I don't know where you're getting your information, but it's wrong. T cells, especially ones that have been activated, have a much longer lifetime, and they do replicate. CART cells have been detected more than a year after infusion.
CART therapy is an outpatient procedure with monitoring for roughly 6-8 weeks afterward. If there's CRS, it's pretty obvious and you need to get to the hospital quickly, but as long as you know what to look for there's no need to stay in the hospital the whole time.
The modified cells absolutely do replicate themselves. They'd be mostly worthless if they didn't. They're activated slightly differently - through one chimeric antigen receptor instead of a T cell receptor and costimulatory molecules - but once activated, they behave like normal T cells and proliferate. CART cells have been detected more than a year after injection, and a small pool probably sticks around for much longer. T cells, depending on how they differentiate, can stick around for more than 10-15 years. It's not known whether these will stay alive for that long, but I'd bet on it.
There's a third path to treat CRS - anti-IL-6 antibodies, which is what's generally used to treat it during CART therapy.
Some of the T cells that were injected are likely still alive - or at least, there are likely some modified cells still circulating. They're often detectable long after the cancer is gone, and probably are still around as non-circulating memory cells even when we can't detect them. The body certainly can't do what the modified cells do in the same way they're doing it - the chimeric antigen receptor does not occur in nature. It's possible that the body is responding to CD19 (the antigen in question) by itself, but highly unlikely. CD19 is expressed on most healthy B cells as well, and the body generally should treat it like any other "self" protein.
The main problem with including an "on" switch for CART cells is that no inducible promoter is good enough at the moment - they all have too high of a baseline activation level when they're supposed to be off.
The CRS isn't caused by the reconstitution of the immune system, it's caused by hyperactivation of the CART cells. Using them earlier, when there's less tumor burden, would likely help with that. Otherwise you'll have to mess with the signaling that causes it in the first place, which is probably possible but will require a lot of work.
Most of the neurological toxicity that has been seen with CART cells has been with those that use the 4-1BB costimulatory domain, while most of the stuff from Penn and CHOP uses CD28, and they have had a lot fewer problems with brain toxicity.
Agreed that all of the side effects so far are treatable - and it seems likely that most of the side effects will go away over time.
The canine and front teeth, obviously. The vast majority of our ape and monkey cousins, as I said, are not herbivores. Chimps and bonobos are known to hunt, kill, and eat other mammals. Many monkeys also eat meat. Gorillas are the outlier among apes and larger monkeys.
Bears have molars, actually. Please do some research before saying things that could be easily disproven by about three seconds on Google. Our teeth are omnivorous.
Well, for one - as I said earlier - most of our ape and monkey cousins aren't herbivorous. It's awfully useful for catching insects (which, you'll note, are not plants).
Humans are categorically not herbivores. We evolved to be omnivores - from the variety of teeth we have (and their placement), similar diets across primates (meat when they can, plant matter otherwise), our gut structure, our long-established archaeological evidence for ancient humans hunting, our good depth perception, and many other things. We evolved to be omnivores.
Khan Academy has some great series. The depth varies quite a bit between subjects - last time I checked, the math parts were much better developed than the biology ones - but it has some really useful stuff.
What I'd like to see are more comprehensive trade school education resources online. Yeah, I know there are instructional videos on YouTube, but they tend to be for quick things (some exceptions, obviously) and it's not always easy to find the good ones.
1) It wasn't made by the POTUS (I don't think he knows how), 2) it's not incitement to violence, and 3) that's not even what the claim was. Incitement to violence is not the same thing as threatening violence (the original claim), and a wrestling gif isn't either of those.
The claim that making a gif of a CNN logo being wrestled is the same thing as threatening violence against the media is such a stupid statement I'm not even sure where to start.
I don't think it's about teenagers having extra money - it's that teenagers are often less productive and have fewer skills or less experience than adults. They tend to be worth less. Making someone pay them a living wage for an adult living by themselves, or a living wage to support more than one person, just means that most teenagers won't get hired at all, and will have to wait later in life to start getting experience.
