But I had a similar though with newspapers. There are quite a few I like. Yet, there are more articles in one that I can read - especially when I want to have other sources as well. So yeah, if there were only a handful of good blogs, it would be the case. But there is a long tail of interesting stuff there.
Anyway, even for the Hacker News, I would like to filter a bit, so to have feed like the hackernewsletter (which I like a lot), but profiled more to my tastes.
Our middle school has banned phones during school hours, and it's been great. Even though most kids own phones and have them in their backpacks, they aren't seen. There are less problems during classes and kids have to talk to each other during lunch instead of going head down in their phones. Parental pushback has been really minimal - most parents love it, and it's good for the kids.
Making no phones a blanket policy in all schools should be an absolute no-brainer.
it's all good until that thing that happens at American schools, happens... That is my one hang up here. It would be idealistic to believe that the Police would protect kids, but in reality there are far too many cases of them being grossly negligent in this exact circumstance... in many of those cases, having a phone played a pivotal role in security. I don't want to get too far into details on HN for the sake of keeping things civil, but I hope you catch my drift.
Im sure there is some happy medium solution here, like putting your phone in a basket or cubby or something like that, at the very least. But I think this is something that has to be seriously addressed and considered. Phones are obviously bad for all of us, more so for children whose minds are far more elastic and far more prone to social alienation. The endless stream of notifications is almost at a gambling / casino level. I think you have to address the root cause of that as well
Between teachers phones, intercoms, cameras, and hardline phones there should be plenty of communication equipment available for a crisis. If anything having a phone could put someone in jeopardy by making noise and giving away position or distracting owner. What is the scenario that it has helped? Have police coordinated response based upon students phoned in reports and telemetry?
>Between teachers phones, intercoms, cameras, and hardline phones there should be plenty of communication equipment available for a crisis.
How does that stuff help when the kid isn't actually at school, but is between home and school somewhere? If the kid can't bring the phone to school at all, then that means the kid can't have the phone on the way to school either. Allowing the kids to bring phones but lock them up during school hours would solve this problem though.
Also, this is US-specific, but what if there's a school shooting? You don't want someone's kid to be able to call their parents and say some last words to them before they're brutally shot, while the entire town's police force is simply standing outside and preventing anyone from entering?
This is the policy at my kid’s school. In fact if a student is caught with a phone then the phone is confiscated and only the parent can pick it up from the office.
Not really. There have been phone calls to 911 during school shootings but reading a few reports, it's never made a difference since schools tend to be hardwired straight to dispatch which is most important. Big failings like Uvalde has been terrible response by first responders which is "Push forward till threat has ended."
Yes, parents have been called by students during incident but that generally makes situation worse as parents run to the school causing delays for first responders.
I was in an American school when 9/11 happened and the school was trying to punish students for calling their parents who worked in the towers to see if they were still alive.
Fucking dictatorship we are in. Let people use technology, especially in an emergency.
Or live in a country where the last school shooting was more than 25 years ago?
Seriously this is such a weird comment. You don't want to say "school shooting" at risk of being uncivil but you think kids should always be prepared for a live gunman to walk into their lives. From my perspective, that's the uncivil part of your comment.
People can vote for things all day but that doesn’t mean anything could be implemented that would guarantee the end of school shootings. We’re talking about a country with estimated an estimated half billion guns in circulation and plenty of those undocumented.
More realistically the phone would be good for calling for advice after you get molested by a teacher. a million times more likely than getting shot. If it's so bad, why not just homeschool?
At any given time, I'm working on like 10 different projects. tmux lets me set up sessions for each of these projects, so that when I leave one and come back in a week, all the context is there (multiple windows, bash history, working directories I was in, etc)
Since I work with big biological data, most of my work takes place on our university cluster, which means my laptop is just a dumb terminal and all of the action takes place on the server. IME, tmux is especially powerful with coupled with mosh, which gives a persistent SSH connection. That means I can be in the middle of a project, close my laptop lid, go home, then later that evening, open my lid and everything is reconnected and just right there. Same if I reboot my laptop - one command to reconnect my terminal with mosh, and I'm back in the middle of my complicated multi-window project.
