I've been seeing a lot of discussion around the dosage gaps recommended by government for the Astra/Oxford & Pfizer/BioNTech vaccines. My thoughts on the potential benefits & risks of such an approach, and the need for much greater transparency around these decisions. Thread.
What is the basis of this?
1) the first dose is likely to confer some degree of protection against disease, so better to roll this out as fast as possible, and
2) that for Oxford/Astra efficacy may be higher when the gap between doses is greater.
Vaccine efficacy among 18-55 yr olds SD/SD dosing was 59% vs LD/SD dosing at 90%.
Is this due to dosing, or differences in gaps between doses?
Differences in gaps don't appear to impact efficacy in this analysis.
It looks like the first dose prevented all severe disease (although numbers were small) in the SARS-CoV-2 vaccine group compared to vaccine control after the first 21 days of vaccination, and <14 days after the 2nd dose.
U.S. is now considering idea of a single vaccination shot, delaying shot #2 until months later. Last wk, I thought that was a bad idea \u2013 the trials that found 95% efficacy were 2 shots; why add extra complexity & a new curveball. But facts on the ground demand a rethink. (1/7)— Bob Wachter (@Bob_Wachter) December 31, 2020
1. Resources for roll-out are limited & fixed & we need to optimise how best to use them within limitations
2. There isn't significant decline in immunity after the 3 wk mark
3. Later dosing will not affect overall efficacy
A key part of the rationale appears to be a bottleneck in vaccine supply (rather than roll-out).
More from Deepti Gurdasani
First, there is strong evidence to support increased transmissibility of B117 - current estimates of increased transmissibility range between 30-70% - from epidemiological evidence examining the differential rate of growth of B117 with respect to other variants & increase in R
There is also evidence from PHE contact studies that the risk of transmission from those carrying the B117 variant is ~50% greater than with other non-B117 variants.
Increased transmissibility, even if a variant has the same fatality rate can increase deaths substantially, because the rate of growth of cases is higher- & more cases means more deaths.
Increased fatality rates also increase deaths- but do so
So how was risk of death with the variant studied?
We don't routinely sequence all samples for the virus. We've found that the variant has a particular deletion which means that some PCR tests on samples with the variant give a different read-out when the variant is present.
I've heard a lot of scientists claim these three - including most recently the chief advisor to the CDC, where the claim that most transmission doesn't happen within the walls of schools. There is strong evidence to rebut this claim. Let's look at
The science shows us that most disease transmission does not happen in the walls of the school, but it comes in from the community. So, CDC is advocating to get our K-5 students back in school at least in a hybrid mode with universal mask wearing and 6 ft of distancing. https://t.co/dfvJ2nl2s4— Rochelle Walensky, MD, MPH (@CDCDirector) February 14, 2021
Let's look at the trends of infection in different age groups in England first- as reported by the ONS. Being a random survey of infection in the community, this doesn't suffer from the biases of symptom-based testing, particularly important in children who are often asymptomatic
A few things to note:
1. The infection rates among primary & secondary school children closely follow school openings, closures & levels of attendance. E.g. We see a dip in infections following Oct half-term, followed by a rise after school reopening.
We see steep drops in both primary & secondary school groups after end of term (18th December), but these drops plateau out in primary school children, where attendance has been >20% after re-opening in January (by contrast with 2ndary schools where this is ~5%).
To recap - NHS capacity is critical in many places. Hospitals have reported oxygen shortages, and doctors are talking about having to choose who to put on ventilatory support. We have rapidly rising case numbers, >50,000 daily reported cases & 981 deaths reported yesterday.
Let's remember that the impact of socialising over christmas hasn't even begun to show in our numbers yet. And that hospitalisations are indicative of infections that happened ~2-3 wks ago (since then we have been seeing exponential rises in cases).
This means even if we act today, and bring R to below 1 right now, hospitalisations will continue to rise for another 2 wks or so - in line with exponential rises in cases over the past 2 weeks. And deaths will continue to rise for 2-4 wks after we act.
Given current doubling periods, this means very conservatively, 20-30,000 deaths over the next 4 weeks or so, which we sadly can't do anything about now, because most of those who will die during this period have already been infected.
U.K. needs to confront— Esther McVey (@EstherMcVey1) January 2, 2021
\u2018The challenge that faces us is to decide - are we going to try to pursue the elimination of Covid-19 regardless of the costs or decide on a tolerable level of deaths (like we do with the flu) in order to return to a normal life?\u2019
Had we adopted an elimination strategy early on, rather than one of tolerating a certain level of infection, we wouldn't be here now. The reason we're here is because the govt never committed to elimination.
