- I think direct post-viral fatigue, including post-COVID is in the head. Specifically, in brain tissues. Something along the lines of an encephalitis or MS -- encephalopathy is probably the best term. A persistent inflammatory condition related to immune dysfunction or persistent infection by something (like reactivated latent viruses, COVID, etc).
- It's very hard to separate post-viral neuronal dysfunction from anxiety, depression, ongoing dementing processes, coincident head injuries, coincident brain disorders, sleep disorders and the like. It's all in the brain after all. (These aren’t exclusive conditions, so some unlucky person must get all of them at once. Heck, for all we know depression is partly a postviral damage disorder.) We need better tech -- maybe a combination of anatomic and functional brain imaging will help one day. Maybe it will be something we can diagnoses between MRI and lumbar puncture/CSF samples.
- I think one day we'll find post-COVID encephalopathy (PCE I'll call it) occurs in less than 1 in 500 ever-infected people and in most it improves over 3m to 1y. In most, but we now believe MS is an infrequent or rare sequelae of Epstein-Barr infection. So we gotta worry that some PCE is not going to get better unless we come up with new treatments.
- There are almost certainly other viruses that cause similar conditions (post-viral encephalopathy). Maybe non-COVID coronavirus URIs aren't as benign as we thought.
Sunday, July 24, 2022
Putting down a marker on post-COVID encephalopathy (PCE)
Saturday, June 11, 2022
Paxlovid indications and the Test to Treat program
Sunday, May 15, 2022
What is Great Replacement Theory?
[Copied over from a tweet stream.]
So now I'm trying to figure out what Great Replacement Theory is. It seems to be one part true and one part sort-of true.
The true part is that we expect a low-melanin blond-red hair (LMB) phenotype to become less common barring genome hacking. That's been well expected since at least the 1970s (perhaps 1870s?). These are recessive genes and migration and differential birthrates mean they will become uncommon.
The sort-of true part is that libs like me don't care about this. It's not just that my white skin is a PITA (thin, burnt, premalignant), it's also that we have a lot more to worry about. Like civilization for example.
The mostly untrue part is that libs/dems are conspiring to accelerate the decline of the LMB phenotype.
It's true we hope the GOP's white nationalism will discourage "non-white" (whatever whiteness is) voters, it's true we encourage immigration as a generally good thing for a low birth rate America that has benefitted from attracting worldwide talent, it's true that we enjoy and appreciate novelty and diversity, and it's true that we think it would quite good if all this led to the GOP to morph into a non-racist opposition party.
But it's not true that this is an explicit conspiracy. It is, perhaps, an emergent result of our not caring that much about preserving a particular phenotype, our interest in preserving human and American civilization and our affection for novelty and diversity. I can, however, see why people who are passionately attached to LMB phenotypes would confuse this emergent result with a diabolical conspiracy.
Thursday, May 12, 2022
Google Search: 1996-2022. RIP.
Alta Vista was a very good search engine. I didn't feel like I was missing much in early 90s; I could answer many questions easily. Then, in 1996, I tried Google Search. I was one of the first users at our dot com startup. It was miraculous.
The 90s web combined with 90s Google Search gave us all the best of world's written knowledge. It was the closest we ever came to a universal library.
Things go a bit rougher after the dot com crash. We started seeing more click-driven fake sites. On the other hand blogs were great and Google more or less kept the crap under control. Then came the 10s.
Sometime in the 10s Google gave up. Search results started to incorporate paid placement. Black hats figured out how to bypass Google's quality filters and generate adware clicks. At the same time blogs died and quality content got harder to find. By 2017 we knew we were in trouble.
Today I searched on something people ask a thousand times a day: "How do Facebook Messenger hacks work?" Google suggested a variant phrasing. This is what I got (click for full size):
Saturday, February 05, 2022
We need non-Apple App Stores - because Apple's store has trash like Luni Scanner App.
[Update 3/6/2022: After I exposed this scam I revisited our purchase history and the listing for the scam subscription had changed. Instead of "Luni" the company and "Scanner" the App it showed:
"Municorn" the app and AlexeyBogdanov272750744 as the Seller.
