I've been working religiously for like 2 years on the jedi academy codebase which is c & c++. It's Ravensofts variant of the idtech3 engine and it's insane how fragile the games combat is to precision and timing changes, I can't get away with adding much without destroying the lightsaber combat qualities. There are certain spots where I can't even add an incrementing i++ counter lmao it presents just enough of a slowdown or shifts something around that I haven't been able to track down that bleeds into the rest of the gameplay, but I am also sticking with the ancient compilers from 22 years ago so as to preserve the fpu characteristics of the game. There are some modern attempts at using this codebase with modern tooling but they've kind of bastardized/refactored all of it and it just feels different/unbalanced wrong. idtech3 is such an incredibly foray into c it's really something else and carmack and team really sent it back in the day.
ravensoft open sourced it in 2013 ish and promptly removed it because they accidentally included a bundled lib but i believe it was then re-added. theres quite a few repos that have it cloned. https://github.com/jedis/jediacademy
what am i up to with it? creating hardened vanilla base servers (no mods) and ensuring it gets compiled in a way that doesnt impact lightsaber combat. everyone has failed to do this for 22+ years because there's lots of subfactions in this game who fail to prioritize this as they have other priorities. tons of people who enjoy the prospect of modding the game or making it something different but the tiny remaining competitive player base has only ever needed the base game and what shipped by ravensoft in 2003. generally the guys who are competitive players arent.. coders. the game is ultra sensitive to mathematical FPU differences and virtually all recompiles of the game in the past decades completely failed to guard this, so every game mod and attempt at creating something better hasn't stuck for competitive players _except_ for something called ybeproxy which was an attempt to hook the original game engine binary and add some security/anticheat layer.. this was the best attempt to date but it still negatively impacts the fragile lightsaber mechanics.
That's so cool! I didn't know they open sourced it. Is your work also open? And how do you check that the frames don't change?
I love seeing people try to revive old games and improve them for players. I've made a couple of contributions to VCMI, an open source implementation of heroes of might and magic 3 that I used to play as a kid and it's so rewarding seeing people use those.
Only about 10% of cancer patients respond to immunotherapy at the moment. While it's great when it works, we have a very long way to go in improving outcomes.
Whilst this might be true in general melanoma does respond particularly well to immunotherapy with 5 year survival rates in excess of 50% for advanced (metastatic) disease and a subset of patients effectively cured.
I'm just a layperson in this and could be wrong here, but my understanding is that cancer tends to survive by accumulating complementary pathogenic properties that individually are of little threat to the body. One of these properties is increased expression of ‘programmed death ligand 1’ (PD-L1), a surface protein on the cancer cell that binds with ‘programmed death protein 1’, a person on the surface of T-cells that, when bound, inhibit the T-cell response. I could be wrong here as well, but most immunotherapies today are of the 'checkpoint inhibitor' variety, which interfere with this binding process in one way or another.
To me this is similar to removing an invisibility cloak from the cancer cells. Now the immune system gets a shot at these cells b/c there's nothing indicating otherwise. In the case of some cancers, like melanomas and some lung cancers they may look sufficiently broken that the immune system just kills them naturally. But if the cancer cells still resemble healthy tissue, it's not super clear to me what is going to provoke a kill response.
I do think it's likely we will ultimately have customized therapies in which cancer cells are extracted, unique features are identified and custom mRNA packages created to emulate those features sufficiently to provoke the immune system to kill them. That, in combination with checkpoint inhibitors, would likely create an effective response.
Wow, what a diverse body of work. Could you give an example of a paper that you feel fits your description of having "almost never even been properly formulated before"?
Indeed, for example this page [1] is absolutely fantastic, it hits a lot of right buttons in my case (history of railways, history of finance/economics, a combination between history of railways and the history of finance, which is even more interesting).
Making a video game about symbiosis, metamorphosis, and mutation, all wrapped up in a tower-defense/strategy-like package, called Chrysalis. https://metamorph.games
A miraculous breakthrough could be on two fronts: artificial "meat organs" for those whose life is at immediate risk and need a transplant, and regenerative biotech/medicine to repair those with damage without requiring surgery.
Either way, implanted devices can be a good bridge from our current situation.
And they are. One of the other 6 finalists were doing "Genetically-engineered pig kidney xenotransplantation". The idea is to "Genetically engineered pig kidneys that will increase the supply of transplantable organs by eliminating the antibody barrier to xenotransplantation."
