Well, United's gone and signed Varane on top of Sancho, next season's gonna be interesting. Anyway, inspired by former United leaguewinner Michael Owen's memetic pickup lines, I figured that I'd do some DuckDuckGo-ing on the EPL players of yore, whom had managed to stick in my memory. Owen - who has by all accounts been doing fine for himself financially through his investments (including crypto), unlike so many retired sportspersons - has apparently gained a reputation for having an unusually boring personality, but that may be a relief compared to, say, Giggs. The Welsh wing wizard has just been charged for another domestic altercation, recalling another club legend in George Best. About that, I never regarded footballers as particularly appropriate moral exemplars, myself.
As for the rest of Fergie's Fledglings, Beckham is... still inordinately famous, part-owner of a new Major League Soccer club, and reportedly whiles away his hours on Lego; Gary Neville's an outspoken pundit who was assistant manager of England for a span, after which he took younger brother (and former Everton captain) Phil on as his own assistant, in a short stay at Valencia. The younger Neville's now managing Beckham's Inter Miami, after being head coach of the English women's team. Nicky Butt did well at Newcastle, before returning to United to coach in various capacities (recently left). Personal all-time fave Scholes has briefly managed Salford City and Oldham Athletic too on top of regular punditry; the former club are by the way part-owned by these Fledglings, together with Singapore businessman Peter Lim (who probably had a hand in bringing the Nevilles to Valencia, though his popularity seems to have taken a dive there)
Solskjær is, of course, current United manager, for which the club have taken some stick for the seeming favouritism, but this squad may finally be good enough to overcome supposed tactical deficiencies; I mean, Ferguson could pull off wins with a single defender, probably thanks to exceptional man-management, football's not that complicated after all. Rooney's managing Derby (who played United a week or two back), and has just wrecked the ankle of one of his youngsters in training. Yeah, sure sounds like his old intensity. Vidic, who was probably up there with Rooney in my esteem amongst United stars of that era, seems to be enjoying his retirement as a homebody. Forwards everywhere heaved a sigh of relief. Ironically, Ferdinand - usually seen as the more cultured of the two - seriously considered a boxing career.
[N.B. Rooney also had an appearance on WWE with Wade Barrett (who's just made a return as a commentator), back in 2015. While still on wrasslin', Shaquille O'Neal made his debut on All Elite Wrestling in March against Cody Rhodes in a tag team match, and took a pretty big bump (about 3:40). Guy's an NBA icon, he didn't need to do that, so props to him.]
Casting the net wider, former fantasy soccer choice pick Jimmy Floyd Hasselbaink went from Leeds to Chelsea with Atletico Madrid in between, and is now managing Burton Albion. Of that Leeds side, Alan Smith came to United, was never the same after a broken leg, and briefly managed Notts County. Harry Kewell took over from Scholes at Oldham but didn't last long either, while Mark Viduka's running a cafe in Zagreb. This seems something of an exception, with many past stars staying in the game in some way - Henry's managed Monaco (Wenger connection?) and is now a coach with Belgium, Lampard was at Derby before returning to manage Chelsea (where Ashley and Joe Cole are coaching), Gerrard's at Rangers (and must be eyeing the Liverpool post), Patrick Vieira's managing Crystal Palace, and Sol Campbell was at Macclesfield and Southend.
Back to work...
It's coming Rome, indeed. Now that was a classic European final, i.e. England enters against a continental team and loses, prefably on spot kicks for that extra dash of savoir faire.
And it all started so brightly, too; United skipper Harry Maguire gave away a tactical corner two minutes in, leading to club teammate Shawberto Carlos smashing it in at the near post, just like that. With Top Right Messi having just broken his international curse at the Copas*, the Wembley set must have thought that an end to fifty-five years of pain might well be descending too. Italy were definitely on the ropes for some time, but England kept to the low-risk style that had seen them concede just the one goal - moreover not from open play - in the tourney thus far, and failed to press their advantage. And of course Italy equalize in the 67th minute, which had England... make next to no adjustments, despite the wealth of attacking talent screaming to run at the geriatric Italian centrebacks; yes, yes, Bonucci and Chiellini might not have allowed a single dribble past them in the tournament, but from how Chiellini had to haul Saka down by his collar, it couldn't have hurt to try?
[*Some had suspected FIFA being willing to find excuses to hold more special editions, until Messi got one; perhaps a sign that he can move on from Barcelona too, before he bankrupts them]
Swap shirts now? Or pants later?
[N.B. The videos kept getting taken down for copyright claims]
Here, let us first acknowledge the enormity of what Southgate had accomplished: by defeating Germany, Ukraine and Denmark, his record of five knockout stage wins in major tourneys (World Cup/Euros) in total, is already two more than what any previous England manager had achieved. Sure, this could be interpreted as England simply being world-class underachievers historically, but it's still something. And yes, his strategy probably isn't the most adventurous, but it's not as if the likes of say Spain in 2010 (six of their seven World Cup matches won by a single goal) or Italy in 2006 (who coincidentally also did Germany 2-0, and Ukraine by three) were ripping their opponents up either. In international games, the players generally aren't too familiar with each other unlike in club competition (exceptions such as Germany/Bayern aside), and thus going for a defensively-sound system dominated by hardworking and disciplined players who will stick to their roles (e.g. Saka) - instead of shoehorning incompatible stars together, as with previous English sides - makes a lot of sense.
Still, it might be said that effectively settling for penalties against Donnarumma, with a close to 40% save ratio from the spot, might not have been the best of ideas, and that's before going into how England have historically had one of the worst records in shootouts (compare Germany) - which Southgate has painful personal experience of, in having his (pretty poor) take saved by Köpke in the semifinals of Euro 1996. But hey, new manager, fresh start, surely it's written in the stars for Southgate to finally exorcise those ghosts? As it was, Kane did his usual nerveless strike after Berardi converted, then Pickford saved off Belotti! Up stepped... Harry Maguire? Plenty of fans must have been scratching their heads, only for Captain Slabhead to absolutely thundercunt what was possibly the best penalty of the year thus far, destroying the camera in the top corner of the goal-netting in the process.
Even the most cynical and long-suffering typical England fan (including yours truly) must have had a flicker of real hope kindled at that. Bonucci scored next, but all England had to do now, was to polish off their remaining three kicks, to end a half-century of hurt. Up stood Marcus Rashford MBE, who sent Donnarumma the wrong way with his delayed hit... only to drive it right off the other post. At this point, there might have been a sinking feeling amongst the more-experienced English fans, that they had gotten the genre wrong. This was not some fairytale Bildungsroman in the making; it was a repeat horror-tragedy.
It was back to square one as Bernardeschi put Italy in front again, before Sancho struck a frankly not-very-good one just slightly left of Donnarumma, which got saved. Pickford had to save from Jorginho, which he impressively did, after the latter tried to roll it to the left post. All eyes then turned to the man to keep England's dreams alive, for the fifth and final regular kick: 19 year-old Bukayo Saka, who had by all indications never taken an official penalty at the senior level, in his life. He managed what was basically a fascimile of Sancho's effort, moreover perhaps the most naive "natural" placement, for a left-footer. And with that, Southgate had successfully passed the torch on, for the next generation.
Carrying on the sacred English tradition
(Source: redcafe.net, from the Daily Express)
Saka had barely broken down before armchair coaches crashed servers all over the Web, raging over Southgate's penalty-taker selections, and the senior players' perceived cowardice at leaving an all-but-teenager to shoulder the ultimate burden. Manchester United fans in particular were not entirely unreasonably upset at Rashford and Sancho being subbed on only for the penalties without a chance to warm-up, especially when it seemed that Maguire and Shawberto were locked-on as national heroes (both deservedly made the tournament's best XI, by the way). About this, my opinion is that having Rashford & Sancho on was actually probably correct, given that England had literally no other recognized penalty specialists available, other than Kane; Rashford had reportedly scored 13 of his 15 official takes - a very respectable 87% conversion rate - with Sancho three from three for Dortmund. On another day, Rashford would have pinged it in off the post, Sancho lifted it a yard or so higher, and the week-long revelries in Merrie Olde England would yet be ongoing, assuming the Jorginho save.
