Bone marrow cancer: Potential drug targets

New research from Mayo Clinic’s Center for Individualized Medicine finds that patients with ASXL1-mutant chronic myelomonocytic leukemia — an uncommon type of cancer of the bone marrow — have distinctive epigenetic changes that can activate harmful genes and cause the cancer to grow faster. The ASXL1 genetic mutation also can transform the disease into the more aggressive acute myeloid leukemia.

The study, published in Nature Communications, helps to clarify a potential therapeutic strategy and adds to the knowledge of ASXL1 gene expression.

Epigenetics refers to chemical modifications of a cell’s genetic material that control how genes are expressed and affect the interpretation of the DNA code. Research shows epigenetics play a critical role in the development and progression of many diseases, including cancer.

“The epigenome in patients with these ASXL1 gene mutations is changed in a way that allows the cancer cells to switch on genes that are detrimental to the patients,” says Moritz Binder M.D., a Mayo Clinic hematologist and scientist, and the lead author of the study. Dr. Binder is a 2021 Gerstner Family Career Development awardee.

“These epigenetic changes don’t affect the DNA blueprint itself,” Dr. Binder explains. “It affects how to the blueprint is read — which pages to read and which pages not to read.”

Chronic myelomonocytic leukemia is a cancer that typically affects people 60 and older. It starts in blood-forming cells of the bone marrow and invades the blood. Nearly 40% of patients with chronic myelomonocytic leukemia have a mutation in the ASXL1 gene.

“Unfortunately, patients with ASXL1 mutations do not fare well and do not respond as well to the treatments currently available,” Dr. Binder says.

For the study, Dr. Binder and his team conducted a comprehensive multi-omics interrogation using a variety of high-throughput sequencing methods. Multi-omics offers the opportunity to understand the flow of information that underlies disease.

The researchers compared samples from patients with and without ASXL1 mutations and analyzed the activity of genes along with molecules around the DNA. The investigation included gene expression and several modifications affecting the packaging of the DNA.

“This allowed us to perform modeling to draw inference about the effect of epigenetic changes in isolation and in concert on leukemogenic gene expression in ASXL1-mutant chronic myelomonocytic leukemia,” Dr. Binder says.

Overall, they found that ASXL1 mutations are associated with the overexpression of key genes that drive leukemia.

“Our study supports the notion that several important leukemogenic driver genes are under the control of regulatory elements in the genome,” Dr. Binder says.

The data suggest that these regulatory elements are only functional in patients with ASXL1-mutant chronic myelomonocytic leukemia and may therefore represent new individualized therapeutic targets. Dr. Binder is planning to translate these findings into early phase clinical trials soon.

“Our study is the basis for ongoing work to further explore ways to target these patient-specific regulatory elements with novel small-molecule drugs, “Dr. Binder says. “With this approach, we hope to restore normal gene expression, or at least treat the cancer cells in a new way to overcome the detrimental effect of ASXL1 mutations.”

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Materials provided by Mayo Clinic. Original written by Susan Murphy. Note: Content may be edited for style and length.

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Physicists find direct evidence of strong electron correlation in a 2D material

In recent years, physicists have discovered materials that are able to switch their electrical character from a metal to an insulator, and even to a superconductor, which is a material in a friction-free state that allows electrons to flow with zero resistance. These materials, which include “magic-angle” graphene and other synthesized two-dimensional materials, can shift electrical states depending on the voltage, or current of electrons, that is applied.

The underlying physics driving these switchable materials is a mystery, though physicists suspect it has something to do with “electron correlations,” or effects from the interaction felt between two negatively charged electrons. These particle repulsions have little to no effect in shaping the properties in most materials. But in two-dimensional materials, these quantum interactions can be a dominating influence. Understanding how electron correlations drive electrical states can help scientists engineer exotic functional materials, such as unconventional superconductors.

Now, physicists at MIT and elsewhere have taken a significant step toward understanding electron correlations. In a paper appearing today in Science, the researchers reveal direct evidence of electron correlations in a two-dimensional material called ABC trilayer graphene. This material has previously been shown to switch from a metal to an insulator to a superconductor.

