This paper's core idea is based on the assumption that circulating LDL is the cause of heart disease. That assumption is false.
Taking satins is proven to reduce heart disease rates, but there are lots of other drugs that lower LDL... many with much more efficacy than satins.
These non-satin drugs do not reduce heart disease rates significantly.
There something else going on here. High LDL is correlated with the development of heart disease, but it does not cause heart disease. Satins do reduce the risk of heart disease and they do reduce LDL, but their positive effect on heart disease rates is not caused by reduced LDL.
There are multiple independent risk factors for heart disease. The major ones are:
- LDL / ApoB
- Blood pressure
- inflammation (hs-CRP)
- Insulin resistance (HbA1c)
- Lp(a): strongest hereditary risk factor.
- eGFR: a measure of kidney function
Non-statin drugs like PCSK9 inhibitors have been shown to reduce heart attacks, strokes, and other cardiovascular events on top of statin therapy. One randomized control trial was FOURIER in 2017: https://www.nejm.org/doi/full/10.1056/NEJMoa1615664
Across different genetic variants, lower lifetime LDL -> lower risk of death. Check out figure 3.
The causality of LDL -> plaque buildup -> 55-60% [1] of heart disease related deaths is also well understood, so it seems clear to me that preventing plaque buildup in the first place prevents over half of heart disease related deaths.
Would like to know if you disagree, "Minimize LDL at all costs" goes current mainstream medical guidance, so I'd like to disconfirm my beliefs if possible.
Graboy has provided the citation I would have given, as well as an excellent explanation. I’m not sure what you mean by “heart disease is clearly not Mendelian”.
My browser underlines the word statin to indicate a misspelling, but does not underline satin. We've been trained to believe the computer is always right when it flags an error, but unfortunately it's not 100% accurate.
Think of heart disease as slow, long-term damage to the cardiovascular system, and cholesterol is what the body uses as a bandaid.
If you have a lot of LDL cholesterol available, your body will use a lot of it, and you'll have stiffer arteries. If you don't have much available, it takes longer for the bandaids to build up.
This is one of the reasons statins reduce the number of heart attacks, but don't always seem to reduce all-cause mortality.
The band aid analogy doesn’t make sense when we consider the MR studies showing the lower your genetically determined LDL-c, the lower your risk of CVD. If everything was randomised except the number of band aids, why would having fewer band aids result in lower CVD risk?
> This is one of the reasons statins reduce the number of heart attacks, but don't always seem to reduce all-cause mortality.
That’s one potential explanation, but I don’t think it’s the most likely one. We tend to see non significant ACM in smaller, less powered trials, or those with lower LDL-c lowering. ACM is simply a less sensitive endpoint - if you have a treatment that reduces CVD incidence, then the “CVD incidence” endpoint will give you significant results with fewer CVD event differences between study arms compared to ACM since your power to detect differences is diluted by other fatal events that aren’t affected by statins (cancer, motor accidents etc).
I bake bread. I have spent a good deal of time optimizing the recipe for deliciousness but also for time efficiency. Proving in a warm oven is a great tip. Also baking two loaves at a time!
All this nit picking about writing style is disappointing. I like that this person got their ideas out there. They are good ideas. Legible and easy to parse == good enough. I don't care about the writing style any more than that and you shouldn't either. It is a waste of everyone's time... yours especially.
It's very nice to hear about someone else who is interested in doing hard things/real things. Seems like there ought to be a meet up or a get together opportunity for people working on stuff like that. Perhaps a get-together where everyone gives a 2-5 minute talk about something they are working on then we all hang out for another hour or two. Seems like alcohol might help get the wheels spinning?
I fully appreciate the need for a catchy headline with a hook (it got me!) but I wonder if these ideas would be more powerful/useful if expressed in positive language rather than doom speak? I guess doom speak is the fashion these days and we all have to conform to the dominant paradigm... at least a little around the edges.
I really enjoyed the piece also, in spite of the off-putting writing style.
It reminds me of the Epicurean hierarchy of desires, the genius Epicurus had it figured out more then a couple of millenia ago: https://en.wikipedia.org/wiki/Epicureanism
The thing about "apps for one" actually resonated with me quite a bit.
The last year I've struggled finding freelance work and I've found myself with more time (and less money) that I would like. I feel guilty, because one side of me feels like I should have spent this time to learn ML or to make an app that makes passive income. The thing is: I have no interest in making "apps" to make money. I wouldn't even know what app to make, because there is no quotidian problem for which I think an app would make my life easier. On the contrary, I don't have a smartphone and apps are making my life harder, as we move towards a world where apps are expected for everything. But instead, I have made a couple of games for my girlfriend's birthdays, and I also made her web portfolio, all forms, I guess, of "apps for one" made for love. Other than that, perhaps, I enjoy tuning my Linux system (recently migrated from Xmonad to Hyprland), a form of making, perhaps, an app for one, in the only tech device that still feels like I can control instead of it trying to control myself. Other than that, I use my time to go to the gym and sometimes to paint or DJ or just party, even though I often spend on Hacker News, Youtube, Wikipedia and other media way more time that I would like to.
