skysight-inc/HackerNews huggingface dataset:
We do have some shaky and hard to interpret data.

Published estimates of trial costs from a 2011 systematic review ranged over an OOM.[1]

A 2017 report focused on 7 top-20 companies and 726 studies from 2010-2015 found " median cost of conducting a study from protocol approval to final clinical trial report was US$3.4 million for phase I trials involving patients, $8.6 million for phase II trials and $21.4 million for phase III trials". [2] These are not all that far off from another 2016 study on cost drivers of pharma clinical trials in the US using means and breaking down costs by therapeutic area. [3]

Plugging the first study's numbers into your 1000-drug profile, we'd have:

$ 1.3 billion for Phase 1 failures (370 drugs)

$ 3.7 billion for Phase 2 failures (435 drugs)

$ 1.8 billion for Phase 3 failures ( 82 drugs)

$ 2.4 billion for Phase 3 successes (113 drugs)

That sums to $9.2 billion spent against 113 successful drugs, or about $80 million per successful drug. This implies the full cost of a successful drug is almost 4x what was spend on its development.

One limit here is we're working with medians, not means, and I wouldn't be surprised if this is an underestimate of clinical trial costs.

Roche has had pretty stable net income (profit) of $9.2-$15.2B/year from 2011-2023 against revenue from $49.9-$72B/year in the same time period. Using this estimate, ignoring inflation, if they ran 1,000 clinical trials per year it would account for a maximum of about 18% of their costs and they'd get 113 new drugs out of it annually.

Obviously that is not what's happening: there are an average of 53 FDA new drug approvals per year across the entire industry. If Roche was the only pharma company running clinical trials, the total cost of those trials would be more like $4B, so a max of about 10% of their annual costs. In reality this estimate makes it seem like it must be substantially lower.

The Congressional Budget Office[4] says total pharma R&D spending in 2019 was $83 billion. With 53 new drug approvals per year on average, that implies about an average cost of about $600 million per drug in R&D spending, compared with the $80 million estimate obtained above.

So this makes it sound like running clinical trials account for only about 10% of total R&D spending. Given that Roche's costs alone look to be in the tens of billions per year, as compared to $83B or so annually for R&D across the industry, it also looks like R&D is only a part of the story on cost drivers for pharma companies. Google is not being helpful on this question (almost all the conversation is on R&D cost, it seems), but my guess is it's costs of manufacture, legal, sales, etc.

[1] https://www.sciencedirect.com/science/article/pii/S016885101...
[2] https://www.nature.com/articles/nrd.2017.70.pdf
[3] https://pubmed.ncbi.nlm.nih.gov/26908540/
[4] https://www.cbo.gov/publication/57126
That’s a strawman argument: nobody seriously considers a different language because of a “fancy min/max”.

However, hygienic macros that fix entire classes of issues (including this) is a more compelling argument.

Not to say that it makes the case, only that the strawman you wrote is not good.
Well, turn off JavaScript in Chrome and you back to Chrome being faster. Turning off JS is obviously not a solution when the complaint is that (assuming the same amount of work) Chrome is faster for some JS.
Karpathy is _much_ more knowledgeable about this than I am, but I feel like this post is missing something.

Go is a game that is fundamentally too complex for humans to solve. We've known this since way back before AlphaGo. Since humans were not the perfect Go players, we didn't use them to teach a model- we wanted the model to be able to beat humans.

I dont see language being comparable. the "perfect" LLM imitates humans perfectly, presumably to the point where you can't tell the difference between LLM generated text, and human generated text. Maybe it's just as flexible as the human mind is too, and can context switch quickly, and can quickly swap between formalities, tones, and slangs. But the concept of "beating" a human doesn't really make much sense.

AlphaGo and Stockfish can push forward our understandings of their respective games, but an LLM cant push forwards our boundary of language. this is because it's fundamentally a copy-cat model. This makes RLHF make much more sense in the LLM realm than the Go realm.
It actually looks 1000% worse than generic-brand macOS. None of the copycats get anywhere near the quality.
Why does an announcement like this not have a screenshot of the feature?
It's a tax in all but name.