What happens when you press page up or down in tmux? Have you configured it to scroll page up & down? Or do you do that via Ctrl-B ] or whatever the magic incantation was?
The first line is a top-level binding to enter copy-mode and immediately scroll up one page. The other two add bindings within copy-mode so you can continue to scroll up or down with those keys.
I also have a small hack in my .zshrc to start scrolling up with `M-v` (like in Emacs) while at a shell prompt:
I used to do all of this type of stuff to get my copy-paste to work in tmux but honestly it's still a pita. The alternative I started using recently (zellij[1]) has copy and paste, scrollback, dump scrollback to editor etc just working out of the box with no fancy configuration required and also has a much saner session management mechanic that also works right out of the box.
This is something tmux inherited from screen, but it from a quick test it looks like they didn't copy the whole thing? You use [ to enter this mode (it's actually for copying text, not just scrolling) and in screen use ] to exit without copying anything. Looks like tmux doesn't have ], at least by default?
Are you claiming that declining fertility is due to plastic, rather than to increasing wealth, education of women, and access to contraception? If so, then I'm going to have to ask you for a) a source and b) a plausible mechanism.
There's very strong evidence that both sperm counts and testosterone levels are going down (wikipedia it) worldwide over the last 60 years.
The mechanism here would be that many plastics are or contain endocrine disruptors. Or just an unknown mechanism (there's just so much about biology we don't know).
I believe there's also evidence that younger generations are having less sex. There's also a claim that people have much less "mature" (i.e. sexually-developed) facial features.
Of course this could all be tested by a proper study.
Now back to your point, your first reaction might be "All my friends aren't having kids because they don't want to, none are trying and can't." But if sex-drive is down across the board that may explain it. America doesn't even self-replace (unless you count new immigrants).
The short answer is, we sequence their genomes, identify mutations that change a protein sequence and are highly expressed, then run those all through suites of algorithms that predict how well they'll be presented to the immune system. (mostly neural networks trained on far-too-sparse experimental data). This prediction is the hard part right now - we still don't understand enough about how the immune system identifies and interacts with these altered peptides to do really accurate predictions of which ones will be most effective. Throw in that these tumors are actively suppressing the immune system in various ways, and it's complicated! There is lots of research going on, though, and lots of promising early results, like this one
How much of the end to end process requires artisanal human touch? In some future day, is there a chance of tailored mRNA is industrialized to the point that we go from biopsy to vaccine as a standard course of care?
Perversely, this is almost the exact opposite of how to solve the problem.
Speaking from experience, the real problem with scientific data (genomics, in particular) is when it is exchanged in plain-text format and then loaded IN to Excel. Automatic type inference is what fails.
Data already in Excel format can be created/modified/exchanged without unintentional conversion if the column type is correctly specified as "TEXT".
Look, I get the impulse, and might have agreed with you 10 years ago. At the end of the day, though, we have to work with non-computationally savvy people who (reasonably) want to look at their data sometimes. Not every lab tech or PI can or should learn Python/R/your favorite scripting language, and frameworks like Galaxy take time to set up and maintain, etc etc. Our job is to meet the users where they are and push the biology forward. Any time that I can push them onto a better path, I'll do that, but sometimes the right move is to tell them: "Yeah, go ahead and play with the data in excel, then tell me what you find", and I'll code something proper up afterwards to verify it, get solid stats and a make a pretty visualization.
This is a great example of where cancer treatment is headed and why it's so hard - namely that cancer isn't one disease, it's many thousands of diseases.
This is a drug that targets lung cancer (~12% of cancers) and only one type of lung cancer (non-small cell lung cancer, ~80% of cases). It targets a particular mutated gene that occurs in about 30% of that subtype. And then, about 50% of those patients respond.