Of course, this leaves the Saka pick, which yeah, still looks inexcusable from where I'm sitting. If Grealish had volunteered - as he is claiming - only to be overridden by Southgate (with Villa fans suggesting some bad blood between the duo), I'd have to lay this one firmly on the manager, who has admittedly taken responsibility for his choices. As many have noted, cup final penalties are far more a confidence and belief thing, than a test of skill. At the professional level, one figures that these players, whether striker, wingback, Slabhead or goalkeeper, should be able to accurately place a stationary ball roughly whereever they want it, over a mere eleven metres. The primary factor, then, is picking the guys who won't let the occasion get to their heads, and wind up shooting not to miss rather than to score - as Sancho and Saka unfortunately did.
Here, we might as well delve into what makes a good penalty kick. To recap, the kick-taker simply has to propel the ball over the goal-line from a distance of twelve yards (approximately eleven metres), between goalposts set 7.32 metres apart, and the crossbar set 2.44 metres above the ground. This is, really, a pretty big target. Opposing him is the goalkeeper, who is not allowed to leave the goal-line before the ball gets kicked. From this, the odds are pretty clearly stacked against the goalkeeper, who is never really expected to make the save, no matter how good he is. This however also translates to a no-lose and lower-stress situation for goalies in shootouts: they won't be blamed for not making saves (well, unless they keep getting humiliated by gag efforts), and might well become a hero for a single stop.
Interestingly, only about 75% of penalties are converted at the professional level despite the taker's advantages, with this ratio remarkably consistent across the top national leagues. Players entirely miss the goal (or hit the post) only about 7% of the time, with the goalkeeper saving the remaining 17%. Now, there have been a plethora of techniques adopted by penalty-takers, ranging from ultra-long run-ups, to sudden pauses and weird stutter-steps (exemplified with the Zaza style), to try and entice the goalkeeper to commit to one side or the other. So the thinking goes, if the goalie takes the bait, scoring becomes all but guaranteed by just putting it to the other side. Goalkeepers nowadays do however have access to counter-research on well-known takers' habits (sometimes condensed into cheat sheets stuffed into socks) - which is perhaps an argument for putting unknown takers on - and can try their own psyche-outs too.
Up, lads, and have at it!
(Original source: dw.com)
However, statistical research seems to point to one simple truth: there's really no need for all that scouting, mindgames and funny prancing. All the taker has to do, is to get it on target and into the top one-third of the goal (i.e. a rectangle over seven metres wide, and some 80cm high), for a nailed-on 100% conversion rate. One might have read about how the top corners are literally unreachable, but it turns out that such precision is entirely unnecessary. In fact, just hitting it honestly into the top half of the goal retains a 97% success rate. The worst one can do, expectedly, is to aim bordering the bottom centre where the goalkeeper's crouching (as Sancho/Saka sadly did). Sure you can't miss and can look smart if the goalie commits prematurely, but on the other hand it gets saved 30% of the time.
Given this, one might wonder whether it is seriously that difficult for a professional player to train to consistently hit a 7.3m x 1.2m target (close in size to the proverbial barn wall) from twelve yards, but the evidence seems to bear out that it's really not that easy in real life, given the mere 75% overall conversion rate by specialists. Some might have managed it, though; while Germany's reputation from the spot is well-deserved, given their 87% record at major tournaments, the Czech Republic has apparently managed a perfect twenty from twenty under the same criteria, and the latest Europa League final (that United sadly lost) had 21 consecutive kicks scored, until De Gea (a goalie, for non-footy followers) had his attempt saved. Notably, United's first two takers Mata and Telles were brought on just for the shootout, so one supposes the lack of a warm-up shouldn't matter overmuch for confident takers.
Some mathematicians and economists have for their part argued that aiming for the middle makes sense under game theory, since both the taker and the goalkeeper should be expected to know the above statistics, and therefore the kickers should sometimes just place it straight at the goalie. To this, all I have to say is that if one of your guys starts spouting about mixed strategies before the shootout at the faculty games, you might do well to relegate him to be the last kicker in the lineup. Indeed, neuroscience suggests that the less one thinks about the kick, the better the outcome can be expected to be.
As to the griping on the order of England's takers, with one particular complaint about Kane and Maguire "frontrunning" to claim the first two kicks - supposedly lower-stress since the shootout can't be lost on misses that early on - I would have to mostly disagree. Of course, you'd ideally want a good taker to anchor the crucial fifth kick if it comes to that, but on the other hand, only the first three takers are guaranteed to have a go. Cristiano Ronaldo for example discovered this to his detriment in the Euro 2012 semifinals, when Portugal lost before it got to his turn. Now, I suppose you could perform some complex modelling to predict the best lineup by estimating each players' conversion rate under various conditions (e.g. when behind, when the last kick was missed, etc.) as parameters, but really it should be simpler to just have all your fellas stay back after training to drill on putting it into the top half of the goal?
Uh, technically not untrue, but next please
Finally, it has been raised on various forums that Southgate might well have been tasked to have players of colour attempt the final few kicks, towards the in-your-face diversity agenda (more on this subject in the future). About this, one believes this mostly a coincidence because, as explained earlier, the first four takers were entirely reasonable picks under the circumstances, i.e. the English squad having very few established penalty specialists; on hindsight, Southgate might perhaps have considered recruiting a few such players (e.g. Jamie Vardy, Danny Ings, James Milner, Dele Alli, etc.) to the squad for just this eventuality, all the more given the unprecedented number of substitutions (five) allowed and his sparse usage of available squad depth in any case, but I guess maintaining traditions takes precedence.
And then there were four
(Original source: twitter.com)
That's my sleep schedule completely messed up again, and this might be the only post in some time due to commitments piling up. That said, this was probably the best set of games to stay up for, in some years - and stay through, given ultra-late comebacks and wins such as Switzerland vs. France, Ukraine vs. Sweden (brütal) and Croatia vs. Spain (ultimately failed). It also reminded on how transient football reigns can be (France [with their usual drama], Germany), and how some supposed national team Golden Generations might never win anything of note - I guess the collective wisdom of the punters was correct after all when they never had Belgium better than about fourth favourites, and Lukaku not getting any contact on a point-blank header reminded me of why I wasn't that upset when he left United for Inter, where he does seem to be better... but Ronaldo-level world class as self-proclaimed? Well...
Say what you want about the latest Ronaldo, but the guy's dedicated (to the horror of Coca-Cola), and he'll at least retire with a Euros under his belt. It might well be England's turn, though, seeing as how they have yet to even concede, and seem to actually have a system in place, fewer clashing egos than at any time in the past few decades, and pseudo-home advantage. Returning to their roots of crosses and big man headers helped plenty too, after the previous tiki-taka fad; what's old eventually becomes new and fresh again.
The past few days have finally seen Ivermectin bust through the mainstream (social) media censorship barrier, so it seems, possibly due to a systematic review on the subject touting "moderate certainty of evidence" for mortality reduction coming out in the American Journal of Therapeutics, which has already been tweeted nearly 20,000 times within the week (if only on three Facebook pages, but more on that later). Sure, there have been critiques largely still centered on quality of evidence and lack of mechanism, but even excluding preprints and two large studies raised as possibly having selection bias, still yields a 35% improvement down from the original 60+ to 80% - and that on one of the hardest endpoints possible, mortality, since it's much harder to fudge death as compared to something like "severe symptoms" (though one might be surprised at how deaths can be accounted for, in other applications)
The systematic review would be backed by new research on possible mechanisms and antiviral effects of Ivermectin (and HCQ, by NUS researchers and others) in journals under the Nature and Lancet umbrellas, which has had an increasing number of netizens wonder at exactly why such investigations hadn't been pursued with more haste, and whether the tide is finally turning on cheap, early, existing interventions, coming after all the raw mainstream media gaslighting. Yes, there are arguments that places supposedly employing IVM, HCQ etc. such as India and Brazil have a relatively high number of cases and deaths, but the point here is that uncertainty over actual breadth of distribution aside, one might imagine that it could well have been worse (i.e. while say 100,000 deaths is a large number, might it not have been 200,000 or more without the early intervention efforts?). As it stands, Indonesia has just become the latest to join the Ivermectin treatment club, with a state-owned firm ramping up production for their 270-plus million people, just over 4% of whom are fully-vaccinated.
