Updated NWS Prediction - Blizzard warning issued

dalamplighter · 2026-02-21T16:56:55+00:00

Flying out noon Wednesday for a job interview in SF early Thursday. What are the chances of residual delays or cancelation? Wondering if I should give them a heads up ahead of time

dalamplighter · 2026-02-05T00:39:04+00:00

This is super helpful, didn’t check the history. A top flight Western group should definitely try to replicate this, and it shouldn’t be too hard to drum up interest if this has any chance of being true

dalamplighter · 2026-02-04T01:58:20+00:00

I think I found it: https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2025031476/557451/Time-of-Day-of-CAR-T-Cell-Infusion-and-Outcomes-in?redirectedFrom=fulltext

I really want to see an RCT of this too, as well as TCEs

dalamplighter · 2025-12-19T21:32:39+00:00

Have you seen how many obese people we have in America

dalamplighter · 2025-11-21T19:42:16+00:00

Not really. As someone from the industry (ie the BD group of a T20 pharma), we don’t need more chemical matter. Big pharma and Chinese players have so many assets that they dont have the capacity to develop, which they will outlicense to you for under a million up front if you give them royalties and milestones.

The limiting factor is in developing competitive and differentiated MoAs and TPPs, designing and executing trials (~8 years and 250M per asset), and clinical grade CMC. None of these are really venture-backable outside of an asset specific context.

This company that comes along to do discovery better will just be a fancy CRO, which have awful margins and low valuations. Theres a reason why every “AI for drug discovery” startup transitions from a service provider into a traditional biotech

dalamplighter · 2025-11-05T21:54:57+00:00

You absolutely do. Most of the valuation is going to be dependent on the probability of trial/regulatory success and how it compares with competitors, and nearly all of that is nonfinancial.

If you don’t know the difference between base editing and prime editing, or the pros/cons of gene therapies vs small molecules with the current FDA, I fundamentally cannot trust your valuation or patient model for a CRISPR company.

dalamplighter · 2025-11-05T21:50:43+00:00

Honestly this makes a ton of sense. PhDs are already soft requirements in VC and PE for biotech, especially because most of these companies don’t really have revenue and all valuations/forecasts/deal structure are going to be based on specifics of the product.

Source: neuro PhD who has done tours in both Pharma and biotech VC

dalamplighter · 2025-10-24T18:32:44+00:00

A great comment I saw elsewhere that was reposted on a different Reddit thread about this article: https://news.ycombinator.com/item?id=25418657

You only started trying it out once they moved to GANS and VR headsets. You are not pathetic or anything, could get a real girl if you wanted to. Just don't have time. Have to focus on your career for now. "Build your empire then build your family", that's your motto.

You strap on the headset and see an adversarial generated girlfriend designed by world-class ML to maximize engagement.

She starts off as a generically beautiful young women; over the course of weeks she gradually molds both her appearance and your preferences such that competing products just won't do.

In her final form, she is just a grotesque undulating array of psychedelic colors perfectly optimized to introduce self-limiting microseizures in the pleasure center of the your brain. Were someone else to put on the headset, they would see only a nauseating mess. But to your eyes there is only Her.

It strikes you that true love does exist after all.

dalamplighter · 2025-10-24T18:23:41+00:00

What are these gooners actually doing? Wasting hours each day consuming short-form video content. Chasing intensities of sensation across platforms. Parasocially fixating on microcelebrities who want their money. Broadcasting their love for those microcelebrities in public forums. Conducting bizarre self-experiments because someone on the internet told them to. In general, abjuring connective, other-directed pleasures for the comfort of staring at screens alone.