So do that math, and you end up seeing that treating one of the most common mutations in one of the most common cancers with what is considered very high efficacy still only helps with about 1.4% of all cancers. This is actually an enormous number for this kind of treatment, and there is a long tail of rare cancers that are going to be much harder to find targeted therapies for.
That all said, this currently appears to be an enormous success story, and the kind of treatment options that have been enabled by genomic sequencing of cancers, followed by many years of drug development and clinical trials. It's fantasically exciting to see us continue to chip away at the problem but by bit and grant people longer lives as a result!
Just because this approach works doesn't mean this is the only approach out there. I sincerely believe that this thought has singlehandedly retarded progress towards more generic cancer treatments. Immune checkpoint inhibition is a clear proof that you could make one drug that could attack a wide swathe of cancers. Heck even chemo is proof of that. If this is the research you want to focus on, please go ahead. But don't tell the public the continuous half truth that every cancer is unique with no commonality with any other cancer. They all literally share the same DNA, they can't be that different. Consider the possibility that the entire cancer research community is just too dumb to discover globally effective drugs. Unless you can mathematically prove its impossibility I'll say let's not make that statement.
Signed, a guy who spent most of his PhD studying cancer.
You’re both kinda right, personalized or targeted cancer therapy is definitely an incredibly promising field and the early results in various cancers are promising. Most notably in disseminated disease.
Simultaneously, one of the largest criticisms of osimertinib in resectable NSCLC has been that some oncologists got overexcited about the DFS results and patients have been unfortunately not receiving the traditional standard of care adjuvant therapy (old school platinum based drugs) which have a proven overall survival benefit (until today osimertinib did not, it now possibly does).
Targeted gene-directed therapy is cool but conventional chemotherapy is still really important.
Why shouldn't he tell the public that every cancer is unique? It's technically true, much in the same way it's technically true you studied cancer but have for years been working with entirely unrelated fields to the advancement of cancer research. You're as much of an authoritative figure on this topic as a random person on the street.
Technically true is how most science education got screwed up in every field of science. We went from educators like Carl Sagan and Feynman who would take great pains to make sure they don't just tell technically true statements to most researchers today blatantly saying misleading technically true statements for a living to get grant money. Every second grant and paper nowadays literally starts with a disingenuous generalizing statement about whatever thing they're studying (xx gene has implications for cancer or whatever). No one says anything because it's technically true but everyone knows it's practically bs. After doing this for decades they start believing their own koolaid.
And thanks for trying to question my expertise. Please look up the no true Scotsman fallacy and see if that may apply here.
> They all literally share the same DNA, they can't be that different.
They share the same DNA in the sense that every cell in that body does. But the different types of cancers have different mutations per cell type and the increasingly precise identification of those is the basis of the recent new treatment options. Histological classifications become less and less relevant, instead mutations and subtypes of mutations give directions for treatment paths. So I think that statement is a bit confusing.
There are also cancers where the root cause is not a cell suddenly stopped functioning properly out of nowhere but instead the rootcause is a virus/chemical (that may or may not still be present in the body/cells).
I meant that every cancer diagnosis is done by a pathologist who describes the looks of the cell/tissue and is trained to assign a cancer classification to it. This is currently changing to genetic testing where the underlying mutation (that is causing the tissue changes) is identified. AFAIK the tissue classification is still the gold standard for most cancer types, but I am positive that this will be completely replaced by the new methods. Medicine will not put the cells under a microscope anymore but into a DNA analyzer instead.
If you mean diagnosing the type of cancer (e.g. clear cell renal cell carcinoma) we've already been using molecular markers for over a decade now.
Since you mention "describing the look": mitotic rate and local staging (depth of invasion, lymphovascular invasion, perineurial invasion) matter far more than any DNA/type of cancer and this isn't changing at all nor will it ever change.
