5 ms·

These summary is just wrong wrt this study: >”Now that Courchesne and Muotri have established that brain overgrowth begins in the womb, they hope to pinpoint i

These summary is just wrong wrt this study: >”Now that Courchesne and Muotri have established that brain overgrowth begins in the womb, they hope to pinpoint its cause, in a bid to develop a therapy that might ease intellectual and social functioning for those with the condition.” There is a slight difference between “beginning in the womb” snd beginning in some odd organoid derived from blood cells. Autism research imho tends to be flaky and this type of press release does not help.

koolala 2y ago
flakey + overfunded = published success
krisoft 2y ago
I don’t understand your complaint. The conclusion of the paper says this: “By embryogenesis, the biological bases of two subtypes of ASD social and brain development—profound autism and mild autism—are already present and measurable and involve dysregulated cell proliferation and accelerated neurogenesis and growth.” It is correct to describe that as “established that brain overgrowth begins in the womb”. It seems you have an issue with that the researchers reached this conclusion from experiments with what you call “some odd organoid derived from blood cells”. I’m not an expert so I wouldn’t know if that is a valid way to make the conclusion but once they do it seems the summary in the article is correct. What do you feel is wrong with the article and what do you feel is flaky with the research?
usgroup 2y ago
They had a neurotypical control group, their effect size is massive, and clearly separates the autistic group from the control group. They reject the null hypothesis that there is no difference between the groups, and argue from literature for an alternative hypothesis. What's the problem?
- libeclipse 2y ago
  The sample size is miniscule (14)
  - MajimasEyepatch 2y ago
    That’s true of most neuroimaging studies. Have you ever tried to get a bunch of people into an MRI for a study? Not easy, not cheap. Like they said, the effect size is large. With a large enough difference, you can distinguish the effect from statistical randomness, even with a small sample size. As with any study, this result must be replicated. But just waving around the sample size as if every study can be like a live caller poll with n = 2,000 is not helpful.
    - bunderbunder 2y ago
      Also this idea that bigger is better with sample sizes can lead to problems on the other side, when we see people assuming an effect must be real because the sample size is so large. The problem is, sample size only helps you reduce sampling error, which is one of many possible sources of error. Most the others are much more difficult to manage or even quantify. At some point it becomes false precision because it turns out that the error you can't measure is vastly greater than the sampling error. Which in turn gets us into trouble with interpreting p-values. It gets us into a situation where the distinction between "probability of getting a result at least this extreme, assuming the null hypothesis" and "probability the alternative hypothesis is false" stops being pedantic hair-splitting and starts being a gaping chasm. I don't like getting into that situation, because, regardless of what we were all taught in undergrad, scientific practice still tends to lean toward the latter interpretation. (Except experimental physicists. You people are my heroes.) For my part, the statistician in me rather likes methodologically clean controlled experiments with small sample sizes. You've got to be careful about how you define "methodologically clean", of course. Statistical power matters. But they've probably led us down a lot fewer blind alleys (and, in the case of medical research, led to fewer unnecessary deaths) than all the slapdash cohort studies that we trusted because of their large sample sizes that were so popular in the '80s and '90s.
      - MajimasEyepatch 2y ago
        That's a great point. If your experimental methodology is flawed, it doesn't matter how big your sample size is. A study like this lets you gather some compelling evidence that you may have a real effect. Then you can refine the technique. Autism is a very active area of research, so I suspect we'll see other groups attempt to replicate this study and adapt its techniques while the original authors refine the technique and get funding to perform larger studies.