Okay, but what constitutes a living wage? One that lets a single person live with shelter, food, gas, clothing (normal expenses)? Or do you mean a living wage where you can also support a family?
I disagree with your interpretation of how the POTUS can exert his authority. If Congress writes a law granting the POTUS power to control border and immigration as he sees fit, and then he decides to - through an EO, say - discriminate based on religion, that's still not Congress making a law about religious freedom. It would be a shitty thing to do, and I'm sure people would challenge it, but it seems to me that while his authority in this matter derives from Congress, they didn't actually break the law.
There are plenty of people who use an AR-15 to hunt in single-shot (rather than semi-auto) mode. More to the point - the argument I was responding to was talking about guns in general, not specific kinds of guns.
To the contrary, it's quite applicable to the gun debate. Any restrictions on buying guns would then be different from buying a car, since you can own a car and use it on private property just fine. Owning a gun and keeping it at home for self-defense is no different from that perspective.
It's a condition of getting it published. They may be unhappy about it, but if they published with Elsevier, they still gave it to them. As an academic, I'm not thrilled about it either, but I have yet to see a proposal for a compellingly better system.
Don't think I don't see you moving the goalposts. You're adding things that weren't initially conditions of the complaint in order to justify it.
Taxpayer-funded research is sometimes funded with the intention of advancing society as a whole. Military spending is funded with the intention of protecting or advancing society as a whole. What's the difference? Should I be able to check out a tank when I want to?
Elsevier does own the copyright. The people who did the research gave it to them. And most government-funded research is available to the public after a period of time, usually a year or two.
Slashdot Mirror
I don't know where you're getting your information, but it's wrong. T cells, especially ones that have been activated, have a much longer lifetime, and they do replicate. CART cells have been detected more than a year after infusion.
CART therapy is an outpatient procedure with monitoring for roughly 6-8 weeks afterward. If there's CRS, it's pretty obvious and you need to get to the hospital quickly, but as long as you know what to look for there's no need to stay in the hospital the whole time.
The modified cells absolutely do replicate themselves. They'd be mostly worthless if they didn't. They're activated slightly differently - through one chimeric antigen receptor instead of a T cell receptor and costimulatory molecules - but once activated, they behave like normal T cells and proliferate. CART cells have been detected more than a year after injection, and a small pool probably sticks around for much longer. T cells, depending on how they differentiate, can stick around for more than 10-15 years. It's not known whether these will stay alive for that long, but I'd bet on it.
There's a third path to treat CRS - anti-IL-6 antibodies, which is what's generally used to treat it during CART therapy.
Some of the T cells that were injected are likely still alive - or at least, there are likely some modified cells still circulating. They're often detectable long after the cancer is gone, and probably are still around as non-circulating memory cells even when we can't detect them. The body certainly can't do what the modified cells do in the same way they're doing it - the chimeric antigen receptor does not occur in nature. It's possible that the body is responding to CD19 (the antigen in question) by itself, but highly unlikely. CD19 is expressed on most healthy B cells as well, and the body generally should treat it like any other "self" protein.
The main problem with including an "on" switch for CART cells is that no inducible promoter is good enough at the moment - they all have too high of a baseline activation level when they're supposed to be off.
The CRS isn't caused by the reconstitution of the immune system, it's caused by hyperactivation of the CART cells. Using them earlier, when there's less tumor burden, would likely help with that. Otherwise you'll have to mess with the signaling that causes it in the first place, which is probably possible but will require a lot of work.
Most of the neurological toxicity that has been seen with CART cells has been with those that use the 4-1BB costimulatory domain, while most of the stuff from Penn and CHOP uses CD28, and they have had a lot fewer problems with brain toxicity.
Agreed that all of the side effects so far are treatable - and it seems likely that most of the side effects will go away over time.
The canine and front teeth, obviously. The vast majority of our ape and monkey cousins, as I said, are not herbivores. Chimps and bonobos are known to hunt, kill, and eat other mammals. Many monkeys also eat meat. Gorillas are the outlier among apes and larger monkeys.
