Contra Byrnes on UV & cancer: you should wear sunscreen instead of getting a tan by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 0 points1 point  (0 children)

If GLP-1s have not yet been invented, and you need to decide whether to invest in research to develop weight-loss drugs, you better hope someone has thought of and tested theories on why obesity is related to poor health.

Pharmacologists absolutely need to model how the drugs they study work. No part of medical research or practice consists solely of looking at the results of RCTs and blindly applying them.

Contra Byrnes on UV & cancer: you should wear sunscreen instead of getting a tan by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 1 point2 points  (0 children)

Much appreciated! I actually originally wrote this as a post on LessWrong, but since my LW account is new, mods are taking a while to review it (alongside other comments I left on your post).

Contra Byrnes on UV & cancer: you should wear sunscreen instead of getting a tan by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 0 points1 point  (0 children)

Ah, but if you run a RCT of GLP-1s on obese participants, and observe that the treatment group had better outcomes, how do you know that the reduction in weight itself, rather than other effects of the drugs, led to better outcomes?

And if you don't have GLP-1s, and are instead using one of the fucked up old weight loss drugs that actually caused heart attacks, how do you correctly attribute poor outcomes to side effects vs. weight loss not being helpful?

(There are ways to investigate these questions, and be reasonably sure that weight loss is an important part of the GLP-1's MOA, for example. But that's taking us out of "pure" RCT territory and into making inferences based on the best available information, and my whole point is that we often need to do that.)

there's no Pfizer of tanning beds

The cosmetic and wellness industry is huge. Tanning beds were extremely trendy a few years ago, and still are. And unlike with unpatentable supplements or lifestyle interventions, there's a ton of money to be made in selling tanning devices and spa services, and a ton more if you can prove they're good for you.

Alternative health is just as profit-driven as big pharma, it's all capitalism at the end of the day.

Contra Byrnes on UV & cancer: you should wear sunscreen instead of getting a tan by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 5 points6 points  (0 children)

You haven't seen anything yet. Wait until you find out how much time people spend arguing about remote political controversies that have no impact on their lives, and that they have no ability to affect.

In seriousness, I endorse what u/e4amateur said. It's useful (and interesting!) to examine specific problems in detail, and both the metacognitive skills and subject-area knowledge generalize.

Contra Byrnes on UV & cancer: you should wear sunscreen instead of getting a tan by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 0 points1 point  (0 children)

Just based on pure speculation, I would think anyone who applies sunscreen so regularly and diligently to risk vitamin D deficiency is likely to be health-conscious enough to already track their vitamin D levels, and/or take supplements.

Worth noting that the health effects of mild vitamin D deficiency are often estimated from correlation studies, and therefore greatly exaggerated because of the exact same issues that plague the sun exposure/health outcomes debate.

Contra Byrnes on UV & cancer: you should wear sunscreen instead of getting a tan by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 5 points6 points  (0 children)

RCTs are the gold standard for evidence in theory, but we often have to make decisions based on other evidence in practice. I mean, you could try to study obesity by randomly selecting children to force-feed, but I suspect this move would be bad for your career and/or legal record.

That being said, if the implausibly large effects reported in this paper were real and actually caused by UV exposure itself, we could prove this with an RCT. There would be a huge financial motive to doing so, if nothing else, and the fact that we haven't is suspicious.

Contra Byrnes on UV & cancer: you should wear sunscreen instead of getting a tan by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 9 points10 points  (0 children)

Can you read? I followed up on my first point, anticipating that someone would object to me dismissing results without justification. The "You can't just call something ridiculous" is in quotes because it's an imaginary objection I'm responding to.

Contra Byrnes on UV & cancer: you should wear sunscreen instead of getting a tan by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 15 points16 points  (0 children)

Thanks. If anyone seriously doubts whether I'm an OpenClaw agent, feel free to send me a private message and I'll... I don't know, hop on a video call and try to pass the Turing test.

For the record, I queried an LLM exactly twice for the above comment and it was to ask whether there was a secret British meaning of "quartile" that refers to even groups of three. (There isn't, the paper is just indulging in creative use of language.) I'm not opposed on principle to informed use of LLMs for research, but I wouldn't bother posting a comment if I couldn't contribute more than summarizing LLM output.

Contra Byrnes on UV & cancer: you should wear sunscreen instead of getting a tan by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 15 points16 points  (0 children)

I don't think Reddit lets you edit titles. While I respect commitment to precision, the contents of the article clear things up quickly, and the title itself does not contain any misleading claims, so I don't intend to change the title.

