Pedalling Towards Bedlam.

WhatWouldJoanDidion
WriteVille


I don't know about you, but...

I yearn for the brake of natural consequences to slow the spinning of a world that has been pushed to the brink by the reckless (and feckless and deadly) pushing and shoving of a coterie of very bad actors.

And so, as I pedal across Lotusland each morning, I find myself cheering on the ever rising petrol prices that are visible on the big boards at the bright and shiny cluster of gas pumps at Oak and 25th.

Yesterday the big boards blinked out $2.13 a litre.

Which gave me a little thrill of consequence realized.

Until.

I also realized that I, too, was starting to spin.


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Where the heckfire have I been?...Started a new administrative job at the beginning of the year and thought I'd take January off from the bloggodome...That stretched out a little....What changed?...Well, as I pedalled home last night the open skies and a brisk westerly at my back felt like...Springtime.
Butchered header and subheader?...This!


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The Silliest Thing Ever Written?

TheWeeklyStandard?

NeverHeardOfItVille

From America's number one conservative public intellectual...

Or some such NYT/PBS/AtlanticMonthly-type thing:

..(P)erhaps the most important belief that the neoconservatives can impart to us is that the American dream is real. The original neocons, the sons and daughters of immigrants, aspired to make it in America and contribute to their adopted home. If libertarians oriented their politics around freedom, and progressives oriented their politics around equality, the neocons tended to orient theirs around social mobility. They wanted to create a world in which poor boys and girls like themselves could rise and succeed. They understood that this ascent required not just economic opportunity, but also the right values...

David Brooks, December 9, 2025

Now, regardless the veracity of the claim regarding the most important imparted 'belief' of the Neocons, it is not clearly stated anywhere in the fine piece quoted above how, exactly, our Mr. Brooks thinks replacing the concept of making America great again with the concept of an America once again dreaming will be an antidote to Trumpism.

Then again, perhaps we should not expect any kind of real, actual thinking from the very same super-fine public conservative intellectual who once did his best, way back in to 2016, to calm the qualms of Republican and Democratic US'ians alike by telling them that rather than Mr. Trump it was for sure  'gonna be Rubio'.

Sheesh.


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Subheader?...In case you missed it (or, more likely, have forgotten), the always money losing den of neanderconnish intellectualism called the Weekly Standard was once our Mr. Brooks employer.



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Wither Gene Editing Blockbusters To Come?

SometimesASequenceIsJustASequence

WhoseCorrectionMayBeTooSmallToProfitFromVille

On Monday we talked a little bit about a new gene editing technology that has the potential to efficiently treat a devastating inherited immunodeficiency disorder.

The work was funded by a biotech spin-off company called Prime Medicine that has already signaled that it will have a hard time funding the further development of the technology as a viable therapeutic. This was reported by Hedi Ledford writing in Nature back in May when the initial results of the work were first announced (sorry 'bout the paywall):

"...Despite these early signs of success, Prime Medicine also announced that it will not develop the therapy, called PM359, any further on its own. “Prime Medicine is exploring options for the continued clinical development of PM359 external to the company,” it said in a statement.

That decision reflects the harsh realities of developing gene-editing therapies for very rare diseases, says David Liu, a chemical biologist at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, and a co-founder of Prime Medicine. “The science has moved far enough that many patients would benefit from these gene-editing treatments,” he says. “But it boils down to an issue not just of science and technology, but of economics.”...

Of course, some of this is little more than biotech posturing and, to be clear, the company has raised significant amounts of money despite the fact that its stock price has fallen significantly since its IPO three years ago.

The thing is, the disease concerned is very rare which, as an editorial in the Guardian noted recently, makes developing the technology any further really difficult given the costs involved and the commercial incentives that drive our current system of drug development:

"...Novel gene-editing breakthroughs are making headlines. But therapies are expensive and complex to develop. The cost of bringing any new drug to patients is now around $2bn, in part because, as Brian David Smith notes in New Drugs, Fair Prices, the “success rate, from discovery to market, is tiny” and there are approved treatments for “less than 10% of the 8,000 diseases that affect humans”. Commercial incentives, he argues, skew innovation towards lucrative cancer drugs and long-term treatments for large populations. Complex gene therapies for very rare conditions are seen as too costly to develop and too small to profit from..."

