30 October 2024

By The Numbers - part the seventy sixth

What's that they say, "payback's a bitch"? First, the Musk Ox makes you his bitch (he he), then your business takes it in the neck.
On Monday, NPR reported that by midday more than 200,000 people had canceled their digital subscriptions to the Post, citing two people familiar with the matter.
What's the over/under in days to hit 1,000,000?

Well, today's total is up to 250,000!! Jeff is so, so not so
Ending them is a principled decision, and it's the right one.
I wonder how The Orange Shitgibbon©anon.'s dick tastes? Is it that geezer mustiness? Not that I would know, of course.

28 October 2024

By The Numbers - part the seventy fifth

What's that they say, "payback's a bitch"? First, the Musk Ox makes you his bitch (he he), then your business takes it in the neck.
On Monday, NPR reported that by midday more than 200,000 people had canceled their digital subscriptions to the Post, citing two people familiar with the matter.
What's the over/under in days to hit 1,000,000?

As of 2023, digital total was 2.5 million. Already nearing a 10% hit. Some bidnezz have gone under losing less. Have fun Jeff. May be the Musk Ox will give you a free ride on SpaceX? Blue Origin you say?

Just after I hit enter on this piece, Jeff's plea that he did nothing wrong, nothing at all popped up. As the many 'experts' on dictators have pointed out: they get going by instilling fear of retribution, and getting self-censorship in return. Note that Jeff says that there was no explicit quid pro quo involved. Well, as a very good line from a L&O episode put it (Claire), "like any good gift, it was a surprise". The Orange Shitgibbon©anon. has made clear, explicitly, he will use DoJ, IRS, and any other arm of the executive branch to attack anyone he finds 'disloyal'. Too bad he lost not only his hair but his gonads, too. A while ago.
"I would also like to be clear that no quid pro quo of any kind is at work here. Neither campaign nor candidate was consulted or informed at any level or in any way about this decision. It was made entirely internally," he wrote.
Jeff had no need to 'consult' with The Orange Shitgibbon©anon. before pulling the plug. He can't do that, because if he admits he's The Orange Shitgibbon©anon.'s bitch, everyone knows he's The Orange Shitgibbon©anon.'s bitch. Them's the words of a scaredy cat self-censor. You betcha.

Hinged

While we were out on the island, the hasp for the new shed door, about 3/4 inch of solid hardwood, was finally installed. These are barn door hinges. Big gorillas. The first attempt failed when the block to hold the receiver bracket split. Ah well. But now it's there, replacing a nicely warped sheet of plywood. Long story.

But, we're here to consider the unhinged. The Orange Shitgibbon©anon. has been on a torrent of spewing shit by the cubic yard. Why? I told The Wife when this got really going a few weeks ago that the answer was as plane as the nose on all the Mount Rushmore faces. It's not well known among the average public, largely because the lamestream media don't talk about it anymore (they used to, a lot), but the fact is that campaigns especially the Presidential variety do a very lot of polling on their own nickel (and the PACs nickels, too). And if a campaign has really deep pockets or the PACs do, they can do more granular polling (larger sample sizes) more often and more widely. As a rule, these internal polls, only rarely exposed to the public before or after a campaign, are more accurate.

Which makes The Orange Shitgibbon©anon.'s totally unhinged behaviour obvious: he knows he's going to get skinned alive. This also explains all the legal attacks being constructed for when he gets his ass handed to him. He's burned every bridge to a constituency except for the neo-Nazis and their fellow travelers. We'll see in a few days, but I can't think of another reason for him to go totall batshit. He has to. It's his only hope.

27 October 2024

Life Imitates Art - part the second

Paula Poundstone admitted once that her teeVee viewing is mostly "Law and Order". Same here. I suspect that she, as I, have no use for Tucker the fucker. And his unhinged rant a few days ago certainly is reason for such.

If you have one of the channels that loops the L&O episodes, get ready for "Surrender Dorothy"/2000
The DA's office believes that a well-known psychologist/author may have driven his daughter-in-law to suicide because her increasing rebellion against his "submissive wife" philosophy would have ruined his reputation and lucrative career.
One can only hope that no one takes Tucker the fucker that seriously.

And, lest we forget
"Honey, I'm Home"
These Right Wingnuts are all that wacko. Dad's always pissed.

17 October 2024

Decorum

Very long time readers may recall references to Bermuda in these musings. That trip, by boat I may add, was before these missives began. But I've been on the email listserve of "The Royal Gazette" since then. Today is one of the few times I've felt the compulsion to share. It seems that the Attorney General of that Overseas Territory went ballistic in court. How very UnBritish.
"The Royal Gazette" asked the Bermuda Police Service if police were called to the court and a spokesman said: "On Tuesday, October 15, 2024, an officer assisted with a minor incident at the courts that was quickly resolved and did not require any further police action. There will be no further comment made."
Imagine if Bill Barr had blown his top? Well... crickets from the back benchers. Merrick Garland? The world is coming to an end.