In addition, when I clicked on the Report a Problem link I see there's an entirely new feature!
Unfortunately, perhaps due to issues with my Store Apple ID, I can't select that Apple ID as a family member. Other family members appear.
--------------- ORIGINAL
There are several good arguments for a non-Apple iOS App Store. The best reason I know if for competing App Stores is that Apple's App Store has many frauds.
Consider the case of the Luni Scanner App; #85 in "Business" in the US App Store.
Luni's is a "mobile app publisher" their site claims they are "the largest french app publisher" (yes, lower case "french"). Their domain information is protected. All their apps are subscription based.
Luni makes a suspiciously wide range of apps with generic names including a "VPN" app, a "Translator" and a "Video Editor":
The VPN app has 22.9K ratings with an average of 4.7/5 by people like "yessirbruh". The 'most critical' ratings (only accessible on iOS) make clear it is a scam with clever subscription pattern that tricks users into paying a high weekly rate.
The Scanner App is the similar scam that bit my family. It has 174K ratings and 5 stars. The vast majority are obviously purchased. The "critical" reviews mention unwitting subscriptions. A screenshot that appears on first launch shows how it works for the "Free" app with add-in purchases:
This covers the entire screen. It appears that one cannot use the App without clicking Continue. In fact if a user closed this screen the App can be used. Of course most naive users, inducing our family member, will click Continue so they can start their "free trial". Except that's NOT what Continue does. Within 3 days charges will start. In our case, not $10 a month, but $5 a week.Scanner App is far from the only scam app on the App Store, and Luni far from the only "publisher" to earn millions from dark subscription patterns. Apple has let this problem fester for years; they are unwilling to fix it.
That's why we need alternative curated high quality App Stores. So we can restrict purchases to a trustworthy vendor.
For me $100 is not a big cost and the experience is a great learning opportunity for my family member. Even so, a reaction is needed. I'm sharing this experience here, but more importantly I'll share a condensed version with our two MN Senators and our Representative and the MN attorney general. If Apple doesn't get the money out of Luni I'll try the AMEX fraud process.
To be clear, the problem is Apple. Luni is just taking advantage of the opportunity they've been given. We need quality App Stores. That requires competition.
Below it the letter I'm sending to our Senators and Representative:
I'm writing to share a family story that illustrates why we need alternatives to Apple's iOS App Store. I hope you will support efforts to force Apple to allow competing App Stores with viable business models.
The problem is Apple has done a poor job keeping scams out the App Store. Recently a vulnerable adult family members was tricked by very sneaky sign up procedure. He unwittingly subscribed to a worthless app for $5/month. Because Apple has no controls on purchases in family sharing accounts I got the bill. It ran for at least 20 weeks before I spotted it and unsubscribed. I submitted a reimbursement request to Apple for 20 transactions.
When I investigated I found the app vendor, Luni, had dozens of similar worthless apps with the same trick subscription process. They have hundreds of thousands of fake reviews. The scam Scanner App was #81 in its category with a 5 star rating. The "publishers" make millions. I'd wager they are a front for anyone who has a good scam app; they create an icon, embed their subscription scam, and take a cut.
The App Store has many apps like this. They make Apple hundreds of millions of dollars a year. Perhaps billions. Apple could have cleaned them out years ago. They could do so many things to make these traps less effective. They've done none of them.
We need a better App Store. Apple doesn't deserve a monopoly on iOS App sales because it's been at best negligent, at worst malevolent. We need higher quality trustworthy curated App Stores in place of Apple's service.
Saturday, November 27, 2021
Civilization, complexity and the limits of human cognition - another attempt at explaining the 21st century
At last count my list of contributing factors to the crash of '09 included ...
- Complexity collapse: we don't understand our emergent creation, we optimized for performance without adaptive reserve
- Mass disability and income skew: The modern world has disenfranchised much of humanity
- The Marketarian religion: The GOP in particular (now the Party of Limbaugh), but also many Democrats and libertarians, ascribed magical and benign powers to a system for finding local minima (aka The Market). The Market, like Nature, isn't bad -- but neither is it wise or kind.