In other words, life science geeks who are trying to develop new therapeutics are constantly pushed to work on indications that exclusively serve large numbers of patients because they are told that they will never be able to garner funding to move their discoveries from the lab bench to anywhere near the bedside if they don't.

So.

Are there other models out there that might give us a better chance of moving all this exciting universe-denting research forward towards the clinic?

Stay tuned...

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Image at the top of the post is from a prime editing explainer from the good folks at MIT.



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The Casinofication Of Everything, Reloaded.

It'sNotJustTheWideWorldOfSports

AnymoreVille


From Judd Legum writing at his Substack:

Two major news networks, CNN and CNBC, recently announced partnerships with Kalshi, an online predictions market. Kalshi allows the public to place bets on a dizzying variety of news events. There are currently Kalshi markets for the winner of the 2028 presidential election, next month’s unemployment rate, next week’s top TV show on Netflix, whether the announcers will say “Cheesehead” during Sunday’s Green Bay Packers football game, and thousands of other future events...

{snip}

...“Kalshi is replacing debate, subjectivity, and talk with markets, accuracy, and truth,” Kalshi CEO Tarek Mansour said in a December 2 press release...

Hmmmm...

Markets, Accuracy and Truth.

Which one of those is not like the other?

Or, put another way, which of the three can be goosed, by either money or algorithms, when required?

Sheesh.


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A Truly Impressive Bit Of 'Prime' That Has Nothing Whatsoever To Do With Free Home Delivery.

WillTheWondersNever

CeaseVille


Chronic granulomatous disease (CGD), one form of which is called p47GCD, is a condition wherein the affected people can't generate and pump electrons into tiny membranous sacs within immune cells. Normally, the pumped-in electrons generate reactive oxygen species in those little sacs that rip up invading bacteria and fungi. Thus, people with p47GCD, which is inherited, can't fight off common infections.

The gene affected in p47GCD is called p47phox, the product of which is a protein that plays a key role in the formation of an electron generator called NADPH oxidase. The inherited mutation in p47phox that messes up the electron generator has been known for some time. The trouble has been that fixing messed up 'loss of function' mutations has been very, very hard, indeed. 

Now, an amazing technology called 'prime' editing, which is CRISPR-based, has been used to fix the inherited p47CGD mutation in patient stem cells that were then coaxed into becoming into immune cells with the newly corrected p47phox gene.

Two patients have received the treatment so far and it appears to be working in the short term. The work has been peer-reviewed and it has just been published in the New England Journal of Medicine. The following is the final sentence from that paper's abstract:

"...NADPH oxidase activity was observed in neutrophils (i.e. a key subpopulation of immune cells with the little electron-pumped sacs that whack bacteria and fungi) within 1 month and was maintained for 6 months and 4 months as of the last follow-up visit in Participants 1 and 2, respectively. These results support further investigation of prime editing of CD34+ (stem) cells to treat p47-CGD..."

Note: the stuff in the brackets, above, is mine and is meant only to be explanatory

This is a truly impressive early stage potential therapy whose development required the melding of fundamental, translational and clinical life science research. Ultimately, its further development could produce an efficient, longterm treatment for this rare but devastating disease.

However, will the development of this potential therapy continue?

Stay tuned...


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Neither Velvet Nor Foggy.

MayYourEarsBeMerry
AndBrightVille


If you need a little listening enjoyment for the next few days...

Hear Mel Torme tell a super young Terry Gross how he and Bob Wells wrote the 'The Christmas Song' (Chestnuts Roasting) in just 25 minutes on a sweltering summer day in Los Angeles in 1945...As an added bonus, Hugh Martin explains how he and Ralph Blaine wrote and then modified 'Have Yourself a Merry Little Christmas', first for Judy Garland and later for Frank Sinatra....Here.