We eased lockdown in May when infection levels were much higher than when other countries in Europe did this. The govt was warned about this, but did this to 'help the economy'. Not only did this lead us into the 2nd wave, the need for further lockdowns harmed the economy further
It's very clear from global evidence that we cannot 'tolerate a level of community transmission' and maintain 'R at or just below 1', which has been our governments policy for a long time. This isn't sustainable & very rapidly gets out of control, leading to exponential rises
Coupled with late action to contain these surges, not only does this lead to many more deaths, and much more morbidity with Long COVID, it also creates a fertile ground for viral mutations to accumulate with a greater risk of adaptation, which is exactly what happened in the UK
Cases have been rising exponentially in England- much of the increase being attributed to the South, although declines have slowed even in the North following easing of lockdown. Much of this is anticipated, and expected, given the behaviour of the virus. 2/N
SARS-CoV-2, like any other viruses mutates as it multiplies (albeit slower than influenza). Mutations occur randomly and most are 'neutral' - i.e. have little to no effect on transmission, ability to evade the natural or vaccine-related immune response
Having said that, few mutations have been shown to be less likely to be neutralised by plasma from patients infected by the usual (wild-type) virus. Whether this translates to a lower response to vaccines or higher risk of re-infection is unclear at the moment.
Also worth noting that just because a variant becomes more frequent in a region doesn't necessarily mean it offers a fitness advantage to the virus. Many mutations rise to different frequencies in different regions due to random processes. The frequency of strains varies globally
More from Government
1. On January 6, 2021, the United States witnessed an unprecedented effort by American citizens to violently subvert the democratic will of the American people...
After months of promoting baseless claims of voter fraud, which were rejected by the judiciary in dozens of cases, President Trump encouraged supporters, some armed, to storm the U.S. Capitol while Congress was certifying the results of a free and fair presidential election...
His incitement led to a violent riot in the U.S. Capitol, five deaths, untold injuries, destruction and vandalism of government property, and incalculable damage to our democratic system and our image abroad...
He played an integral role in breaking the 220-year streak of peaceful transfer of power between political parties during U.S. elections. (End of point 1).
STATE DEPARTMENT DISSENT CABLE POINT 2:
The Department of State should explicitly denounce President Trump's role in this violent attack on the U.S. government. Just as we routinely denounce foreign leaders who use violence and intimidation to interfere in peaceful democratic...
2/10 Most States protested the declaration as it was in breach of the law of the sea at that time. Such baselines also converted high seas within the Country into internal waters thus invited strong objection from maritime powers having strategic military interest.
3/10 Indonesia was not comfortable with the label of ‘breaker of international law”, and stood up for its defences by fighting for recognition in the UNCLOS making conferences. Indonesia was neither silent and nor keep it unresolved, but ready to talk and compromise.
4/10 A prominent international law scholar, Mochtar Kusumaatmadja,translated the declaration into a legal narrative,using the language of international law, thus understood by maritime lawyers. Then skillfull Diplomats i.a. Hasjim Djalal brought the texts to the diplomatic table.
5/10 Mochtar explained behind the unilateral Declaration: Indonesia has to ensure and safeguard its national and political unity as well as its territorial integrity, the very viability of Indonesia as a nation. He emphasized: seas shall connects instead of separate its islands
I don’t think the sharp opposition between “hard-edge populism” & “conservative orthodoxy” holds. Many of the Trump administration’s achievements were boilerplate conservatism. Its own website trumpets things like “massive deregulation,” tax cuts, etc. /2
The claim that Buckley and “key GOP politicians banded together to marginalize anti-Communist extremism and conspiracy-mongering” of the JBS has been widely repeated lately but the history is more complicated. /3
This tweet by @ThePlumLineGS citing a paper by @sam_rosenfeld and @daschloz on the "porous" boundary between conservatives, the GOP and the far-right is relevant in this context.
There's a great paper called "The Long New Right" that tells the story of the GOP/conservative movement's failure to police extremists for the last 50 years.— Greg Sargent (@ThePlumLineGS) January 28, 2021
It's highly relevant to the insurrection and Marjorie Greene's lunacy.
I summed it up here:https://t.co/DTlzGomy5h pic.twitter.com/Dhc38CDuE2
This is a separate point but I find it interesting that Gaetz, like Roy Moore did In his failed Senate campaign, disses McConnell. What are their actual policy differences? MM supported taking health care away from millions, a tax cut for the rich, conservative judges, etc. /5
"Voters don\u2019t care about how the D\u2019Hondt system works or about how you\u2019d geographically carve up a regional assembly... They want results.\u2070"@spellar on why Labour should stop obsessing over constitutional issues: https://t.co/W0zsire5xI— LabourList (@LabourList) February 11, 2021
The state of our constitution is a bit like the state of the neglected electric wiring in an old house. If you are moving into the house, sorting it out is a bit tedious. Couldn’t you spend the time and money on a new sound system?