- dkarl 2y ago
  There's a step left out, which is how they know that what happens in the BCO models also happens in real brains in developing fetuses. That might be context known from previous research, but it isn't explained in the linked article, as far as I can see.
  - sandworm101 2y ago
    They don't. Doing studies on living human fetuses is an admin nightmare. So they use analogues. Black hole physicists also resort to analogues as thier subjects are similarly difficult to manipulate.
    - deleted 2y ago
      [deleted]
    - zeroonetwothree 2y ago
      Not a good analogy since only one of those is actually present on Earth.
      - sandworm101 2y ago
        But both are untouchable.
        robwwilliams 2y ago
        You can image and get in vivo estimates of brain volume. Here is a paper that does so: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583264/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583264/
    - nathan_compton 2y ago
      I would hope that the epistemological status of medical discoveries exceeds somewhat that of knowledge of black holes.
  - mumblemumble 2y ago
    I don't think you need that specific interpretation to decide that this work reveals something important. We have a phenotypic difference that leads to a big in vitro difference, and it's not a huge jump to infer that that would also lead to an in vivo difference, even if the in vivo presentation is unknown, or the exact details of the presentation aren't the same. Here's the conclusions section from the research paper this article is summarizing: By embryogenesis, the biological bases of two subtypes of ASD social and brain development - profound autism and mild autism — are already present and measurable and involve dysregulated cell proliferation and accelerated neurogenesis and growth. The larger the embryonic BCO size in ASD, the more severe the toddler’s social symptoms and the more reduced the social attention, language ability, and IQ, and the more atypical the growth of social and language brain regions. This is not making any huge logical jumps that I noticed. All it's saying is they found a strong correlation. And the researchers seem to be well aware that there are still dots to connect. In the limitations section, it explicitly points out more-or-less the very thing that the researchers are being accused of not thinking about in this HN thread: The genetic causes and cellular consequences of decreased Ndel1 activity and expression correlated with ASD BCOs enlargement remain to be specified. A limitation of most previous ASD patient-derived iPSC-based models is lack of within-subject statistical linkage of ASD molecular and cellular findings with variation in ASD social phenotypes. Without this, future ASD iPSC reports will continue to have limited impact on our understanding of the genetic, molecular and cellular mechanisms that cause the development and variation in the central feature of ASD: social affect and communication. Which brings us to an important thing about interpreting popular science literature: it's unwise to assume that what's in the popularization of the research accurately reflects everything the scientists who published the work think or know. Attempting to eliminate these kinds of details is one of the primary goals of science journalism. For better or for worse. https://molecularautism.biomedcentral.com/articles/10.1186/s13229-024-00602-8 https://molecularautism.biomedcentral.com/articles/10.1186/s...
- deleted 2y ago
  [deleted]
- robwwilliams 2y ago
  I did not see information on the ancestry of the 9-10 ASD toddlers or on the even fewer neurotypical controls. May have missed this. As for large putative effect sizes this is often due to subtle batch processing differences between cases and controls. Where they all processed by the same tech in an interleaved way? All stored in the same way over this very long duration study? Authors do discuss batch controls but with single digit sample sizes I regard statistics as fundamentally unreliable. I am also not convinced by the claim of any over-proliferation of neurons in autism during development. It is certainly a highly controversial result. See notes above by “subiculum…” and the Li et al paper he cites.