Bears have molars, actually. Please do some research before saying things that could be easily disproven by about three seconds on Google. Our teeth are omnivorous.
Well, for one - as I said earlier - most of our ape and monkey cousins aren't herbivorous. It's awfully useful for catching insects (which, you'll note, are not plants).
Humans are categorically not herbivores. We evolved to be omnivores - from the variety of teeth we have (and their placement), similar diets across primates (meat when they can, plant matter otherwise), our gut structure, our long-established archaeological evidence for ancient humans hunting, our good depth perception, and many other things. We evolved to be omnivores.
Khan Academy has some great series. The depth varies quite a bit between subjects - last time I checked, the math parts were much better developed than the biology ones - but it has some really useful stuff.
What I'd like to see are more comprehensive trade school education resources online. Yeah, I know there are instructional videos on YouTube, but they tend to be for quick things (some exceptions, obviously) and it's not always easy to find the good ones.
1) It wasn't made by the POTUS (I don't think he knows how), 2) it's not incitement to violence, and 3) that's not even what the claim was. Incitement to violence is not the same thing as threatening violence (the original claim), and a wrestling gif isn't either of those.
I can't tell if you're trolling or not, but that's not what Citizens United said.
Look everyone, someone's moving the goalposts!
This article and comment was about the person who made the gif. Trying to drag "but Trump is bad!" into it just makes you look foolish.
Making a gif of the CNN logo being wrestled is in no way the same thing as threatening violence.
The claim that making a gif of a CNN logo being wrestled is the same thing as threatening violence against the media is such a stupid statement I'm not even sure where to start.
I don't think it's about teenagers having extra money - it's that teenagers are often less productive and have fewer skills or less experience than adults. They tend to be worth less. Making someone pay them a living wage for an adult living by themselves, or a living wage to support more than one person, just means that most teenagers won't get hired at all, and will have to wait later in life to start getting experience.
Okay, but what constitutes a living wage? One that lets a single person live with shelter, food, gas, clothing (normal expenses)? Or do you mean a living wage where you can also support a family?
I disagree with your interpretation of how the POTUS can exert his authority. If Congress writes a law granting the POTUS power to control border and immigration as he sees fit, and then he decides to - through an EO, say - discriminate based on religion, that's still not Congress making a law about religious freedom. It would be a shitty thing to do, and I'm sure people would challenge it, but it seems to me that while his authority in this matter derives from Congress, they didn't actually break the law.
I mean technically the First Amendment only references Congress and says nothing about the Executive Branch.
There are plenty of people who use an AR-15 to hunt in single-shot (rather than semi-auto) mode. More to the point - the argument I was responding to was talking about guns in general, not specific kinds of guns.
To the contrary, it's quite applicable to the gun debate. Any restrictions on buying guns would then be different from buying a car, since you can own a car and use it on private property just fine. Owning a gun and keeping it at home for self-defense is no different from that perspective.
Only on public roads.
I know people who only get enough to eat because they can hunt. I'd say that's a productive use for guns.
So you're letting people at Vox decide that these jokes are racist? Vox?
Reviewers are often unpaid (or paid very little), but the editors tend to be full-time employees at the journal and are paid pretty well.
It's a condition of getting it published. They may be unhappy about it, but if they published with Elsevier, they still gave it to them. As an academic, I'm not thrilled about it either, but I have yet to see a proposal for a compellingly better system.
Don't think I don't see you moving the goalposts. You're adding things that weren't initially conditions of the complaint in order to justify it.
Taxpayer-funded research is sometimes funded with the intention of advancing society as a whole. Military spending is funded with the intention of protecting or advancing society as a whole. What's the difference? Should I be able to check out a tank when I want to?
Elsevier does own the copyright. The people who did the research gave it to them. And most government-funded research is available to the public after a period of time, usually a year or two.
I'm not seeing the issue with this.