In our local district, rather than have individual buses for elementary, middle school, etc., they are having one driver pick up the elementary kids, drop them off, the go back out and pick up the older kids. They had to change the start times for elementary and high school to make this work, and they're also paying the drivers more, but it seems to be working. One issue is that if a single driver goes down (illness, etc.) it's a huge hit to logistics, and subs are hard to come by. But mostly they've made it work.
If you have a plan and motivation, go for it. Assuming you need to make money, you can either be self employed, in a partnership, or employed by someone else. The first requires you be a good business person, which is not a common innate trait but can be learned to some extent. The second is often a great option if you have equally motivated partners with complementary strengths. The third usually requires some sort of signalling to get employers to hire you. Having a degree is part of that signalling. This is, of course, completely ignoring that some professions require a degree, like being a doctor, which is rewarding work. As a teenager, you often have no idea what you will find meaningful and rewarding later in life, making this type of decision quite risky.
This isn't a randomized controlled trial, so I wouldn't put much stock in the results, although it should provide a catalyst for further study (if it hasn't already).
Fetishizing RCTs is a source of much harm in medical policy.
A correctly-designed RCT can give more confidence in a result, particularly to non-statisticians, but very large effect and cohort sizes should not be ignored. We could tell just from the topical statistics that smoking was a major cause of lung cancer and other harms, despite the tobacco industry insisting nothing was proven.
Typical RCTs with only a few hundred patients deliver much less resolution than this result. We do still need trials to home in on the molecular agent, but Tdap is already proven safe, and wise to stay current on, so it would be foolish to "wait and see". If it turns out Tdap (e.g.) protects only some patients from dementia, you are anyway safe from tetanus infection.
It is similar to the case where arginine supplements appear to cut epithelial tissue side effects of SARS-2 vaccines. It needs more study, but arginine is cheap and perfectly safe, so starting immediately to administer arginine supplements alongside vaccination is the prudent course.
Some RCTs even yield spurious results, as a consequence of poor design or execution, such as those lately promoted as showing that anti-depressants have no effect.
"Fetishizing" RCTs (i.e. realizing their importance) is a source of no harm, because it is the best design we have to determine whether some intervention actually helps people live longer or better. Effects from other kinds of studies should of course be weighed accordingly. Fetishizing observational/non-random studies is the source of harm. Taking the Tdap is very unlikely to hurt you, but calling this single study "astonishing" and implying that it indeed shows a 40% reduction in risk (it doesn't) is hyperbolic.
If you aren't astonished, you're not paying attention. This study was conducted over six years, on two independent cohorts, involving tens of thousands of patients.
A moment's consideration shows why an RCT to check tobacco smoke and lung cancer was impossible. We are nonetheless 100% confident, in the entire absence of an RCT, that smoking does directly cause lung cancer. The sort of fetishism you promote is exactly what delayed institutional recognition of the fact, by decades.
Ask any professional statistician about failure modes of RCTs. Be prepared to listen for a long time. Instead of worshipping blindly at the altar of RCTs, we should pay attention to what actual statisticians have to say about actual results.
Judea Pearl, in a recent book, "The Book of Why", provides a readable, in-depth exploration of statisticians' fundamental relationship with causuality, and the historical development of statisticians' decades-long loss of their ability to form conclusions from observational data, and their recent recovery. We are all healthier now that we know how and when we may confidently act on results of observational studies, without fetishism.
And yet, due to its design, it is still entirely plausible that there is no, or very little effect. We just don't know.
The reason institutions delayed smoking has nothing to do with RCTs and everything to do with regulatory capture and corruption. Even in the presence of RCTs (which wouldn't be ethical, of course) this still would've happened.
That RCTs have failure modes does not change the fact that they are the best we have in the face of confounding variables - they simply require good design. This claim about Tdap is not like smoking...we don't have the same understanding of the underlying biology nor the massive effect sizes from other studies.
I have read the Book of Why and Probabilistic Reasoning in Intelligent Systems. There is nothing within those books to indicate animus against well designed RCTs. Rather he advocates, as I already did, for intelligent combination of sometimes sparse RCTs with the large N of observational studies.
Your wholesale invention of "animus against well designed RCTs" anyway explains your impassioned defense of fetishizing RCTs. I have never encountered any such animus, and doubt you have, either.
You reveal that you missed that Pearl spells out circumstances where observational studies do suffice to demonstrate what you insist requires an RCT.
And, you show you missed the entire section on the historical events that led to your and others' continuing fetishization of RCTs as the only possible means to demonstrate causation, and their lack to make any such demonstration impossible, which you continue to insist upon, against reason.
Your late admission that RCTs may be poorly designed, and thus fail to demonstrate what they claim, contradicts your previous fetishistic insistence on RCTs' infallibility.
