The nanoneedle salt stress test – too good a clue to leave abandoned on the lab bench?

Bron said:
Isn’t it explained by the fact that Rahim specifically needed NIH funding and Davis wouldn’t compete with a student? Unless you know that they did apply earlier and OMF refused?
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Well, I don't think it is made clear whether there was one or two grants, "Rahim Esfandyarpour needed to not only get one of his grants funded to get tenure at the University of California at Irvine where he was working, he needed to get an NIH grant funded.". If there were two, with one needing to be funded by the NIH for whatever reason, then that would still leave the possibility of OMF funding the other.

OMF part funded the original work, "This work was supported by National Institutes of Health Grant P01 HG000205 and Open Medicine Foundation.", https://www.pnas.org/doi/10.1073/pnas.1901274116, which was published in 2019. I don't know whether Esfandyarpour applied for further funding from them or not but we have heard repeatedly about the woes of failing to get further funding from the NIH for this, so I think it is reasonable to assume that he would have done, which if he had done then raises the question of why they wouldn't have funded him.
 
I got the impression that it was as much to do with him being an early career researcher who needed to move on to a post with more prospects of long term funding, tenure etc. It wouldn't be reasonable to hold back his career on the basis of a few thousand pounds funding for a single OMF funded project if there were better prospects elsewhere.
 
Andy said:
Well, I don't think it is made clear whether there was one or two grants, "Rahim Esfandyarpour needed to not only get one of his grants funded to get tenure at the University of California at Irvine where he was working, he needed to get an NIH grant funded.". If there were two, with one needing to be funded by the NIH for whatever reason, then that would still leave the possibility of OMF funding the other.

OMF part funded the original work, "This work was supported by National Institutes of Health Grant P01 HG000205 and Open Medicine Foundation.", https://www.pnas.org/doi/10.1073/pnas.1901274116, which was published in 2019. I don't know whether Esfandyarpour applied for further funding from them or not but we have heard repeatedly about the woes of failing to get further funding from the NIH for this, so I think it is reasonable to assume that he would have done, which if he had done then raises the question of why they wouldn't have funded him.
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Andy said:
Well, if he has moved on to other things (he now appears to have his own lab, with lab news dating back to April 2019 - https://faculty.sites.uci.edu/esfandyarpourlab/ ) then I don't understand why Ron should then feel such reluctance to continue to investigate the nanoneedle.
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Yes it seems a very odd principle to stick to when so much is at stake imo. Like an honourable thing generally but in this situation incredibly frustrating.

But I'm glad this UK study is going ahead and heartened they have already replicated the US results.
 
As far as the OMF released news I’ve read go, Rahim needed a NIH grant. Nothing would have prevented, or prevents, the OMF to fund a study for Rahim and Davis outside of such a grant (if it was obtained), nothing would have prevented the OMF to hire somebody to continue this work in collaboration with Rahim (or just have his name as coauthor on the paper if he has insufficient time due to commitments in regards to this grant/tenure) etc.

It’s also been 5 years since then, either he has obtained such a grant by now and if he hasn’t, it doesn’t make much sense to me to halt other work if it was indeed promising. It’s very reasonable to say something like “we’ll do a quick break until you sort out your grant/tenure situation”, or “let’s wait and see, hopefully your career progresses and you can hire your own PhD/post-doc to continue this work” but once 5 years have past and nobody is working on it anymore, then nobody is in competition with anyone anymore and the grant argument really doesn’t make sense anymore. It might have been a decent argument 3 years ago, but certainly not anymore. Would one in 20 years still be saying "we've got a biomarker tool but we can't work on this and that's why are studying biomarkers that have absolutely nothing to do with the theories and biomarkers we found 20 years ago"?

I’ve looked at some of Rahim’s papers and it seems that the funding declared in those isn’t NIH funding, but of other funding sources (see for instance https://www.sciencedirect.com/science/article/abs/pii/S0010854523000139?via=ihub), so I also don’t see how OMF funding would be substantially different to that.

Usually researchers just move on, mainly because things don’t look promising enough to pursue them when comparing them to other things. At least someone picked it up again, hopefully in the case of negative results, we'll get to know of those too.
 
