” says Suzanne Ortega, CGS president and the principal investigator of the project, called Supporting Mental Health and Wellness of Graduate Students. “We’ll be offering advice about policies and resources that will help students in crisis while also creating an environment where graduate students can thrive.”

The project, supported by nearly US$280,000 in grants from the Alfred P. Sloan Foundation and the Andrew W. Mellon Foundation, will gather input through surveys of administrators at CGS’s 500 or so member institutions across the world, along with focus groups that will probably involve students as well as those advocating on behalf of students. A key part of the conversation will take place at a workshop for students, administrators and mental-health specialists that is tentatively scheduled for October next year in Washington DC. An initial report of findings and recommendations for policies is scheduled to be published in December next year.

Unmet needs

The pressure, competition and stress experienced by graduate students puts them at high risk for mental-health issues, Ortega says. Precise estimates of the prevalence of anxiety and depression in this population remain elusive, she notes, and graduate students need and deserve thoughtful, evidence-based support. “We’re convinced by the need,” she says. “We know that a significant minority of graduate students have clinical symptoms of distress.”

Nance Roy, the Jed Foundation’s chief clinical officer, says that few effective mental-health programmes aimed at graduate students are currently offered at academic institutions. The Jed Foundation assisted universities in developing guidelines that will help to address undergraduate mental health, but Roy points out that graduate students have different needs and life situations that could require tailored approaches. For example, graduate students might find it especially difficult to take time off when they’re feeling overwhelmed. “They may not be able to just step away from a research project,” she says. “We want to promote people taking time off if they need it.”

Roy is also concerned about mentorship, a crucial aspect of graduate training that doesn’t always receive much scrutiny. “That relationship needs a tremendous amount of attention,” she says.

Ortega and other investigators have identified some innovative approaches that deserve a closer look. Boston University in Massachusetts, for example, instituted a holiday policy this year that ensures two weeks, or ten working days, of paid holiday every year for PhD students on annual stipends. “The idea is that this will foster work–life balance, which is a big part of student wellness,” says Ortega.

Another is the Mental Health Bill of Rights and Responsibilities that was adopted by the graduate education department at Vanderbilt University in Nashville, Tennessee, in February. The document states that, among other things, any student who seeks mental-health treatment through the university will be assigned a care coordinator who can help them to navigate the system and connect with resources.

Mark Wallace, a neuroscientist and dean of the Vanderbilt University Graduate School, says that the bill of rights was a product of many discussions between graduate students and university leaders. “This approach ensures that everyone has a role to play in tackling mental-health issues on our campus, whether they be students, faculty or staff,” he says.

Covering new ground

Ortega says that the CGS initiative is the first of its kind in the United States and Canada. She and other investigators were partly inspired by other mental-health schemes, including the UK Council For Graduate Education’s first International Conference on the Mental Health & Wellbeing of Postgraduate Researchers, which took place in May (and was supported by Nature Research).

The CGS will co-host a global summit, Cultural Contexts of Health and Well-Being in Graduate Education, at the University of Manchester, UK, on 1–3 September. “There’s a growing recognition of these issues in Europe,” Ortega says.

Ortega and Roy hope that their project will inspire universities around the United States to take a closer look at at what they’re doing — or not doing — to promote the mental health of graduate students. The results should also lay the foundation for a future of better support for graduate students, including more scientifically rigorous studies of issues that this group faces, Ortega says.

“Graduate-student mental health and well-being has become one of the hottest topics that our graduate dean members want to see addressed,” Ortega says. “Clearly, we have a lot of work to do in the next 22 months.”

https://www.nature.com/articles/d41586-019-02584-7?utm_source=Nature+Briefing&utm_campaign=0a58fd4efb-briefing-dy-20190902&utm_medium=email&utm_term=0_c9dfd39373-0a58fd4efb-44039353

William Shuttleworth, 71, of Newburyport, Massachusetts walked across the country for over three months. He told NBC 7’s Lauren Coronado he did it all for U.S. veterans.

Shuttleworth left Massachusetts on May 15 and arrived at his last stop in San Diego on Sunday.

An Air Force veteran himself, Shuttleworth said he wanted to raise awareness for veteran’s issues like suicide, healthcare and homelessness.

“To know that you can still do this at my age of 71 and do this for veterans… It’s pretty emotional,” Shuttleworth said. “It’s pretty honoring to be able to do this.”

His journey took him 3,600 miles or 10 million steps across the country. He said he wore out five pairs of shoes along the way.

Shuttleworth claimed the only items he needed for the trip were a 28-pound backpack with two changes of clothes and a tent.

