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When will this shit end?


Chrisp1986

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6 minutes ago, crazyfool1 said:

yep we will ask the question .... one of my group just said its not allowed from mixed bubbles ... we will see :) 

Tier 2

 

organised indoor sport, physical activity and exercise classes will only be permitted if it is possible for people to avoid mixing with people they do not live with (or share a support bubble with).

https://www.gov.uk/guidance/local-restriction-tiers-what-you-need-to-know#high-alert

Edited by Copperface
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10 minutes ago, Copperface said:

Tier 2

 

organised indoor sport, physical activity and exercise classes will only be permitted if it is possible for people to avoid mixing with people they do not live with (or share a support bubble with).

https://www.gov.uk/guidance/local-restriction-tiers-what-you-need-to-know#high-alert

I’m an instructor at the gym -although confusing, guidance says classes can resume as before lockdown. Because everyone is kept 2m apart, there isn’t any mixing between households. Well, that’s the theory.

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39 minutes ago, Zoo Music Girl said:

I thought that was a great line from Whitty. I think they did a good job at getting the right tone today personally, Boris aside. I liked that Whitty also said most of the public are following the rules despite what others might think. Whether true or not it enforces the right message.

Agreed, you hear so much about people selfishly breaking the rules you forget that the vast majority are doing what they can to follow the guidance, I know myself and many other friends and family are doing so 

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6 minutes ago, Euphoricape said:

I think with half the Internet planning to come down to Cornwall next week we will end up in tier 3 by Christmas.  I know how important tourism is and my livlihood depends on it, but I would ask everyone to stay away until the vaccine is here.

Surely “half the internet” won’t actually be going to Cornwall in the dead of winter? 

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2 minutes ago, Euphoricape said:

It felt like that during the summer. That was when cases were minimal everywhere though, its a different story this time. 

Are people really going to go all the way down to Cornwall just because they can go for a pint there?

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36 minutes ago, Euphoricape said:

I think with half the Internet planning to come down to Cornwall next week we will end up in tier 3 by Christmas.  I know how important tourism is and my livlihood depends on it, but I would ask everyone to stay away until the vaccine is here.

I'm not going all that way just for a pint.

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14 minutes ago, zahidf said:

In my local

IMG-20201126-WA0014.jpg

Sorry but that’s slightly taking the piss. I fully appreciate publicans have to earn a living but these rules are in place for a reason. They’ll be the people that are hurting if we have a 3rd lockdown.

You see this quite a lot people trying to find any small loophole in the rules when they are put in place to try to save lives. 

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13 minutes ago, Toilet Duck said:

No need to apologise for asking questions!

So, yes they both stimulate antibodies that target the same thing, but they do it in two different ways. Basically, the coronavirus is coated with protein spikes, and this is the most recognisable part for our immune systems. We can trick our immune system into thinking it has seen the virus before if we expose it to the spike protein (then we develop immunological memory and can clobber the virus if we do get exposed to the real thing). Older vaccines did this by injecting dead virus, then we developed ways of using live virus that had been altered so it couldn’t cause infection (live, attenuated vaccines). Then we developed ways of making specific proteins in the lab so could just make synthetic spike protein and use that (subunit vaccines...Novavax and the GSK/Sanofi vaccines coming down the line are these type).

The most recent development is genetic vaccines. These use the genetic code for the spike protein, and when we administer it, our own cells make the spike protein and switch on our immune response. The difference between the Pfizer/Moderna vaccines and the Oxford one is how they deliver  that genetic code (instructions for making the spike protein) into our cells. The Pfizer/Moderna ones use nanotechnology to get the instructions into our cells, the Oxford one uses a harmless cold virus. The problem is, our immune system can not only target the spike protein our cells make, but also the virus used to deliver the instructions. The nanotechnology coating used for the Pfizer/Moderna vaccines is inert as far as our immune system is concerned (it’s basically made from the same thing that surrounds every cell in our body, so just fuses with our cells and delivers the instructions straight in). So, when Pfizer/Moderna give their second shot, they just boost the immune response to the spike, since this is the only immunological memory that was formed by the first injection. When the second shot of the Oxford vaccine is administered, if there was an immune response to the virus carrying the instructions first time around, this too will be amplified and may actually destroy the virus before it gets to deliver the instructions for the spike. 

This was seen before with SARS vaccines, but a chimp virus was used this time instead of a human one to get around this. The Russians used a human virus, but used two different ones for each shot so that any immune response to the first one wouldn’t target the second one. My guess with regard to the Oxford vaccine is that the lower dose in the first shot doesn’t efficiently elicit an immune response to the virus delivering the spike instructions, but the higher dose does (or, Oxford suggest it more closely mimics natural infection...we’ll have to wait and see!).

However, everyone is getting hung up on the number of participants that have gotten the reduced dose regimen, but actually in terms of efficacy (how well it works), this doesn’t matter. The number of events is the important thing (how many people end up infected). The number enrolled on the trial is picked in order to hit that required number of events. If you have a large effect, then you need fewer events (so, 90% efficacy needs fewer than 50% efficacy to show a statistically significant result). Oxford obviously feel they have enough events to show this, even though the total number of participants in the trial is relatively small (at the start of the trial you basically have to estimate how many people you will need, not knowing what the rate of transmission of the virus will be like...all the trials at the moment are lucky in that transmission is widespread). 