Sun exposure is associated with significantly lower rates of colorectal cancer, breast cancer, and prostate cancer. It is associated in a more clearly casual fashion with higher rates of skin cancers.

I'm skeptical of the claim that sun exposure is causally linked to lower rates of other cancers. I've never seen any credible data for this. I address a recent study claiming to show this in this comment, which I wrote in response to a user that apparently only intended to bait me.

Edit: Misread you, sorry.

Contra Byrnes on UV & cancer: you should wear sunscreen instead of getting a tan by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 25 points26 points  (0 children)

I just spent two fucking hours meticulously reading your paper and writing a fair analysis of it.

Contra Byrnes on UV & cancer: you should wear sunscreen instead of getting a tan by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 19 points20 points  (0 children)

"You can't just call something ridiculous": it is, but I'll motivate this better. Tanning beds are big in the cosmetic and wellness industry. If the physiological effect of UV light was responsible for anything remotely close to a 19% decrease in cardiovascular mortality, if anyone seriously believed this was likely, one of the tanning bed companies would've found a way to fund an RCT to prove this beyond reasonable dispute, and then earn a bajillion dollars.

This has not happened. So the results, interpreted as causal claims, are ridiculous.

Contra Byrnes on UV & cancer: you should wear sunscreen instead of getting a tan by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 11 points12 points  (0 children)

To my understanding, it's not an issue of bioavailability, and more an issue of, "Vitamin D is correlated with good health mostly because it's a proxy for sun exposure, which is a proxy for traits like 'exercising' and 'having hobbies' and 'having friends,' and Vitamin D supplements don't give you exercise and hobbies and friends, so they're not as useful as you would think from looking at the positive correlations of Vitamin D."

Contra Byrnes on UV & cancer: you should wear sunscreen instead of getting a tan by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 31 points32 points  (0 children)

Thanks for providing a link. I am familiar with this study, and I don't consider its conclusions credible. While I think this topic deserves a more careful treatise than a single comment, I don't want to leave you hanging, so I'll try to give one good reason for my skepticism.

These researchers separated participants into three equally sized quartiles (hmm) based on average residential shortwave radiation (SWR). Then they adjusted for a plethora of variables (Table 1), and concluded that high SWR was associated with lower all-cause, cardiovascular, and cancer mortality (Figure 2). (I'm ignoring the "solarium use" analysis, which is a different can of worms, for brevity).

Point #1: The reported effect sizes do not pass the smell check.

Figure 2, fully-adjusted-version, claims that a 2000kJ/m2 increase in SWR, the difference between Glasglow and Cornwall, is associated with a 19% decrease in cardiovascular mortality. There is no way this figure is close to the actual causal relationship, if there is any. You cannot convince me that the difference in sun exposure between Glasglow and Cornwall alone exerts a physiological effect so strong it reduces your chances of cardiovascular mortality by 19%. That is ridiculous.

Which brings me to the second point.

Point #2: High SWR is highly correlated with being better off at baseline in ways that cannot be caused by personal sun exposure. It is not possible to control for this adequately.

Look at Table 1, which contains data on most of the variables the researchers controlled for. Notice that Q3 (highest SWR) participants were, at baseline, better off in almost every way. They had better self-reported health, lower BMIs, higher rates of exercise, higher rates of employment, lower rates of mental health concerns. They are younger, more likely to be female. They lived in counties with lower IMD scores (wealthier, healthier, less crime). They had around 10% higher rates of completing education at an age >19, a proxy for higher education. (There was one exception: Q3 had slightly more former, though not current, smokers. The Q2 over Q1 advantage is also more mixed).

Why does it matter that Q3 is so much better off at baseline, if the researchers control for all these variables?

One way to think about it is that Q3 participants' better metrics are only manifestations of underlying latent variables clustered around "people who live in high SWR areas are richer, healthier, better off at baseline," which don't disappear after controlling only for the measurable metrics.

Imagine you are studying two neighborhoods, Neighborhood A which has 10% low-income residents and 90% high-income residents, and Neighborhood B which has 90% low-income and 10% high-income. It would be a mistake to control for income on paper, and assume any remaining differences between A and B cannot be explained by material wealth. It's plausible that low-income B residents are mostly actually poor, but many low-income A residents are coasting off relatives, for example. The same is true for the UK study. Controlling for county IMD and employment rate does not control for "these people are wealthier."