Nature and company, to eat humble pie soon?
Just to make it clear, I think claims of "obliterating 97% of cases" are quite likely an exaggeration, but the mainstream media - and its English subset in particular - has probably been doing no favours with its censorship. However, with Ivermectin gradually entering the wider consciousness - as through an emergency podcast by Joe Rogan, now perhaps also in social media jail - outright silence has become less tenable, with the local press for example slightly disappointingly quoting Merck's lack of support without mentioning their own competing new drugs, and a "concerning lack of safety data"; the New York Times likewise lumped Ivermectin together with a bunch of other remedies before tying them to "reports of respiratory and liver failure", and while the Daily Mail referred dismissively to it as "a drug in nit shampoo", the rest of the article seemed a relatively fair assessment in a sea of FAKE NEWS offal, with Fox News seemingly the only ones to stand up for free speech - and even then, only after a sudden change of heart.
Do note that not too long ago in other contexts, Ivermectin had been feted as a "multifaceted wonder drug" with a Nobel Prize awarded and statues made for its saving millions in Africa from preventable river blindness, and now it's a "nit shampoo drug" or "horse paste"... which might lend some pertinent insight into the true motivations of certain corporations and organizations. Sure they might promulgate diversity statements and hang rainbow flags all around their premises, but when these outfits have to actually forego profits in service of these people, one might be shocked at how quickly nothing can be done. Dr. Kory did try playing the minority card in his Senate testimony ("I have seen so many vibrant fathers and mothers of families die in my ICU. And most importantly, the majority are minorities, Black and Latinos, many of them poor and often without access to private doctors for early treatment"), but yeah, virtue signalling don't work with real money involved, ya see.
It might or might not have pained the venerable BBC News to report that Ivermectin would be studied as a possible treatment in Oxford's PRINCIPLE trial - barely a fortnight after calling it a bogus remedy, recall. Actually, the inclusion of Ivermectin had been delayed since January here, but better late than never, no hurry there. Sadly, there remain the same worries that the trial had been designed not to play to an early treatment's strengths, by allowing patients having symptoms up to 14 days, when proponents have always urged immediate use.
[*On more careful reading, the dosage is possibly multiple tablets at 300 micrograms/kg bodyweight, which would seem to result in relatively generous doses over the three days. I apologize unreservedly for this error.]
One could hardly get further away if one had tried...
The Western medical establishment appears to be gearing up to dismiss all prior research on Ivermectin anyhow, with the Minnesota study for instance hailed as "the first trial of its kind". Seeing as how the WHO and BMJ seemingly can't even separate studies involving early from late treatment in their analyses, one senses this is going to be a long, hard drag. Put another way, if one were to run a study involving the vaccination of subjects already showing symptoms, and tried to use the results to declare that vaccination doesn't work, one would rightly be slammed for misuse of treatments and gross dereliction of duty; do the same for proposed prophylactic/early treatments, and the medical establishment will just accept it at face value. And then there are the essentially null-finding RCTs, with no severe cases/deaths encountered in both treatment and control groups. Great for the participants, perhaps, but somehow they are also (gleefully) held as evidence that the treatment doesn't work.
In Oxford's defense, their initiative towards developing a vaccine to be sold at-cost (with AstraZeneca) was one of the (sadly few) great humanitarian gestures of the pandemic, but look at where it got them: savaged for relatively-low (but still respectable) efficacy, and sued by the European Union for under-delivery. As The BMJ has bemoaned, the AstraZeneca vaccine lost the PR war badly, which might be understood in relation to their non-profit motive; a big drawback of not charging extra, one realizes, is that there is then no warchest of funds to buy influence with, including with FAKE NEWS correspondents. There's a saying in Chinese on such: 杀人放火金腰带, 修桥补路无尸骸 - or no good deed goes unpunished, put more colourfully.
And it might have been gotten away with too, with the aid of overt psychological manipulation, had it not been for the escape potential of the many emerging coronavirus variants leading to a (grudging?) recognition of an urgent need for interventions beyond vaccines by the likes of a Lancet taskforce, vaccine rollout setbacks, and a warning from the FDA just yesterday on how the mRNA vaccines might cause heart inflammation in rare cases. This could have contributed to the WHO's official advice being briefly updated to include "Children should not be vaccinated for the moment" in bold type, which very hilariously had Facebook censor the WHO itself - though to be fair, national health ministries have been gainsaid by Twitter before - which might beg the question: who exactly defines what is truth, for these
Quite a bit going on the past week - caught a few choice Euro matches: England vs. Croatia, France vs. Germany, England vs. Scotland (still sans Sancho) and Portugal vs. Germany, that last of which had by far the most entertainment value. I remain backing Belgium for this tournament. Mr. Ham's right schnozzle has also swollen up, and may take some fixing.
I had wanted this to be short and casual, so it'll mostly be a follow-up of the last one. As it stands, three FDA advisors have resigned over the agency's approval of Aducanumab to treat Alzheimer's, and since it's not IVM or HCQ, the folks over at r/medicine have found themselves free to slam the FDA for approving the drug despite it merely reducing the level of amyloid plaques in the brain, when it is not even established that said plaque is associated with Alzheimer's. Well, Biogen will have about a decade to milk the desperate public for all their worth, over the near-unanimous objection (10 against, one polite chap abstaining) of their own advisory committee. Given this, one wonders what the point of scientific investigation is, since it seems easier to just control the gatekeeper journals and FAKE NEWS outlets, and have them skew the facts to match.
On vaccines for example, mixed results continue to be reported, with Novavax claiming 90% efficacy and 100% protection against moderate and severe disease in a Phase 3 trial (though barely 50% against some variants), alongside CureVac sadly falling at the first hurdle with 47% efficacy. However, from reports that 29% of deaths in the U.K. from the Delta variant (fast displacing the original strain, so it seems) came among the fully-vaccinated, and a number of hospitalizations within that group in Indonesia and the Seychelles - the latter being one of the most-vaccinated nations globally - one would have cause to suspect statements on guaranteed protection. Such real-life experience appears to have had Costa Rica reject the Sinovac vaccine (commonly used in both Indonesia and the Seychelles), though it seems to have retained some fans here. Otherwise, the 1% difference in claimed efficacy between Pfizer & Moderna appears to have tilted the scales for more-kiasu locals.
And then there's resorting to plain old outright censorship, with YouTube removing a discussion on Ivermectin between a (very published) M.D. and a biology Ph.D. (though one supposes they should have the right to broadcast their thoughts regardless of qualifications nonetheless), Amazon deleting the website of a group of American physicians advocating for early treatment, Twitter literally blocking a link to a peer-reviewed journal on an Ivermectin study and apparently banning accounts pointing such behaviour out, and Instagram warning against the picturing of a box of the medication. Such wholesale blacking out of discussion is increasingly incongruous as the evidence continues to mount, as is beginning to filter out into mainstream debate*, including by a Canadian Member of Parliament and concerned doctors.
Let's face it, Singapore didn't get our ample vaccine supplies due to our charming good looks (okay, maybe a bit), but being willing to cough up a billion bucks - which many other countries, including most of our neighbours, might not be willing or able to do. The lobbying for IVM continues in Malaysia by medical and other associations, with a clinic reportedly raided for offering it on conscientious grounds. Indonesia's been petitioned by the FLCCC, Slovakia seems to have approved it, Portugal's considering, and South Africa, Trinidad and Tobago, Jamaica, Namibia etc. seem to be pushing hard. Further, Duterte's following the footsteps of other leaders hated by globalists (e.g. Bolsonaro, GEOTUS) in (quite rationally) calling for the matter to be settled with all haste through holding definitive trials.
