https://en.m.wikipedia.org/wiki/Muir_Woods_National_Monument Muir Woods, home of the old-growth coast redwoods, was originally preserved by politician William Kent. But when a water company planned to build a dam (which would flood the woods) and threatened to use eminent domain when Kent objected, he had to donate the park to the federal government in order to actually preserve it as a place of natural beauty.
surrogate endpoints in clinical trials are generally evaluated with a meta-analysis, in which the trial-level correlation between the surrogate and “gold standard” endpoint is compared. Do trials that find a larger treatment vs. control effect on the surrogate endpoint also find greater effects on the “gold standard” endpoint? Mostly these are done in only a handful of diseases, primarily cancer where things like response rate or progression-free survival are compared to the “gold standard” of overall survival.
https://etherospharma.com/our-team/ Laura Dugan, whom I funded for her work on carboxyfullerene SOD mimetics extending lifespan and preventing neurodegeneration, has a biotech company now; and Jack Scannell, the predictive validity guy, is the CEO!
Jack Scannell’s thesis: we have more and more ways to screen targets and drug candidates, but they have lower predictive validity, so more drugs fail in the clinic and the cost per successful drug keeps rising.
solution: care more about what screens, animal models, etc you use! just because it’s “industry standard” doesn’t mean it doesn’t suck!
It seems like many people propose “generalization from their own example” as a model for the entire humanity. And it can be quite annoying when people around you agree on a model that doesn’t fit you at all… and when you point it out, they dismiss it by saying that you are in a denial. Because they have examined their own minds deeply, and found out that it was true… yeah, possibly so, but that doesn’t necessarily make it true about the others.
everyone likes whatever popular people around them like—no I don’t
if we legalize gay sex, everyone will want gay sex and families will fall apart—no I don’t feel tempted at all
people are only charitable to other people if they expect them to reciprocate—no I often don’t expect that
links 2/25/25: https://roamresearch.com/#/app/srcpublic/page/02-25-2025
https://en.m.wikipedia.org/wiki/Cherenkov_radiation blue glow from particles moving faster than the speed of light in a medium (like water)
https://dsq-sds.org/index.php/dsq/article/view/5824/4684
https://en.m.wikipedia.org/wiki/Muir_Woods_National_Monument Muir Woods, home of the old-growth coast redwoods, was originally preserved by politician William Kent. But when a water company planned to build a dam (which would flood the woods) and threatened to use eminent domain when Kent objected, he had to donate the park to the federal government in order to actually preserve it as a place of natural beauty.
https://www.osv.llc/our-fellows O’Shaunessy Ventures fellows
surrogate endpoints in clinical trials are generally evaluated with a meta-analysis, in which the trial-level correlation between the surrogate and “gold standard” endpoint is compared. Do trials that find a larger treatment vs. control effect on the surrogate endpoint also find greater effects on the “gold standard” endpoint? Mostly these are done in only a handful of diseases, primarily cancer where things like response rate or progression-free survival are compared to the “gold standard” of overall survival.
https://open.library.ubc.ca/soa/cIRcle/collections/ubctheses/24/items/1.0072082 lesion count as a surrogate for relapse rate in [MS
https://www.sciencedirect.com/science/article/abs/pii/S0895435608001698 LDL as a surrogate in statin trials
https://onlinelibrary.wiley.com/doi/abs/10.1111/bjh.18217 PET complete response as a surrogate in follicular lymphoma
https://www.sciencedirect.com/science/article/abs/pii/S0003496724224262 serum urate is a poor surrogate for gout flares!
https://ascopubs.org/doi/abs/10.1200/jco.2005.08.156 PSA is a poor surrogate for survival in prostate cancer
https://www.sciencedirect.com/science/article/abs/pii/S0272638616002146 protein urea as a surrogate in kidney disease
https://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30314-0/abstract albuminuria isn’t great as a surrogate in kidney disease
https://www.sciencedirect.com/science/article/pii/S2666168322026842 progression-free survival is ok as a surrogate in metastatic urothelial cancer
https://www.bmj.com/content/bmj/375/bmj-2021-066381.full.pdf pathological complete response is a terrible surrogate for survival in early breast cancer
https://www.thelancet.com/pdfs/journals/eclinm/PIIS2589-5370(21)00010-9.pdf event-free survival is a much better surrogate in early breast cancer
https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools list of FDA-cleared companion diagnostics for determining who should use a therapeutic. these are almost all genetic tests for cancer mutations.
https://research.manjarinarayan.org/ Manjari Narayan’s personal website
https://etherospharma.com/our-team/ Laura Dugan, whom I funded for her work on carboxyfullerene SOD mimetics extending lifespan and preventing neurodegeneration, has a biotech company now; and Jack Scannell, the predictive validity guy, is the CEO!