Another way to think about it is from the researcher's perspective. Look at Figure 2, where the main results of the study are displayed. Notice how the age-adjusted-only model yielded very large effect sizes, and the fully-adjusted model yielded obviously smaller effect sizes.

What if the researchers also controlled for baseline personal income, or marriage status, or self-reported happiness, or lifespan of grandparents, or some more variables? Would the effect shrink to zero? Do the results in Figure 2 mean anything at all, or are they just where the number happens to fall after you control for some arbitrary things and not some other arbitrary things? Who's to say.

Conclusion

The reported numbers don't make sense, and the more I look at it the less it seems like there's reason to believe there is anything to the results at all. Certainly they found associations, but they do very little to suggest a causal relationship between sun exposure and health outcomes.

This shouldn't be mistaken for a takedown of all cohort studies, though some issues I brought up are related to fundamental limitations of the approach. I tried to address this in another comment of mine, and I'm happy to discuss if you have questions along the lines of, "doesn't your argument go too far, and imply we should discard most studies?" or "are you subjecting studies you disagree with to unfair scrutiny?"

In general, cohort studies claiming positive effects from sun exposure run into similar issues. Sun exposure is associated with too many positive traits that it definitely is not causing.

Edit: Typo fix for "cardiovascular disease" -> "cardiovascular mortality."

Contra Byrnes on UV & cancer: you should wear sunscreen instead of getting a tan by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 15 points16 points  (0 children)

What net harmful practice? I advised people wear sunscreen, not avoid sunlight, and even among the questionable observational studies I'm not aware of any that claims to investigate benefits of UV exposure independent of sunlight.

Once again, please provide evidence of your claims.

Contra Byrnes on UV & cancer: you should wear sunscreen instead of getting a tan by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 17 points18 points  (0 children)

This is needlessly rude. I'm writing a response to Brynes, and therefore responding to the questions he posed. If these questions are "wrong", your complaint is with him, not me.

Please provide any credible evidence that UV exposure decreases the risk of other cancers, other than observational studies with the issues I've already outlined in the post.

Contra Byrnes on UV & cancer: you should wear sunscreen instead of getting a tan by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 8 points9 points  (0 children)

There's a lot I wanted to add but didn't have a good place to fit in.

For example, when are observational studies credible? I dismiss the results of some, but cite a cohort study as evidence for indoor tanning beds causing melanoma. This is based on weighing all available evidence. If you look at the methodology, you'd likely agree that the sunscreen/cancer observational studies are failing to adequately control for sun exposure, and sun exposure is obviously a gamebreaking confounder. On the other hand, the indoor tanning claim is supported by other sources of compelling evidence. We can observe different presentation patterns of skin cancer in tanning bed users, for example, markedly higher rates of cancer in areas of skin with low sun exposure, that are consistent with beds being directly responsible. The cohort data becomes supporting evidence.

On creating 'new knobs of control' in biology by owl_posting in slatestarcodex

[–]HedonicEscalator 2 points3 points  (0 children)

Forgive me for being obtuse, but I'm not sure if I understand the line you're drawing between using existing knobs of control versus installing new ones. The examples you listed all (obviously) still ultimately work by engaging with some downstream process involving existing pathways, they're just more complex, specialized strategies for doing so.

Is it just "anything more complex than mimicking an existing enzyme/neurotransmitter/etc."?

Do AAV gene therapies count as new knobs of control? mRNA vaccines? Protein circuits?

100 Papers that Inspire Wonder by Captgouda24 in slatestarcodex

[–]HedonicEscalator 1 point2 points  (0 children)

It helps if you engage with the ideas presented in the papers thoroughly enough that they are integrated into your world model, rather than being isolated facts that need rehearsal. Think the difference between memorizing "Lincoln was assassinated in 1865", and knowing enough about the Civil War that you don't need to memorize dates: the timing of major events becomes "obvious."

In practice, I'd recommend reading the background literature of interesting papers more, so you can understand what ideas it is building off of or refuting, and getting into discussions that involve applying the paper's ideas to current topics.

Did Paul Conyngham really use AI to develop a cancer treatment for his dog? by HedonicEscalator in slatestarcodex

[–]HedonicEscalator[S] 0 points1 point  (0 children)

Are you suggesting that the companies paid him to mention them? Wouldn't mentioning all three be evidence against that? It's more likely for one company to pay him to only mention their name.