This, mind, is a lot more than the WHO and other national taskforces are doing, with the WHO seemingly content to display a 0.19 odds ratio (95% C.I.: 0.09-0.36) mortality outcome for Ivermectin with an accompanying "very low" certainty of evidence rating on their living guidelines page, and wait for better trials to fall out of the sky. Meanwhile, the U.S. has devoted nearly US$5 billion towards new early treatment pills for the coronavirus, apparently without bothering to check existing (out of patent) candidates, which might be considered against the FDA decision above, and a history of such collusion in profiteering. If it's any consolation, latest reports from the UMinn study ("many people were having less extreme symptoms") and the TOGETHER trial ("very optimistic that it will [have a treatment effect]", if moderated) suggest positive results, if only because other countries are expediting their own studies (with about twelve in India alone), coming amidst seemingly backwards critique on "non-evidence-informed medicine" - WHO's job was that supposed to be, to begin with?
[*Including a Language Log reference in the comments section of the relevant Science Translational Medicine discussion. Never thought I'd see the day...]
Now you see them, now you don't!
Informal missives have played quite the role in the ongoing coronavirus saga locally, the earliest such of which was probably the advice by four doctors to wear a mask if possible, from last February; this would be dismissed by a medical chief, but well, we know what happened. After a long lull, unofficial channels would be called back into action with a Dr. Lye from the NCID calling on Singaporeans to "do much more beyond what government dictates" - including forming and sticking to small social bubbles - in the middle of May, right before the latest wave. Fearmongering or otherwise, we remain in all-but-lockdown, so I suppose it was not too far off credibility.
Not all such open letters have been home runs, though; a few days after Dr. Lye's plea, a group of twelve doctors would appeal to MOH to approve a (particular?) "killed-virus vaccine" with an accompanying host of reasons, mainly a focus on balancing the relative harmlessness of the coronavirus for children, with the unknown long-term effects of mRNA vaccines. For their pains, the dissenting dozen would have their arguments trashed by a Senior Minister of State for Health, the local expert committee and further an expert on emerging infectious diseases at Duke-NUS. This has led to eleven of the doctors retracting their opinion; well, to be frank, I can admire those who stand by their convictions, and it might be noted that the points on short and unknown potential long-term effects of mRNA vaccines had been addressed by one expert telling The State's Times that "...we should not worry about what happens 10 to 20 years later. We will deal with future problems if and when they arise". That's one way to think about the issue, I suppose.
These doctors' advocacy for killed-virus vaccines would be interpreted as a drive to get Sinovac approved by some - which it has, just last week, under the Special Access Route (i.e. not as part of the official national vaccine programme). Some have identified an undercurrent of "pro-[China], anti-vax propaganda" among middle-aged boomers in recent years (which I have observed personally), for which the Manglish grammar (example message) has been suggested to act as a filter of sorts (as with email scams), and/or foster relatability. On this, Dr. Lye of WhatsApp warning fame has (been prodded to?) call out the inaccurate science on Sinovac viz-a-viz mRNA vaccines, in particular emphasizing that there remains hardly any data on Sinovac's efficacy, which I suppose is true. Notably, even the Moderna option appears not especially popular locally, so limited expected uptake for a vaccine with only 60+% self-claimed efficacy is hardly unthinkable.
Dr. Lye's latest message will be referenced several more times in the following exposition - as it just has by Dr. Danny Soon in the local news on drug safety (which includes an observation on Viagra's unexpected off-label uses resulting in happy endings, har har) - but now, the more-specific analyses:
Have A Cold One Two
"Straightforward Trade War doesn't sound so bad now, eh?"
"Now that you put it this way..."
Beneath the "scientific" figures for efficacy and transmissibility and whatnot, however, it can hardly be denied that a deeper and more ominous battle has been brewing under the prim and proper facade. Regrettably, the millions of excess dead from the coronavirus will probably be regarded as an appendix to what will very probably be recognized as Cold War II. Personally, I had been hoping for a sensible, restrained, businesslike, honourable approach to the likely-unavoidable conflict, as pursued by the previous U.S. administration, where demands and transactions were laid out clearly; instead, it's sadly shaping up to be another dirty affair involving copious mindf**kery, as the first edition was. The new admin has only doubled down on the hostility, expanding the previous more-circumspect list of China-based companies banned from investing in America, while fanning military assets across the Pacific and not-so-subtly assembling an anti-China coalition.
A fuller discussion on geopolitical developments would really warrant a post of its own, so we'll restrict ourselves to the role that the coronavirus, the vaccines and other related therapies are playing in The Greatest Game at present. This topic had been raised this March too, of course, and I would have to put it as a draw tilting America's way, for now. In China's favour, they have managed to keep a tight lid on virus spread - officially, at least - through methods incompatible with democratic governance. This twofold achievement - both in on-the-ground pandemic management results and internal narrative control - stands in stark contrast to the self-sabotage brought about to a large extent by competing political parties jostling for advantage at all costs, and amplified by the mainstream FAKE NEWS, in America. Simultaneously, China has also been pretty overtly flaunting their scitech capabilities, most prominently their unmanned Moon and Mars landings over the last half a year.
Left largely unsaid, though, is that these accomplishments are literally fifty years behind the state-of-the-art, and in the natural head-to-head contest of scientific ability that everybody cares about - i.e. vaccine development - China remains some distance off the best of the West. Their Sinovac/Sinopharm offerings based on traditional killed-virus tech have achieved efficacies of just 51% to 79%, as compared to the roughly 95% claimed by the spanking-new mRNA vaccines, before delving into the ancillary signal of them being unable to even come up with any numerical estimates against the coronavirus variants. One downside of officially claiming to have all but eradicated the virus domestically, whatever the degree of truth, is that one can then hardly present research based on nonexistent local cases. Of course, it doesn't seem that complicated to liaise with hard-hit foreign nations to obtain such data... just that China has, for whatever reasons, been unable to do it. I'm not saying that this sort of hamstringing is good in a humanitarian sense, but it does suggest that China may not have all that many firm friends willing to defy the current world order for them, out there.
One could, then, view the soft rejection of Sinovac versus Pfizer/Moderna (and wise diversification of sources in inviting Sanofi etc. for the future) as a hint towards a country's leanings, though to again clarify, I maintain no preferences where it comes to the purer pursuit of science and medicine; I simply call it as I see it. Well, a mutual (probably one-sided) vaccine passport might take the sting out of it somewhat, and there might be a delicious irony in handing off the excess Sinovacs to Taiwan (okay, or neighbouring countries), after the apparent collapse of their Pfizer/BioNTech deal over an unseen technicality. This comes as the formerly tinfoil-hatter Wuhan lab leak "conspiracy theory" turns out to be a distinct possibility after all (but more on that next time), which has China's state media now warning about preparing for nuclear war, as America sets up for a deeper probe into the theory. Ah, for firm, logical, optimistic, professional international diplomacy again...
The Early Treatment Cures The Worm
Was there really *nothing* that could be done for early cases?
The previous two blog posts have already been centered about the potential of early treatment, which I do sincerely believe is the biggest story not being told right now, as described by a NY Times bestselling author, whose actual formerly-prize-winning investigative journalism would somehow be blanket-rejected by the mainstream media to the extent that he had to publish it in a local Pennsylvanian magazine that his wife is the editor of (shades of Dr. Tambyah, the MS-IHU HCQ study and the IJID, methinks). Being in Singapore, it is easy to forget that access to vaccines - and moreover having the luxury to quibble about Pfizer vs. Moderna vs. Sinovac - is actually a rare privilege, with barely 12% of the global population having received at least one dose of any vaccine as of today, despite over 2 billion doses supposedly administered. While the current POTUS is pushing to vaccinate the world, he appears unlikely to even reach his domestic goals despite some more-progressive states going as far as to offer weed for jabs, and India for one may have some choice words about grand vaccine supply pronouncements; in any case, more-realistic timelines expect vaccinations in less-developed countries to drag well into 2023, at best.