It's not fair to the taxpayer to have to pay for a broadcaster which is biased against you. Even Media Bias agrees that the BBC is left wing: https://mediabiasfactcheck.com/bbc/ .

State news organizations shouldn't exist because it's impossible to build a one which is unbiased. It will always be biased toward the establishment (which is center left in the UK but varies by country).
Curious about the low-power and sleep mode improvements!
Personally, I’ve switched to kagi. I’m not sure it’s objectively better, but the weird spam results seem to be gone, and I found them so painful I’ve never been tempted to retry an unsatisfactory result from kagi in google.
On the one hand, I completely agree with you (I can prove it with a pile of tools restoring the layout to something more compact), but on the other hand, I am deeply disappointed with the state of current browser experience.

The last innovation that really made a difference for me was the reader mode. I'm sure changing the relationship between tabs and bookmarks would improve things even more, and being able to treat my history as a knowledge store would make web browsing even better.

But even then, I don't want such experiments in my main browser. That's supposed to be dependable. Maybe what I want is a separate browser/profile/mode where features trickle into my main browser after I am comfortable with them.
Home security giant ADT says it was hacked
Elon Musk Has Turned X into His Personal Political Playground
Arc browser does this, you should check that out
Should be applied to aircraft in general, yes.

It is mind boggling just how many things need to work perfectly constantly consistently to maintain safe flight. This goes for both Boeing and Airbus (and Embraer, Cessna, et al.); all of General Electric, Pratt & Whitney, and Rolls Royce; etc.
Could not the main compilers get involved and add builtins so an ifdef makes the common path on the main compilers like gcc use builtins and the slowdown only hurts those using the less mainstream compilers? If it takes off the other compilers would quickly add the feature.
As someone who used to travel regularly between Zurich and Frankfurt (Zurich - Hamburg line ICE) I can 100% tell you that distance is *NOT* the root cause of DB's reliability problems. Infrastructure decline is. From lack of electrification, badly maintained rolling stock, insufficient tracks you find everything. Swiss railways deal with problems like lack of capacity and geography. Deutsche Bahn deals with a lack of maintenance and investment.
> a visually appealing GUI

I think it requires a combination of things: a good taste, a sense of visual design and programming. The first two is more of art form.

Most of the developers on these projects are really good at programming but its rare to get a good combination mentioned above AND willing to work on open source over multiple years consistently.

Update: Also someone in the decision making hierarchy needs to have a keen sense of design. Example: Steve Jobs learnt calligraphy and even though he did not actually designed it he would certainly veto and pass feedback to the developers.
I’ve read an interesting analysis of that situation, or rather the ass-covering culture in government adjacent power structures in Germany: The authors concluded that government agencies and offices are often led by lawyers, and therefore fostered a lawyer-inspired culture—which pretty much follows Conway‘s law. Over time, this has led to a management style overwhelmingly concerned with a fear of liability, and ass-covering instead of innovation.

That rings very true with me as a German.
There are links on how to install this on various distros right on the landing page (section "Try it out on your favorite distro!").

E.g. for Arch this leads to https://wiki.archlinux.org/title/COSMIC
I wish that blog post showed a screenshot of these features so that I didn't have to go download the nightly just to see what they look like.
Seems like the ideal is for group 2 to be producing the DE and working in concert with group 1 who's responsible for the distro. How exactly to arrive at this result is another question.
Yes, just like you also do with Airbus too, and any other plane manufacturers. You already factor in risk every time you set foot in a car, too, and a car is a far more dangerous vehicle. Danger from crashing is an inherent danger in travelling faster than on foot, and when you're on foot you're also facing the risk of being hit by those moving in those fast vehicles.
Yes those langs have large runtimes. But even for compiled native languages, if you have a lot of dependencies you will require containers sooner or later. Go doesn't really have the huge dynamic-linking ecosystem. But, if you do and then project X and project Y diverge on versions... you have a problem.