“It was some tough times once I got to Blythe and El Centro. It was 114 degrees a couple days. It can melt you.”

“On the average day I burned about 7,000 calories. That’s a plate of lasagna, nine by 13. I can eat that every day and lose weight,” Shuttleworth joked.

When asked why he made the journey, he said, “Veterans were willing to put their life on the line for every breath of fresh air that we have. Don’t you think that’s worth a lot?”

As Shuttleworth finished his walk in San Diego, he was greeted by supporters and veterans from all over the U.S.

Shuttleworth added, “I can’t let these people down now. I have a mission to accomplish and I’m not going to let it go. I probably won’t walk across America again, but I can do a lot more by continuing my advocacy.”

William Shuttleworth said his next big project is to create a non-profit organization focused on veterans and homelessness.

Shuttleworth’s website has more information about how to support his cause: https://vetsdontforgetvets.com/


Tracks made by Yutu-2 while navigating hazards during lunar day 8, which occurred during late July and early August 2019.

By Andrew Jones

China’s Chang’e-4 lunar rover has discovered an unusually colored, ‘gel-like’ substance during its exploration activities on the far side of the moon.

The mission’s rover, Yutu-2, stumbled on that surprise during lunar day 8. The discovery prompted scientists on the mission to postpone other driving plans for the rover, and instead focus its instruments on trying to figure out what the strange material is.

Day 8 started on July 25; Yutu-2 began navigating a path through an area littered with various small impact craters, with the help and planning of drivers at the Beijing Aerospace Control Center, according to a Yutu-2 ‘drive diary’ published on Aug. 17 by the government-sanctioned Chinese-language publication Our Space, which focuses on space and science communication.

On July 28, the Chang’e-4 team was preparing to power Yutu-2 down for its usual midday ‘nap’ to protect the rover from high temperatures and radiation from the sun high in the sky. A team member checking images from the rover’s main camera spotted a small crater that seemed to contain material with a color and luster unlike that of the surrounding lunar surface.

The drive team, excited by the discovery, called in their lunar scientists. Together, the teams decided to postpone Yutu-2’s plans to continue west and instead ordered the rover to check out the strange material.


Yutu-2 found a strangely-colored substance in a crater on the far side of the moon.

With the help of obstacle-avoidance cameras, Yutu-2 carefully approached the crater and then targeted the unusually colored material and its surroundings. The rover examined both areas with its Visible and Near-Infrared Spectrometer (VNIS), which detects light that is scattered or reflected off materials to reveal their makeup.

VNIS is the same instrument that detected tantalizing evidence of material originating from the lunar mantle in the regolith of Von Kármán crater, a discovery Chinese scientists announced in May.

So far, mission scientists haven’t offered any indication as to the nature of the colored substance and have said only that it is “gel-like” and has an “unusual color.” One possible explanation, outside researchers suggested, is that the substance is melt glass created from meteorites striking the surface of the moon.

Yutu-2’s discovery isn’t scientists’ first lunar surprise, however. Apollo 17 astronaut and geologist Harrison Schmitt discovered orange-colored soil near the mission’s Taurus-Littrow landing site in 1972, prompting excitement from both Schmitt and his moonwalk colleague, Gene Cernan. Lunar geologists eventually concluded that the orange soil was created during an explosive volcanic eruption 3.64 billion years ago.


Strange orange soil was discovered on the moon by the Apollo 17 mission in 1972.

Chang’e-4 launched in early December 2018, and made the first-ever soft landing on the far side of the moon on Jan. 3. The Yutu-2 rover had covered a total of 890 feet (271 meters) by the end of lunar day 8.

The Chang’e-4 lander and Yutu-2 rover powered down for the end of lunar day 8 on Aug. 7, and began their ninth lunar day over the weekend. The Yutu-2 rover woke up at 8:42 p.m. EDT on Aug. 23 (00:42 GMT Aug. 24), and the lander followed the next day, at 8:10 p.m. (00:10 GMT).

https://www.space.com/china-far-side-moon-rover-strange-substance.html

Thanks to Kebmodee for bringing this to the It’s Interesting community.

During lunar day 9, Yutu-2 will continue its journey west, take a precautionary six-day nap around local noontime, and power down for a ninth lunar night around Sept. 5, about 24 hours hours ahead of local sunset.


A group of independent biologists say they plan to copy a costly gene therapy. Are they medicine’s Robin Hood or a threat to safety?

by Alex Pearlman

Citing the tremendous cost of new drugs, an international group of biohackers say they are creating a knock-off of a million-dollar gene therapy.

