Crémieux Profile picture
Feb 20 17 tweets 6 min read Read on X
The biggest news today should probably be about one of the Executive Orders from yesterday evening.

Trust me, it's big.

The President just authorized DOGE to start cutting regulations🧵 Image
This order starts off huge.

Remember those recently-created DOGE Team Leads going into every agency? They're going to work with agency heads and the OMB to review all of the regulations across a number of huge categories.

Which categories? Let's see.

Image
The first category is those rules and regulations which violate the law of the land: unlawful and unconstitutional regulations, things that agencies enacted but which they shouldn't have been able to. Image
Now you might ask: Who decides what's lawful or unlawful, constitutional or unconstitutional, a good or a bad interpretation of statutes, prohibitions, and the law writ large?

Try to keep up, because the administration outlined this a few days ago:
The next category of regulations that DOGE will be purging is sizable.

DOGE was tasked with purging the federal government of socially significant regulations that Congress didn't roll out, and regulations that are costly for private entities without benefitting the public more. Image
This next category of regulations is where things get huge.

DOGE will be purging all regulations that impede innovation and infrastructure, make it harder to response to natural and manmade disasters, and just generally anything unnecessarily standing in the way of business. Image
Now obviously this is a major task, but don't worry: the next section says which regulations to focus on first.

It says to focus on regulations that are particularly important. This is totally logical: get rid of the big barriers to growth first, and then move down the list. Image
The next section might be my favorite part of this whole Order.

This section calls for an end to bureaucratic overreach.

It says that if a bureaucrat is doing more than they're required to, they need to stop it. This means fewer bureaucrats abusing their 'authority'. Image
Additionally, if agencies are currently engaged in overreach in the enforcement of rules and regulations, they're going to stop.

This can also apply to rules and regulations that the President does not want enforced in a given way based on his valid interpretation of said rule. Image
And finally, the Order says what to do with new regulations:

Run them by DOGE, and if they're a barrier to business or a burden on the public, they won't go into effect.Image
Every new regulation will be reviewed and every existing regulation will be reviewed too, and all barriers to growth that can be extirpated from the Federal Register will be extirpated from it.

This authority is expansive and unprecedented, and the admin was building to this.
And just to be sure, there's still more to come.

DOGE is enabling the digitization of records, the installation of modern systems and tools that will enable the U.S. to be governed in a modern, rapid, and flexible way.

That's its purpose, is making a 21st-century government.
And why?

Well obviously because regulations are burdensome, the spending has been too high, and so on, but this Order contains another clue. Image
One of Trump's goals is ending the secret fourth branch of government that persists between Presidencies and ensures Democrats are always in power.

It is an explicit goal of this Administration to end the "Administrative State."
In their Fact Sheet on this Executive Order, the Presidency stated that it is their goal to end the extreme burdens on the American people from this unconstitutional fourth branch of government, and to stop them from prying into American lives forevermore. Image
It is hard to overstate how huge this Order is.

There are hundreds of thousands of federal regulations, and a very large portion of them can be stripped back with executive authority alone.

And now, DOGE has been enabled to start that process, with all that entails.
That entails a lot, but I'll cut myself off here. And keep in mind, this is just the first month of this administration.

Here's the Executive Order: whitehouse.gov/presidential-a…

Here's the Fact Sheet: whitehouse.gov/fact-sheets/20…

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More from @cremieuxrecueil

May 19
The beta blocker propranolol reliably impairs memory consolidation. Image
The above result is for healthy volunteer samples. This is the result for clinical samples.

It's effectively the same picture. Image
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.
Read 5 tweets
May 15
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 🧵Image
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. Image
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. Image
Read 18 tweets
May 14
The association between LDL reduction and coronary heart disease (CHD) risk reduction is sizable and confirmed by

- Prospective cohort studies
- Mendelian randomization
- RCTs

There really is no room to deny it. You can't get clearer than this: Image
The evidence that LDL causes ASCVD is totally unequivocal, and minimizing LDL is essentially a free lunch for cardiovascular health.

Same situation with lp(a), so thank god new therapeutics are here that make both things trivial. Image
On the lp(a) point, if you haven't seen the good news, here it is:

We're going from having zero effective drugs for this to having five seeming to fly through trials and nearing approval and release.

America's top cause of death is approaching being fully preventable.Image
Read 4 tweets
May 14
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🧵Image
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. Image
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. Image
Read 25 tweets
May 13
🇺🇸🇺🇸🇺🇸

America's GLP-1 for weight loss is superior to Europe's GLP-1 for weight loss!

🇺🇸🇺🇸🇺🇸 Image
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.

Novo Nordisk has noticed this fact and is trying to create its own competitor for Tirzepatide and Retatrutide.

Their solution so far has been to work with a Chinese firm on combination Cagrilintide/Semaglutide.

Only problem? It performs no better than Semaglutide alone. Image
Read 9 tweets
May 12
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. Image
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.

The West should not forfeit the future to China.

Read 4 tweets

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