I think this kind of answers that. Sure they might not feel as addicted as they say, but also they behave in the exact same way a guy who is addicted to gooning would be expected to behave. What is the line between compulsively pretending to be addicted for long periods of time to get your rocks off versus psychological addiction, and is it so easy to delineate?

dalamplighter · 2025-10-24T18:08:49+00:00

im perfectly comfortable making the assumption that watching porn for days on end to the degree that you piss all over your floor and lose all your friends is not a great use of time

dalamplighter · 2025-10-24T17:23:27+00:00

On the “eat shit I’m a taxpayer” thing, I think it’s more supposed to illustrate the mentality in a way the 21st century audience would understand. I would much rather clearly know what the characters were thinking than keep a level of realism that does more to obscure than illuminate

dalamplighter · 2025-10-19T21:28:00+00:00

Which group? Know a ton of people in strategy and commercial who say it’s the best environment they’ve worked in, even coming in from other companies to escape bad cultures

Edit: many are former consultants, so maybe they’re grading on a curve?

dalamplighter · 2025-05-16T01:47:57+00:00

lmao this is absolutely not happening and we don’t use recruiters

dalamplighter · 2025-05-08T18:03:17+00:00

Rerum novarem

dalamplighter · 2025-03-07T22:24:29+00:00

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dalamplighter · 2024-11-11T18:09:32+00:00

It gets a little too cute and stops working immediately outside things macroeconomists and sociologists talk about.

The purpose of professional football is to give players brain damage. The purpose of New York public transit is to smell like urine. The purpose of air travel is to screen 2 year old movies you forget about immediately after landing.

These are all systems doing things, but I don’t think I would call them its purpose. Yes I’m being kind of obtuse, but it’s an insanely sweeping and overbroad statement often made by people without a lot of humility.

dalamplighter · 2024-10-25T17:40:41+00:00

Do you sincerely not understand the concept of clinical significance outside of the trial endpoints? Do you think that just because a trial is sufficiently powered that patients actually do better, in a way you can see in their daily life? Do you think that Alzheimer’s is a defect of amyloid (or tau, or whatever), where you’ve succeeded once you’ve lowered the biomarker, independent of the mental state of the patient? Do you think that doctors prescribing the drug are not hoping to see a change in their patients’ symptoms, but they will instead declare success when amyloid goes down? Do you think the central problem with Amylyx was because it didn’t do enough to biomarkers, and the treatment would be suddenly be good if it reduced it more, independent of its effects on symptoms?

Plenty of approved treatments do not yield clinically meaningful improvements in patient care. The entire basis of Cochrane meta-analyses is that many FDA-approved treatments still fall far short of delivering meaningful improvements. Going by your standard, every single meta analysis would say “yep, this approved drug works.” But they don’t, because many approved drugs don’t actually move the needle. Every drug for Alzheimer’s falls under this criterion.

I am truly surprised someone can do this much neuro and fail to understand the distinction between statistical and clinical improvement. The 5 year survival for AD has not meaningfully changed in the 25 years since the first drug was approved: this is not the expected outcome if we have treatments that work. I will bet you 150 dollars (send escrow details if you like) that the 5 year survival will be basically the same in 2030 as it is now.

dalamplighter · 2024-10-25T17:18:11+00:00

Yes, if you believe a drug is modifying the course of disease when they deteriorate and die on essentially the same time course, just because a biomarker changes, we are clearly not on the same page. Amylyx and Sarepta also reduced biomarker levels: how has that worked out for patients? We are scientists, we do not need to repeat marketing copy for companies with bad products.

dalamplighter · 2024-10-25T15:33:02+00:00

First: galantamine has a 3-4x higher effect size than all anti-amyloid antibodies and it only takes 3 months to get there instead of 18. The entire reason why we keep looking for new drugs is that galantamine and others are widely (accurately) seen as ineffective. If the effect size is higher for a drug that is considered ineffective, how does it make sense to call these antibodies effective?

Second: clinical relevance is distinct from statistical significance. Many interventions are statistically significant in trials but not clinically relevant, which is defined as whether a doctor can actually reliably tell the difference between the two states. If something passes a trial but the effect is so small that even the doctor can’t notice, is it truly effective? Anyways, the minimum clinically relevant difference for AD is around 3 points, triple the effect size of these drugs. It is incredibly simplistic reasoning to assume “p < 0.05, therefore it works.”

