Sugoi & Yokunai

Venting doesn't reduce anger. I never thought it did. Only calming maneuvers do.

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In northern Brazil, near the city of Belém, a strip of rainforest about eight miles long was cleared to build a four-lane highway in advance of the COP30 climate summit that began on Monday. The highway, dubbed Avenida Liberdade, is intended to handle the surge of delegates and dignitaries expected for the gathering.

...Critics are pointing out the blatant irony of cutting down a protected rainforest for a climate conference that is itself aimed, among other things, at halting deforestation.
“They ripped the hell out of the Rainforest of Brazil to build a four-lane highway for Environmentalists to travel.

Gavin Newsom will be there.––– 良くない–––

The findings suggest that intensive meditation can trigger very similar brain activity to that which has been previously documented with psychedelic substances. 

“We're seeing the same mystical experiences and neural connectivity patterns that typically require psilocybin, now achieved through meditation practice alone,” added Patel. “Seeing both central nervous system changes in brain scans and systemic changes in blood chemistry underscores that these mind-body practices are acting on a whole-body scale.”

Urolithin A supplements rejuvenated the aging immune system in just 28 days. It's rare to see a clinical trial demonstrate something like this, instead of just in vitro or in mice/rats. I don't usually link those articles. But here, it was shown that in a healthy middle-aged cohort, urolithin A supplementation expanded the CD8+ lymphocyte population, enhanced mitochondrial biogenesis, and modulated inflammatory pathways towards a more youthful profile. Paper here.  

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This report has been on the news, claiming that the mRNA vax was associated with less inflammatory complications than getting COVID-19 itself in those younger than 18.  Paper here. Is that really true? Let's dive in.

First of all, I noticed that the study population was from the cohort 1/01/2020 to 12/31/2022. While the vaccination cohort was from 8/06/2021 - 12/31/2022.  The latter period was when the original dangerous strain was largely gone and we were starting to see the milder omicron strain. So already, the vaccinated group consisted of those who were infected by milder disease than the "non-vaccinated group".  They recognized this, and tried to introduce adjustments that they thought would compensate for this. They should have just studied both from the same time period. 

The second thing, is look at the raw numbers:

Really not a whole lot of difference between the two populations. The highest difference is in Kawasaki disease, which is not even connected to COVID-19.  For myocarditis and pericarditis there was LESS incidence with COVID than with the vaccine!  The reason they included Kawasaki disease is because they thought that some cases of heart inflammation might not be counted as COVID but as Kawasaki, so they didn't want to miss the diagnosis – so they threw it in and counted it!  

So it would seem that there is no big difference whether you got the vax or not. But then they did something questionable (to me). They based it on the observation that when you got sick with COVID you were mildly ill but there were a more drawn out period of events. Whereas if you got the vax, you got really sick in the beginning, but afterwards there were very few events. 
So they make calculations of what they called aHR (adjusted hazard ratios) and found that the risk of getting some complication was higher in non-vaccinated than vaccinated, just because the vaccinated got all their bad events at the beginning. 

The main conclusion is based on this figure:

where you can see that the main disadvantage of getting sick with the virus was just in the inflammatory conditions, but most of these children had Kawasaki disease. I haven't heard anyone saying that the vax prevents Kawasaki disease in children, so I would attribute this to a difference in how this diagnosis was made.
These are calculated 6-month absolute excess risk, and makes the vaxxed group look worse because the events are scattered out over the year, rather than bunched up at the beginning like with the vax. The selection of 6 months as the estimation point was arbitrary. I would have used another technique called "area under the curve" to see overall differences, rather than just at one timepoint. 

There's the usual trust issues, and concerns about return on investment. I'm not that interested in this because I know that many or most companies are still feeling their way with AI and many are just using public chat bots with no prompt training. And that generative AI tools we have now are still fairly early, despite their already impressive achievements. We're not where we need to be, and much of what we see is illusory, in terms of real comprehension and understanding, which is what we really need to see.

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An illegal immigrant convicted of sex crimes in Oregon, a sanctuary state for unlawful immigration, held various advisory positions on state policymaking committees as a so-called “Latinx” community leader.

This looks really promising. In 2018 this group found the antibodies to CD40 were potent antitumor agents, but there was platelet and hepatic toxicity that precluded systemic administration. But if you inject it directly into the tumor, the side-effects are much reduced, and there are no dose-limiting toxicities. Furthermore, you see an abscopal effect!  Here's a nice diagram that shows all the things CD40 agonist antibodies can do.  The upregulate MHC molecules and increased expression of OX40L, 4.1BBL, CD80 and CD86 which are costimulator antigens that can engage with CD28 on T-cells to enhance antitumor activation. Not shown in the diagram is that CD70 and also be upregulated, which engages with CD27 on T cells and NK cells to activate them as well.  On macrophages, agonist CD40 antibodes turn them from the M2 phenotype to the more active antitumor M1 phenotype. And when these antibodies find to CD40 ligand on tumor cells, apoptosis is triggered, and the dead cells release antigens which the immune system can recognize and train against. This explains the amazing results seen in the phase I study. 

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