Hear 'This American Life's' very first Christmas show from 1996, wherein David Sedaris tells the tale of being a Macy's Christmas Elf way before Will Farrell ever met Zoe Deschanel while wearing green tights....As an added bonus you get to hear the late, great David Rackoff tell the tale of how he once played a store window Freud for an entire Christmas season...Here.

And, finally, this podcast has little, if anything, to do with the Christmas season...It's just that Tweedy guy from Wilco/Musical Dadland talking about just about everything under the songwriting sun...Here.

Have a great holiday everyone!


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The Rot At The Heart Of The Stream-O-Verse.

WhatWouldBurlDo

IvesVille


From deep in the bowels of Reddit, one user shouts a high wattage truism out into the void...

"(T)heir entire existence relies on being slightly more convenient than piracy."

Meanwhile.

Where the heckfire can I find an uncut, crisp and sharp version of Frosty The Snowman?



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Personally, I still kinda like Reddit. It seems to be one of the few gigantic online platforms, like Wikipedia, that hasn't totally ensh*ittified...
Tip 'O The Toque to Katherine Trendacosta writing at one of my new favourites, Techdirt.




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The Advent Jukebox, Revisited!

 

It's Bigger E!

Backed with the lost (old) boys of never lab...

You can find more of E.'s advent jukebox offerings....Here....and...Here.

Or, with fewer copyright takedowns...Here.

Happy, hippy, and hippest of holidays everyone!

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Why Would Anyone Go There?

CancellingPlaydates

BetweenFriendsVille


From Chris Michael, writing in the Guardian:

All tourists to the United States would have to reveal their social media activity from the last five years, under new Trump administration plans.

Customs and Border Protection (CBP), an agency under the Department of Homeland Security (DHS), would also require any email addresses and telephone numbers visitors have used in the same period, and the names, addresses, birthdates and birthplaces of family members, including children...

And, it would appear that many Canuckistanians have already decided not to go there:

...Statistics Canada said Canadian residents who made a return trip to the US by car dropped 36.9% in July 2025 compared with the same month in 2024, while commercial airline travel from Canada dropped by 25.8% in July compared with the previous year, as relations between the two countries plummeted...

The thing is, most of that initial drop was based on a fuzzy notion of tarrif-driven patriotism.

However...

If the new US'ian 'plans' are enacted the reasons not to go will be personal.

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Twenty-Five (Or -Six) Minutes Before Four In The Morning.

NotQuiteCohen
TimeVille


When I was a teenaged kid, and just starting to pay attention to popular music as punk started to break, the band formerly known as the Chicago Transit Authority was so prolific and ubiquitous that their music seemed like wall paper.

And sometimes, like with the infamous and very popular compilation Chicago IX, which was released in 1975, it seemed like all the walls, in every single house everywhere, were being re-papered with, well, the same paper.

Anyway...

That particular compilation is 50 years old now, which means that it is being re-worked and re-released seven ways to Sunday.

But now, somehow, that old wallpaper is kind of comforting, and even a little bit interesting when you see and hear it done in more of a jam bandish-type way (see above).

And best of all, it means that two of the original horn players, Lee Loughnane and Jimmy Pankow are out and about talking about how they all got together at DePaul university and made all that music in the first place. They even talk a bit about the magic and the math of how the original horn arrangements were composed in a way that even a music theory dunderhead like myself can understand and enjoy.

You can listen to a long form conversation with Mess'rs Lougnane and Pankow...Here.


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Tangential allusion to an ear worm in the subheader, especially given that we're not that far from the 'end of December?...This!


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William Gibson's Overdrive

NeitherAleph

NorOracleVille


Regarding the image above of 19th century writing desks or 'slopes' as they were known...

From the mind of the estimable Mr. Gibson:

"Bronte sister laptops!"

Stick that in your steampunk genre and smoke it!



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Advent Jukebox...Day 5.

WhereCarolers

SingBelowVille


The two E's were over last night to get the decorating for the season started in earnest.

And what could be better to kick-off said season than covering a good ol' fashioned murder ballad, courtesy the Felice Brothers...

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You can catch more of E., sans the old guy,  continuing the Advent Jukebox tradition....Here.



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HST Friday - Sometimes A Favour Is Just A Favour...