So all in all, I find it difficult to write code these days with the joy of when I was younger, and it is hard to motivate myself if there's no money involved, with the exception of those gestures of love. It saddens me, because I believe it is such a powerful and beautiful skill. But I just find the current state of world and how "technology" is used to extract capital out of all human relationships rather depressing. The current wave of "AI" only makes the problem worse, and adds an dark sense of impending doom...
It’s not just like that to be spaced out visually. It suggests slowing down, taking your time, digesting each sentence. Not just racing to the end so you can drop a thin take and keep scrolling.
HN particularly has this "let me critique their writing style and write them off because of it" kind of undercurrent to every blog thread.
I guess it's just the way programmers operate, the text is just code, and they don't like the way it's written. Or, some tendency to boast how it should have been written.
there are waves of people like us. it's the zeitgeist of the era for a sub-category of coders/hackers.
i, too, started baking sourdough bread. and DIY, electronics, music for myself.
i suspect a double digit percentage of that subcategory also dabbles in lisp/clojure/emacs and another double digit subsection abandoned AAA for indie gaming. and a single digit percentage might have enjoyed ruby in the old times.
I asked my agent to rewrite this in a more traditional style, if it's helpful to anyone:
A defining experience of our age is a paradoxical hunger: we crave more even when we have an excess, and we crave less while more accumulates around us. It is a vague hunger we often can’t articulate, a deep sense of wanting something fundamental. This is the essence of "thin desire": a craving for something undefinable and ultimately unattainable, from a source with no interest in providing it.
The distinction between "thick" and "thin" desires is simple: a thick desire is one that changes you in the process of pursuing it, while a thin desire does not. Consider the desire to understand calculus versus the desire to check your notifications. The desire to learn calculus is thick; it transforms the learner, revealing new patterns in the world and expanding their capacity to care about new things. The desire to check notifications is thin; afterward, you are the same person you were five minutes before. A thick desire transforms its host; a thin desire merely reproduces itself.
The business model of most modern consumer technology is to exploit this distinction. It identifies a thick human desire, isolates the part that produces a neurological reward, and then delivers that sensation without the enriching substance. Social media offers the feeling of connection without the obligations of friendship. Pornography provides sexual satisfaction without the vulnerability of partnership. Productivity apps can give a sense of accomplishment without anything of substance being accomplished.
This thin version of desire is easier to deliver at scale, easier to monetize, and far easier to make addictive, resulting in a cultural diet of pure sensation. Yet, despite getting what we want with such efficiency, we are not happier. Surveys consistently show rising anxiety, depression, and loneliness. Perhaps we have become so proficient at giving people what they want that we have prevented them from wanting anything truly worthwhile.
Thick desires are inherently inconvenient. They cannot be satisfied on demand and often take years to cultivate. Mastering a craft, reading a book slowly, or becoming part of a genuine community requires sustained effort. These pursuits embed us in webs of obligation and make us dependent on specific people and places—all of which is pure inefficiency from the perspective of a frictionless global marketplace.
As a result, the infrastructure for thick desires—workshops, apprenticeships, local congregations, front porches—has been gradually dismantled. In its place, the infrastructure for thin desires has become inescapable, residing in the pocket of nearly every person. Grand programs to "rebuild community" often fail because they try to apply the same logic of scale they hope to escape. The thick life, however, doesn't scale. That is the entire point.
The antidote, therefore, may not lie in large-scale movements but in small, deliberate, and beautifully inefficient acts. Bake bread; the yeast is indifferent to your schedule, and the process teaches a patience that the attention economy has stripped away. Write a physical letter and send it through the mail; it creates a connection that exists outside the logic of engagement metrics. Code a software tool for just one person; building something that will never be monetized is a beautiful heresy against the assumption that all creations must serve millions.
These individual acts will not reverse the great thinning of our culture. But the thick life is worth pursuing anyway, on its own terms. The person who bakes bread isn't trying to fix the world; they are simply trying to spend an afternoon in a way that doesn’t leave them feeling emptied out. They are remembering, one small act at a time, what it feels like to want something that is actually worth wanting.
To put it politely, nobody gives two shits about what "your agent" said, in case you were wondering why this was downvoted to hell. This reply adds nothing to the conversation, and it also doesn't take a mastermind to figure they, too, can paste the post in ChatGPT and get a summary out of it. Also, reading a summary instead of the sources butchers the post entirely.
Hopefully you'll spare us the spam next time. Have a good day!
There are so many great reasons to distrust "The Science"... perhaps the greatest is that without powerful and persistent skepticism, science simply isn't science. Questioning and skepticism is profoundly fundamental to the scientific process. "Trust the science" or worse yet "Believe the science" are statements that are about as destructive to the foundation of science as one can get.