For the first time, the researchers directly detected electron correlations in a special insulating state of the material. They also quantified the energy scales of these correlations, or the strength of the interactions between electrons. The results demonstrate that ABC trilayer graphene can be an ideal platform to explore and possibly engineer other electron correlations, such as those that drive superconductivity.

“Better understanding of the underlying physics of superconductivity will allow us to engineer devices that could change our world, from zero-loss energy transmission to magnetically levitating trains,” says lead author Long Ju, assistant professor of physics at MIT. “This material is now a very rich playground to explore electron correlations and build even more robust phenomena and devices.”

Superlattice

An ABC trilayer graphene, stacked atop a layer of hexagonal boron nitride, is similar to the more well-studied magic-angle bilayer graphene, in that both materials involve layers of graphene — a material that is found naturally in graphite and can exhibit exceptional properties when isolated in its pure form. Graphene is made from a lattice of carbon atoms arranged in a hexagonal pattern, similar to chicken wire. Hexagonal boron nitride, or hBN, has a similar, slightly larger hexagonal pattern.

In ABC trilayer graphene, three graphene sheets are stacked at the same angle and slightly offset from each other, like layered slices of cheese. When ABC trilayer graphene sits on hBN at a zero-degree twist angle, the resulting structure is a moiré pattern, or “superlattice,” made up of periodic energy wells, the configuration of which determines how electrons flow through the material.

“This lattice structure forces electrons to localize, and sets the stage for electron correlations to have a huge impact on the material’s macroscopic property,” Ju says.

He and his colleagues sought to probe ABC trilayer graphene for direct evidence of electron correlations and to measure their strength. They first synthesized a sample of the material, creating a superlattice with energy wells, each of which can normally hold two electrons. They applied just enough voltage to fill each well in the lattice.

Electron boost

They then looked for signs that the material was in an ideal state for electron correlations to dominate and affect the material’s properties. They specifically looked for signs of a “flat band” structure, where all electrons have almost the same energy. The team reasoned that an environment hosting electrons with a wide range of energies would be too noisy for the tiny energy of electron correlations to have an effect. A flatter, quieter environment would allow for these effects to come through.

The team used a unique optical technique they developed to confirm that the material indeed has a flat band. They then tuned down the voltage slightly, so that only one electron occupied each well in the lattice. In this “half-filled” state, the material is considered a Mott insulator — a curious electrical state that should be able to conduct electricity like metal, but instead, due to electron correlations, the material behaves as an insulator.

Ju and his colleagues wanted to see if they could detect the effect of these electron correlations in a half-filled, Mott insulating state. They looked to see what would happen if they disturbed the state by moving electrons around. If electron correlations have any effect, such perturbations of electron configurations would meet resistance, since electrons naturally repel each other. For example, an electron that attempts to move to a neighboring well would be pushed back by the electron already occupying that well, even if that well can technically accommodate an additional electron.

In order to overcome this resistance, it would require an extra boost of energy — just enough to overcome the electron’s natural repulsion. The team reasoned that the magnitude of this boost would be a direct measure of the electron correlation’s strength.

The researchers supplied the extra boost using light. They shone light of different colors, or wavelengths, onto the material, and looked for a peak, or a single specific wavelength that the material absorbed. This wavelength corresponded to a photon with just enough energy to kick an electron into a neighboring half-filled well.

In their experiment, the team indeed observed a peak — the first direct detection of electron correlations in this specific moiré superlattice material. They then measured this peak to quantify the correlation energy, or the strength of the electron’s repulsive force. They determined this to be about 20 millielectronvolts, or 1/50 of an electronvolt.

The results show that strong electron correlations underlie the physics of this particular 2D material. Ju says the Mott insulating state is particularly important, as it is the parent state of unconventional superconductivity, the physics of which remains illusive. With this new study, the team has demonstrated that ABC trilayer graphen/hBN moiré superlattice is an ideal platform to explore and engineer the more exotic electrical states, including the unconventional superconductivity.

“Today, superconductivity happens only at very low temperatures in a realistic setting,” notes Ju, who says the team’s optical technique can be applied to other 2D materials to reveal similar exotic states. “If we can understand the mechanism of unconventional superconductivity, maybe we can boost that effect to higher temperatures. This material forms a foundation to understand and engineer even more robust electrical states and devices.”