koolala 2y ago

flakey + overfunded = published success

krisoft 2y ago

I don’t understand your complaint. The conclusion of the paper says this: “By embryogenesis, the biological bases of two subtypes of ASD social and brain development—profound autism and mild autism—are already present and measurable and involve dysregulated cell proliferation and accelerated neurogenesis and growth.” It is correct to describe that as “established that brain overgrowth begins in the womb”. It seems you have an issue with that the researchers reached this conclusion from experiments with what you call “some odd organoid derived from blood cells”. I’m not an expert so I wouldn’t know if that is a valid way to make the conclusion but once they do it seems the summary in the article is correct. What do you feel is wrong with the article and what do you feel is flaky with the research?

usgroup 2y ago

They had a neurotypical control group, their effect size is massive, and clearly separates the autistic group from the control group. They reject the null hypothesis that there is no difference between the groups, and argue from literature for an alternative hypothesis. What's the problem?

libeclipse 2y ago
The sample size is miniscule (14)
- MajimasEyepatch 2y ago
  That’s true of most neuroimaging studies. Have you ever tried to get a bunch of people into an MRI for a study? Not easy, not cheap. Like they said, the effect size is large. With a large enough difference, you can distinguish the effect from statistical randomness, even with a small sample size. As with any study, this result must be replicated. But just waving around the sample size as if every study can be like a live caller poll with n = 2,000 is not helpful.
  - bunderbunder 2y ago
    Also this idea that bigger is better with sample sizes can lead to problems on the other side, when we see people assuming an effect must be real because the sample size is so large. The problem is, sample size only helps you reduce sampling error, which is one of many possible sources of error. Most the others are much more difficult to manage or even quantify. At some point it becomes false precision because it turns out that the error you can't measure is vastly greater than the sampling error. Which in turn gets us into trouble with interpreting p-values. It gets us into a situation where the distinction between "probability of getting a result at least this extreme, assuming the null hypothesis" and "probability the alternative hypothesis is false" stops being pedantic hair-splitting and starts being a gaping chasm. I don't like getting into that situation, because, regardless of what we were all taught in undergrad, scientific practice still tends to lean toward the latter interpretation. (Except experimental physicists. You people are my heroes.) For my part, the statistician in me rather likes methodologically clean controlled experiments with small sample sizes. You've got to be careful about how you define "methodologically clean", of course. Statistical power matters. But they've probably led us down a lot fewer blind alleys (and, in the case of medical research, led to fewer unnecessary deaths) than all the slapdash cohort studies that we trusted because of their large sample sizes that were so popular in the '80s and '90s.
    - MajimasEyepatch 2y ago
      That's a great point. If your experimental methodology is flawed, it doesn't matter how big your sample size is. A study like this lets you gather some compelling evidence that you may have a real effect. Then you can refine the technique. Autism is a very active area of research, so I suspect we'll see other groups attempt to replicate this study and adapt its techniques while the original authors refine the technique and get funding to perform larger studies.
dkarl 2y ago
There's a step left out, which is how they know that what happens in the BCO models also happens in real brains in developing fetuses. That might be context known from previous research, but it isn't explained in the linked article, as far as I can see.
- sandworm101 2y ago
  They don't. Doing studies on living human fetuses is an admin nightmare. So they use analogues. Black hole physicists also resort to analogues as thier subjects are similarly difficult to manipulate.
  - deleted 2y ago
    [deleted]
  - zeroonetwothree 2y ago
    Not a good analogy since only one of those is actually present on Earth.
    - sandworm101 2y ago
      But both are untouchable.
      - robwwilliams 2y ago
        You can image and get in vivo estimates of brain volume. Here is a paper that does so: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583264/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583264/
  - nathan_compton 2y ago
    I would hope that the epistemological status of medical discoveries exceeds somewhat that of knowledge of black holes.
- mumblemumble 2y ago
  I don't think you need that specific interpretation to decide that this work reveals something important. We have a phenotypic difference that leads to a big in vitro difference, and it's not a huge jump to infer that that would also lead to an in vivo difference, even if the in vivo presentation is unknown, or the exact details of the presentation aren't the same. Here's the conclusions section from the research paper this article is summarizing: By embryogenesis, the biological bases of two subtypes of ASD social and brain development - profound autism and mild autism — are already present and measurable and involve dysregulated cell proliferation and accelerated neurogenesis and growth. The larger the embryonic BCO size in ASD, the more severe the toddler’s social symptoms and the more reduced the social attention, language ability, and IQ, and the more atypical the growth of social and language brain regions. This is not making any huge logical jumps that I noticed. All it's saying is they found a strong correlation. And the researchers seem to be well aware that there are still dots to connect. In the limitations section, it explicitly points out more-or-less the very thing that the researchers are being accused of not thinking about in this HN thread: The genetic causes and cellular consequences of decreased Ndel1 activity and expression correlated with ASD BCOs enlargement remain to be specified. A limitation of most previous ASD patient-derived iPSC-based models is lack of within-subject statistical linkage of ASD molecular and cellular findings with variation in ASD social phenotypes. Without this, future ASD iPSC reports will continue to have limited impact on our understanding of the genetic, molecular and cellular mechanisms that cause the development and variation in the central feature of ASD: social affect and communication. Which brings us to an important thing about interpreting popular science literature: it's unwise to assume that what's in the popularization of the research accurately reflects everything the scientists who published the work think or know. Attempting to eliminate these kinds of details is one of the primary goals of science journalism. For better or for worse. https://molecularautism.biomedcentral.com/articles/10.1186/s13229-024-00602-8 https://molecularautism.biomedcentral.com/articles/10.1186/s...
deleted 2y ago
[deleted]
robwwilliams 2y ago
I did not see information on the ancestry of the 9-10 ASD toddlers or on the even fewer neurotypical controls. May have missed this. As for large putative effect sizes this is often due to subtle batch processing differences between cases and controls. Where they all processed by the same tech in an interleaved way? All stored in the same way over this very long duration study? Authors do discuss batch controls but with single digit sample sizes I regard statistics as fundamentally unreliable. I am also not convinced by the claim of any over-proliferation of neurons in autism during development. It is certainly a highly controversial result. See notes above by “subiculum…” and the Li et al paper he cites.