Also containers can automate deployment easier. Like the line from bare server -> full deployment is much faster if you use containers.
With experience you'll realise that despite things being done safely and carefully, mistakes can and do pop up.
Seriously. I'm genuinely curious what the thought process was that led to this idea.
(2019)

Previous discussion: https://news.ycombinator.com/item?id=20410126 (248 points, 115 comments)
A ridiculous concept — the only people that win in that are the incumbent producers.

“I make a better widget at a lower price than BigCorp” — yet nobody will ever find out about it because advertising that fact would be illegal. Journalists would become supremely powerful and (more) supremely corrupt. Just like radio DJs in the 20th century determined what music sold (and were often bribed accordingly,) the same thing will happen for literally everything. Journalism would become even more like advertising but people wouldn’t be able to tell the difference. I don’t want the equivalent of radio DJs determining what products and services win.

Many professional sports would disappear, Motorsports, soccer, many olympic sports would cease to exist at the highest level. The Olympics themselves would no longer be broadcast (who would pay for it?) Kid’s little league teams would lose local business sponsors. Everything would be pay-per-view assuming the economics worked at all. Newspapers would all shut down. TV stations would disappear. Radio would be limited to small amateur stations — if that because the moment the host mentions a product, service, song, they’d be sued (wrongly or rightly) for potentially advertising. New restaurants would never survive (how will anyone know you exist: Signage and logos are all advertising.)

Basically it would be North Korea with people shopping for inferior state-produced goods at inferior state run supermarkets reading state-approved messages about the greatness of the Dear Leader and his progeny.

Even word of mouth referrals would be subject to lawsuits “can you prove you didn’t get a free cookie in exchange for saying something to your friends about this bakery?”

An absolutely dystopian nightmare.

And if there were an advertising ban, you can bet politicians would exempt themselves from such a ban.
The issue is that trains need tracks. Tracks are very expensive and a limited resource. The stricter you are about time the more trains you can pack into a given amount of trackage.

A bus uses a road and doesn't have a problem like that because there is far more road than the buses need.
> modular desktop environment that allows everyone to develop/choose the basic modules they want. For workspaces, windows, docks, and any other window arrangement and quick access features.

But here you are already assuming that all these developers want to have a modular desktop environment. Not everyone wants that, or workspaces, or docks or whatever.

So yeah, if everyone wanted the same thing, I guess we could end up with one desktop environment that covers everything everyone wants. But (fortunately), the world is more complicated than that :)
This reminds me of how ~25 years ago I wrote little C macro library to perform safe (non-overflowing, and/or saturating) integer arithmetics and comparisons, however the small application I wanted to use it in had the compiler crash after 2-3 hours due to insufficient RAM+swap when compiling a single source file using those macros. It turned out the macro expansions made the translation unit grow to GB size, which must have been 4-5 orders of magnitude over its original size.
Really? The last one resulted in an attempt to send fake electors, a Presidential demand to fake the results (which is apparently legal), and finally an incursion into the final legislative counting.

And before that there have been numerous ways of making voting difficult, from mass striking valid voters from the rolls to intentionally putting too few machines.

I suppose the actual voting machines might be secure but that seems like the least of it.
I regularly use 'split-view' with Firefox with the aid of a window manager, PaperWM (which is a horizontal scrolling WM for GNOME) to be exact. Just drag the tab out of the tab bar and the newly created window is automatically tiled to a sort of 'split-view' right next to the original one.
> I'm just as excited as you are for side tabs, but I don't think browsers need to be constantly innovating their UI.