Against this backdrop, it is easy to understand why many of these up-and-coming nations would be eager for anything at all that might help - and on the cheap - and on this, one would sadly have to admit that global health authorities have perhaps been worse than useless thus far. With bullshit, one can at least use it as fertilizer to grow crops (if not, please, as coronavirus treatment), and it doesn't draw large salaries to stomp potential remedies. We have probably said more than enough about HCQ since the previous year's #Lancetgate, and if that were too politically-compromised, there were always options as benign as Vitamin D and even sunlight exposure, the former of which increasingly seems to have an association with coronavirus severity and mortality. Now, one doesn't want to oversell such results, certainly, even if you'd be really hard-pressed to overdose on Vitamin D; at some point, I think it reasonable to say that, look, one can kill oneself with anything if stupid enough, it's not really a valid excuse to shut stuff down.
HCQ for one appears to be enjoying a minor renaissance of sorts, with a number of new studies finding that, well, if you aren't an idiot with the dosages and apply it early enough, there's likely some benefit to be had. Please note, however, that I am hardly being picky in promoting potential early treatments here - if povidone-iodine throat spray or Vitamin C+Zinc gets you 20+% absolute risk reduction over the baseline of Vitamin C alone, with Vitamin C by itself not unlikely to have some minor protective effect, excellent - recommend it by all means! Instead, the powers that be appear more interested in insisting that the evidence is not good enough by stating that there is no evidence (note the shift in implication), while demonstrating a distressing lack of interest in verifying the impact of all but any of these inexpensive and accessible mitigations.
There are, one supposes, a number of very good reasons for finding such early treatments, in addition to (not replacing, mind) vaccines. Firstly, as just mentioned, vaccines are and remain unavailable to large swathes of the global population, and it must border on the criminal to deny these people improved odds upon infection through some common medication, if it were available and efficacious. Secondly, the efficacy of the non-mRNA vaccines that many of those in less-resourced countries will likely have to rely on, has never been particularly high; from 50% to 80% has been reported for the likes of AstraZeneca, J&J, Sinovac etc. on the original strain, with reduced efficacy probable for variants - and given that new (and future) variants seem to crowd out the old, one might expect the practical efficacy to be towards the lower end. Thirdly, it is becoming increasingly accepted that the coronavirus is here to stay in some form or other anyway, so one would expect a continuing need for early treatment - and, as a bonus, there are indications that being infected may have a similar protective effect as vaccination, which seems to imply that if a patient is treated early and recovers, he's safe too.
Well, among the many contenders for salvator mundi from the coronavirus, one candidate has stood out from the pack in recent months: Ivermectin.
The Case For & Against IVM
What constitutes "reliable evidence"?
[N.B. For convenience, the cited sources , & ]
In many ways, the story of Ivermectin (IVM) has paralleled that of HCQ; huge excitement amongst some front-line practitioners at a potential easy, cheap sorta-fix to the pandemic, and then silence, derision and outright animosity from major health agencies and organizations. IVM's story has been well-recounted by Capuzzo and others, with much of its initial advocacy coming from Drs. Paul Marik and Pierre Kory in the States. Notably, the latter's earlier support for steroid usage in hospitalized patients has contributed to it becoming current standard of care (with Dexamethasone; though observe how even that has been spun on Wikipedia, against the word of a single critic), so it can hardly be claimed that they are entirely unqualified to speak on the matter. They, along with a number of other doctors, have since formed the Front Line COVID-19 Critical Care Alliance (FLCCC) to promote their I-MASK+ prevention and early treatment protocol, which includes IVM, Vitamins C and D3, Zinc and a number of other common medications, in what by all means appear to be entirely unremarkable doses.
So the story goes, largely vindicated by the acceptance of steroid treatment in late-stage patients, Dr. Kory went before the U.S. Senate pushing for Ivermectin to be considered by the NIH, only to be boycotted by eleven of the fourteen Senators on the committee (many of whom, one might note, have been amply funded by Big Pharma) - and to rub it in, the testimony and later podcasts on the subject would be entirely censored on YouTube (since rehosted elsewhere or restored). Now, one wonders - the doctor might not be entirely correct, perhaps he might be exaggerating somewhat, but is he not allowed to say his piece? Mind, if spreading inaccurate information warrants a ban, the channels of the WHO, NIH, CDC etc. would probably have to be set on fire and dumped into a pit, long ago.
Anyway, the months since Dr. Kory's December testimony have seen the FLCCC and other proponents apparently manage to convince a number of local authorities throughout the world to give IVM a shot, and given that one can hardly expect the actually-infected to be content with sitting on their arses and waiting to know whether they're part of the unlucky bunch, take-up appears to have been pretty broad. Mexico City appears one of the early success stories, for one, and it is hardly a stretch that places such as India, South Africa, Argentina and Peru, where anti-malaria drugs such as HCQ and IVM might have already been widely used, would be willing to give it a go. The impact in these places have been reported to be astonishing - a dizzying plunge in the number of coronavirus cases and deaths. Of course, correlation is not causation, something else might have been responsible, and I'm not a huge fan of relying on trends as evidence for, say, the utility of face masks either. So, let's move on to the actual trials on Ivermectin.
Now, recall when IVM was being derided as HCQ v2.0, in some quarters? This is hardly a baseless comparison, given that they are both common, cheap and slandered by supposed health authorities; however, if initial indications hold up, IVM is distinguished by one characteristic, that furthers its claim to be an improved Version Two: it really, really works.
Is this a vaccine?
It's not too hard to kill a treatment with a weak-to-moderate effect (to be explored later), but according to the evidence put forth by the FLCCC and other IVM supporters, the efficacy of IVM is so obvious as to be undeniable. Perhaps cognizant of the issue over RCTs and having the bulk of the evidence base outright denied for HCQ, there have been a relatively-large number of RCTs run for IVM at this point - about twenty - and they apparently almost all point, and strongly at that, in the same direction: IVM very good against the coronavirus. Moreover, it has been observed that the general effect has hardly changed with additional RCTs over time, further suggesting that the experiments are relatively unbiased.
Now, the opposition. There is, to begin with, the usual argument that the above evidence is insufficient (oft further twisted into "there is no evidence" in the mass media) and that more trials are needed. To this, the counter has been that there have already been over 50 trials involving over 18,000 patients, about all pointing the same way, and that (more expensive) drugs have been approved with far fewer trial participants, and while showing far weaker effects, and with many accompanying claims not actually backed by RCTs. As for IVM being applied in various combinations, my perspective remains that the findings should remain largely valid if IVM is the common factor there, further following the machine learning intuition on the strength of combining multiple heterogeneous/weak learners.
There is an interesting connection with Dr. Lye's message here, in which he warns that Ivermectin had not been proven effective, and that "evidence cited for Ivermectin in COVID included the faked database company called Surgisphere which led to two journal retractions from the prestigious NEJM and Lancet in 2020" (i.e. #Lancetgate), and that "...a large trial on ivermectin conducted at a dormitory by National University Hospital doctors including Dr Paul Ananth Tambyah was not effective in preventing Covid-19". To this, it should be evident to my longtime readers that #Lancetgate had been crafted to discredit HCQ as its main objective, and no direct reference to IVM could be found in the retracted fake Lancet paper, in the first place. On the second point, the NUS/NUH Seet et al. paper purporting the efficacy of HCQ (notably unmentioned by Dr. Lye) appears to actually indicate a significant reduction of acute respiratory symptoms and symptomatic coronavirus by IVM, just that it was hidden in a data table. This 50% reduction in progression to severe symptoms (moreover with relatively low 12mg total doses compared to the other RCTs) was then what was included in the ivmmeta.com meta-analysis, congruent with their practice of pooling analysis on the most serious outcome reported, which one supposes is not entirely unreasonable.
The FDA's current stand, for posterity
That clarified, other objections to early treatment with IVM include its danger, which one supposes cannot be much greater than any plausible medication, given how IVM had been considered by the WHO and various (formerly?) prestigious medical journals for mass administration even for young children, against malaria. And then there are jibes at IVM being "horse/dog medicine", but frankly it is unsurprising that anti-parasitics can work on both humans and other animals - and if we were going by this logic, many perfectly-good antibiotics would have to be forsworn. And next there are the objections that Merck - the original patent holder of IVM - has not supported its use against the coronavirus, but it might be observed that their patent has since expired and IVM is being produced as a generic drug in many countries, that Merck has been developing its own new experimental therapeutics (for which they have just signed a US$1.2 billion deal with the U.S. government), and that an actual discoverer of IVM - the Japanese Nobel Prize winner Satoshi Omura - appears actually supportive of its possible application against the virus.
