Bryan, I know you have mentioned that some of your autoimmune issues started before you started avoiding the sun. Regardless, I believe this information is important for you to read, maybe it will just tickle your curiosity, and maybe it will get integrated into your team’s model of understanding going forwards. In this long post I'll try to lay out some of the complexity present within the light-immune system axis, with the aim of reinstating humility when it comes to understanding such complex systems, and preventing the iatrogenic mistakes that come from reductionist thinking and the dunning-kruger effect of being at the cutting edge of knowledge and testing, which can lead to losing the forest for the trees. This is meant to be helpful. It aims to expand the perspective you take on light, cus from the outside it looks like youre still treating sunlight as solely a source of vitamin D (which you then just supplement instead), religiously avoiding midday sun, umbrellaing and creaming away the entire UV spectrum, and discounting the rest of what that light is actually doing in the body. I just think your model of the trade-offs of sunlight are incomplete. UV is about 3% of the solar spectrum. Tiny sliver. But humans (and life in general) evolved bathing in it for hundreds of millions of years. When something that small has been a constant selective pressure for that long, biology tends to wire it in as a signal (not just a stressor). The dose means everything, and we can see the body constantly tuning this dose to our benefit with changing behavioural patterns and skin melanin content. The field that studies this properly is photo-neuro-immuno-endocrinology. The core finding is that skin isn't just a barrier. Its a full peripheral neuroendocrine organ. When UV hits it, keratinocytes and melanocytes and mast cells and Langerhans cells start producing and releasing a whole orchestra of messengers. POMC and its cleavage products (ACTH, alpha-MSH, beta-endorphin), CRH, urocortins, enkephalins, serotonin, melatonin, even TRH/TSH and thyroid hormones locally, catecholamines, endocannabinoids. Cool stuff. And these dont stay in the skin. They enter circulation, they activate the central HPA axis, they signal immune tissue. Your skin is essentially broadcasting systemic instructions coded by the light it's exposed to. Of course it does, the body takes in as much information as it can to calibrate an allostatic response to maintain homeostasis. That in and of itself renders any model of understanding that suggests supplementing D is adequate, completely reductionist. You cannot pill this. A vitamin D capsule doesnt trigger cutaneous and central POMC. It doesnt release beta-endorphin from your skin into your brain. It doesnt drive the urocanic acid photoisomerisation pathway. These are photonic signals that cannot be short-cutted. It is proof of work. Now to bring it back to your specific situation. You have autoimmune thyroid disease and now autoimmune gastritis. Two autoimmune conditions closely tied together. Your whole intervention stack for the AIG is aimed downstream at the immune activation itself. Damp the cytokine signalling (JAK/STAT, IL-17), rebuild regulatory T cells (low-dose IL-2, iTregs), and at the frontier, CAAR-T to delete the rogue B cells. It is impressive and genuinely awesome what we can do these days. But I fear it lacks coherence. We measure and measure and measure what we can, and think we see the whole picture. But we don’t. Low-level tinkering while ignoring high-level evolutionary inputs puts you in danger of iatrogenic dunning-kruger maxxing. Meanwhile UV light is one of the oldest Treg-induction and tolerance signals we have, and you're blocking it 24/7. Why would this not be the first thing you integrate into your protocol? To prevent some skin damage? Remember, trade-offs… they are inescapable in this biological world. Just because you can’t measure them immediately, doesn’t mean they won’t rear their ugly head years later. This isn't as hand-wavy as it may first seem to the uninitiated. The mechanism is mapped out quite nicely already. UVB hits the skin → Langerhans cells (the resident antigen-presenting cells in the epidermis) migrate to the draining lymph nodes → they induce antigen-specific, Foxp3+ regulatory T cells → those Tregs circulate and dampen inflammation systemically. Sasaki (I’ll put references at the end btw) showed in 2017 that UVB exposure inhibits atherosclerosis in mice by expanding exactly this CD4+Foxp3+ Treg pool and suppressing pro-atherogenic Th1 activity. When they depleted the Langerhans cells, the protection vanished completely. LC-dependent immune-regulation. UV radiation suppresses experimental autoimmune encephalomyelitis (the MS model) independent of vitamin D production. And the MS latitude gradient (way more MS the further you get from the equator) has never been fully explained by vitamin D levels alone. UVB seems to be doing tolerance work through the POMC → alpha-MSH/ACTH axis, peptides with anti-inflammatory and neuroprotective activity. Then theres urocanic acid. UCA sits in your stratum corneum, and when UVB hits it (280-310nm) it photoisomerises from trans to cis-UCA. cis-UCA is water soluble, enters circulation, shows up in serum and urine, and is a potent systemic immunomodulator. In a psoriasis model it dropped IL-23 and bumped PD-L1 on Langerhans cells. IL-23/IL-17 driven autoimmunity. It seems clear that the direction of your interventions and the direction of your light avoidance are contradictory. You're trying to build tolerance pharmacologically while removing a free, evolutionarily-tuned tolerance input at the environmental layer. Remember forest for the trees. Now, it cuts both ways (it usually does in Nature). Remember, trade-offs… always. UV genuinely has two faces. It photodegrades folate (esp UVA), which is why melanin evolved as a shield in high-UV latitudes. It damages DNA, generates ROS, and yes chronic, excessive, burning exposure raises skin cancer risk. The pigmentation gradient across human populations IS the evolutionary compromise between making enough vitamin D & absorbing general benefits of the spectrum of light and not frying your folate and genome. So the answer is never to block everything OR to bake all day without exception. Its dose, context, spectrum, skin type, latitude, season, timing. Intuition understands this. And wavelength specificity is where any strategy attempting to block certain wavelengths and distorting the natural spectrum of sunlight really falls apart, because UVA and UVB are NOT interchangeable. They hit different chromophores and activate different circuits. An example would be a study looking at UV eye irradiation in a mouse colitis model. UVA through the eye IMPROVED the colitis. UVB through the eye WORSENED it. Opposite outcomes in the same organ with a different wavelength. UVB is around 1000x more biologically potent per photon (minimal erythema dose) and mostly hits the epidermis. UVA penetrates deeper to the reticular dermis and works more through ROS and NO release. When you deploy a UV umbrella and broad-spectrum sunscreen you aren't making a precise call, you're nuking the entire signalling band cus you only accounted for one output (vitamin D). Also the skin isn’t the only organ doing the sensing. The eye is a second, separate light antenna wired into the same central machinery. UVB through the eyes drives the hypothalamic POMC response through an NO-dependent route via the ciliary (parasympathetic) ganglia and the ophthalmic branch of the trigeminal nerve. UVA is different again, it reaches the retina and signals to the brain via the optic nerve. Different wavelengths, different nerves, different circuits, all feeding into the same neuroendocrine control centre. This is what coherence starts to look like. Sunglasses-outdoors-always habit isnt neutral. It blocks a key signalling channel into the hypothalamus that your body spent hundreds of millions of years designing & perfecting. And regarding vitamin D, the biggest lesson I think conventional medicine could learn is to move away from a ptolemaic model of understanding. It puts vitamin D at the centre of the UV universe and assumes everything orbits that one molecule, so blocking UV + supplementing D looks like a clean win with no cost (trade-offs trade-offs trade-offs). The actual biology is Copernican. UVB spins off a whole constellation of photoproducts (the CYP11A1-derived hydroxymetabolites, lumisterol, tachysterol, once assumed inert, now known to be enzymatically activated and bioactive in serum) hitting multiple nuclear receptors (VDR, RORs, AhR, PXR), running in parallel with an entire neuroendocrine and immune signalling network that has nothing to do with serum 25(OH)D at all. I don't think you can capsule this constellation. Or the tolerance signal your immune system reads through your skin. All this to say, maybe it is worth considering the idea that UV light is not a pure toxin. Maybe, through the course of billions of years of evolution, Life figured out a way to incorporate some of that high photonic energy into something useful. Maybe it figured out a favourable trade-off. pnas.org/doi/10.1073/pnas.23… pubmed.ncbi.nlm.nih.gov/2719… pmc.ncbi.nlm.nih.gov/article… pubmed.ncbi.nlm.nih.gov/2289… pubmed.ncbi.nlm.nih.gov/2531… pubmed.ncbi.nlm.nih.gov/2030… pubmed.ncbi.nlm.nih.gov/1253… pubmed.ncbi.nlm.nih.gov/2742… pmc.ncbi.nlm.nih.gov/article… pubmed.ncbi.nlm.nih.gov/1388…