If that was the only trial they had, then they’d have safety questions, as there isn’t enough participants to pick up rare adverse events. But, they have other trials at the higher dose and haven’t seen any safety problems, so this answers the safety question for them (if it was the other way around, they’d be in trouble, ie a few people on the high dose and loads on the low dose). So, I think their efficacy data is probably fine and their safety data too. They still have two outstanding questions...should they be using the reduced dose? And how does it perform in an older population? As it stands, they have enough data to go for emergency use authorisation using the full dose and this may change when they get more data on the reduced dose regimen (indeed, the final approved use of the vaccine may be like that). Instead of just tacking on a study with the reduced dose to their existing trial in the US (I’d have done this), they’ve decided to do a whole new one comparing the high vs low dose regimens (laudable, but I’d still have amended the trial in the US as well to add a low dose arm). Anyway, I’ll have a look at the paper when it is published and let ye know what I think! (I’d still expect them to apply for EUA shortly based on 60%+ efficacy and no safety issues...and I’d expect them to get it for the full dose regimen). 
 

Thanks! Did I hear right when one of the scientists involved in an interview said even among those who still contracted COVID, none required hospitalisation? (I’m not sure if i misheard it as no article seems to have given this much attention)- So even if it’s only 60%, that’s not so important if it prevents severity of illness?

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6 minutes ago, Mr.Tease said:

Thanks! Did I hear right when one of the scientists involved in an interview said even among those who still contracted COVID, none required hospitalisation? (I’m not sure if i misheard it as no article seems to have given this much attention)- So even if it’s only 60%, that’s not so important if it prevents severity of illness?

Alas, I haven’t being paying too much attention, so not sure of the details, but if the paper is out over the weekend, we’ll get a better idea. Oxford are still happy with the results and they know what they are doing (if it was just the drug company spin, I’d be a bit more suspicious). 

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28 minutes ago, Toilet Duck said:

No need to apologise for asking questions!

So, yes they both stimulate antibodies that target the same thing, but they do it in two different ways. Basically, the coronavirus is coated with protein spikes, and this is the most recognisable part for our immune systems. We can trick our immune system into thinking it has seen the virus before if we expose it to the spike protein (then we develop immunological memory and can clobber the virus if we do get exposed to the real thing). Older vaccines did this by injecting dead virus, then we developed ways of using live virus that had been altered so it couldn’t cause infection (live, attenuated vaccines). Then we developed ways of making specific proteins in the lab so could just make synthetic spike protein and use that (subunit vaccines...Novavax and the GSK/Sanofi vaccines coming down the line are these type).

The most recent development is genetic vaccines. These use the genetic code for the spike protein, and when we administer it, our own cells make the spike protein and switch on our immune response. The difference between the Pfizer/Moderna vaccines and the Oxford one is how they deliver  that genetic code (instructions for making the spike protein) into our cells. The Pfizer/Moderna ones use nanotechnology to get the instructions into our cells, the Oxford one uses a harmless cold virus. The problem is, our immune system can not only target the spike protein our cells make, but also the virus used to deliver the instructions. The nanotechnology coating used for the Pfizer/Moderna vaccines is inert as far as our immune system is concerned (it’s basically made from the same thing that surrounds every cell in our body, so just fuses with our cells and delivers the instructions straight in). So, when Pfizer/Moderna give their second shot, they just boost the immune response to the spike, since this is the only immunological memory that was formed by the first injection. When the second shot of the Oxford vaccine is administered, if there was an immune response to the virus carrying the instructions first time around, this too will be amplified and may actually destroy the virus before it gets to deliver the instructions for the spike. 

This was seen before with SARS vaccines, but a chimp virus was used this time instead of a human one to get around this. The Russians used a human virus, but used two different ones for each shot so that any immune response to the first one wouldn’t target the second one. My guess with regard to the Oxford vaccine is that the lower dose in the first shot doesn’t efficiently elicit an immune response to the virus delivering the spike instructions, but the higher dose does (or, Oxford suggest it more closely mimics natural infection...we’ll have to wait and see!).

However, everyone is getting hung up on the number of participants that have gotten the reduced dose regimen, but actually in terms of efficacy (how well it works), this doesn’t matter. The number of events is the important thing (how many people end up infected). The number enrolled on the trial is picked in order to hit that required number of events. If you have a large effect, then you need fewer events (so, 90% efficacy needs fewer than 50% efficacy to show a statistically significant result). Oxford obviously feel they have enough events to show this, even though the total number of participants in the trial is relatively small (at the start of the trial you basically have to estimate how many people you will need, not knowing what the rate of transmission of the virus will be like...all the trials at the moment are lucky in that transmission is widespread). 

If that was the only trial they had, then they’d have safety questions, as there isn’t enough participants to pick up rare adverse events. But, they have other trials at the higher dose and haven’t seen any safety problems, so this answers the safety question for them (if it was the other way around, they’d be in trouble, ie a few people on the high dose and loads on the low dose). So, I think their efficacy data is probably fine and their safety data too. They still have two outstanding questions...should they be using the reduced dose? And how does it perform in an older population? As it stands, they have enough data to go for emergency use authorisation using the full dose and this may change when they get more data on the reduced dose regimen (indeed, the final approved use of the vaccine may be like that). Instead of just tacking on a study with the reduced dose to their existing trial in the US (I’d have done this), they’ve decided to do a whole new one comparing the high vs low dose regimens (laudable, but I’d still have amended the trial in the US as well to add a low dose arm). Anyway, I’ll have a look at the paper when it is published and let ye know what I think! (I’d still expect them to apply for EUA shortly based on 60%+ efficacy and no safety issues...and I’d expect them to get it for the full dose regimen). 
 

Super clear and helpful as always, thanks so much!

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