NothingDigitalWillSetYou
FreeVille

'Nobody gives a mojo wire as a present, right?'

That was Hunter Thompson, writing to Dick Goodwin, by physical letter, in late 1975 about the early version of the Xerox telecopier (i.e. the 'mojo wire') that Jann Wenner sent him in an effort to crank up his writing output during the upcoming 1976 US'ian presidential campaign.

****

Speaking of US'ian presidents and 'presents'...

...Trump has issued more than 2,000 pardons and commutations this year — 10 times the number he pushed through in his entire first term...

But, nobody gives a pardon as a present, right?

Well...

...(N)otorious is the (pardon) case of billionaire Binance founder Changpeng Zhao, dubbed “crypto’s richest man,” who had previously pleaded guilty to money laundering that U.S. prosecutors said benefitted Hamas terrorists and Russian drug dealers. Zhao “rehabilitated” himself by helping to boost the Trump family’s crypto venture, which “raked in about $1.4 billion in revenue over the past year … far more than the president’s real-estate portfolio ever earned annually,” according to The Wall Street Journal. When Trump was asked about this shady pardon on 60 Minutes, he said he didn’t know who Zhao was...

Cazart!

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Pardon stuff is from a recent piece by John Avalon in Rolling Stone (web archive link) which is no longer owned by the good Mr. Wenner.

Image at the top of the post?...Bill Murray as the Docktor and the departed Bruno Kirby playing a Wenneresqueish character in 1980's JohnnyDepp-free, and Uncle Neil-infused, 'Where The Buffalo Roam'.


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Maybe If It Was Made Of Bananas...

RaffiWas

RightVille


Well, well, well, whadd'ya know:

Earlier this year we noted how the Trump administration had cooked up a half-assed wireless phone company. Even calling it a “phone company” was being generous: the branding deal was basically just a licensing agreement and a lazy coat of paint on another, half-assed, MAGA-focused, mobile virtual network operator (MVNO) named Patriot Mobile, which itself just resells T-Mobile service.

What was supposed to set the venture apart was a “bold” new $500 Trump T1 smartphone.

To pitch the phone to unsuspecting rubes, the original press release had a badly photoshopped rendition of the device, peppered with claims the phone would be “proudly designed and built in the United States.”

It didn’t take long for the folks behind the phone to pull all the made in America claims from the website. And while originally the phone was supposed to launch in August or September, not long ago it was delayed until October 31. As November drew to a close, there’s still no sign of the device...

Hmmmm...

Would you like Trump steaks with that?


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The above is from Karl Bode writing for TechDirt.
Earworm in the header, of course...This!

Snark in the subheader?...This!



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A Bubble For The Shedding?

ThisAin'tNoPartyThisAin'tNoDisco

ThisAin'tNoFoolin'AroundVille


Depending on where you've been looking, you might have come across a story or two that questioning where all the monetization/growth will come from to support the hugely big investments in AI.

Well...

What if the overlords behind all that over investification don't give a hoot-in-heckfire about real growth because they have instead gone all in on the 'shedding'?

Patricia Cohen of the NY Times has been chasing that story (web archive link):

The stock market bounces in recent weeks are just one indicator of the profound uncertainty and heightened risks running through the global economy and financial system.

It’s not simply that the hundreds of billions of dollars flooding into artificial intelligence investments might turn out to be a bubble. Or that the use of cryptocurrencies in mainstream banking is spreading even as their values have plunged after soaring to record highs...

{snip}

...The stock market run-up — the S&P 500 is still up about 14 percent this year despite the recent shivers — could foreshadow widespread economic gains. But (Harvard economist Kenneth) Rogoff doesn’t think that is the case.

“A big part of the high stock prices is not a reflection of high future growth,” he said. Rather, it is a sign that A.I. is expected to boost productivity and shrink employment. “The firms all think they’re going to shed a lot of labor, and that’s why the profits will be high,” he said...

In other words...

Our over investified AI overlords may not actually be betting on economic growth, but instead betting on economic collapse.

Collapse for all of us who are not over OIAI overlords that is.


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Earworm not so subtly dropped into the subheader?...This!

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