- The occult inflation of shrinking quality: What happens when buyers can't figure out what's worth buying. Aka, the toaster crisis - yes, really.
- performance-based executive compensation and novel, unregulated, financial instruments: a lethal combination. See also - You get what you pay for. The tragedy of the incentive plan.
- Disintermediating Wall Street: Wall Street became a fragile breakpoint
- The future of the publicly traded company: A part of our problem is that the publicly traded company needs to evolve
- The role of the deadbeats: too much debt - but we know that
- Firewalls and separation of powers: a culture of corruption, approved by the American electorate, facilitated dissolving regulatory firewalls
- Marked!: Rapid change and the Bush culture made fraud easy and appealing
I put Marked! pretty low on the list, but maybe I should bump it up a bit. The Hall of Shame (Clusterstock) lists a lot more fraud than has made the papers [1]...
- Fairfield Greenwich Group: quietly complicit in the Madoff fraud?
- Angelo Mozilo: white collar mobster
- Sam Israel: a $400 million fraud. In the old days, he'd have been front page news. I never heard of him.
- Many more, each of which would have been in the news once - including: JS Forte, RS Piccoli, JG Ossie, D Palmer, A Nodel, Marc Dreier.
- Those swindlers who have made the news... Allen Stanford, and, of course, Mr. Madoff.
By 2010 I was focusing on RCIIIT: The rise of China and India and the effects of IT.
... The Rise of China and India (RCI) has been like strapping a jet engine with a buggy throttle onto a dune buggy. We can go real fast, but we can also get airborne – without wings. Think about the disruption of German unification – and multiply than ten thousand times.
RCI would probably have caused a Great Recession even without any technological transformations.
Except we have had technological transformation – and it’s far from over. I don’t think we can understand what IT has done to our world – we’re too embedded in the change and too much of it is invisible. When the cost of transportation fell dramatically we could see the railroad tracks. When the cost of information generation and communication fell by a thousandfold it was invisible ...
In 2016 and again in 2018 I tried to explain Trumpism by contributing factors (I was too optimistic about Murdoch's health though):
- 65% the collapse of the white non-college “working class” — as best measured by fentanyl deaths and non-college household income over the past 40 years. Driven by globalization and IT both separately and synergistically including remonopolization (megacorp). This is going to get worse.
- 15% the way peculiarities of the American constitution empower rural states and rural regions that are most impacted by the collapse of the white working class due to demographics and out-migration of the educated. This is why the crisis is worse here than in Canada. This will continue.
- 15% the long fall of patriarchy. This will continue for a time, but eventually it hits the ground. Another 20 years for the US?
- 5% Rupert Murdoch. Seriously. In the US Fox and the WSJ, but also his media in Australia and the UK. When historians make their list of villains of the 21st century he’ll be on there. He’s broken and dying now, but he’s still scary enough that his name is rarely mentioned by anyone of consequence.
- 1% Facebook, social media, Putin and the like. This will get better.
That 1% for Facebook et all is pretty small — but the election of 2016 was on the knife’s edge. That 1% was historically important.
A few months ago I listed 3 causes for the post-COVID supply and labor shock economics of 2021:
1. Wealth became extremely concentrated.
2. Returns on labor for 40% of Americans fell below modern standard for economic life.
3. Good investments became hard to find.
It's almost 2022 now, so we're into almost 25 years of the world not making sense any more. So now I'm digging even deeper for a root cause.
Today I'm going with Gordon's Law: the complexity of a complex adaptive system will increase until it reaches a limiting factor. Our civilization is a complex adaptive system and its complexity increased until it hit a limiting factor -- the complexity capacity of the average human. These days between 40 and 50% of American's can't handle civilization 2021 (sometimes I call this mass disability (see also). Witness among other things, The Great Stupidity of the FoxCovians.
It's a variant of the "Future Shock" Toffler wrote about 52 years ago. I don't have a fix; I don't think the world will get less complex. Our technologies are moving too fast. Maybe we'll just get used to not understanding the world and civilization will stumble on regardless. After all, for most of human history the world was incomprehensible -- and we did manage. Sort of. Mostly without civilization though ...
