One dose of mRNA vaccines

This is Joseph

I am starting to see the hot take of "why don't we experiment with giving only one dose of an mRNA vaccine". For example, see this. 

So let us count the reasons that this isn't a great idea.

1. The vaccines were tested from phase 1 to phase 3 to find an optimal formulation. People looked at the single dose antibody titers, as compared to two doses, and it was a lot worse. This casts doubt on the durability of the immunity.
2. Vaccine manufacturers look at these subgroups. the main Moderna trial had 30,351 participants and an efficacy of 94.5% (95% CI 86.5-97.8%). In the one dose subgroup there were 996 participants in the vaccinated group, and 1,079 in the placebo group with 7 cases vaccinated group and 39 cases placebo (80.2%; 95% CI 55.2-92.5%). So we know even short term efficacy is less.
3. The Oxford vaccine had more participants in the low-dose/high-dose subgroup, with 3 cases in the vaccinated arm and 30 in the placebo arm (efficacy 90·0%, 95% CI: 67·4 to 97·0)
4. In US dollars and sold in the US, the Oxford vaccine is $4 per shot versus $15/$19.50 for the mRNA vaccines. So it is a lot cheaper.
5. The Oxford vaccine looks able to make 3 billion doses in 2021, whereas the two mRNA vaccines (combined) look to be able to produce 2 billion doses. So there is more expansion in capacity by adding Oxford than splitting the Moderna or Pfizer doses up. 
6. This ignores Sputnik V and Sinovac, which are approved in some countries already/ These vaccines claim > 90% efficacy *(Sputnik V and Sinovac). These are both based on low case counts (bad) but no worse than the one dose sub-group for Moderna. 
7. Oxford can "be stored and transported at normal refrigerated temps of 2 degrees to 8 degrees Celsius (36 degrees to 46 degrees Fahrenheit) for at least six months" whereas Pfizer must be kept at -70 degrees Celsius until six hours before use. That is a huge logistical advantage. Moderna's vaccine is better for logistics, but it is also the vaccine with the lowest production levels. 
8. Even if the Oxford subgroup is due to the Texas Sharpshooter fallacy, the efficacy of the pooled vaccine estimate is about 70% (either you use the sib-groups or you don't). This is likely not significantly different than one dose Moderna and will likely be more durable

So if we want to argue for an ethical imperative to move quickly, the easy way forward is to approve the Oxford vaccine. There is almost no case where the one dose of mRNA vaccine approach is going to be better than just adding in the next tier of vaccines -- which have trials. Now it is possible that the FDA might decide that they are inferior and should not be given an emergency use authorization. But the one dose approach would require trials (timed to measure durability) and would take years to complete (versus actionable data now -- seriously, the Oxford vaccine has a Lancet publication so the data can be scrutinized). 

In a similar vein, the best thing we could do with Modern is . . . make more of it. Solves the one versus two dose problem if there is enough for everyone. If we really wanted to make a difference -- why not pay Moderna to drop the patent and make it universally free? 

Or push out the Oxford vaccine faster? Hilda Bastian has some concerns with the Oxford vaccine, but at least we have the data to make an informed risk-benefit tradeoff with it (and more data is coming soon when the US trial concludes). 

The handling of the Western mega-fires is another reminder we live in a solution-phobic society

We've had some nice showers recently. We're supposed to get more tomorrow (Monday) with winter storm warnings promising snow in the mountains. It is, of course, welcome. The West always needs water and we've had a fairly dry fall which in recent years has meant fire season threatened to stretch into the winter.

But while the rains are bringing a respite from the mega-fire, they are also a tragically wasted opportunity. Despite a virtually absolute scientific consensus as to the steps we desperately need to be taking, almost nothing is being done and very few people seem to care.

Writing for the LA Times, Bettina Boxall has an excellent account of the depressing details.

When COVID-19 blew a hole in California’s spending plans last spring, one of the things state budget-cutters took an axe to was wildfire prevention.

A $100-million pilot project to outfit older homes with fire-resistant materials was dropped. Another $165 million earmarked for community protection and wildland fuel-reduction fell to less than $10 million.

A few months later, the August siege of dry lightning turned 2020 into a record-shattering wildfire year. The state’s emergency firefighting costs are expected to hit $1.3 billion, pushing the California Department of Forestry and Fire Protection’s total spending this fiscal year to more than $3 billion.

The numbers highlight the enormous chasm between what state and federal agencies spend on firefighting and what they spend on reducing California’s wildfire hazard — a persistent gap that critics say ensures a self-perpetuating cycle of destruction.

 ...

Fire scientists have long called for a dramatic increase in the use of prescribed fire — that is, controlled burns that trained crews deliberately set in forests and grasslands during mild weather conditions.