The drug being copied is Glybera, a gene therapy that was the world’s most expensive drug when it came on the market in Europe in 2015 with a $1 million per treatment price tag. Glybera was the first gene therapy ever approved to treat an inherited disease.

Now a band of independent and amateur biologists say they have engineered a prototype of a simpler, low-cost version of Glybera, and they plan to call on university and corporate scientists to help them check, improve, and test it on animals.

The group says it will start sharing the materials and describe their activities this weekend at Biohack the Planet, a conference in Las Vegas that hosts citizen scientists, journalists, and researchers for two days of presentations on body implants, biosafety, and hallucinogens.

“This was developed in a shed in Mississippi, a warehouse in Florida, a bedroom in Indiana, and on a computer in Austria,” says Gabriel Licina, a biohacker based in South Bend, Indiana. He says the prototype gene therapy cost less than $7,000 to create.

Experts briefed on the biohacking project were divided, with some calling it misguided and unlikely to work. Others say the excessive cost of genetic treatments has left patients without options and created an incentive to pirate genetic breakthroughs.

“It’s a fairly big deal to see biohackers turning their focus to gene therapies because the potential consequences can be quite large,” said Rachel Sachs, an associate professor of law at Washington University in St. Louis and an expert on drug pricing. “They may see themselves as serving the interests of the patient community.”

This year the Swiss pharmaceutical firm Novartis introduced another gene therapy, Zolgesma, for spinal muscular atrophy, with a price of $2.1 million. Because of the cost, some parents have struggled to obtain it for their children and the treatment is unlikely to be made available in most of the world.

Disrupting the narrative

The gene therapy that the biohackers say they are copying, Glybera, was approved for people with an ultra-rare blood disease called lipoprotein lipase deficiency. But it didn’t prove cost-effective and was pulled from the market in 2017 by its manufacturer, UniQure. To date, only one insurer, in Germany, is known to have paid for the treatment.

Andreas Stürmer, a biotechnologist and environmental engineer who is based in Linz, Austria, says after the idea of reverse engineering the treatment occurred to him he brought the concept to Licina. Their collaboration took place through Facebook messages and Skype calls, and included help from David Ishee, a biohacker in Mississippi.

In another recent example of copy-cat gene therapy, a biohacker in Florida in 2018 produced and ate an oral gene therapy for lactose intolerance using a 20-year-old scientific paper as a recipe.

“It’s about disrupting the narrative,” says Licina, also the cofounder of SciHouse, a community biotechnology lab in Indiana. “It was like, ‘Well, why not?”

One reason not to is that copying and selling the drug could infringe on UniQure’s intellectual property. Tom Malone, a spokesperson for UniQure, says the company had not been informed of the biohacking attempt. He says it still owns a patent on the drug but it does not believe there is strong demand for the treatment. “To that end, a “knock off” version of Glybera would likely face significant regulatory and commercial hurdles,” says Malone.

Also, the US Food and Drug Administration has said it is illegal to sell do-it-yourself gene therapy supplies. Still, some biohackers feel confident grabbing information from published papers, even if some of it has been patented. “This thing is protected 10 different ways,” says Ishee. “I don’t care. Because I’m not selling it.”

Get the job done

To make their knock-off, the biohackers checked the original Glybera papers for the information about the genetic sequence of the gene that patients require corrected copies of. They then placed an order with a gene synthesis company for a copy of the DNA, which was added to a circular genetic construct called a “minicircle.” When added to a cell, the mincircle will begin manufacturing small amounts of the lipoprotein lipase enzyme.

That is an important difference from the original Glybera, which employed an injection of viruses into the leg muscle to deliver the gene. Viral “delivery” is a complex undertaking but is the most commonly used strategy in gene therapy. The biohackers don’t have access to viruses because of their high cost, but say minicircles can potentially be injected, too.

Robert Kotin, an expert in gene therapy production, calls the minicircle technology controversial and says it has shown contradictory results. While minicircles, unlike viruses, could possibly be readministered time and again, they are not as efficient in getting cells to follow genetic instructions.

“It’s not the same [but] it can get the job done. It’s just less efficient,” says Ishee of the minicircles, which are based on his design. He thinks they could be injected over a period of half a year. “It’s like if you wanted to dig a swimming pool or a pond—you could buy a backhoe and dig it in a day or you could do it with a shovel at no cost over several months.”

https://www.technologyreview.com/s/614245/biohackers-are-pirating-a-cheap-version-of-a-million-dollar-gene-therapy/

Thanks to Kebmodee for bringing this to the It’s Interesting community.