True. I avoid the 2 largest chromium browsers because their innovations have a goal of exploiting end users.
Correct

I can’t understate the popularity though

I currently work with four Lachlans amongst team of ~20-30
So this kind of "platform independence" approach is something I have been hired to figure out a few times before as a tech consultant

Often a very similar story to yours, what I find that works consistently:

- Start small, don't plan to replace the whole platform in one go, but instead figure out what elements can be separated and replaced individually. Even if this means having to integrate with the existing platform it will be the better approach

- Have a migration plan, even if you are replacing individual pieces of functionality each piece will involve retraining users and have its own quirks, so have a plan not just for the data and tech migration but for the user side of it

- Focus your development efforts in the core of the business, leverage open source and SaaS for the rest – with a rebuild it's very easy to end up going way above budget and time if you focus on the wrong thing, this should also reduce scope creep

- When it comes to onboarding developers the most important thing you can do is document everything as well as you can – that way if developers leave half way through the project you reduce the impact, and new developers will be able to ramp up quickly and overall be less frustrated
So the big companies can spend more and the startups wouldn’t be able to advertise at all. That’s not solving anything.
> was that people on that street were now 50% less-likely to be killed in a shooting.

If shootings were randomly distributed by a mechanical process with uniform distribution among everybody who has the address registered on this street, it would be true. But that's not how shootings work. You confuse a simplifying assumption - that is made for the purposes of modeling, because it's impossible to model the life of every person - with actual reality of what is happening. What is happening is if there's a shootout every day on the street, and you live on that street, and you are a sane person, you would be afraid to go on that street, because the next person shot could be you. And that's the rational behavior, while "I don't care for the shots I hear, these numbers on screen say it's ok" is wildly irrational.

> If you have an area where 1 person every day is killed, and half the people leave, you would absolutely say the quality of life in that area declined. Everyone is twice as likely to die.

Again, no, because shootings aren't a random lottery allocated uniformly by independent metric, like an address. It's connected to your behavior, so if you go to the street where shootings happen, you risk being shot. And how many people are registered on the same street has very little to do with that.

> it's a crazy-good proxy for the thing we worry about – "how likely is crime in this area to affect me?"

And again, it would be, if we were dealing with uniform random distribution. That's not what actually happens - if 100 people live in a safe neighborhood and I have to walk the street where druggies hash out their quarrels - the averages are not going to help me. Remember, Bill Gates walks into a bar... how richer have you just become by sitting in that bar?
I'm praying and hoping they fixed the ADC.
That's true, but give it a few weeks and AliExpress will be full of dirt cheap Pico/ProMicro-compatible RP2350 boards with USB-C.

I recently bought a dozen RP2040 ProMicros with USB-C and 16MB flash for about $2.70 each, and there's variants with smaller flash for even less.

This store, if you're wondering: https://www.aliexpress.com/item/1005006130019224.html
This happens in Liu Cixin's "Three Body Problem" books. Many of the characters experience life in eras starting from the near future, to a semi-utopian era a couple of centuries from now, to when humanity fights the aliens 400 years from now. They go into cold storage and are awakened when there is something for them to do.
> he knows most of his staff would resign in protest, and that would also be the end of SpaceX's government contracts, and thus basically the end of SpaceX.

I agree - it would be completely irrational.

I just think Musk does irrational things from time to time.

There's nothing wrong with that, it's his right as a private individual. I do irrational things myself sometimes.

But if I was at NASA in charge of manned space flight

and you gave me a choice of staking my crew's safety on Musk alone, or Musk but with Starliner as a backup option

I would keep the backup option around
If the executives figure out a way to actually guarantee no ads targeting children, Mr Beast will be crushed.
Evansm7/pico-Mac: Run the popular umac emulator right on your Pi Pico
The Constitution does not mention judicial review at all. Since it's ambiguous, it must be unconstitutional; therefore the Supreme Court must stop doing it. This is the same logic.
Yes. A stronger test would be guessing the results of as-yet-unpublished experiments.
On a Mac I use Rectangle Pro for something similar, snapping my windows next to each other. It's not perfect but it does allow multiple sets of tabs at once.
Yeah, Back to Black (the movie) was really disappointing. Wish they could have done better by Amy Winehouse.
FYI the model is almost 150GB: https://huggingface.co/Qwen/Qwen2-Math-72B-Instruct/tree/mai...
Why? What will we find?
[dupe] More discussion on announcement post: https://news.ycombinator.com/item?id=41192341
In the context of standards used for certification, I would count only flights from before certification was complete.

