There are people who desperately want this to be untrue🧵
One example of this came up earlier this year, when a "Professor of Public Policy and Governance" accused other people of being ignorant about SAT scores because, he alleged, high schools predicted college grades better.
The thread in question was, ironically, full of irrelevant points that seemed intended to mislead, accompanied by very obvious statistical errors.
For example, one post in it received a Community Note for conditioning on a collider.
But let's ignore the obvious things. I want to focus on this one: the idea that high schools explain more of student achievement than SATs
The evidence for this? The increase in R^2 going from a model without to a model with high school fixed effects
This interpretation is bad.
The R^2 of the overall model did not increase because high schools are more important determinants of student achievement. This result cannot be interpreted to mean that your zip code is more important than your gumption and effort in school.
If we open the report, we see this:
Students from elite high schools and from disadvantaged ones receive similar results when it comes to SATs predicting achievement. If high schools really explained a lot, this wouldn't be the case.
What we're seeing is a case where R^2 was misinterpreted.
The reason the model R^2 blew up was because there's a fixed effect for every high school mentioned in this national-level dataset
That means that all the little differences between high schools are controlled—a lot of variation!—so the model is overfit, explaining the high R^2
This professor should've known better for many reasons.
For example, we know there's more variation between classrooms than between school districts when it comes to student achievement.
The beta blocker propranolol reliably impairs memory consolidation.
The above result is for healthy volunteer samples. This is the result for clinical samples.
It's effectively the same picture.
This result holds up to corrections for publication bias. In fact, there's barely any evidence for publication bias, and trim-and-fill does nothing here.
So I'm reasonably confident in the memory formation impairment effects of propranolol based on this evidence.
Today the New England Journal of Medicine published the second big win for lifesaving N-of-1 gene therapies.
They might have just saved a baby's life from being snuffed out by a fatal, ultrarare metabolic condition.
This is good for the baby, but maybe for many others too 🧵
The deficiency the baby was born with is carbamoyl-phosphate synthetase 1 or CPS1 deficiency.
CPS1 is a mitochondrial enzyme that is involved in detoxification during the urea cycle. If you lack it like this baby, you tend to see hyperammonemia (ammonia buildup) right away.
This buildup is typically but not always deadly.
Roughly half of those who develop the condition in early infancy end up dying from it.
And for those who don't, the result is usually not a good life: dialysis, mental retardation, liver transplantation, restrictive dieting, etc.
People might be able to limit the side-effects of GLP-1 drugs by avoiding Ozempic/Wegovy and instead using Mounjaro/Zepbound.
The reason has to do with Zepbound's other ingredient besides GLP-1: GIP🧵
GIP is short for either gastric inhibitory peptide or glucose-dependent insulinotropic polypeptide.
It was originally called gastric inhibitory peptide, but people now prefer the 'insulinotropic' name because the gastric stuff rarely happens in normal circumstances.
Basically, it's an inhibiting secretin hormone that holds back gastric acid secretion somewhat and stimulates insulin secretion a lot.
The timeline of key discoveries undergirding GIP's therapeutic potential is quite long and leads all the way back to the 1970s.
If you've been following along, you already knew this.
Tirzepatide (Zepbound) and Retatrutide (no name yet) add GIP and GIP + Glucagon, respectively, making them more effective products. Not only that, but they might even have milder side effects.
Pharmaceutical R&D is on death's doorstep and its current rebound is fragile and temporary.
Returns are already below the cost of capital, and any additional harms to profitability will drain the life-blood of the future, instantly snuffing out biomedical progress.
I am talking about the engine of survival, the thing that explains so much of why so many of us are alive today, and the thing that will keep you alive in the future.
This is also the thing that might eventually bring you immortality.
Destroy it, and we all lose.
Attacking pharmaceutical returns right now is also a form of redistribution of future returns to a state enemy, China.