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"Rahim Esfandyarpour needed to not only get one of his grants funded to get tenure at the University of California at Irvine where he was working, he needed to get an NIH grant funded."
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I understood that to mean that it's not enough to just get any grant, you need an NIH grant to get tenure at UC Irvine. Given that he's now a principal investigator with his own lab, I assume he got tenure.

EndME said:
nothing would have prevented the OMF to hire somebody to continue this work in collaboration with Rahim
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It seems like a very specialised and obscure area of expertise. Perhaps once he left, there was no one else with requisite knowledge who could fill the post. ME/CFS is a highly stigmatised field of research. If you're a hotshot young bioengineer, you can pick to work on something else that's not going to sully your resume.
 
It drives me up the wall that no Long Covid researcher has tried to replicate the nano-needle finding in a well-defined post-covid ME cohort. There are now various efforts to replicate the microclots and cortisol findings, which are clearly important. But the PNAS nanoneedle study has to be almost the most compelling bit of research ever published on ME. That no Long Covid researcher is looking at it speaks to the failure of the LC field to listen to the pre-existing ME literature.
 
RaviHVJ said:
it speaks to the failure of the LC field to listen to the pre-existing ME literature
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A recent LC paper with overlap findings with ME studies on mitochondrial impairment, also using Seahorse technology, was guilty of this.

SNT Gatchaman said:
I didn't see any ME/CFS literature referenced and I don't think it was even mentioned, though they report that 75% of the patients had fatigue, 55% PEM, 65% orthostatic intolerance.
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However, it seems to me more common than not that recent LC papers at least refer to ME/CFS. It would be good if we end up with more long-awaited replication studies for some of the 1990s-2000s findings that LC researchers independently discover.
 
Sid said:
Would be good to know more about this. The blurb from ME Research UK implies that they were able to detect a difference between ME and MS, though I should add that a statistically significant difference between groups does not necessarily mean the test can differentiate in a clinically useful manner.
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I recall that the American Army MS study, i.e. which indicated EBV was usually the cause of MS, used a biomarker - degradation of myelin. So I'm always a bit surprised re discussion of separating MS from ME.
 
RaviHVJ said:
But the PNAS nanoneedle study has to be almost the most compelling bit of research ever published on ME. That no Long Covid researcher is looking at it speaks to the failure of the LC field to listen to the pre-existing ME literature.
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I m not so sure. I have never been able to work out what the nano needle study could possibly mean. The geometry of the apparatus did not seem to be appropriate for cells. I think it may be that the LC field has rightly ignored the study because nobody else familiar with blood cell structure/function can work out what it could mean either.
 
FMMM1 said:
I wasn't suggesting it was - more that I can't really see why people are interested in separating MS from ME - surely it's relatively easy to diagnose MS i.e. measure the level of the (myelin) degradation product in the blood?
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There may be similar things going on in PBMCs in MS, the disease is not confined to myelin injury.

Specific myeloid signatures in peripheral blood differentiate active and rare clinical phenotypes of multiple sclerosis (2023, Frontiers in Immunology)

Twin study reveals non-heritable immune perturbations in multiple sclerosis (2022, Nature)

Mitochondrial Impairments in Peripheral Blood Mononuclear Cells of Multiple Sclerosis Patients (2022, Biology)

Inferring Multiple Sclerosis Stages from the Blood Transcriptome via Machine Learning (2020, Cell Reports Medicine)

PBMC of Multiple Sclerosis Patients Show Deregulation of OPA1 Processing Associated with Increased ROS and PHB2 Protein Levels (2020, Biomedicines)

Aberrant STAT phosphorylation signaling in peripheral blood mononuclear cells from multiple sclerosis patients (2018, Journal of Neuroinflammation)
 
Jonathan Edwards said:
I m not so sure. I have never been able to work out what the nano needle study could possibly mean.
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When there's a really dramatic finding, but no one understands what is being measured, it may just be measurement error of some sort. There might be some factor in how the tests are done, always in a particular order, that build up a static charge, or leaves the nanoneedles altered by the first sample, or some such thing. It might be a valid finding, or it might not. I'm waiting for replication and an explanation for what is found.
 
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