But if you ignore the wiring, you’ll find that you can’t safely install the new sound system. And your house may well catch fire.
Any programme for social democratic government requires a state with capacity, and a state that has clear mechanisms of accountability, for all the big and all the small decisions that in takes, in which people have confidence.
That is not a description of the modern UK state.
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What is pyramiding?
It is simply adding to your winners.
Why use pyramiding?
1. It makes your winners bigger than your losers.
• Because you are adding positions when your trades are going your way, you are increasing your gains but your losers will be small comparatively.
2. You lose less during Draw-down time ( it saves you from losing big during whipsaws )
• Many times when the market is in sideways mode, Entering a trade with full risk might not be the best idea.
• So, you test the waters with a small position first, it could be ⅓ or ¼ of your total risk.
• So if the Breakout fails or whipsaws come, then you will only lose a small part of your overall risk.
• Then when position starts to go in your favor you can add to it.
3. It helps you to concentrate on a few trades,
They say that don’t put all your eggs in one basket, but don’t put them in too many either.
• See, Everyone can see charts and find breakouts, pullbacks etc.
Thumba poo is a tiny white flower which grows in all areas. These flowers are used for treatment for sinus. Small children who have polyps in Nose are told to crush tumbha leaves and apply in nose part.
There is an interesting story of Thumba and
Mahadeva. Thumba flowers were not taken for Shiva Pooja. Saddened to this Thumba prayed sincerely and Mahadeva appeared before her.
She was surprised that Shiva had appeared before her. Instead of saying that she wants to under his feet always, she said
She said that her feet should be on his head. Shiva accepted her prayers. It is because of this Thumba flower is placed in the head of Shiva Linga.
Om Namah Sivaye
But they are also the best decisions I’ve made in my life. Here’s what my experience has been like with two young ones.
2/ Before kids, I was all about my startup life. I built an awesome edtech company with my wife, and we sacrificed many years (filled with joy and pain) to get our nut. We traveled a lot. We ate out. We hung out with friends every weekend.
Then we decided to have kids...
3/ When our first kid arrived, we attempted to be very active parents--that didn’t work out so well. It turns out that being a stay-at-home mom or dad is way harder than we could bear, psychologically and physically.
4/ We had to accept that we were better off throwing money at the problem and got a wonderful nanny + other support, so we could go back to work. That decision currently costs us $80K/year (now for 2 kids in f-ed up bay area rates), but was right for us.
5/ For me, I try not to work between 5pm and 9pm during the week, so I can dedicate time with family. Weekends are all family time. But I have to make up those lost hours of productivity by starting work at 5am. On average I get 5 hours of sleep per night, which is not enough.
Batman does this by permanently recapitulating his own trauma: solving crimes for other people, protecting them. But that's actually just the beginning; he also recapitulates his own experience of orphanness by essentially raising several orphans
Dick is an orphan in the traditional sense: dead parents. Batman sees it happen. Jason, less so: missing dad, known mom who eventually dies. Tim, even less so: parents are around a while, and involved, before both dying. Carrie, even less than that: negligent parents.
Steph: evil father, who openly works against her. And then there's Damian, whose parents are both alive and yet both have identities that totally obliterate their role as his parents. He doesn't relate to them as a mother and father; he can't, and neither can they.
In all these different cases, Batman tries all these different ways of making orphanness for them not what it was for him: Either by trying to teach them the (arguably poor) coping skills early that he learned over a very long time, or by literally legally adopting them, etc.
On startups, writing, and your career:
People don't have short attention spans:
• They finish 3 hour Joe Rogan episodes.
• They binge 14 hour shows.
They have short *consideration spans:* they must be hooked quickly.
Point: Don't fear making great, in-depth content. But, ensure your first minute is incredible.
In observing friends who’ve sold startups and made millions:
After a year, they’re back to toying with their old side projects.
They used their money to buy a nice home and eat well.
That’s it. They’re otherwise back to who they were.
Point: Aim to be fulfilled, not rich.
Reading many books is the most socially accepted vanity metric for adults.
You get zero kudos for reading 100 books a year.
You get massive kudos for learning efficiently and making interesting things.
Bloggers who post frequently (2x/wk) are rarely worth reading consistently.
I read for insights. And no writer can generate profound insights on a fixed schedule.
I aggregate writers who publish sporadically. When they post, they truly have something to say.