This research was supported, in part, by the National Science Foundation, the Simons Foundation, and the MIT Skoltech program.

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Massive study shows urbanization drives adaptive evolution

Rochester Institute of Technology contributed to a massive study on a tiny roadside weed that shows urbanization is leading to adaptive evolution at a global scale. As part of the Global Urban Evolution Project (GLUE) project, scientists from 160 cities across six continents collected more than 110,000 samples of white clover plants in urban, suburban, and rural areas to study urbanization’s effects on the plants. It is the largest environmental evolution study ever and the results are published in the journal Science.

Scientists in each city used the same process to collect white clover samples and test them for a particular chemical anti-herbivore defense compound that also affects their stress tolerance for factors such as extreme heat and weather. Assistant Professor Kaitlin Stack Whitney from RIT’s Department of Science, Technology, and Society led a team of five environmental science students working on a senior capstone project to participate on Rochester’s behalf. In October 2018, they collected 650 samples at 41 sites along a straight path from downtown Rochester to Black Creek Park in North Chili along New York State Route 33A.

“We were picking through this tiny roadside weed, but it’s fascinating how you can unpack these global issues about urbanization and climate change by looking at this very overlooked plant,” said Stack Whitney. “There are these big global forces that are affecting how those plants are growing, what they’re doing, and whether or not they can respond to stresses in that very localized environment.”

The GLUE project was an opportunity for the RIT students to get hands-on, impactful research early in their scientific careers. Environmental science alumna Kristina Chomiak ’19, ’21 MS, who will begin pursuing her Ph.D. in sustainability in the fall, said the collaborative experiment helped solidify her interest in research.

“For me at that point personally I hadn’t had a ton of research experience,” said Chomiak. “It was exciting to be able to follow a protocol and actually conduct this wet lab research. And it was even better that it would be published and would be meaningful to the scientific community.”

Chomiak said she is excited to see the full results of the study and learn how the data they collected in Rochester compares to that found from other cities. She said that locally the team did not find a significant difference in adaptation between the urban and rural areas, but they hypothesize that is because Rochester has more snowfall than other cities involved in the study, meaning the white clover plants are less under attack here.

Participants in the first GLUE study, led by the University of Toronto Mississauga, are now discussing additional ways to leverage the data and organize follow-up studies. Stack Whitney plans to participate in at least five follow-up studies.

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Materials provided by Rochester Institute of Technology. Original written by Luke Auburn. Note: Content may be edited for style and length.

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What Is a Deeper Relationship?

As I’ve been reading through recent feedback emails regarding the upcoming Guild course, I’ve seen various expressions of a desire for “deeper relationships.” What does that actually mean?

Many people shared that their current social circle feels too fragmented. They have their work associates, their family relationships, their online friends, and perhaps a few other networks like for hobbies or fitness. That by itself isn’t a problem, but what people perceive as problematic is that they’re only able to connect with each of these groups with a few limited aspects of their personalities and interests. They feel blocked from expressing their whole and complete selves with anyone.

A related desire that many people expressed was for more “growth-oriented friends.” One of the most common words I saw in people’s emails was the word “like-minded.” People crave social circles with others who have similar values and interests. They’re tired of investing in relationships with people who seem too dissimilar.

I’d say that many people are looking for what we might call full-range friendships. They find it tiresome and draining to have a wide array of relatively shallow connections. I think much of the time when people say they want more depth, what they actually want is more range within the people that they connect with most often. People are tired of investing in low-compatibility connections. They want to see much higher compatibility across multiple interests.

One thing that a lot of people want is a close-knit circle of friends, and within that friendship circle, they want to see a really good range of like-mindedness. Many people prefer not to have so much fragmentation in their social lives. They don’t want activity partners and professional colleagues and romantic connections and mastermind partners and travel buddies and online friends who are all different people. They’d ideally love to invest in people with whom they can connect with across multiple dimensions – like a travel buddy who’s also great at creative and business masterminding and who’s into having rich spiritual discussions and who can go out for a nice vegan meal and a movie together.

Some people would also prefer if their social circles served as a source of romantic and sexual connections too, either directly with one or more of their friends or by finding good matches through their friends’ referrals.

So people want their social circles to provide more value to them, and they especially want to see more value and engagement per person.