By The Numbers - part the seventy fourth

For some years, all of them while I've been keeping track, the pharma bulls have bitched and moaned about the onerous steeplechase that has to be navigated to get these wonderful (new, occasionally) drugs approved. About 3 decades ago, FDA more or less caved to this bitching, and created a less onerous track called, as one might expect, accelerated approval. The gig was that if a drug had stat sig (mostly), clinically meaningful (mostly) benefit before doing a PIII trial(s), and (mostly) targeted an unmet need in the population, then the drug could be sold. The gotcha was that this was a conditional approval, requiring a full-blooded PIII trial post-approval.

The cynical among us (raises hand, very high) found this regime ripe for gaming. And so it has been. Today's Derek Lowe post reviews a rigorous study of these accelerated approvals in oncology. It ain't a pretty sight. In fact, recently FDA now requires that the all-important full-blooded PIII be underway before the accelerated approval can be granted; fobbing off the PIII has not been as rare as hen's teeth.
But the trends in these oncology trials are worth noting: the failure rates of the traditional Phase III oncology trials have been gradually falling over this period (with an overall Phase III failure rate of about 41%, but currently at 34%), whereas the confirmatory post-marketing Phase III oncology trial failure rates have been increasing in recent years, from around 14% during the 1992-2015 period to 33% in 2016-2023.
Conmen will con.

And, it's worth knowing that truly good new drugs don't have to complete a PIII. If the sponsor really, really believes that New Drug X is better than high button shoes, then the sponsor has the option to schedule (not make up as the trial goes along; mostly) interim analysis. It's a bit more convoluted than simply doing the same arithmetic that gets done with the full data set after all patients have been run through the trial; the stat requirements are a tad more stringent. If New Drug X meets the stat requirements, and FDA agrees with the trial data, then New Drug X will get standard approval before trialing all patients. But, as I say, if the sponsor really, really believes in New Drug X, then such is the more ethical avenue.

One might wonder how much worse the situation is in the CNS world. Alzheimer's strikes a familiar note. If you watch carefully on the teeVee, the mood altering compounds display some less than stellar efficacy in the fleeting, tiny print at the end of the advert.

Here's another report in that same space.

16 October 2024

End of the Hype?

Well... it did have to happen, and may be it has. ASML has tanked bigly, stock market wise. As I type, it's down $180 from Monday's close and bouncing up a little and down a bit more. Seems that demand for their bottleneck machines is predicted, by them, to wane going forward. The AI chipmakers are collateral damage. May be the AI fever has broken? One hopes so.

14 October 2024

Captain Obvious

Well, today's gobsmacking revelation just popped up on CNN
"The biggest single, best predictor of how someone's going to vote in American politics now is education level. That is now the new fault line in American politics," Sosnik told David Chalian on the "CNN Political Briefing" podcast.
I've never heard of Sosnik, but if he really, really believes this is "now", he's an idiot. Smart people, at least 99.44% of them, vote liberal/progressive/pussy today and since the beginning of the Republic. In order to keep control in the hands of the dirty boot idiots, we get the Electoral College and 3/5 and so on. FDR gave so much to pull the dirty boot idiots out of the muck that they think they pulled themselves up by their bootstraps, and immigrants and Jews and Negroes and HighSpanics are taking it all away.

As the topic has arisen in these essays over time, the cause has been since the beginning of the Republic: the dirty boot folk have always elected politicians who do all they can to keep them in dirty boots; sick, poor, and uneducated.

Which brings us to the only reason to question immigration from the shithole countries: such countries are (nearly?) all dictatorships, and have been for generations and even the escapees are enured to such treatment. The MAGAnauts ought to be welcoming them with open arms. Why do you think that the Central and South American immigrants tilt toward The Orange Shitgibbon©anon.? He's what they know.

13 October 2024

By The Numbers - part the seventy third

Well, I suppose it had to happen. The anti-vaxx crowd has organized and exploded. This report in the NYT (there are myriad others) makes the lunatics obvious. And gives them publicity they probably shouldn't get. Be that as it may.

It's the No Nothing Party gone beserk. They really do want to party like it's 1829. If the mRNA vaccines, not to mention the decades old childhood vaccines (not mRNA), were turning people into vegetables and the like, you'd think there'd be widespread reporting on such. Fox and Newsmax and such. Crickets.

Number of jabs of Covid mRNA in the USofA: 677 million. Of that total, aprox. 83,000 are Novavax, a 'traditional' type.

So, with all that mRNA circulating in the blood of witless Americans, you'd expect to see some instances of mRNA's perniciousness. Crickets. Yes, there are some rare cases. Here's the real skinny (if you believe in science): non-trivial side effects are about a handful per million doses, and occur in otherwise healthy young-uns.

Here's the CDC report on incidence of myocarditis deaths. Of course, the MAHA cabal will insist in roaring voice, that CDC/FDA/space lasers from Mars are conspiring to keep the gullible on the verge of death. No one was found to have been killed by mRNA caused myocarditis. Zero.