There was one flight with two crew to the ISS: the same test Starliner is currently attempting.

I agree with your analysis that Boeing does not deserve to have lowered standards. I'm suggesting that neither did Crew Dragon before certification. I'm not suggesting their systems or records are comparable, I'm simply arguing that unproven systems should be tested rigorously before being certified for human-rated spaceflight.
Having been in that situation and developed SW in house as well as hired third-party firms to do so, based on my experience I would go with in-house if 1) you have very specific requirements that need to be well understood and implemented, and which may require close collaboration with the teams who are actually using the SW; 2) the SW in question is mission critical; 3) you want to be able to make changes/adjustments fairly quickly without the overhead of administrative/contractual dealings with a third party (i.e., whether it fits under existing SOW etc.).
DOJ antitrust chief is 'overjoyed' after Google monopoly verdict
OS window managers do a better job of that. Split view inside the browser has some thorny issues around making sure the user knows what resource they are interacting with. There is a lot of complexity when it comes to focus/blur in HTML, CSS, JS, etc.
Why not just do that with your window manager??
They are quite shit and you still need to get dropped off and picked up from them.

Anybody who mentions it online is only trying to win an argument and literally never uses it because it’s shit. You only use it if you don't have a car.
I thought the entire point of the human/expert feedback was in domains where you can not exhaustively search the depth of the space? Yes, if you can go deeper in the search space, you should do so. Regardless of how bad the score is at the current spot. You only branch to other options when it is exhausted.

And if you don't have a way to say that something could be exhausted, then you will look for heuristics to choose more profitable places to search. Hence the HF added.
Adding to this battery fires are glorious. A skyscraper battery fire would end up in the history books. Such a massive storage system must not be anywhere near people and modules must be engineered as compartments to burn themselves out by design so that firefighters need not risk their lives. I like your idea of a vertical shaft. Fire suppression chemicals can at least move downward fast and could be engineered so that gravity takes it where it needs to go in the correct proportions and flows.
No it does not literally say that. It would if the crime were be allocated by a random uniform lottery to every person living in the city. That's not how the crime works.
People are just used to how Apple GUIs look like. I could do the same thing, look at the macOS dock and exclaim that it's ugly because the bottom margin is noticeably larger than the top margin. It's all a matter of taste.
> you do you, but watch your market share always be niche.

As long as I can use the OS I like and how I like, I don't care about metrics like market share.
New batteries are stretchable enough to wear against the skin
Imagine what the equivalent templated C++ code will expand to!
Super Street Magazine Archives – 2002 On
Engineered dust could help make Mars habitable
Well, and then there is Gnome. Where the aesthetics are appealing but the usability is a scornful afterthought.
Poetry Was an Official Olympic Event for Nearly 40 Years. What Happened?
Maybe you are not aware, but swiss trains dont go back to sleep after they arrive at a destination. They stop for 3-5 minutes, and then continue to their next destination. All day long, from morning till evening. Geneve to St. Gallen with like a dozen stops is pretty long way. Especially when you drive it 6 times a day.

Also generally the length of the tracks dont magically change. It is possible to create a timetable: which train should be where when, and then stick to it.

Note that before the DB, SBB were anoyed with some models of french or italien trains, which broke down regularly, putting too much pressure on the integrated timetable.
Yeah was about to say - i3 solves this as well, and does so in a general way rather than each app having its own split pane implementation.

Sometimes I want two browser session side by side. Sometimes I want a browser session next to Gimp or my IDE. Sometimes I want a 3-row terminal with that thing I’m keeping an eye on just below the browser.

i3 to the rescue!
> Some sort of back pressure mechanism is needed to dissuade folks from moving to high climate risk areas

Isn’t that in the gap between $900 and 77bn?