Some people said the ideal size of their primary social circles was relatively small, typically in the range of 6-10 people. Some also want to see a nice gender balance in their friendships, especially if their current social circles feel imbalanced.

Most people don’t really want large social circles. Some lamented that their social circles already feel too big and complex, and they have a hard time keeping up with everyone. Others shared that they have no meaningful social circle to speak of yet, and they don’t want to shift towards something huge and expansive. They’d simply love to have a tight-knit group of friends that they can connect with regularly.

Another factor I saw expressed was what someone described as outreach fatigue or coordination fatigue. Some people serve as the main hubs of their social circles, and if they don’t keep actively inviting people and planning activities, nothing happens. This becomes exhausting after a while. Many people would prefer to have more resilient, self-maintaining social circles. People also want the option to socially engage sometimes and disengage at other times, so they can enjoy some solo time as well when they need it.

So when people say that they want deeper relationships, it’s a whole package of desires. The specifics are different for each person, but there does seem to be a common core of people wanting high-efficiency, full-range relationships. This is better for people’s energy. It’s better for their happiness. And it’s better for fitting into people’s busy lives.

This makes a lot of sense to me, and it aligns nicely with my own social development path. The social expansiveness that came from blogging and speaking has been rewarding, but it can be tiring to keep up with so many casual connections if I overdo it. This made me want to compact my social circle, both online and offline, and spend more time connecting with people who have a lot in common. And I can tell you that this works very well. It’s more relaxing, peaceful, and chill, and it feels more heart-aligned too. That said, I still enjoy phases of meeting and connecting with a lot of different people, but I see that more as the frosting on top of the cake.

The good news is that if a close-knit group of friends is what you want, you can create that, and we’ll be working on this together in the upcoming Guild course. However, it should be obvious that if you’re not there yet, you’ll need to start making different decisions socially.

I’d say that a good place to start is to reflect upon what it means to have deeper relationships with people. What does that actually mean? Is depth really the best word to describe what you want, or are you really looking for more compatibility or more range or more efficiency or more resilience in your individual relationships? I can help you get more clarity about this during the course, but I encourage you to start thinking about this now. What kind of social circle would you love to experience as your personal friendship guild?

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Covid: Positive tests rise but critical care stable

Positive tests rise for 12 days in a row, but this is not reflected in critical care numbers.

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Thames Valley pilot study to check for rare condition

Babies born with spinal muscular atrophy (SMA) have better prospects if it is picked up at birth.

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‘Dangerous’ tanning products promoted by influencers

Sprays and injections containing “melanotan-2” may lead to cancer, doctors tell a BBC News investigation.

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Dying patients living longer than expected lose NHS funds

More than 1,300 people a year are having their palliative care funding withdrawn, BBC analysis shows.

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While I Love To Think in Terms of Frames

This week a couple of people asked me about frames and reframing and how I got into using this particular approach to personal development, so I thought I’d share a quick piece about this. Our courses in particular includes lots and lots of different frames for solving practical problems in many areas of life.

What Is a Frame?

A frame is a way of representing a problem or situation. With respect to self-development, a frame typically assigns meaning to events.

I think you’ll ready understand this with a simple example.

Suppose someone says: My wife cheated on me.

The word “cheated” is a way of representing events. Cheating implies that the wife broke a rule or did something inherently wrong. This framing casts her actions as problematic. Apparently she did something she wasn’t supposed to do. She crossed a line.

If you use that frame, it’s surely going to influence how you approach the situation and the people involved.

But is that the only frame that could be used for the same events? No, of course not.

What was the apparent event? The wife supposedly had sex with someone else. By itself that event doesn’t mean anything. But of course humans love to assign meaning, partly because the assignment of meaning motivates us to make decisions, take actions, and make sense of the world.

So what other frames could we use here?

