BC DESIGN
Saved by @CodyyyGardner

@PaoloWalnuts I looked into this as I was very surprised and thought it could be quite dangerous to go against the trial design.

I learnt a lot while i was doing it! There are a lot of misunderstandings and quite a few counterintuitive bits as well.

Thread...

 @pcmac41 @PaoloWalnuts There's some obvious stuff like the fact that the JCVI is a longstanding body with a lot of very bright folks on it. Also, again stating the obvious, immunology and immune responses are really complex.

I've worked on a mAb and i will happily admit i didn't get the details! 1/
@pcmac41 @PaoloWalnuts To digress a little, i think AZ have serendipitously learnt lots about adenovirus vaccines through the seeming unplanned hiccups in their study. This is all brand new tech and it wasn't entirely obvious beforehand that small initial dose and long interval would be good. 2/
@pcmac41 @PaoloWalnuts It makes sense afterwards (for an adenovirus vx) and it also confirms why longer time between doses can be good. You let the vx get all the way through "teaching the body how to respond a little bit, and once it's developed its response it's way more efficient with the booster 3/
@pcmac41 @PaoloWalnuts Which begs a critical question that really bothered me: why did pfizer go with a 21dy regime? We have to trust what they say don't we? 4/
@pcmac41 @PaoloWalnuts Well... it's complicated.

I know how limited pfizer are in what they can claim. If they don't have data to prove something they can't claim it, even if it *really* is obvious. They have data on 21 days so they either stay quiet or they say the data support 21dy interval. 5/
@pcmac41 @PaoloWalnuts That's basically the law on how you can market any drug, and companies have rightly got into big trouble in the past for promoting use of medicines in ways they don't have data to support. 6/
@pcmac41 @PaoloWalnuts Key thing here is that an absence of proof that something works is just that. It's NOT proof that something won't work.

So, why choose 21 days? 7/
@pcmac41 @PaoloWalnuts A lot of the time spent developing drugs is in phase 2a where you try to find an effective dose and an effective dosing regime. Where you have a single dose that's easy: run three groups of pts - placebo, dose 1, dose 2. Which is best and do you have dose dependent effects? 8/
@pcmac41 @PaoloWalnuts But this is a pandemic and we need this vx yesterday. We don't have 2-3 years to get this perfect as there'll be lots of dead people this vx can save. (Also being first to market is a good thing for the company).

21 days should long enough to work but quick enough to get data 9/
@pcmac41 @PaoloWalnuts So in many ways it kind of is that simple, and the theory behind a longer duration is sound.

I'll try to hunt out the threads i came across. 10/
@pcmac41 @PaoloWalnuts One thing did strike me though. A lot of the people criticising this plan were bright folks: Drs, biologists, medics, even the odd chemist. Generally folks who do believe in science ahs in the regulators. What gives? 11/
@pcmac41 @PaoloWalnuts Well, partly, it's folks bright enough to be dangerous but who are not experts in the complexities of immunology (hello! 👋).

I also think it's been poorly communicated though. I understand why - in many ways JVCI, SAGE, MHRA et al have a lot to worry about right now! 12/
@pcmac41 @PaoloWalnuts But it's also something that sounds initially odd, that cobras some bright folks and is really quite scary for those who are directly affected. It's horrible and frightening to be told your appt is being delayed. Better communication would be good. 13/
@pcmac41 @PaoloWalnuts Also, the rationale is excellent. If i have 20 doses and 20 people i can give all of them 85%* protection or half of them 95% protection.

Clearly, in this case, giving everybody 1 dose will provide much more protecting and save very many lives.

*I'm coming on to this... 14/
@pcmac41 @PaoloWalnuts The pfizer data clearly show that the vx is giving excellent protection after 20 days. But wait? It's only 50% effective after 20 days? Right?

15/
@pcmac41 @PaoloWalnuts Wrong.

The numbers are skewed by all the pts who were infected before they were given the vx, or in the 7-14 days after it was administered. The fact that those folks get covid doesn't tell us how effective the vx is (just how long it takes to start working). So? 16/
@pcmac41 @PaoloWalnuts So we ignore them when working out how effective it is. And when we do that we can see that the first dose prevents about 85% of the infections that are seen in the placebo group.

