🧶🧵 Turning 30 today and reflecting on what I’ve learned over the last decade, hopefully this is useful for other people looking for inspiration in solving hard problems:
1) you will not regret doing hard things that create impact 2) be willing to do the work
3) idea and proof of concept is the first step of many 4) build relationships outside of work 5) spend the time figuring out what you are willing to spend 10-20 years on
6) there will be noise, take the feedback that makes sense and keep improving 7) seek to do what needs to be done and to be fair and kind 8) you will not please everyone, focus on what matters 9) embrace the ebbs and flows and cyclical nature of creative work; the order and chaos
10) create cycles to focus on different aspects of your personal, physical, spiritual and business growth 11) try out many hats and explore fit of different philosophies and frameworks 12) embrace uncertainty and stick to your vision 13) don’t give up on your dreams
14) people in your corner will move you forward the most and other people will try to hold you back — pick your battles wisely 15) develop skills in diplomacy 16) understand network and second-order effects 17) take care of your health, it is your greatest investment
18) periods of decompression inspire creativity 19) periods of compression inspire execution 20) small teams innovate 21) keep going if you are aligned with your mission, vision and values 22) keep learning 23) make new mistakes and don’t repeat old ones 24) have fun 25) share
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Important to note that the left diagram is “mean total lipid concentration,” while the smaller organs in the right diagram are “total lipid concentration.” One measure average detection in each organ for each rat, while the other measures total activity of combined rat organs.
There will need to be separate diagnostic criteria for long-COVID sufferers and for those who recover from COVID and have long-lasting secondary effects... this will require new drugs and biologics to rejuvenate damaged tissues, not just manage viral load.
Additionally, edge cases which will be increasingly more common e.g., autoimmunity (whether precipitated by COVID or pre-existing and exacerbated) — will require new looks at autoimmune dampening strategies.
It would be a bad move to simply continue classifying COVID as a binary outcome of survival vs. death, and hospitalization or not. Our entire healthcare system needs to be revamped to prioritize improving people’s health and preventing chronic conditions, not just treating them.
Nicotine exhibits 6.6-fold stronger binding for ACE2 in the presence of the SARS-CoV-2 spike protein, and reduces the binding affinity of the spike protein for the ACE2 receptor.
The effects of nicotine on increasing antibody binding affinity to the SARS-CoV-2 spike protein in competition with ACE2 should also be explored.
With new variants exhibiting even stronger ACE2 binding than the original strain of SARS-CoV-2, and while coupling these findings to the decreased binding affinity of neutralizing antibodies to some of the new strains, nicotine may end up serving an immune-enhancing purpose.
An analysis of 96,057 COVID-19 cases among a ~1.5 million population between March and December of 2020 found a 50% increase in cases during days of low wind speed (<5.5mph) than on days of high wind speed (>5.5mph).
This is an argument for mask wearing.
It will be good to see more data that accounts for individual time spent outdoors versus indoors over the course of a week or two, and integrating contact tracing data and the like. And, creating better assays in outdoor environments to simulate breathing and exposure thresholds.
In the above study, they adjusted an 8-day moving average case count to account for lag between infection and presentation of symptoms.
Some research on changes in neutralizing antibody potency of some SARS-CoV-2 variants of concern (VOC): namely, 1) E484K, 2) N501Y, 3) ∆69/70 + N501Y + D614G, and 4) E484K + N501Y + D614G. Out of these VOCs, E484K mutants are showing greatest escape potency for vaccinated serum.
N501Y:
"The N501Y mutation in SARS-CoV-2 spike leads to morbidity in obese and aged mice and is neutralized by convalescent and post-vaccination human sera" medrxiv.org/content/10.110…
Recalling a conversation with a successful biotech founder who had raised several hundred million with 2x exits, asking what I can do to move things forward faster. He told me to stop and smell the roses.
Good reminder that working more doesn’t always make things move faster.
Certainly, the founder mindset should be “what else can I do,” and setting up to do the critical things at superhuman speeds. At the same time, especially when it is a long game, the clarity of silence and resetting your mind can lead to hyper-productive, time-saving insights.
“[W]e've come to believe that world-class performance comes after 10,000 hours of practice. But that's wrong. It comes after 10,000 hours of deliberate practice, 12,500 hours of deliberate rest, and 30,000 hours of sleep.”