Here are some other possible frames for the same events:

  • My wife enjoyed herself with a new side partner.
  • My wife craved some extra variety and had a lovely fling.
  • My wife is polyamorous.
  • I have a really horny wife.
  • My wife is good at making people happy.
  • I’m in an open marriage.
  • My wife hates me and is doing this to get back at me.
  • I haven’t been as attentive to my wife as I should have, so no wonder she strayed.
  • My wife is a sinner and is going to hell.
  • My wife has ruined our family.
  • Many people will assume that she strayed because of me.
  • My wife must have a mental disorder.
  • My wife has unmet needs.
  • Apparently I’m not enough for her.
  • We never should have moved to this city because it obviously corrupted my wife.
  • My wife has been taken advantage of by some marriage-ruining creep.
  • Human beings are such sluts.
  • All of my relationships end in ruin; it was only a matter of time before something like this happened.

Some frames assume that the marriage is broken or threatened while other frames don’t. Some frames define an event as a problem while other frames might even define that same event as normal or even as an opportunity. Some frames assign blame to individuals while other frames don’t blame anyone.

This is similar to looking at events optimistically or pessimistically except that you have many more options available to you.

Where Did I Learn Framing?

I would say that I learned this concept from computer programming and also from mathematics. I started learning to code when I was 10 years old, and I learned that there are multiple ways to transform an idea into computer code.

Any problem can be defined in different ways. Some definitions make a problem easier or more efficient to solve. Other definitions make a problem more difficult to solve.

When I was writing computer games in the 1990s to run on 386, 486, and Pentium computers, efficient code was important. Otherwise the game would run too slowly to be playable. Why write 100 lines of code if you could use a 10-line solution instead? The difference often came down to how I approached the problem to begin with.

It wasn’t enough to just solve a problem. I often had to find more efficient solutions than the standard approaches if I wanted to do something creative. Sometimes the best way to devise a more efficient solution was to step back and define the problem in a different way.

Suppose a game needs to do a lot of trigonometric calculations for objects that spin or rotate. If you want those calculations to be done faster, you could try to optimize your code to be more efficient. But you could also look at the problem from a different angle, no pun intended. You could instead pre-calculate as much as possible and save it in a lookup table, which is generally much faster than doing calculations while the game is running. The sine of 40º is always going to be the same, so there’s no need to compute it more than once, and the same goes for every other angle you may need to compute. Instead of having your game doing sine and cosine calculations during gameplay, you could just precompute and save all the sine and cosine figures for every 1º or 0.1º (whatever resolution you desired) and then just load the precomputed answers when you need them.

On a similar note, I remember learning a technique called compiled sprites. Instead of saving animations as graphics and using standard functions to display them on the screen, for a couple of games I did some extra preprocessing of the graphics to essentially turn them into code. So if I needed to draw a dragon on the screen, I bypassed drawing the dragon with a general purpose drawing algorithm (i.e. a block transfer or “blitting” function), and I had the computer pre-generate custom code specifically to draw the dragon in a more efficient way. So I basically reframed the dragon as code instead of as graphics.

I suppose a less geeky analogy would be if instead of filling your fridge with food from the grocery store, which you must assemble into meals, you had someone come over and do a week’s cooking for you, and then they stored all the complete meals in your fridge for you to enjoy later. Some years ago I hired a local chef to do that for a few months, and it was indeed more efficient to have a fridge full of meals instead of a fridge full of ingredients to make meals.

In mathematics I also learned that if I wanted to solve a problem, there were usually many ways to do it. Sometimes a problem that would take 20 steps to solve with the textbook approach could be solved in 5 steps if I just looked at it from a different angle to begin with.

So I got into reframing for efficiency reasons. The purpose of reframing was to find a smarter or quicker way to solve a given problem. It’s not about working harder. It’s about using less energy and effort to get a similar or better result.

Reframing for Motivation

There’s also the fun and engagement factor to consider. Some approaches to problem solving are boring while other approaches can be more lively and stimulating.

When I was younger, I often got stuck partway through big creative projects. I was good at starting big projects, but I wouldn’t always be able to maintain enough momentum to finish them, especially when I ran into setbacks along the way. I suffered from a lot of partially finished projects. Of course when you don’t finish a creative project like a computer game, it provides no value for anyone else, and you get paid nothing. At least that’s how it worked while I was an indie developer. I invested years in projects that were never completed. They were learning experiences at least, but it would have been nicer if I could have moved more of them across the finish line.