The battle rages on in academia too, and while there have been a number of complementary meta-analyses - hardly unexpected given the published evidence, unless there is some hidden trove of negative studies in addition to the contested Colombian study that made it to JAMA - there has hardly been a lack of opposition in that sphere. A commentary in BMJ Evidence-Based Medicine, for example, claims improper collation of evidence in other meta-analyses (though it may be telling that they did not simply conduct their own proper such analysis as a refutation, instead of just stating an opinion), and the argument that in vitro experiments suggest that unsafe dosages are required for impact - on this, one might shrug and figure that maybe it doesn't work in (simulated) theory, but if it works in practice (as measured by the various RCTs), what is the complaint here?
One other group did write up their own meta-analysis against IVM, which was so hilarious that it deserves special mention. The initial preprint included ten RCTs, with the primary thesis that IVM did not reduce all-cause mortality versus the controls (RR=1.11), along with a host of other claims that IVM bad. Those following the IVM situation would unavoidably be puzzled at how they managed to come up with that finding by combining any ten of the existing RCTs - almost all strongly positive, mind - and quickly found that the authors had swopped the IVM and control results for a key component study, and that when corrected, the relevant RR is about 0.34 (i.e. 66% reduction in fatalities, broadly in line with other meta-analyses). Now, I don't like to slam researchers too hard for such mistakes, we have probably all made them, and the authors did go on to correct the transposition in the second version... while seemingly nudging the study weights around to leave the effect marginally non-statistically significant (RR=0.37, 95% C.I.: 0.12-1.13). Well, I'll be watching out as to which mainstream media outlets cite this paper in their articles, if it somehow gets published, to argue that yes, 63% fewer deaths, but why should you care?
CCP propaganda, or a despairing cry at an uncaring, mad world?
The Trial By Fire (And Worse, Politics)
In any case, the momentum for IVM seems to have reached something of a critical mass of late; at least one British doctor has resigned his practice over the IVM/HCQ cover-up, even as the British Ivermectin Recommendation Development Group (BiRD) gets their summit kicked off YouTube, and guest editors step down from the Frontiers in Pharmacology journal over what they viewed as unwarranted suppression of papers suggesting positive results for IVM in early treatment. If it's any consolation at all, social media platforms appear to be wavering on the censorship and misdirection, likewise belatedly in the scientific community. Notwithstanding Gavi, the Vaccine Alliance going as far as to pay for Google Adwords to advertise against IVM (when the FLCCC/BiRD etc. have always maintained the necessity of vaccines in the first place), IVM has been going places.
While application in the West appears still limited, with a prominent convert in Germany, adoption in less-developed (and vaccine-short) regions of the world seems to only be increasing. India and Brazil aside (the latter for which BBC News continues to smear IVM as a "bogus remedy" by stating that "according to several leading health authorities, there's no evidence to back up those claims"), ASEAN appears to be getting very interested as well, as foreshadowed in the previous blog post. Indonesia is beginning IVM distribution in Kudus after an encouraging meta-analysis by researchers from Pelita Harapan University, and Malaysia's Ministry of Health has started a 500-person I-TECH study on IVM in high-risk patients, apparently after popular lobbying and with underground prescription already taking place. Much the same is happening in the Philippines, with the University of Philippines set to hold trials, alongside a newly-submitted bill to enable emergency use of IVM in Japan (its homeland, after all), and more encouraging results from Israel.
The counterstrikes have begun, so it seems, with the Directorate General of Health Services in India suddenly removing IVM (together with multivitamins and Zinc) from their guidelines, though it appears that their reach is limited to only three hospitals, and competing guidelines continue to support IVM (and HCQ, etc.), only several weeks after indications that they were ramping up IVM (and other protocol drug) production. However, Goa - one of the first states to defy the WHO's utter incompetency - seems to have made a sudden U-turn. Concurrently, the U.S. medical establishment has arranged several trials on IVM and related early treatments, among of which the most prominent are probably the ongoing TOGETHER trial (which dismissed HCQ after finding a hazard ratio of 0.76, 95% C.I.: 0.30-1.88 for preventing hospitalization), a forthcoming 1,100-person trial from the UMinn group that had provided the NEJM study oft pointed to as proof of HCQ's inefficacy (and which some have already observed to be rigged against IVM in its recruitment), and a huge 15,000-person ACTIV-6 trial by the NIH that has already drawn US$155 million in funding, and is only scheduled to finish up by 2023.
Well, one might expect three broad scenarios, for these forthcoming American and non-American trials:
The Reputation & Future Of Medicine
In his missive, Dr. Lye claimed that "[Medical] Doctors are well respected in our society". One can hardly disagree with that. Physicians do heal the sick, after all, and while lawyers for example also (sometimes) exonerate the innocent, the habitual difference in the level of vitriol from jokes directed at these two honoured professions might indicate a gap in their public image (not intended as a knock on lawyers, I know a few, they're nice fellas really). It would, therefore, be a real shame if the good name of medicine were to be dragged into the gutter, for being a Big Pharma-Big Government complex accessory to unnecessarily denying plausible and accessible treatments for early-stage patients, against its primary calling. Singapore appears to have avoided the worst of the U.S. Sickcare system's excesses thus far, as from last month's tangle between the SMA and insurers towards keeping the sector honest, at least.
Before continuing, I must clarify that I have nothing against the business side of medicine, or even the pharmaceutical industry in principle. Developing new drugs and cures takes resources, after all, and one can hardly expect the scientists and doctors to work for free. One believes there a lot of people with noble intentions in medicine and pharma. Say that the current standard of care for some disease is a US$10/month drug that is 70% effective. If a pharma firm invents an improved drug that is 90% effective, well, they should be able to charge what they want for it (even if much of the basic research had been done at universities with public money, fine); one hopes that they are sensible and not outright maliciously profiteering (which sadly, does not always seem the case), but one can hardly deny that the firms have the right to set their price.
Ethics in medicine is not always a simple affair, and it can be hard to insist on where the line is to be drawn (e.g. on the Right to Try), but purposefully sabotaging existing medications in a manner that does not maximize their efficacy, must certainly violate it. And, to be entirely honest, one senses that the public trust in doctors and medical experts is not as high as it was or could be, and not exactly trending higher. Errors are entirely forgivable if committed in good faith (though possibly irritating if common sense would have suggested otherwise, as with the initial recommendations on masks and border closures). There may be no coming back for a long while if the deception is thought to be intentional, however, which the Ivermectin/HCQ saga is threatening to blow the lid off on. One can scarcely imagine the blow to the profession's prestige were it found to work adequately in some countries, only to be clamped down by the medical establishment and a cabal of "top journals" in others. Eventually, despite the best efforts of the corrupt FAKE NEWS, the dissonance is likely to become too great to maintain.
More than enough has been said about the different-seeming standards of evidence for cheap remedies against vaccines (which have by the way minted nine new billionaires) and expensive novel drugs - note the grousing over the FDA approval for Biogen's Aducanumab for Alzheimer's a few days back (when one supposes that plenty of protein would do much the same), and of course the persistent media shilling for US$3,000+ a course Remdesivir, when the WHO's own supposed-authoritative SOLIDARITY trial couldn't even eke out any significant effect (not that I'm against anyone trying it, if they think it may help). One popular explanation has been that alternative treatments had to be blocked for the (non-approved) vaccines to get emergency use authorizations (EUA), which does seem the kindest possible explanation for what has happened, if those involved sincerely believed that mass vaccination was the best way out. Not saying I agree with the logic, just saying that it at least sounds within the bounds of probity and sanity.
