partington

The question is not whether ivermectin has been shown to have anti-viral  properties in a dish of cells -it has, and this is not seriously questioned..

The question is: can it be used as an antiviral drug to treat Covid-19 or other viral diseases in human beings?

For example, the question of its effectiveness against an actual disease is directly addressed in the abstract you cite about dengue  (not a published paper, but a report of a talk or poster given at a meeting, so not really evidence in scientific terms). As I'm sure you read, this actually says Ivermectin does NOT have any clinical effect on the course of the disease  :

"A once daily high dose of oral ivermectin treatment for three days was safe and accelerated clearance of NS1 antigenemia in dengue infection. However, we did not demonstrate the clinical efficacy of ivermectin at this dosage regimen. Pharmacokinetic and pharmacodynamics study of ivermectin may help to understand this finding."

quote from"Ivermectin for adult patients with dengue" https://www.escmid.org/escmid_publications/:/material/?mid=66397

The last sentence says that further  pharmacokinetic and pharmacodynamic studies may explain this lack of clinical effect .  This simply refers to studies determining whether enough of the drug gets  into the body and stays around long enough to be effective.

What is often not clear to people not involved in drug development is that showing the activity of a compound on cells in dishes is very, very far from showing an activity as an effective drug, and nearly all compounds discovered fail between these two stages.

With ivermectin, its antiviral effect on the SARS-Cov-2 virus requires doses in a dish that would be toxic if achieved in human blood, and therefore it is hard to see how it could be effective without being poisonous at the doses required.

It is also hard to see how it could be effective at the much lower doses given for antiparasitic activity, its common use, since blood concentrations achieved are not enough to halt the virus in a dish.

See this free article in Antiviral Research June 2020 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172803/

Again however a convincing properly conducted large scale clinical trial would settle this issue, and if ivermectin worked it would be adopted world wide. Where it is being used (e.g. India) it does not seem to be helping much so far.

6 minutes ago, Neeranam said:

 

Seems to do  a lot. 

 

I hope you realise I am joking , and think that recommendations like this based on nonsense advertisements, are worthless and stupid!

This was entirely satirical, based on the idiocy of my joke recommendation  to use hemorrhoid cream to treat Covid, itself an afterthought to an absurd suggestion to just use anything available with no evidence to treat Covid...

Interestingly, one of the main constituents of Anusol, the natural product Peru balsam, is known to have antiviral properties!!!

What more evidence do you need?

I am going to stick it everywhere.

"Peru Balsam is extremely soothing to the senses, and may reduce stress levels and mental exhaustion. For the skin, Peru Balsam must be diluted by about 2% and massaged into the skin to smooth broken and damaged skin. 

https://www.miraclebotanicals.com/peru-balsam-essential-oil

17 hours ago, sharksy said:

I often get ill in Thailand if aircon pointed at bed.  Now I understand why.

 

Getting colds from air conditioning

As air is pulled over the coils in an air conditioner, condensation is produced. This moisture can create an ideal environment for bacteria and mold to grow if not cleaned regularly. Another cause of air conditioning sickness is running an air conditioner too cold.

Source: google

Colds are not caused by bacteria or mold - they are caused by viruses.

This quote is therefore from an unreliable or casually inaccurate source.

"Google" is not a source - you can find arguments that the Earth is flat or that the Queen of England is a lizard on google.

A source has to be attributed with a link so you can judge whether the site giving this information is even remotely trustworthy, or merely  [as so many are] some pseudo information to populate a site largely in existence to present ads.  

5 hours ago, AlexRich said:

Sorry, you’re guessing that is true, but you are wrong. Rio Tinto is listed in London, as is Gem Diamonds, and both generate profits outside the UK, as do many others. My original point, and advice to the guy who asked, is correct. If you are a British citizen permanently resident in Thailand and purchase UK shares through an offshore brokerage, neither the dividends nor the capital gains will be subject to UK tax. It is only subject to Thai tax under limited circumstances, which can be avoided by holding the gains/dividends offshore and only transferring to Thailand in the next or future tax year. 
 

You are free to doubt that this is true, but you’d be wrong to.

Ok, without getting obsessed by this, and this will be my last post as it's not that big a deal, where a stock is listed has nothing to do with where it is domiciled, and therefore where the earnings are deemed to arise.