All languages covey information at a similar rate when spoken (39bits/s). Languages that are spoken faster have less information density per syllable! One of the coolest results in linguistics.

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Last week, public software markets suffered significant compression. MongoDB fell 24%; UIPath fell 36% ; Salesforce fell 15% ; Workday was down 11%. Weaker revenue projections tend to cause sell-offs. These large drops aren’t unprecedented. In 2016, valuations fell 57%. Is it different this time? Growth rates have changed meaningfully. The 25th, 50th, & 75th percentiles for public growth rates have halved in the last 18-24 months. The grey bar indicates Covid ending & marks the beginning of the slide. Each of these percentiles is now meaningfully lower than the average over the past decade. Top quartile companies in 2024 grow at the same rates as bottom quartile companies in 2018. Future revenue ramps have been the dominant driver of software valuations for the vast majority of the last decade. When they fall, valuations compress. Some context is helpful : during the same period, total software revenue across the public companies grew from $124b to $592b. The overall market has ballooned. In the last 12 months, public software companies will grow on average 17%, which will add $100b in revenue across these businesses. Looking at the changes in software revenue, we see that the market is on a straight line to surge past $100b. Covid catalyzed $100b in new software revenue bookings in 2022. At a 6x revenue multiple, that’s $600b in market cap. There’s plenty of value creation to be seized. But for many of the largest companies, the law of large numbers & the bigger bookings figures demanded by financial plans impose challenges. Salesforce has sustained double-digit revenue growth for two decades as a public company. With 150k+ customers, saturation is a challenge, despite a broad product suite to cross-sell. With $35b in 2024 revenue, Salesforce’s 10% revenue growth target is $3.5b net new bookings - equivalent to adding Atlassian’s or Crowdstrike’s entire revenue this year. Also, the average age of these companies is now 20 years old since founding. The lack of software backed IPOs in the last few years aside from one or two exceptions has meant the old guard dominates these indices. The average number of VC-backed software companies in the US in the last three years is less than a third of the average over the last decade. Instead, the 40-60% wild horses grow in the private markets, absent from these figures. Some of the older software companies are slowing - a natural part of the lifecycle. But it would be a mistake to extrapolate that to the entire market. The private markets hide the fastest growing companies. tomtunguz.com/weakness-in-so…

Is Klay Thompson vandalizing houses in Sacramento with bricks? Twitter's AI Grok suggests this may be the case after a copypasta went viral.