Do you mean this literally or figuratively? Isn't one of the serious problems with tumors that the mutation rate inside them goes through the roof? (And then they eventually figure out how to be metastatic?)
Isn't there a high chance that research aimed at one type of cancer will end up transferrable to other types? Either the actual treatment/drug, or at least the methods and approaches to designing the treatment.
Agreed! This specifically is for adjuvant osimertinib for EGFR+ Stage IB–IIIA completely resected NSCLC.
The headline here is really strong -- and the actual abstract is much more sober: "5-year OS rate was 88% with osimertinib vs 78% with placebo" [Full abstract is here: https://meetings.asco.org/abstracts-presentations/219805 ]
P.S. Hi Chris! (I think I picked up a summer student from you last week!)
Think about that... If the committee whose job is approving this medicine get results in on Friday, but don't sit down to approve it till the following Monday, then 4098 people die unnecessarily.
It always surprises me how little effort we put into getting things from the lab to the people quicker.
As soon as we have compelling data some discovery (medical or otherwise) might help lots of people, it should be almost a manhattan project type effort to get it into the hands of everyone worldwide asap.
Other areas of medecine do do things in a rush - like an ambulance breaking the speed limit to maybe save one guy. Yet we wouldn't allow breaking the speed limit when delivering a new treatment to save thousands of lives.
What's really inefficient is that every trial needs to spend (hundreds of) millions on writing up the whole thing, IRBs and FDA (and additional authorities) paperwork, recruiting, data analysis, etc. while these could all be standardized. (There are companies that do this, but they are just expensive middlemen. There was a great substack (?) post detailing a lot of these, but now I can't find it.)
Yet the harm from that (10,000) was in many ways tiny compared to the harm from not deploying treatments that turn out to be good.
For example 780,000 people died of polio between 1988 and today. Yet for all that time there has been a cheap, low risk, well tested, near 100% effective vaccine (many in fact). And polio is probably one of the better cases because governments and charities have been pushing it pretty hard.
The polio vaccine has been approved by the FDA during all of that time. Therefore, I don't understand how the deaths during that time provide evidence that the FDA should approve drugs faster.
Edit: Also, polio eradication efforts where a Manhattan project style heroic effort.
Not sure if you're specifically referring to the drug in this article but osimertinib has been FDA approved for ~8 years and has been part of routine clinical practice for quite a while now.
The system is actually really fast at getting promising cancer therapies into the hands of patients, especially when there aren't good alternatives.
Even if something isn't yet approved and the patient is ineligible for a clinical trial, an intervention can be offered to patients under compassionate grounds/special access.
the FDA face an unenviable challenge: how to promote healthcare innovation without endangering patients?
regulations that are too loose may cause suffering and death while regulations that are too strict will delay or block prevent helpful treatments.
regulating healthcare is extremely difficult and largely a thankless job.
one solution is to approach national healthcare like national security and let people volunteer for treatments like volunteering for the army.
in short, overstate risks but let patients decide.
adopt cigarette-simple consent forms that state in bold words that an experimental treatment is likely to cause death or crippling side-effects like paralysis, blindness, stroke, Alzheimer's, or worse.
perhaps require multiple signatories from family members to guard against irrational behavior.
this protects the FDA while minimizing barriers to innovative therapies and treatments.
> in short, overstate risks but let patients decide.
Then you have to battle the people selling highly marked up snake oil as an 'experimental' treatment - when every expert could tell you this treatment is already well known to be ineffective.
> Then you have to battle the people selling highly marked up snake oil as an 'experimental' treatment - when every expert could tell you this treatment is already well known to be ineffective.