Reframing helped me remedy that situation, so now I’m way better at fully finishing big projects. They may sometimes take longer than I expect, but I have gotten good at finishing them. Since 2018 I launched and published 4 major courses which collectively include more than 200 lessons as well as tons of bonus content. Soon we’ll be launching our 5th course, called Guild, which is about social alignment, and I’m super confident that will be completed too. Reaching this point also gives me more flexibility to experiment since even when I’m doing something a bit unusual, I know how to stay motivated till it’s complete, and I have reframing to thank for that.

Instead of framing course development as a solo creative endeavor, I frame each new course as a social experience. Instead of going into my cave and working on my biggest creative projects alone for months on end, my creative projects are more like spirited parties that I invite people to attend. So first I invite the people, and then I engage with them and do my best to serve them creatively, lesson by lesson, till the course is complete. This approach is very effective and satisfying, and it’s a win for all involved.

This people-first framing works really well for me, as opposed to the content-first framing I tried using in the past. I realized I also use this framing for blogging, which is why I’m still actively blogging after more than 17 years on this path, and I still feel motivated to do it. Sometimes I take weeks off from blogging, often because I’m being more active in Conscious Growth Club or maybe working on personal projects, but I still enjoy writing and intend to keep going with it. I don’t think of blogging so much as writing content but rather as communicating with real people. The content framing often feels a bit cold and even creepy to me… so blah and lifeless. I find it more motivating to know that I’m always writing for real human beings, and the motivate to write arises from the flow of energy among us.

For many days in a row now, I’ve been reading feedback from people about their intentions and desires for the new Guild course. I emailed my list 8 days ago and shared a bit about the course, inviting people to tell me more about their social challenges. As I read and take notes and reflect upon what people are sharing, my motivation to do the course is increasing day by day, and so is the flow of creative ideas for what we could include. I’m also thinking of doing something a bit more creative format-wise for this course.

I’m not sure what the exact launch date will be, but I always get a strong signal when it’s time to launch. And I often find that this synchs up pretty well with when people are feeling ready to begin. So I like using the framing of allowing the universe… or my intuition… or the collective social energy of all involved to help move the project forward at just the right pacing. Admittedly I still sometimes struggle with being patient when I feel that progress is a bit slower than I’d like, but it never actually helps to force it. As long as the social energy has been invited in, I know that I need to trust the way this energy likes to engage and let it work its magic, and an avalanche of creative flow will soon follow. I can always tell that we’re getting closer to launching when the feeling of motivation starts amping up.

Applying Framing to Personal Development

Whenever I get stuck with a particularly challenging problem, I like to step back and consider how I’m framing it. What is the problem I’m trying to solve? What is the goal I’m trying to achieve?

I love to write out my intentions and reflect upon them. That helps me see their potential limitations. Then I consider other ways of looking at the same situation. What other angles could I use? What other kinds of intentions could I set?

Being flexible with my framing allows me to solve many problems more enjoyably and more efficiently.

I especially pay attention to how a particular framing affects me emotionally. Many common frames seem very boring, and if I use them I’m not going to feel very motivated. Trying to make more money is one example – by itself that framing is an all-around dud.

I prefer to think of money as the result of doing something fun, engaging, creative, and socially beneficial. That may be why I haven’t had a job or a boss in 30 years. I like to work on interesting creative projects where money is a predictable side effect. And since my creative projects are framed as social experiences, instead of asking how I can make more money, I will ask a different kind of question, such as: What kind of growth experience would people appreciate next?

So I don’t fuss over jobs or money. I think of my work life as a stream of interesting shared experiences. This is probably closer to how people think when they’re traveling or on vacation. If your work isn’t at least as motivating and rewarding as your vacations, perhaps you ought to reframe your entire approach to work.

Don’t be stubborn and clingy with your frames. If a frame isn’t working beautifully for you, drop it and try a different frames. There are so many other frames to explore that it makes zero sense to remain clingy with a frame that isn’t even giving you the results you want.

I often say to people: Don’t blame yourself. Blame the frame. There’s no point in beating yourself up for getting poor results if you’ve been using the wrong tool for the job. Just pause and acknowledge that you’ve been using the wrong tool all along. Then reach for a different tool. And keep trying different tools (or frames) till you find something that truly works.