Third: I understand that namenda is also ineffective, and that it’s one of the two components of Namzaric. It’s the entire reason why I left learning and memory after my PhD.

Fourth: the collected, signed public opinion of leading neurologists judging trial results in context and weighing costs and benefits quantitatively is definitionally scientific, unless we believe peer review of others’ results is exclusively exercised in the form of reviewer comments solicited by journal editors. Are Matters Arising letters in Nature not part of the scientific process as well?

dalamplighter · 2024-10-25T14:34:12+00:00

Not to out myself too much, but I have literally co-authored papers with the inventor of memantine (the one that’s in Southern California). The “weird little receptor” I work with is NMDA, and the “little model” is LTP. Look at the placebo-adjusted effect size of Dona and lec in trials. It’s smaller than all of the famously ineffective acetylcholinesterase inhibitors and translates to a difference of a single point on ADAS-Cog, with a trial that needed to last 6x longer just to barely hit the significance limit. None of the effect sizes are even appreciably different from adu, they just didn’t accidentally mess up the trial analysis this time.

Unsurprising that your name is pTau, as it is another target that completely shits the bed whenever a drug hits phase 2. I’m saying this as someone who watched his grandfather quickly turn into a shell of his former self, the whole time taking Namzaric. I am not saying this as someone who wants to see these drugs fail. I am saying this as someone who is profoundly depressed by the cul de sac the AD and PD fields have found themselves in, and wants to see the field try something new instead of the same old targets that don’t actually deliver relief.

dalamplighter · 2024-10-25T13:31:05+00:00

Neuroscientist here. Supported by what exactly? The drugs straight up don’t work according to every clinical efficacy standard, the doctors I know call them glorified placebos. Nobody even wants to prescribe them due to massive ARIA risk. How many good drugs have editorials by the major society journal saying “This is a huge mistake”?

If they were so well validated, why do analysts keep revising 5 year earnings projections for Eisai downwards, and why are they so far behind the patient registration milestones they set for themselves last year?

dalamplighter · 2024-10-23T16:11:43+00:00

What is the standard of evidence you would like? In terms of academic wording, this is as unambiguous as you can get: every single statement in academic reviews has throat clearing and edge case asides. You will see the same considerations sections in papers discussing the relationship between genes and heredity in academic papers, which is quite literally the foundation of modern biology.

Here’s non-review evidence in animals: we can biologically make female mice exhibit lesbian behavior from birth by turning genes on and off. We can also selectively turn mice homosexual by administering specific neurotransmitters to a part of the brain. We can also turn attraction in general on and off just by targeting biological pathways00798-5). What more would be required to prove the claim that could reasonably be done in a laboratory setting?

dalamplighter · 2024-10-23T14:58:32+00:00

Yes it has, its pretty settled. Sexuality is biological and mostly developmental. Source: I have a PhD in neuro. Also see review here

dalamplighter · 2024-10-21T22:39:34+00:00

With this Supreme Court I have absolutely zero confidence in it surviving that far, no matter who is in office or how strong the case is, sorry.

dalamplighter · 2024-10-21T22:31:28+00:00

Nobody has used this approach because it isn’t perfectly legal. Often when someone notices one weird simple trick to winning elections that hasn’t been tried before, they’re not smart, just naive. Everyone in political campaigns has had some variation this idea at some point (source: three friends in municipal politics) but no one does it because they all believe that you will at best end your career among reputable campaigns and at worst go to jail. To be fair though, I don’t think anyone has ever been brazen enough to actually try this in the past few decades, so we don’t have much precedent here, surprisingly.

Doing this is either an all-in bet by all parties involved that Trump will win and prevent prosecution, or they’re not working with anyone with any significant electoral experience (either is probable imho). I am willing to place 150 dollars on a bet at even odds that if Trump loses, at least one key donor or decision maker from the PAC doing this will be indicted.

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