Jack Scannell’s thesis: we have more and more ways to screen targets and drug candidates, but they have lower predictive validity, so more drugs fail in the clinic and the cost per successful drug keeps rising.
solution: care more about what screens, animal models, etc you use! just because it’s “industry standard” doesn’t mean it doesn’t suck!
https://www.nature.com/articles/s41573-022-00552-x
https://ora.ox.ac.uk/objects/uuid:a03f3f9a-c8d0-47b0-9ced-7473fdcf6ca8/files/r8336h262x
https://www.nature.com/articles/d41573-020-00059-3
https://goldlabfoundation.org/presentations/damn-compass-full-speed-ahead-quality-beats-quantity-drug-rd/
melanocortin/leptin-related hereditary obesity
https://www.cell.com/trends/endocrinology-metabolism/abstract/S1043-2760(99)00213-1?large_figure=true
https://www.sciencedirect.com/science/article/abs/pii/S0304394098004017
https://pubs.rsna.org/doi/abs/10.1148/radiology.168.2.3393649 you can measure liver iron overload with imaging in thalassemia
James M. Wilson discovered the AAV, the family of viruses most used in gene therapy
https://www.med.upenn.edu/apps/faculty/index.php/g275/p9746
discoveries of cancer genes/mutations:
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1349-7006.2008.00972.x a chromosomal translocation with ALK in solid tumors (which was unknown before 2008)
Monica Hollstein discovered TP53 mutations and EGFR amplification in cancer
https://www.science.org/doi/10.1126/science.1905840
https://aacrjournals.org/cancerres/article/48/18/5119/492885/Amplification-of-Epidermal-Growth-Factor-Receptor
Robert A. Weinberg seems to have done a LOT of discoveries of oncogenes
https://biology.mit.edu/profile/robert-a-weinberg/
https://www.cell.com/cell/abstract/0092-8674(83)90017-X NRAS
https://www.nature.com/articles/312513a0 HER2
Michael Stratton discovered BRAF and RAS and BRCA2 mutations in cancer; also established the Cancer Genome Project
https://www.sanger.ac.uk/person/stratton-mike/
https://aacrjournals.org/cancerres/article/62/23/6997/509398/BRAF-and-RAS-Mutations-in-Human-Lung-Cancer-and
Mary-Claire King discovered the BRCA1 susceptibility mutation for breast cancer
Mark Skolnick, founder of Myriad Genetics, sequenced BRCA1 and BRCA2
https://en.wikipedia.org/wiki/Mark_Skolnick
Jose Baselga developed Herceptin
https://en.wikipedia.org/wiki/Jos%C3%A9_Baselga
John Mendelsohn developed cetuximab
https://en.wikipedia.org/wiki/John_Mendelsohn_(doctor)
Garth Powis discovered KRAS
https://academic.oup.com/jnci/article-abstract/104/3/228/973198#google_vignette
https://www.appliedinvention.com/ Danny Hillis’s company
https://en.m.wikipedia.org/wiki/Danny_Hillis
https://gsb-faculty.stanford.edu/benoit-monin/topics/do-gooder-derogation-moral-social-comparison/ people are especially eager to derogate “do-gooders” to alleviate feelings of comparative inadequacy. These are the sorts of studies that don’t replicate but I find the theory plausible.
https://en.wikipedia.org/wiki/Harold_Washington
https://en.wikipedia.org/wiki/The_Patriot_Game
https://en.wikipedia.org/wiki/John_Bull symbol of the UK
https://en.wikipedia.org/wiki/Brother_Jonathan precursor of Uncle Sam, symbol of New England
https://en.wikipedia.org/wiki/Tiny_Broadwick pioneering female aviator and parachutist
https://www.panoramaortho.com/wp-content/uploads/2017/09/History-of-DXA-2107-PDF.pdf bone density DXA scans date back to the 1980s
https://www.nature.com/articles/s41390-022-02101-z Claude Bachmann discovered NAGS deficiency, a genetic disease
https://link.springer.com/chapter/10.1007/978-1-4757-6903-6_6
https://link.springer.com/article/10.1186/s13023-016-0406-2 it’s treatable!
https://en.wikipedia.org/wiki/N-Acetylglutamate_synthase_deficiency
https://everythingstudies.com/2022/05/24/the-political-is-personal/
It seems like many people propose “generalization from their own example” as a model for the entire humanity. And it can be quite annoying when people around you agree on a model that doesn’t fit you at all… and when you point it out, they dismiss it by saying that you are in a denial. Because they have examined their own minds deeply, and found out that it was true… yeah, possibly so, but that doesn’t necessarily make it true about the others.
everyone likes whatever popular people around them like—no I don’t
if we legalize gay sex, everyone will want gay sex and families will fall apart—no I don’t feel tempted at all
people are only charitable to other people if they expect them to reciprocate—no I often don’t expect that
...probably many other examples like that.