Frames Versus Beliefs

The idea of beliefs and getting your beliefs right is very popular in personal development circles. Personally I think this is really lame and gets a lot of people stuck. Sometimes I wish I could purge this field of its clinginess with beliefs. We don’t actually know how this reality works, so any belief is just a guess anyway. Historically speaking, our guesses are usually wrong or at best inaccurate.

A belief is basically a frame that you weave into your identity. Is that a good idea? Well… imagine taking a hammer and gluing it to your palm. You’ll surely get really good at hammering if you do that, but it’s going to get in your way and limit your performance sooner or later. Heck… maybe that’s why your wife cheated on you. 😉

You can use beliefs, but do so very sparingly. I’m willing to weave veganism into my identity and make that a permanent part of my character because I’ve been vegan for more than 25 years, and there are no appealing alternatives, nor do I expect there ever will be. I’m happy to solidify that framing in terms of my behaviors. Even so, I still have access to the frames that I used before I was vegan, and while I don’t use them behaviorally anymore, I can still use them to understand other people’s behaviors.

Most of the time, however, it’s best to stay nimble and flexible with your framing. I don’t subscribe to any religions or philosophical systems because they’re all limiting. I prefer to keep my mindset adaptable because that gives me many ways to solve problems and keep making interesting improvements. Just as I learned to write computer code in multiple programming languages, I like being able to think with different mindsets. There isn’t one mindset to rule them all. There are some really powerful and versatile tools, but I don’t need any of them glued to my palm.

One thing I’ve noticed is that I seem to be getting happier as I age. I find life more satisfying and fulfilling. I enjoy my work and my relationships with other people more. I feel more centered. And these feelings don’t seem to come from taking pride in accomplishments so much. They seem to arise more from building up my reframing skills, problem-solving skills, and social skills.

Don’t try to be a one-frame wonder. This life is full of mystery, and none of us really know how it works behind the scenes. There is no singular answer to life, the universe, and everything. So be curious. Keep exploring and experimenting, especially with your mindset. Discover through direct testing which frames and mindsets work best for you. And please don’t get clingy with frames that aren’t filling your life with beauty and delight. If a frame isn’t working for you, look upon it with fresh doubt. Doubt is actually the key to reframing, such as when you say, Hmmm… I doubt this is the best way to define the problem. Could there be a better way of looking at this?

Ya think? Of course there’s a better way.

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Do ‘behavioral psychedelics’ help patients make lasting, positive change?

Despite their reputation as illicit drugs, psychedelics may find new, legitimate roles in treatment for anxiety, depression, stress disorders, addiction, and other mental and behavioral health problems. But ensuring they do requires developing rigorous, standardized methods to study and apply the results, according to a new report.

In a perspective published in Frontiers in Psychiatry, researchers from UCLA Health and Harvard Medical School coin the term “behavioral psychedelics” — “the study of psychedelics to foster intentional changes in habits and behaviors to improve health and resilience.”

“Changing human behavior may sound simple but is exceedingly difficult, especially for behaviors that arise from years of thinking and acting in relatively rigid, routinized ways,” write the authors, George Slavich, PhD, professor of psychiatry and behavioral sciences at UCLA and research scientist at the UCLA Semel Institute for Neuroscience and Human Behavior, and Edmund Neuhaus, PhD, assistant professor of psychology at Harvard. “One emerging strategy for accomplishing behavior change involves using psychedelic compounds to make the mind more malleable and open.”

According to the authors, “psychedelics-assisted psychotherapy” may provide many health benefits and even cost savings, but the current therapeutic approach is poorly targeted.

“Looking forward, we believe that further refinement is needed to operationalize and test [the] components to establish a best-practice standard of care for treating psychiatric, addiction, somatic, and behavioral health problems,” they said.

The authors say their behavioral psychedelics concept is intended to develop “targeted approaches for therapeutic change that help people achieve enduring functional improvements in self-care, social connection, and family, school, and community responsibilities to help them live the life they desire.”

“Psychedelic compounds have the potential to turbocharge the process of transforming the mind, and the race to realize their benefits is in full swing. To maximize these benefits, we believe this work should include behavior as a treatment target with measurable treatment metrics to establish best practices and guidelines,” Slavich and Neuhaus write.

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Materials provided by University of California – Los Angeles Health Sciences. Note: Content may be edited for style and length.

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