They have urged federal agencies to thin more overgrown stands of young trees in the mid-elevation Sierra Nevada and let nature do some housekeeping with well-behaved lightning fires in the backcountry.

They point to the dire need to retrofit older homes to guard against the blizzard of embers that set neighborhoods ablaze in the most destructive, wind-driven fires.

Yet year after year, state and federal funding for such work remains a pittance compared to the billions of dollars spent on firefighting. 

...

[Jessica Morse, deputy secretary of the California Natural Resources Agency, which oversees Cal Fire] cited an August agreement between the state and the U.S. Forest Service in which they each committed to annually treating 500,000 acres [a fraction of what researchers say we need to be doing. -- MP] of California forest and rangelands by 2025 with a variety of fuel-reduction practices, including prescribed fire, thinning overgrown woodlands, timber harvest and grazing.

Yet this memorandum of understanding is non-binding and includes neither money nor staffing.

Maybe we should state all days as Eve powers

 

Little Nemo Meets Lieutenant Kijé

 A few years ago, I was playing around with the very cool open-source video editor, Kdenlive. It's powerful yet remarkably intuitive and, you know, free.

The images are from Winsor McCay. The music is by Sergei Prokofiev, though you may know it better from the many artists like Greg Lake and Sting who have borrowed it over the years.

Merry Christmas from Little Nemo

 

Twas the night before Christmas...

 

It's the thought that counts

If you've gone through the holidays without hearing "Sugar Rum Cherry"...

 ... you have not had a cool Christmas.

Fifty-two years ago

I was working on a highly critical post on the space colony movement when I happened to channel surf across this Nova episode commemorating the anniversary of Apollo 8. As often happens with that show, I quickly found myself engrossed and watched the whole thing.

Given all the bullshit we've seen in recent years around manned space travel, it's important to remember just how fantastic the story of Apollo was.

Here's the preview:

 

And if you have time:

Even the hitchhiker with the axe is nervous around the hitchhiker with the chainsaw

The crazy Trumpists are turning on the even-crazier Trumpists https://t.co/Nlr8dZLDSl

— Jonathan Chait (@jonathanchait) December 19, 2020

 Complete with Michael Flynn.

At the White House on Friday, President Trump held what may have been his most deranged meeting yet. In it, the president raged at his loyalists for betraying him, and discussed taking extralegal measures to overturn the election.

The meeting, first reported by the New York Times, included lawyer and conspiracy theorist Sidney Powell, convicted felon Michael Flynn, and Rudy Giuliani. One plan floated at the meeting was for Trump to appoint Powell as a “special counsel” overseeing allegations of voter fraud. Powell’s voter fraud claims are so fantastical she has been mocked even by other far-right legal conspiracy theorists. Andrew McCarthy, a former birther and author of one book titled How Obama Embraces Islam’s Sharia Agenda and another calling for his impeachment on multiple counts, has described Powell’s vote-fraud claims as “loopy.”

 ...

 But the election was not close enough for him to pursue either strategy, whatever chance he had for some kind of Bush v. Gore replay has passed. The measures he is now contemplating lie outside the normal framework for resolving election disputes, and would require, at minimum, almost uniform levels of GOP support.

Trump does not have that. Indeed the striking thing is that he is veering to positions so extreme and self-defeating that even his loyalists have blanched. Perhaps the most alarming fact about the Friday meeting is that Giuliani, who has spent months spreading fantastical claims of imagined voter fraud, became a quasi-voice of reason. Giuliani has proposed using the Department of Homeland Security to seize and examine voting machines — a move the Department has resisted — but even Giuliani opposes appointing a nutter like Powell.

We've gotten a lot of use out of this ad over the years.

Dr. Jill Biden

 This is Joseph.

There is a terrible article in the Wall Street Journal. See this excerpt below:

The argument is a bit muddled, but it seems to be that honorary doctorates are occasionally given to poor choices (this is an earned doctorate) and that standards have slipped. I think standards slipping is simply incorrect on the face of it, at least over in my area. The sheer amount of work that is required to accomplish a PhD has most definitely not decreased (at least not radically). Certainly there is no particular reason that a PhD (or Ed.D., like Jill Biden has) should not have the honorific of Dr. 

The last argument is that it is confusing with physicians, who have started using the same honorific despite having a clinical M.D. I think it is appropriate that modern physicians are also addressed as Dr. but see no reason that it should exclusive to them. In fact both dentists and pharmacists also have clinical doctorates, earned at great effort as well. 

It is true that it might be gauche to be Dr. X at a party, a criticism that applies to both physicians and academics. But in any context that Mrs. Biden would be appropriate, Dr. Biden would be even more appropriate. Not having out with friends, but in contexts in which Joe Biden would be Mr. Biden there is no reason for it not to be Mr and Dr Biden where they are present as a couple. 

