THREAD: Understanding pivot. Growing pressure from world population life-style will reach a point where it is damaging the capacity of Earth systems to an extent where life support will be challenged. It is simply a question of at what stage governments act. 1/X

With @franklowery our new study on attributes of T cells that contribute to successful cell therapy in cancer patients in @ScienceMagazine today w/ colleagues @slgoff_SB, @NCI_CCR_SB @theNCI a TL;DR thread on key findings with caveats :) 1/10

has a long history of using tumor infiltrating T cells (TILs) to treat cancers since well.. before I was even born. We analyzed our most successful melanoma ACT trial for cell surface phenotypes in TIL infusion products of patients (aPD1/immunotherapy naive) /2

Surprisingly we found a CD39- TIL subset (CD39-CD69-, DN) associated with ACT-response. TBH we were expecting the opposite (CD39+). We only included CD39 bcz multiple groups (e.g. Simoni et al, 2018) had reported CD39+ as enriching for anti-tumor/neoantigen reactive T cells. /3

CD39- DN TILs RNA/epigenetics resemble stem-like memory progenitors, and in vitro were able to self-renew, and give rise to other CD39+ subsets. OTOH the most dominant subset of patient infusion products were CD39+ CD69+ (DP) and these guys were terminally differentiated.. /4

So, to clarify we specifically analyzed tumor-specific mutation-reactive Tcells. Turns out, ACT-responders had pool of neoantigen-reactive TILs in the CD39- phenotype, while non-responders did not (despite other irrelevant CD39- Tcells) -> not all CD39- T cells are bystanders /5

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Get a cup of coffee.

In this thread, we'll cover *State Quantities* and *Flow Quantities*.

This mental model can help us analyze many different entities -- from complex engineering systems to publicly traded companies.

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A "State Quantity" is something that's associated with a *specific point in time*.

For example, the number of followers a Twitter account has is a state quantity. This number can go up and down over time. But at any one *specific* time point, it's fixed.

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Similarly, the amount of cash a company has is a state quantity.

This cash balance can also rise and fall over time.

But pick any one *specific* time point -- and the company can only have one *specific* cash balance at that time point.

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By contrast, a "Flow Quantity" is something that's associated with a time *interval* rather than a time *point*.

For example, the number of followers gained by a Twitter account is a flow quantity. It's meaningful only when we specify a time interval (eg, the last 30 days).

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A simple analogy is that a State Quantity is like a photo -- a snapshot at a particular *point* in time.

But a Flow Quantity is like a video -- a record of events that take place during a particular time *interval*.

In physics, energy is that which is causally invariant or symmetric with respect to time. Said differently, energy is never created or destroyed, it is conserved in the universe.

Now there is a question about information. Is information causally invariant? Does information remain the same with respect to time? To understand this, let's first understand what energy is, then attempt to understand what information is.

The strange thing about energy is that it is this universal currency that seems to be interchangeable between the different forces in nature (i.e. electromagnetic, strong, weak and gravity). It is that thing that makes change possible.

Now let's assume that the universe is computational in nature. That is, anything we see in nature is a consequence of computation. That is, there is computation underneath the physics that is driving the universe to change.

What does it mean then that information is conserved in this computational universe? Also, how is energy conservation related to information conservation?

"We have purposely avoided directly confronting the issue of masks because it is such an emotional and political issue. Like waving a red flag in front of a bull, the topic elicits strong emotions which overwhelms

We wear a mask in the hospital and don a N95 mask, gown and gloves when we see a patient known to have COVID-19. Masks are used for source control when patients are admitted with various types of infectious respiratory diseases

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After the visit, we dispense of the gown, gloves and change into our regular surgical mask to continue patient rounds. In public, we wear a cloth mask to comply with executive orders and as a courtesy to others who feel afraid and uncomfortable.
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Like most of you, we rarely wash the mask, we stick it in our pockets, pick it out of the glove compartment or off the floorboard when we need it.

In truth, we wish masks worked. If they did, it would be a cheap, and easy way to control the spread of Covid.

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The idea that they protect not only their wearer, but also those people around them seems noble. We wished masks worked because citizens are spending billions of dollars on them.

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https://t.co/xvP6tVlIaE
Quite a surprise. Ferguson isn’t qualified to comment on such things. He lacks understanding of basic biological concepts, partly explaining why his predictions are often so extreme.

That said, I’ll take him as an ally. It’s clear we’re already at herd immunity. How can I be sure? London had a huge peak of excess deaths in spring. The timing of peak deaths showed clearly that the pandemic was self-limiting. Recall much debate about whether the interval...

...between lockdown & peak deaths was long enough for lockdown to have been the cause of reducing deaths? The answer was “no”. But it was close & I can understand people thinking “well, it’s close, so perhaps it was lockdown that did it?”, thereby establishing a foundational...

...myth favoured by those who genuinely believe lockdown saves lives (it clearly doesn’t).
I’ll get to London & here immunity. But those wavering about the evidence about lockdown in spring really will benefit from cogitating on this graph.

In blue are the 30 trusts with the earliest date of peak deaths in spring. In red, the 30 with the latest peak deaths. For me, this is proof that national lockdown, which began Mar 23, played no role whatsoever in turning the pandemic. You’ll see some areas had peak daily...