Isn't that easily solved by requiring all experimental drugs and procedures to be provided free of charge with the cost footed solely by the provider?
indeed. this is a thorny problem with no perfect solution.
on the one hand, you may throttle promising treatments and on the other hand, you may increase useless treatments.
publishing results is one way to mitigate snake oil, though this obviously doesn't eliminate the problem.
the general framework is to maximize transparency and freedom.
letting people volunteer for national healthcare like they can for the national army increases freedom, but we must also increase transparency to combat snake oil.
Anyone should be allowed to take any medicine that they desire. The FDA can still approve treatments, the problem with the FDA is that forbid patients from access to treatment they desire.
Although that is suspiciously large. Looking at the numbers I think it should be much lower. A 51% reduction doesn't mean it helps 51% if the people. In this case it looks like about 10% of the people are effected given the 88% vs 78% survival rates, right? Maybe something like .28% of all cancer?
These are ballpark numbers to be sure, and yeah, my off the cuff comment didn't get that exactly right. I also simplified things quite a bit to try to get the broader point across - Thanks for following up!
I mean, the people who die of cancer are the problem. If 88% survive instead of 78%, 55% of those who would have died survived (taking these numbers just from your comment).
The way forward then seems to be personalized therapy for each case. There have been some limited trials with CRISPR that look promising, but mainstream adoption is still likely years away.
Personalized therapy might possibly not work for a really long time. Consider each drug to be a code change at heart of the most critical code running the code of your body. Clinical trials are the integration testing and ab testing equivalent of making sure this change doesn't have side effects. Personalized therapy means you have no way of testing in a comparable system. Unless you're gonna clone babies of yourself give them the same cancer and see if it treats them and doesn't kill them (and then pull a Prestige)
I am not a scientist, but there are technologies like taking a specific mRNA or protein and making the immune system primed against it for a specific HLA. This makes it possible peptide and mRNA vaccines personalized for a person (you can choose a protein/mRNA specific to the cancer this person has and for her HLA type.
This looks as enough close to personalized therapy for me. There are prediction tools available online.
I hate to be that guy, because it seems like there is some interesting science behind this press release hype. There are, however, many many miles between "effects in a mouse model" and "human therapeutic", let alone "cure". I wish them the best of luck as they consider safety and efficacy in clinical trials.
Correct. However, research models like mice play a critical role in revealing key mechanisms of actions for many diseases. One can crudely think of it as a reverse engineering challenge - picking apart the key functions and program flow from obfuscated object code. Not all of the program logic or functions will have 1-1 correlates to humans, but these models can provide important clues for new therapeutics that might work in people. These types of experiments simply can’t ethically be done in humans.
And I entirely agree with your other point: university press releases are notorious for hyping research. It does the biomedical field a disservice, and gives the impression clinical trials are but an afterthought. Nothing could be further from the truth.
I'm not saying that there aren't other mechanisms (sustained inflammation, etc) that might contribute to the aetiology of some other cancers, even without clear viral integrations, but we can state pretty strongly that many cancers are not directly caused by cancer.
It's true that the whole problem of cancer therapy is "how do I target these cells over here, while avoiding the rest of your healthy cells, when they look mostly the same" And you're right that this is a really exciting and promising approach!
A partial list of the "catches" at present are
1) tumors are really good at down-regulating the immune system. If they weren't, they would have been cleared already
2) we're still fairly bad at knowing which of the many mutations in a tumor are going to be good neoantigens - that is, which ones the immune system will be good at recognizing and ramping up against
3) It's expensive to design personalized therapies for every patient, but may be necessary (see some of my other comments below)
4) Tumors aren't single cells, they're collections of them that can have different characteristics. Just like with other therapies, sometimes immunotherapies kill 99% of the tumor, but leave that 1% to come roaring back. (same idea as antibiotic resistance)
So yeah, lots of hurdles to overcome, but overall, I'm genuinely excited about the rapid progress we're making in the area of immunotherapies. It's impossible to overstate the effect that sustained research funding has had on the rate of advances in this field.
The solution is to be okay with missing some things instead of trying to drink from the firehose.