Still, if this were the case, perhaps a better way might be to, you know, just tell the truth? Something like, "there are a number of promising early interventions, but we believe vaccines to be the more reliable solution, so let us withdraw the EUA requirement for there not to be any alternatives, so no possible mitigations are overlooked"? And then just get POTUS or the head of the NIH or Congress or whoever you need to overwrite the EUA, because it's not like any of these currently seem very interested in upholding even the Constitution, nowadays? Maybe... maybe humanity is NGMI, after all.
With language exchange included in the making!
[N.B. Original version/tempo]
[N.N.B. Note Tesla, "Superme", etc. as signifiers]
[N.N.N.B. Can't deny that the unity that money can buy (as at the end of the video), does seem tempting at times...]
(Sources: theindependent.sg, wikipedia.org)
For the first time in living memory, the announcement of the The Nobel Prize in Physiology or Medicine would be moved forward from its usual date in October, and an unprecedented special award session convened by unanimous acclamation of the Nobel Committee, upon global clamour to recognize what has been described as possibly the "breakthrough of the century", hailed by some to be the greatest scientific discovery since Einstein's formulation of general relativity in 1915. The monumentous feat had been achieved by researchers from the National University of Singapore, who demonstrated for the first time in human history "the possibility of running a randomized controlled trial on inexpensive medications towards mitigation of a coronavirus pandemic, on over three thousand subjects, and actually publishing the results", from the Prize citation.
"Nobody was expecting this." eminent retired climatologist and member of the Swedish Academy Sven Ludvig Sjögren said, as he presented the golden medal to Professor Paul Anantharajah Tambyah, president-elect of the International Society for Infectious Diseases, who was representing the Singapore team. "I had been assured by all my colleagues in the field that this was absolutely impossible, with known current technology. They estimate that NUS is ten, no, maybe twenty years ahead of everybody else. It's incredible."
Professor Tambyah would humbly credit the rest of the study team, and the volunteer participants, as he accepted the prize. In doing so, he becomes the first Singaporean Nobel laureate ever, and only the third such to be associated with his country, after physicist Sir Konstantin Novoselov, and the late biologist Sydney Brenner. Singapore's flagship university has been steadily building its reputation since its founding as what would become the King Edward VII College of Medicine in 1905, but doubts remained over whether it had achieved the heft to truly consider itself amongst the world's premier colleges. Any such remaining misgivings would be well and truly extinguished today, as the National University of Singapore revealed itself at the forefront - nay, far and away setting the pace - of contemporary scientific endeavour.
What made the achievement so singular was that it had required simultaneous major discoveries in multiple disciplines, but amongst these various wonders, the sheer scale of the system that they had assembled would overawe the entire community. Tsun-Tsang Cheung, pioneer of quantum mechanics from [Not-A-Country Redacted] and of late involved with the Google team that had claimed quantum supremacy three years ago, would attempt to place the NUS feat in context. "We did it with 54 qubits in our quantum computer, the group from China's University of Science and Technology got up to 76 qubits, and IBM is claiming more than 100 - though I have something to say about that. But then, just imagine, somebody comes out of the blue with three thousand qubits, with undeniable proof! You don't expect these kinds of paradigm leaps nowadays, with all the collaboration going on between top groups!"
"Not just three thousand, three thousand and thirty-seven." Cheung's former MIT classmate - and now leading particle physics experimentalist at CERN - Esteban Alvaro Julián Delgado corrected, while shaking his head in admiration. "I truly did not think it within the realm of material plausibility. It is well-known that there is no analytical solution to the three-body problem, so it staggers me to even dream about the computational power and theoretical genius needed to manage not three, not thirty, but over 3,000 of those bodies at once. It beggars belief."
Given this, the accompanying Nobel Lecture would be one of the longest in years, as Professor Tambyah was invited to share the basics of his team's numerous groundbreaking innovations with the wider world. The short introductory keynote delivered by Dr. Justin A. Sokratis, former President of the U.S. National Academy of Sciences, would touch on the dangers of partisan politicization of the subject and the abject irresponsibility of the mass media, before Tambyah took to the podium before the packed Stockholm Concert Hall to reveal what had hitherto been some of the most eagerly-awaited secrets in various fields.
There was an electric silence as Professor Tambyah began his presentation by displaying an unfamiliar figure to the rapt audience, which had a green bar at the top, and many regularly-sized cells covering the remainder of the image.
"This is a screenshot from a program we call 'Microsoft Excel'" the good professor started. "You see, we assign each of our subjects with a random identifier, and each row then corresponds to one of the anonymized subjects." As the distinguished audience oohed and aahed, Professor Tambyah would demonstrate the capabilities of the spreadsheet live. "Every column, then, represents the data for a single day, the medication that the subject consumed for the day. H for HCQ, I for Ivermectin, Z for Vitamin C and Zinc, X for a missed dose, and so on. The second-last column shows the treatment arm that the subject had been assigned to, and the final column has the result of the antibody response test for the coronavirus, at the end of the study. Look, you can add data for a new subject, simply by clicking an empty cell and typing on the keyboard."
Professor Tambyah would go on to demonstrate features like "pivot tables" and "macro functions" for half an hour before a deserved intermission, during which the stunned audience struggled to digest what they had just witnessed. "I have never seen mathematical structure like that." whispered Dr. Dimitri Rabinovich, legendary topologist, Fields Medal nominee, and emeritus chair at Moscow State University. "There appear connections to infinite-dimensional manifolds and symmetric lattice methods, but I confess it beyond my full comprehension. It's so... dynamic. Changing the value of one matrix item affects the values of multiple other cells, in an ordered n-ary fashion. Honestly, I have not felt so excited since my sabbatical in France with Grothendieck, as a postdoctoral fellow in the 1970s. I feel young again!"
The sense of wonderment only intensified as Professor Tambyah continued the dissertation after the break, as he imported the data into another unknown software that he called "Stata", ran a "logistic regression" with "random effects", and produced a metric that he named the "derived odds ratio", moreover with esoteric references to "Wald p-values" and "bootstrap confidence intervals". More than a few of the attendees were seen furiously scribbling into notebooks, as they strove to catch up on all the new statistics being revealed.
"It's almost unfair." probabilist bon vivant James Kenyon Rugger, often spoken of as favourite to succeed to the Lucasian Chair of Mathematics at Cambridge, griped whilst staring at his copious shorthand. "Generating three thousand random numbers, indeed. How can one man know so much?"
[Editor's Note: Professor Tambyah would clarify after the ceremony, that the Stata scripts for the analysis had been coded by his second-year intern Vikul Chakrabarti, who has sadly been unable to make it to Sweden due to having been called up for his annual reservist stint with the Singapore infantry. Chakrabarti would however be able to take time off from latrine duty, to modestly decline the praise received.]
The second part of the lecture would turn to pharmacology, as Professor Tambyah briefly covered the long medical history of hydroxychloroquine, with a line diagram of the compound's molecular arrangement prominently projected on the screen behind him. Strangely, not a few members of the American contingent were observed taking cover under the tablecloth or making the sign of the cross with tremulous hands for this segment, but these behaviours would be dismissed as delightful quirks not uncommonly seen with academics. There would be a unified gasp as Professor Tambyah extracted a single white tablet, and swallowed it before the assembled dignitaries.
"He didn't need to do that!" world-famous entomologist Susan J. Barthemalow, renowned for her seminal tomes on tropical beetle diversity, wheezed as she patted her chest, trying to recover from the shock. "I thought he was going to die! Yes, I had been consuming HCQ weekly together with the rest of the party and the locals when we were on expeditions in Sumatra back in the Eighties, but The New York Times has their experts writing that it's literally poison, and if you can't trust the Times, who can you trust? Once I read that, there was nothing I could do but call in a professional biohazards squad, to dispose of the leftover bottles I had kept in my attic, before disinfecting the house."
Cornell organic chemistry professor Sebastian Kolakowski, who is also the founder of the early-stage biomedical startup Konari, would sense opportunity even as he handed Dr. Barthemalow an extra glass of water. "Just between you and me, I don't think Dr. Tambyah and the Singaporean team are revealing everything here." he nodded, a twinkle in his eye. "We all reserve a few trade secrets, eh? I mean, he's still standing and talking like nothing has happened, obviously he has done something to the molecule, an extra bond or amino or such. Well, the possibilities are endless, Konari is ever ready to discuss business."