We don't need to worry about the vaccine being effective after 1 dose. It is, stunningly so. 17/
@pcmac41 @PaoloWalnuts What we don't know is how quickly the response to the first dose will fade. But the intervals only increased to 12 weeks, not 12 months and as i said earlier there's reason to imagine that this may well be more effective for similar reasons to why it works for the AZ/ox vx 18/
@pcmac41 @PaoloWalnuts Enough now. I'll try to find the threads and the tweeters who deserve to be followed in this and link them below. Fin.
@pcmac41 @PaoloWalnuts It was a conversation with @ChrisMcQuilla13 and @chemistrykaren got me thinking twice about my initial instinct that this was the wrong thing to do. Chris also made a summary point that i think is bang on the money:

https://t.co/5nw32LPiEk
@pcmac41 @PaoloWalnuts @ChrisMcQuilla13 @chemistrykaren That introduced me to @sandyddouglas with this fascinating thread

https://t.co/WkD6pFZVbz

@Sandyddouglas
@pcmac41 @PaoloWalnuts @ChrisMcQuilla13 @chemistrykaren @sandyddouglas Later I also came across this thread where @petermbenglish (via @trishgreenhalgh ) gave me a lightbulb moment about why pfizer chose 21 days

https://t.co/U3OEnGOrpw

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👇


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We included the partners of the festival in the most integrated way by making them part of the actual space such as this car for a well known German brand. We also focused on the screens in the lobby through a system of spritesheets.
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Thread on models and bounded contexts 1/9

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10 ideas that changed my life: (thread)

Illustrations by @visualizevalue

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Neumorphism is a trendy UI style nowadays. So let's create a neumorphic form using few simple steps

THREAD🧵


Neumorphic design is another UI design that has become popular these days.

Making neumorphic effect is actually pretty easy using only just CSS box-shadow

We'll be creating a neumorphic form in steps👇🏼

2.

STEP 1:

Place a light source(virtually) on screen. In this example I'm considering that my light source is placed top left corner of the screen

3.


STEP 2:

Create a container div and set background color slightly darker than white. I picked #ecf0f3

* Make sure that the color of body and container should be same

CONTINUE...

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As we placed our light source on top-left corner, make sure left and top border of container should be brighter than right and bottom border.

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It's quite instructive looking at fonts with problems! I see the same mistakes when Latin-accustomed designers tackle Southeast Asian scripts. Here are the main ones...

1. In Latin, we make the arches of m a bit narrower than in n, but this is not a universal principle! As a rule don't assume this applies to other scripts. Don't start condensing letters with more bowls in Burmese or Thai. Use the same element...


...but be aware of exceptions! Better to take your lead from locally-designed fonts, where native designers know the proportions. There's no substitute for careful examination of plenty of other designs...

In Latin, though we may not see it, we balance shapes towards the baseline. The bottom half of B, 3, S or H is larger than the top half, as we see when flipping these letters. This is not a universal rule!


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Budhwar - Budhi Vasa
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This stem is burnt and rubbed against the grinding stone in mother's milk or warm water to get a paste


The procedure to make it is in the link

https://t.co/uo4sGp7mUm

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For children who haven't got their speech and is delayed than usual should feed this vasa on these days in week atleast for 6months. Don't get carried away with this dialogue
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We're basically fucked.

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Techies take weird, improbable visions, and make them realities: some BS pitch deck to a VC, mixed with money and people, really does turn into some novel thing.

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ok never mind I'm fucking doing this now.

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THREAD: What is Golden Crescent and Golden Triangle and how it impacts India?

Golden Crescent region of South Asia - comprises of Afghanistan, Iran, and Pakistan - which is a principal global site for opium production and distribution.


Golden Triangle is the area where the borders of Thailand, Laos and Myanmar meet at the confluence of the Ruak and Mekong rivers. The Golden Triangle is called so because of the triangular shape formed by the locations of New Delhi, Agra and Rajasthan on a map.


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- Golden Crescent is world’s leading opium and cannabis producing region since 1983.

- Its proximity to Indo-Pak border has worsened the trafficking of hashish and heroin into Indian soil

- Trafficking happens through the border states of J&K, Punjab, Rajasthan and Gujarat.


- Golden Triangle is leading opium producing region of the South-east Asia, also an ancient narcotics supply route to North America & Europe.

- Myanmar-Northeast nexus is recognized by NCB as the root of heroin & chemical drugs

- Myanmar produces 80% of heroin produced in world
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