Almost all Vanguard ETFs are listed in London on the LSE, and can be purchased through UK stockbrokers, but their earnings are called "foreign" on all tax statements from UK stockbrokers, because they are all domiciled in Ireland.

This means if you are resident in the UK you have to pay tax on them, but if you are not resident in the UK you don't, because they are foreign earnings.

Rio Tinto Zinc is a multinational which is domiciled in both Australia and the UK simultaneously. I freely admit I have no idea what the tax treatment of these shares involves!

15 hours ago, AlexRich said:

Sorry, you’ve lost me? If a UK citizen is non-resident for tax purposes then any gains or income earned overseas is not subject to UK tax.

 

 

 

The point is the dividend gains or income from UK company shares held in an offshore brokerage are NOT "earned overseas" in the site of the brokerage, they are earned in the UK , despite where they are held and paid.

In just the same way the dividend gains  or income from a Luxembourg company shares held in a UK brokerage are earned in Luxembourg, despite where they are held and paid.

I interpreted this statement from above quote as supporting this conclusion:

The fact that the broker is overseas doesn't change whether the dividends you earn are from a foreign entity (e.g. Ireland, US, Luxembourg etc) or from a UK entity

4 hours ago, AlexRich said:

 

 

But if he is based in Thailand and he is using an offshore brokerage to buy UK shares then any gains or dividend income is not subject to UK taxation. The personal allowance in this situation becomes irrelevant. It would only be relevant if he was buying UK shares using a broker situated in the UK. And as I stated, the advice is to set up an offshore brokerage.

 

Well this is the point where I am doubtful.  I think that the taxation is incurred because of the place where the income arises and not the place where it is paid, so the location of the brokerage is not relevant.

(This is a separate issue as to whether this payment would ever become known to the UK tax authorities, although with CRS agreements it might.)

For example if you are a UK non-resident and you have a UK brokerage account, (say opened before you became non-resident), then foreign dividends owned through and paid directly into this UK brokerage are not taxable, even thought the brokerage is onshore in the UK, and the income is paid into the UK.

I can't see then why dividend payments arising in the UK, owned through and paid directly to an offshore brokerage, would not be taxable as UK arising income irrespective of where they are paid.

There isn't any indication  on the HMRC page that the dividends from UK companies are treated differently according to where the shares are held, or where the dividends are paid? I'm not an expert though.

EDIT however I did find this exchange on Money saving expert site:

https://forums.moneysavingexpert.com/discussion/6003086/degiro-vs-foreign-income

anigys wrote: »

I have a brokerage account in DeGiro (what is a Dutch company, I think). There, I have a number of ETFs, domiciled in the UK, Ireland and the US. I wonder how the income from the dividends of these ETFs is considered regarding being "foreign" (there, eg. is a separate personal allowance for foreign dividends).

There isn't a separate personal allowance for foreign dividends vs UK dividends, unless you mean that you are a UK resident but non-UK-domiciled individual and you are hoping to use the 'remittance' basis of taxation.

I thought the UK and Ireland are considered "UK dividends" and the US ones "foreign". Is this correct,

The UK ones are considered UK dividends, and the Irish ones and US ones are both considered "foreign" dividends because they are not "UK" dividends.

or, eg., are all dividend in DeGiro foreign because it's a Dutch broker?

The fact that the broker is overseas doesn't change whether the dividends you earn are from a foreign entity (e.g. Ireland, US, Luxembourg etc) or from a UK entity.

On 3/23/2021 at 6:45 AM, AlexRich said:

You could set up a brokerage account outside the UK, as you are no longer a UK resident for tax purposes. That means that any capital gains or dividend income is not subjected to UK tax. 

Just need to point out that this is only completely true of dividends/interest from non-UK domiciled investments, which are not taxable at all by the UK.

Dividends or interest arising from UK companies or banks,  or from any fund or ETF that is domiciled in the UK, are only completely non-taxable if you do not need to use your personal allowance - currently around £12,570 - to offset other kinds of UK income, such as rent from a UK property.

If you have no UK  income other than the UK-arising interest /dividends then this is indeed non- taxable (this is referred to as "disregarded income" by HMRC). 

If, though, you also had £12,570 income in the UK from other sources, like rental from a house, you would have to either choose to use your personal allowance to offset  tax on that £12,570, and pay tax on UK-arising dividends/ interest OR not pay tax on UK-arising dividends and interest, and pay tax on the £12,570 other income. 