The defense of it is actually even worse:

“Why go to such lengths to highlight a single op-ed on a relatively minor issue?” wrote Mr. Gigot, who elsewhere said the responses reflected “what was clearly a political strategy.” “My guess is that the Biden team concluded it was a chance to use the big gun of identity politics to send a message to critics as it prepares to take power. There’s nothing like playing the race or gender card to stifle criticism.”

While I agree that arguments should be allowed and that stifling them is bad, a bad argument does not become good just because it uses gender. Further down Mr Gigot points out that this bad argument applies to male PhD and Ed.D.'s as well. True. What is missing is a compelling reason to change etiquette just because some people may not know that the term Dr is used by several classes of professions. To take an example from his piece, Dentists and Pharmacists don't deliver babies -- do we drop their Drs as well? What about an MD who specialized in an area where they never delivered a child -- does the cardiac surgeon have to say "I have a medical degree but I have not yet delivered a child so call me Mr"? To say it is to see how silly the arguments are. 

And this:

He also noted that Mr. Epstein’s argument that holders of doctorates should not use the “Dr.” honorific applied to men as well as women, and he said criticizing Mr. Epstein’s use of “kiddo” to refer to Dr. Biden was misplaced, since Mr. Biden has also used the term in reference to his wife. He compared the Biden staff members’ tweets to those in which President Trump has referred to the press as the “enemy of the people.”

Ok. I don't actually believe that I need to say this but here goes. A spouse may often address their partner in a far more informal way than a third person. If a random woman can up to me and called me "honey" or "lover", it would be alarming even if my spouse can say such things. If the point of the article is to be about etiquette then why does it start like this by making a far more gauche gaffe than going by Dr in an informal social engagement? Over-familiar strangers seems like a worse etiquette concern than an EdD holder going by (her properly earned title of) Dr. 

Finally, we have a new sport of people making fun of her dissertation. Honestly, I can't even. A dissertation is a teaching document that shows a program of research. Of course they vary in quality and not every dissertation will shine. But the question of whether the underlying research was adequate to justify a degree has already been determined by a panel of experts in the research she undertook. 

In any case, I have probably put more thought into this than the original article writer did. But it seems like a very weak argument and not one that has added much to the discourse. 

Do professors still put New Yorker cartoons on their doors?

 

 

 

 

 

 

 

 

This is actually the origin of the phrase

"[Quibi] was bedeviled, from the beginning, by the very antiquated belief that in order for a startup business to succeed, it must actually succeed."

More from  Albert Burneko's piece on the death of the born-terminal Quibi. In this section, Burneko takes one of those bizarre ideas we've mostly come to accept and forces us to face its utter absurdity.

Catastrophic tech-startup failures are the best kind of story that can exist in America in the 21st century, and the only kind of good story that can come out of an industry whose successes are pretty much uniformly horrifying and abominable. I treasure them. American society increasingly resorts to an abstract, Process-ized, anti-human concept of what it even means for a venture to “succeed” or “fail”: Uber, as an example, has never come close to conventional profitability, has ravaged what were once thriving taxicab industries in many American cities, has replaced stable and reasonably normal cab-driving jobs with an underclass of quasi-employees hustling absurd work-hours to barely break even, and at best merely facilitates the dispersal of the very concept of gainful employment into the purgatorial gig economy in which a person increasingly monetizes every moment of their waking life to keep the lights on… and is, by most reckonings, one of the signal success stories of Silicon Valley.

...

In light of all this it is a source of very nearly orgasmic delight to be reminded that a would-be disruptive tech venture can, in fact, just straight-up fucking fail.

One fun kind of startup failure is the kind that makes wild claims about its ability to deliver a revolutionary product, hoovers up ungodly sums of investor money, then never delivers anything even vaguely recognizable as the product it promised, and collapses as it becomes crystal-clear that its founders were big-talking phonies and investment money was the only kind of money their company would or could ever make. At least a couple of Elon Musk’s various companies, for example, are at various points along this story arc; the eventual hilarious stories of their failure are like unrealized assets, Christmas presents waiting to be opened. When a standard Silicon Valley founder-type (that is to say, a moral idiot who watched The Social Network with the sound muted one time) applies this template to an actual regulated industry (laboratory blood-testing, say), the result is many very serious felonies, but honestly this kind of thing is a hoot even when it’s just some cockamamie nonsense about using algorithms to find previously hidden oil deposits.

Another kind is a little more innocent, but ultimately much funnier: The startup that actually delivers a product, but an obviously worthless one that nobody wants. You may recall Juicero, the company that produced a large, heavy, $400 WiFi-enabled countertop juice press for squeezing fruit juice out of Juicero-branded bags of fruit juice, and which capsized when some of its marginally less stupid early adopters discovered that they could just squeeze the juice out of the bags (of juice) with their hands. What makes this variety of startup failure so magical, what gives it its, ah, juice, is that it functions as an index of the gap between the class of putative business-savvy investor sharks who dump their money into these ventures and the real world, itself largely filled with doofuses who spend their money on stupid things, but no significant number of whom would ever think “Ah yes, a large expensive internet-reliant device, that is what I need in order to get some fruit juice.”