There would be a minor commotion as liveried attendants removed a guest from the back of the hall, as he raved about "needing to check the speaker for his QT-prolongation", but the talk would swiftly resume as if nothing had happened.
Professor Tambyah would defer to head nurse Aisyah Sharifah, who had overseen the day-to-day running of the trial experiment, in explaining how its immaculate safety standards had been maintained. "Before we enroll a subject in the trial, we have them undergo a simple intelligence test, in which they are instructed to write down their name, and not stick the pencil up their nose. All of them passed. Given this, we trusted that they would not do something as stupid as consume all the pills at once, not that even that was likely to be fatal anyway."
At this astounding revelation, there would be a buzz of conversation throughout the place. "Can we do this?" one of the doctors seated at a table filled with the heads of various Californian hospital clusters was heard asking. "I don't know, sounds like a... revolutionary, even radical concept." came the reply. "We shouldn't presume too much about the I.Q. level of our residents." And then, in a lowered tone. "They said they gave HCQ to 432 humans, and none of them died, or at least vomited blood? You are never getting me to buy that!"
Three hours after its inception, Professor Tambyah would complete his speech by explaining how he managed to get the study published ("It really, really helps when the learned society that you are going to be President of, issues the journal"), and finally an exhibition of "drag-and-fill" in "Microsoft Excel"; the sparkling exposition seems destined for the annals of history, from the extended standing ovation that followed. More worldly concerns would inevitably bubble to the fore, as those from the many different nations represented, ruminated over how they could gain access to these earth-shattering life-saving National University of Singapore advances for themselves.
"Singapore may be a little red dot, but as they have shown today, they are in science second to none." Indonesian colonel and health ministry attaché Djoko Handayani said. "We believe that they will be more than willing to show ASEAN how they did it. We had advisors from Abrgan BioRegen, one of the U.S. pharma giants, but when we discussed running trials with potential remedies costing US$1 or less per dose, they could never get completed. Then our vitamin warehouse burnt down in the night. But once we considered options at US$100 or more per dose, everything started working, but clearly we cannot afford that for the general populace. So I think Dr. Tambyah and his team are doing a great service for humanity."
Bradley N. Schmidt, special consultant to the U.S. National Institutes of Health, had to accept that their tiny city-state ally had stolen a march on the United States here, but that America were confident of regaining leadership in the area, with sufficient funding. "From what we have learnt today, we should be able to run 1,000-person RCTs with drugs costing about US$80 or more per dose by the end of the year, and 2,000-person RCTs at around US$50 per dose by the end of 2023. But the consensus here remains that we shouldn't go much lower than that, because that would be unsafe for the compan... I mean, the consumers. What we really need is a new Manhattan Project to inspire the latest generation, and if Congress earmarks, say, US$1 trillion over ten years, we should get to RCTs with ten thousand participants by the end of the decade."
"Ten thousand." Schmidt repeated. "Five digits. Think big!"
Before the consultant could continue, however, he would be swarmed by an impassioned throng of Indian scientists, who demanded that the U.S. do more to help their country out materially. "America says India is good friend in the Quad, sir, that we make one billion doses of vaccine together, but now our people are dying in droves from not having enough vaccines for ourselves! We gave America HCQ last year, sir, but America is now not helping at all, it is all pay, pay, pay! Please do needful, sir, or if not, at least give us our HCQ back!"
Mr. Schmidt would attempt to explain his way out of the situation. "We follow the Standard Corporo Model of Clinical Trials here in the States. In the model, trial parti-cle-cipants - customos - create a strong repulsive force between them, so you can only gather so many of them together in a confined space, before the trial falls apart. The difficulty is something like keeping the plasma contained in nuclear fusion. Usually there are signs before trial failure, like the principal investigator turning up ashen-faced after a strange phone call, which tends to lead to early termination. Or he just gets reassigned."
"To hold the customos particles together in a trial, you need to dope the substrate with dollarinos." Schmidt waved a greenback demonstratively. "The dollarinos possess a weak interaction force, so you need a lot of them to counter the repulsive force of the customos; the bigger the trial, the more customos, thus the more dollarinos required, capisce? Or that was how they explained it to us, at the Big Pharma-sponsored conferences that I attended. I might have forgotten some of the details, because of all the nice young ladies in miniskirts giving out free samples, but the point is that you can't really blame us if your rupeeno to dollarino conversion rate is bad. This is just fundamental physics, take it up with Nature!"
The closing statements for the day would be made by Kenyan stateswoman and ethicist Niara Mwangi, who launched into a heartfelt plea for the world to come to their senses against the pandemic. "I do not need to repeat the human toll that is being imposed. The cost-benefit calculus is moreover straightforward. There have been over 170 million COVID-19 cases worldwide, and over 3.5 million deaths. If an early intervention were only 10% successful, that still makes 350,000 lives. But when I check the knowledge base that the WHO is depending on for such early treatments, as maintained in the BMJ, we basically know next to nothing about whether any of them work! It is over fifteen months into the pandemic - how can this be the case? Can anyone here please explain it to me?"
Mwangi's more-easily comprehensible appeal would be a welcome change of pace for the audience, after Tambyah's often-impenetrable abstract novelties, and Jeong Dae-Seong, the venerable South Korean elder of analytic philosophy from Sungkyunkwan University, could only agree with her. "It is not really my domain, and alas much of the brilliance that Dr. Tambyah introduced has been lost on me, but morally the case seems clear. I have studied evil in its many guises as the central focus of my career, and I can think of little that is more quintessentially evil than knowingly withholding or discouraging investigations into accessible mitigations, during a plague."
"Really, it's a transparent travesty." Todai University star epidemiologist Yahiro Watanabe smirked. "A less gracious man might note that it is exceedingly unlikely that those stalling RCTs into affordable early treatments do not understand what the probable outcomes are, from the results of the many non-RCT experiments, and that these people - some heading major journals and health organizations - are mostly trying to save their own sorry hides. Such a man might also declare that there is nothing that these fuckers could offer him in this life or the next, that could possibly give him half as much pleasure as watching these very sanctimonious hypocritical cocksuckers get the comeuppance that they so richly deserve."
"But I am a reserved and polite man, so I would never say such a thing." Watanabe continued, bowing slightly, with palms pressed together in supplication. "Ah, so."
A Connecticut physician, seated at the same table at Jeong and Watanabe, confessed that he was of the same opinion on gathering more information on early treatment and HCQ, but requested to remain unnamed. "Please, you must understand, I have not yet finished paying off my loan for medical school, I need this job. And my parents would be so, so disappointed if I got struck off the register, as they are threatening with dissident doctors in the States. I thought this kind of censorship and forcible circumscription of a doctor's own best judgment would occur only in North Korea or China, like when they shut down the Wuhan whistleblower who was trying to inform the public, but I was wrong. I really cannot do anything, I am sorry."
There would remain a few scattered detractors of the NUS team's approach, nonetheless, and an elderly gentleman in top hat and monocle would express his dissatisfaction. "I say, these upstarts are providing therapy before the buggers become bedridden, wot. Never heard of such rubbish in my life; tremendously unsporting and all that, these ching-chong gooks. What has the world come to? Bloody Asians!"
Dr. Rugger did not seem to hear that, though, as he cradled his head in his hands. "Wald p-values." he muttered. "Regression... logistic. Wow."
Update: The Nobel Prize in Physiology or Medicine has since been discontinued, after The New York Times, Washington Post, CNN, MSNBC, Facebook, Twitter, YouTube, OnlyFans, PornHub, several elite general science and medicine journals, a sneaker retailer, a fast food chain and the top ten pharmaceutical firms by market capitalization released a joint statement accusing it of being racist and a symbol of Swedish neoimperialism. It will be replaced by the Brawndo-Duff Beer Award for Socially-Equitable Health, from 2022 onwards.
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