But, that's not the Big Kahuna of the MAHA crowd. The Big Kahuna is that mRNA, however administered or why, alters DNA of the patient. Um, nope. And, btw, Nebraska isn't a hotbed of Leftist elite.

The lunatic fringe, on a revenge ride like the surviving Earps, will wreak havoc and death to the USofA. Be careful who you vote for.

11 October 2024

Junk Yard

Commie Law and the Junk Yard Dog© is a recent title. The latter is Walz, of course. His latest contretemps is the call to get rid of the Electoral College. The sort of bomb throwing one expects from the Junk Yard Dog. Not quite on the level of MTG's assertion that Sleepy Joe and Commie Law have been engineering hurricanes to devastate Red Counties just before the election. Get the hell out of Hurricane Alley. Blowback has ensued.

Today brings new reporting of backpedaling. Ah well.

But the notion boils down to the simple choice: do you want a Damn Gummint run by chucklehead hillbillies? They'll steal all the moolah from the Rest of Us to pay for living in Tornado Alley, Hurricane Alley, filthy Hollers, and any Desert they can find (with myriad water guzzling golf courses, of course; water supplied by the Great Lakes). And insisting that Earth is 6,000 years old and must be taught to first graders. Who don't get lethal vaccinations, of course.

Sleepy Joe squeaked out an EC win, but with 7,059,526 more total votes than Alzheimer's Ronnie, II. Covfefe!

The EC was created for the same reason as the 3/5 thing: to bring along the slave states, and guarantee them more than one-man-one-vote. It's right up their with the rule for deciding a tied EC: the House votes the President, but not on the House seat count, but by states, which just happen to be more MAGA. That's quite a catch, that Catch 22.

08 October 2024

By The Numbers - part the seventy second [update]

Well... it's been clear for some decades that Big Time college sport, first football then basketball, were merely instructional leagues for the pros. Now the bandaid of "amateurism" has been ripped off. What's the over/under on years until Big Time college sports no longer require any classes for Big Time college athletes?
[A] group led by former Disney executives-turned-investment professionals has proposed a 70-team super league featuring schools from the four power conferences that would infuse up to $9 billion in private capital cash into the sport.
What's that olde saw? "I went to a fight and a hockey game broke out". I went to a football game, and no one went to class.

I wouldn't find it quite so repulsive if at least some, preferably mostly, of those billions went into the academic functions of the schools. And, if memory serves, a lot of Big Time college sports (in the Red states, most) are state schools. Reminds me of those speed traps in the small town Red South. [update... didn't take long, did it?] Well, the bet is off, mostly. It's already here. Color me Shocked!! Shocked I say!!!
Last April, near the end of his third semester on campus, Sanders attended an in-person class for the first time. It was filmed for his social media accounts.

07 October 2024

The Worm Turns

Once again, a report from Derek Lowe. This one is especially nice, since it is another feather in the cap of the Cambridge-Boston biotech hat. Well... mostly, but the other one went to UMass Med and teaches there now. That's in Woosta, which is mostly 'around Boston' to most folks.

Gentle Reader likely remembers the whacko crowd yelling that mRNA was going to do such horrible things to the bodies of those who got the vaccines. And right now, God damn it! Haven't heard from them in some time, now have we? I mean, for the MAGAnauts to believe their bullshit, they really, really should have been insisting that the Blue State pointy headed smart people get vaccinated early and often. So that they would die off next week, and the MAGAnauts could take over the planet. Kind of like zombies. But I digress.

The report is about the development of microRNA, and why it's important. Again, one needn't be a medicinal chemist etc. to get the gist of what's going on.
That went from model organisms like fruit flies and zebrafish all the way to humans, and further experiments showed that yes indeed, this microRNA system was involved in timing of gene expression in cells from all of these organisms. In fact, it seemed to be a very important part of the gene expression machinery in every creature with left/right symmetry in their bodies.
Which must piss off the Evangelical Radical Right Wingnut crowd a whole bunch. If they ever find out. There's zero chance that Fox or Newsmax or the Butt Fuck Crier will carry the story.
And that, folks, is what a Nobel Prize-worthy discovery looks like.

05 October 2024

Different Ox - part the first

Well, we're in it again. Another hurricane devestates some place, in the Red states. One might wonder whether those Evangelical Radical Right Wingnuts will vote against another bailout, like they did with Superstorm Sandy? After all, that happened in rich Blue states, mostly, and they deserves to fend for themselves. And they ain't no such a ting as climate change.

I'm willing to bet that the Evangelical Radical Right Wingnuts are pleased as punch that Asheville, home to flower power hippie types, got thoroughly wiped out. God's punishment.
The hurricane damaged an estimated 80 percent of the buildings in the River Arts District of Asheville, N.C., and upended the lives of artists who had recast the city as a cultural force.
Will try to keep an ear to the ground. I'm pretty damn sure that Asheville will be on the short end of the stick when the Congressional delegation and state legislature get around to doling out the Bongo Bucks for rebuilding. God got rid of them infidels, and not a dime to put 'em back together. No sireeee.