...

But there’s another sad generation gap manifesting itself in Quibi’s crashing failure: It was bedeviled, from the beginning, by the very antiquated belief that in order for a startup business to succeed, it must actually succeed. Like, as a company that makes and sells a product, even! They dumped over a billion dollars into this thing, they built it at an absurd scale, they gave Quibi programming creators ownership of their shows instead of fashioning some flamboyantly evil legal framework for extracting even their own personal names from them, because they actually thought they were starting a company that would create and sell a good product and fill what they perceived to be an actual opening in the entertainment industry. Those dolts. Those absolute fools! A startup company isn’t an industrious venture that makes and sells a worthy product; a startup company is a plywood box containing a whiteboard with arrows and numbers on it and as few employees as possible, which gets passed around among progressively meaner and more craven moral dwarves until it can no longer sustain even the flimsiest illusion of extractable vitality, and then is dissolved.

The median tech industry startup is all but explicitly smoke and mirrors, rooted in “fake it till you make it” overpromising and theater; startup culture valorizes bullshitting and/or outright deceit as a kind of capitalist derring-do. And while the “make it” part of the formulation certainly can mean “delivering on the good and/or service the creation of which is the company’s nominal reason for existing,” exponentially more often it means sustaining the illusion of efficiency and productivity long enough to secure a huge sale to a larger entity. Often the larger entity knows it’s buying bullshit, and is happy just to squat on a patent or break up a workforce that might theoretically have posed competition had it fallen into the hands of someone who intended to run it as an actual business. There’s an entire industry based on finding out the shit big tech firms haven’t patented yet, creating fake companies only nominally working on the same thing, and then essentially extorting the big companies into paying off those fake companies’ owners. Quibi could have done this. In the hands of a purer charlatan, one not beholden to a dead old world’s notions of business success, it would have had a purely for-appearances staff of four people and a minuscule budget, required show creators to sign over their firstborn children in exchange for dirt, and emptied itself into Amazon’s featureless all-devouring mass a month ago, to the downright criminal enrichment of its founders and early investors.

 

Working from home brings its own set of distractions

Living in LA, I do most of my work from the patio. I generally have the area to myself with little but my short attention span to keep me from concentrating, but yesterday I found myself caught in the middle of a territorial dispute that went on for most of the morning.

Yes, IP matters

 Albert Burneko (late of Deadspin) has a wonderfully snarky rant on the demise of Quibi.

Quibi, the subscription digital streaming platform that aired five-to-10-minute TV episodes exclusively on mobile devices, died yesterday. Personally I like to imagine that it happened because Quibi gained sentience just long enough to hear a one-sentence description of itself, and then immediately lowered itself into a vat of molten steel like the Terminator. 

The official story is a lot more boring, though not without its charms. The brainchild of megalomaniacal former Disney and DreamWorks head Jeffrey Katzenberg and serial executive-class remora and wildly failed gubernatorial candidate Meg Whitman, Quibi burned through, at a conservative estimate, somewhere between $1 billion and $1.75 billion in investment or seed money or whatever over the slightly more than two years of its existence, only for its creators to discover within three months of its actual product launch that, whoops, no one, anywhere, wanted to pay money to watch seven-minute TV episodes on a phone. Here is a fun detail from the Wall Street Journal‘s story about the company’s demise:

    The decision to hire the reorganization firm came after starting a process to sell the company, The Wall Street Journal reported. Quibi pitched suitors including Comcast Corp.’s NBCUniversal on a sale, according to people familiar with the matter, but would-be buyers were put off by the fact that Quibi doesn’t own many of the shows it puts on its platform.

This touches on one of those ideas that has been lurking in the background of a lot of the posts we’ve done over the years. There is a growing disconnect between the way business analysts and accountants value businesses and the investors and business journalists see them.

One of the many ways that Quibi pushed the business plan of Netflix past the point of parody was with its approach to intellectual property. NF spends a substantial chuck of its budget for originals on shows it has little or no ownership of. This fact isn’t hidden but it’s been downplayed by the company and virtually ignored by the financial press.

Quibi took this to the next level and purchased almost no rights to the content it produced. Once again, the press and the investors paid no attention – based on the “rules” (I’m sorry but I can’t bring myself to type the word without scare quotes) of the new economy, these things don’t matter – but when serious professionals tried to value the company, the fact that it had spent $1.75 billion dollars and had nothing to show for it but a crappy brand was something they found difficult to overlook.