Personal circumstance and the  balance between the exact amounts  of UK-arising dividend/interest  income and other kinds of UK income will determine which choice results in least tax.

If the  total of both your UK-arising non-dividend/interest and dividend /interest income is less than £12,570 this is still all offset by using your allowance so the question doesn't arise.

This is explained on UK HMRC site here: https://www.gov.uk/government/publications/non-residents-and-investment-income-hs300-self-assessment-helpsheet/hs300-non-residents-and-investment-income-2017

When I was in Thailand I used an app called Taxcalc, downloadable from https://www.taxcalc.com.

Works on Windows and Macs, now costs around £30, and  allows you to do up to 6 returns.  

It had all the supplementary pages including non-residence, and worked well, e.g. alerting me to the fact that dividends and interest from investments domiciled outside the UK (like nearly all Vanguard funds and ETFs) weren't taxable at all.

It is very easy to use, guiding you through with interactive questions - you can do your entire return in minutes and submit online.

Saved me a lot of hassle and worth it in my opinion!

17 hours ago, simple1 said:

 

I find your claim to be extraordinary, got any facts to back up your claim? Collaboration between Uni researchers and pharma has led to the development of treatment / mitigation of cancers from which I benefit, without which I wouldn't be posting this response. Pharma developing cures for cancers would generate massive profits for the shareholders and cost saving for government. 

Yes exactly. These claims are utterly incredible, and make no economic, or even common, sense.

A pharma company that developed a genuine effective cancer treatment, free of the side effects and disadvantages of toxic chemotherapies, would have a gigantic and guaranteed income stream.

All subsequent generations will continue to develop cancers so the need for these drugs will continually recur.

Additionally, because upwards of 200 genes are involved in causing cancer, there are literally hundreds of different kinds of cancer, because each kind  is caused by mutations or dysregulation of only a handful of these 200 genes in various combinations.

So a large number of very different drugs or therapies will need to be developed in order to treat the different types of cancers - again a huge motivation and opportunity for continued drug development.

It just doesn't make any sense to "not want to" do this, both on moral and economic grounds.

Fortune Town, big computer electronics mall right next to Praram 9 MRT station in Bangkok used to have battery deposit bins around the place, but I haven't been there for 3 years, so don't know if they are still around.

40 minutes ago, Badger18 said:

The (anecdotal) evidence I have is that people who were shielding are being offered the mRNA vaccines whereas the general population are being offered the AZ one. They are giving the shots at different sites, for sure, but the invitations I have heard about are for specific sites, so in effect for specific vaccines. At the very least, going back in the hope of getting an mRNA vaccine would be a huge gamble because (as you say) most of the supply is AZ.

That depends on your point of view. I'm not yet 40 and am not really concerned about getting a terminal bout. What I'm concerned about is a) long covid b) the possibility of passing it on to someone who might get really sick and die, in the worst case a loved one and c) the ability to travel. Now that the SA strain is out there it doesn't look as though the AZ vaccine is going to help with any of that. From the data available so far, I think the Pfizer is going to offer a lot more protection, although it's fair to say we don't have a complete picture yet.

 

I'm expecting the issue of protection against earlier strains to be fairly academic by August, at least in the UK, because so many people will be protected against those strains by then that pretty much all the covid around will be of the virus-busting type. Once they lift the lockdown over there the SA strain will quickly become dominant. At that point I think you can say the first generation AZ vaccine is obsolete from the point of view of an under-40 with no other risk factors. I'm not expecting to be offered the second generation one until well into 2022, and who knows what other variants will emerge in the meantime.

Yes I see your point as a 40 year old.

Travel is going to be a bust no matter what vaccine you get, and the extent of transmission protection conferred by all the various vaccines  is still a bit of an unknown quantity.

I'm not sure I share your optimism about the mRNA vaccines being that much better against variants given the lab studies coming out, and if the UK doesn't enact a careful track and trace (which it has shown an inability to perform to date) then I agree the SA variant will run unchecked through the UK by summer.

So death and serious illness prevention still make it worth while to vaccinate high risk groups now, but for your purposes you are probably right in your scepticism.

I'm in the UK now and got the AZ one last week, my sister -one year older, living 30 miles away and not in a different risk group - got the Pfizer one about a week earlier.