The whole point of science was that everyone has access to the true nature of the universe which we can discover through theorizing and experimentation. Empirical experience is the great equalizer that puts the Arch Duke of Where-and-What or the Highest of High Priests the on the same footing as, say, Joseph Preistly or Benjamin Franklyn. Questioning and skepticism must be accepted from all quarters. To say that only the most select, distinguished and credentialed can be admitted to the discussion smacks of priesthood and aristocracy.
The argument that we need to re-persuade the people to trust in science is missing the point by such a wide margin as to be a symptom of the problem.
It is more or less the same as fretting that people aren't going to church so much any more.
The science should not be trusted. The science should be tested. Those who say "Trust the science" have completely lost the thread.
Ammonia will (and does) leak into the environment where it becomes a part of the natural nitrogen cycle. The end result of the natural nitrogen cycle is N2O (aka laughing gas) which is a greenhouse gas 250-350x more powerful than CO2.
Running the world on ammonia, even if logistically possible, will likely accelerate climate change, not slow it.
This is an excellent question. Firstly, there are some very major differences between bringing a species back from extinction and saving a species from extinction. Perhaps the most radical difference is cost, with resurrecting an extinct species being likely impossible but best case costing at least 4 orders of magnitude more.
If the cost of a chicken egg was $10,000 it would likely not be worth the trouble. At $0.15 or $0.60, though, chicken eggs provide an excellent value and are nice to have around!
The real question here is why intervene to keep a species from extinction? The answer is that genetic diversity is massive valuable. The trouble is that the value assessment is very hard to calculate concretely and that value is also very hard to extract in the form of direct profits.
Let’s take the banana as an example.
The global banana market had sales of about $140B in 2023… clearly people value bananas. Today 99% of global trade in bananas is in a single variety, the “Cavendish” banana. But it was not always so. Until the 1950’s the world’s dominant banana was the “Gros Michel”. Over the course of the 1950’s the Gros Michel went commercially extinct as a result of “Panama Disease”. Researchers scoured the world to find a banana not susceptible to Panama Disease that could replace the Gros Michel in commerce. What they found is the Cavendish.
Today, a new strain of Panama Disease has evolved to target the Cavendish. Extinction of Cavendish is proceeding more slowly than that of the Gros Michel, but it seems more or less inevitable at this point.
The fact that we are likely to see 2 varieties of banana go commercially extinct within a single century, is kind of nuts. It seems that the half-life of a commercial banana variety is less that 50 years. The only reason we still have commercial bananas today is because of the rather deep genetic diversity in bananas the earth continued to possess in the 1950’s. That genetic diversity is significantly diminished today.
If we value the banana market as a perpetual annuity with the 2023 growth rate of 7% and a discount rate of 3%, the net present value of the banana market to the citizens of the world is approximately $3.5 Trillion.
How much is it rational to spend preserving this perpetual annuity? Anyway you slice it, the answer is very big… and very much bigger than is currently being spent to preserve the genetic diversity of the banana today.
What was the value of the American Chestnut tree? Hard to say, but it is clear that the loss was massive. I've read estimates that the American Chestnut provided (as fodder) something like 10% of the energy for the pre-extinction American transportation system as well as a substantial winter food source for all kinds of livestock, game and people. Just as transportation energy the yearly value of the American Chestnut would have been about 2% of US GDP.
None of these joints is novel in the slightest. Still, is it awesome to have them so well documented. Additionally, the CNC makes them much much easier to use!
If the glue has failed, there are some serious craftsmanship issues regardless of the joint type.
With the exception of the joints labeled "...with key" these joints are all very remote from the types of joints used in traditional Japaneses temples which do not use glue.
These are mostly western style joints, which are also very beautiful and useful, but generally expected to be assembled with glue.
Agree that you "can't expect the glue to deal with the forces"
A good craftsman would not choose a joint that would see such high stresses.
Additionally if the glue is chosen and applied properly, the wood that the glue adheres to should fail long before the glue.
That said, glue is not as simple as it may seem. There are many different types and proper surface prep and application makes a huge difference to ultimate strength.
For example, many people will mix 2 part epoxy until it "looks mixed" which for a clear epoxy happens pretty quickly. In truth, the resulting bond strength is far more closely related to the amount of mechanical energy that has been transferred into the mixture than the visual uniformity.
Lots of ways to go wrong with glue... but a good craftsman should be well aware of these.
This goes against the conventional wisdom that a properly glued wood junction is stronger than the wood itself, and that under such forces it is the wood that will fail.
The wood would've failed at the same place if you'd carved a whole chair in that shape out of a solid piece of wood. The problem is that the design concentrates forces at the joint (or the "junction") in a way that no material can withstand.
Taking satins is proven to reduce heart disease rates, but there are lots of other drugs that lower LDL... many with much more efficacy than satins.
These non-satin drugs do not reduce heart disease rates significantly.
There something else going on here. High LDL is correlated with the development of heart disease, but it does not cause heart disease. Satins do reduce the risk of heart disease and they do reduce LDL, but their positive effect on heart disease rates is not caused by reduced LDL.
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