8 minutes ago, Badger18 said:

Yeah the next issue on my radar is where I can go for the jab. I can go and get it in the UK sometime in May or June, but I'm only eligible for the AZ one and the way I see it that's going to be obsolete by about August anyway, so better to stay here if the situation stays the same. I can't see the US preventing the pharma companies selling to private hospitals once their population has been done, so maybe it will be possible to go there for the jab (as a non-US citizen, I mean). If they're going to be through by July that's really not that bad. If the Pfizer and Moderna jabs continue to hold up against new variants, there'll be a slack period once Europe and North America have been done, because there aren't any other large blocs that will spend the money, and boosters won't be due yet. In that scenario there could easily be supply for private hospitals in Thailand towards the end of this year.

There are no specific eligibility criteria for each kind of vaccine,  AZ or Pfizer or Moderna in the UK. 

The vaccine you get depends simply on what is available at which particular vaccination centre or GP surgery you attend, on the day you attend it.

Of course it is more likely you will get the AZ one simply because it is easier to store and there are more doses available, but there is no "eligibility". 

Also the AZ one will not be obsolete by August because it will still stop you getting a terminal bout of even the resistant variants, and will still protect against the majority. The mRNA ones are also deficient in protection against the SA variant for example (see UK news https://www.itv.com/news/2021-02-18/pfizer-and-moderna-coronavirus-jabs-less-effective-against-south-africa-covid-19-variant????

"The Pfizer/BioNTech and Moderna Covid-19 vaccines appear to be less effective against the South African variant when compared to other versions of the virus, two laboratory studies suggest.

The papers, published in The New England Journal of Medicine (NEJM), are based on experiments using blood samples from vaccine trial participants.

But experts believe most coronavirus vaccines should still prevent severe disease."

That is the vaccine can be stored at temperatures attainable by any decent domestic freezer.

The news articles are again expressing the story wrongly, though some may consider this semantics, it actually isn't.

 The virus variant cannot "reduce the amount of antibodies" the vaccine produces.  

How can it, when the blood samples taken from vaccinated people already exist, are stored, and have had no contact with the SA variant? 

The existing vaccine causes the production of many different antibodies that can stick to many different places on the spike protein.  

What is happening is that vaccinated people produce the same amount of all these antibodies as usual, but because the SA variant spike protein is a different shape around the variant amino acid site, the antibodies produced by vaccination that would stick to that exact site on the original virus no longer recognise that site. The other ones that stick to different areas of the spike can still recognise the SA spike and so can still potentially neutralise the virus. Therefore there is no reduction in any antibodies, some just fail to find a target on the new variant.

The tweak will be to construct mRNA and adenovirus sequences so that they code for the SA variant as well as the original type, and use a mixture of the two (and possibly other sequences as well if other evading variants are discovered ).

1 hour ago, Cobra666 said:

Learn how to read.

 

The thread is about the AstraZeneca vaccine, but this goes for all companies developing the mRNA vaccines. None of them have isolated the virus.

 

As for the Chinese, I would not trust them to give the world a vaccine. As we know, this virus came out of China, and a long with it pictures of people falling over in the streets that was pushed through media. I wonder why nobody is falling over in the streets in the west like that? Could it be that this is an information warfare? Because that is exactly what it is, and like I have mentioned before I work in healthcare and nothing about the media spin to this is linked with real life.

Still utter nonsense I'm afraid.

All the companies developing both mRNA and adenovirus (AstraZeneca) vaccines must of course have isolated the virus,  because the way they test the antibodies produced by subjects in phase 1/2 studies for neutralisation activity (prevention of infection)  is to add plasma from vaccinated people together with isolated virus to dishes of cells in culture, and measure how much infection is inhibited.

It is essential to check this before you embark on a huge trial involving tens of thousands of people.  Stores of the isolated virus are in fact now available from central biological repositories for researchers to use.

Here is the link to the paper published on the AstraZeneca phase1/2 trials detailing this:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445431/#sec1

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial    Lancet. 2020 15-21 August; 396(10249): 467–478.

and here is the extract describing the neutralisation test from the appendix of that paper:

For the Pfizer mRNA vaccine neutralisation test they actually inserted code for a fluorescent protein to the genome of the isolated SARS CoV-2 virus, so they can directly measure infection of cells by measuring fluorescence inside the cell. So not only have they isolated the virus but they have made their own different versions of it!  This is detailed for the Pfizer mRNA vaccine phase 1/2 study here:

 https://www.nature.com/articles/s41586-020-2639-4

Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults   Nature volume 586, pages589–593(2020)