Friday, October 29, 2021
The Cybernated Generation: Time Magazine, April 2nd 1965
First check out the Time magazine covers for 1965. That was a very long time ago. Things have improved.
Now look at the April 2nd issue and particularly The Cybernated Generation. Every generation since 1965 has been declared cybernated or digitized or meta-sized.
The article is fascinating as a history of computing and our understanding of its impact -- and as a cultural artifact about a world of white men in white coats. There are no women save a secretary to "pass" at. There is no melanin. There are nerds. Some hyperbole aside there's not a lot that the author missed about the world to come...
As viewed by Sir Leon Bagrit, the thoughtful head of Britain's Elliot-Automation, the computer and automation will bring "the greatest change in the whole history of mankind.
... Boeing announced plans two weeks ago to outfit jetliners with computer-run systems that will land a plane in almost any weather without human help. A new "talking computer" at the New York Stock Exchange recently began providing instant stock quotations over a special telephone. In Chicago a drive-in computer center now processes information for customers while they wait, much as in a Laundromat. The New York Central recently scored a first among the world's railroads by installing computer-fed TV devices that will provide instant information on the location of any of the 125,000 freight cars on the road's 10,000 miles of track...
... In 1834 an eccentric Englishman named Charles Babbage conceived the idea of a steam-driven "Analytical Engine" that in many details anticipated the basic principles of modern computers.
... Even if no further advances were made in computer technology, some scientists maintain, the computer has provided enough work and opportunities for man for another thousand years....
... The most expensive single computer system in U.S. business is American Airlines' $30.5 million SABRE, a mechanical reservation clerk that gives instant up-to-the-minute information about every plane seat and reservation to American's 55 ticket offices. ...
... Computers now read electrocardiograms faster and more accurately than a jury of physicians. The Los Angeles police department plans to use computers to keep a collection of useful details about crimes and an electronic rogue's gallery of known criminals. And in a growing number of schools, computers have taken jobs as instructors in languages, history and mathematics...
... IBM is far and away the leader in the field, both in the U.S. and abroad...
... The computers have also spawned the so-called "software" industry, composed of computer service centers and independent firms that program machines and sell computer time (for as little as $10 an hour) to businesses that do not need a machine fulltime....
... Because computer technology is so new and computers require such sensitive handling, a new breed of specialists has grown up to tend the machines. They are young, bright, well-paid (up to $30,000) and in short supply. With brand-new titles and responsibilities, they have formed themselves into a sort of solemn priesthood of the computer, purposely separated from ordinary laymen. Lovers of problem solving, they are apt to play chess at lunch or doodle in algebra over cocktails, speak an esoteric language that some suspect is just their way of mystifying outsiders. Deeply concerned about logic and sensitive to its breakdown in everyday life, they often annoy friends by asking them to rephrase their questions more logically....
Until now computer experts could only communicate with their machines in one of 1,700 special languages, such as COBOL (Common Business Oriented Language), Fortran (Formula Translation), MAD (Michigan Algorithmic Decoder) and JOVIAL (Jules's Own Version of the International Algebraic Language). All of them are bewildering mixtures that only the initiated can decipher. Now some computers have reached the point where they can nearly understand—and reply in—plain English. The new Honeywell 20 understands a language similar enough to English so that an engineer can give it written instructions without consulting a programmer. The day is clearly coming when most computers will be able to talk back.
... Each week, the Government estimates, some 35,000 U.S. workers lose or change their jobs because of the advance of automation. There are also thousands more who, except for automation, would have been hired for such jobs. If U.S. industry were to automate its factories to the extent that is now possible—not to speak of the new possibilities opening up each year—millions of jobs would be eliminated. Obviously, American society will have to undergo some major economic and social changes if those displaced by machines are to lead productive lives.
Men such as IBM Economist Joseph Froomkin feel that automation will eventually bring about a 20-hour work week, perhaps within a century, thus creating a mass leisure class. Some of the more radical prophets foresee the time when as little as 2% of the work force will be employed, warn that the whole concept of people as producers of goods and services will become obsolete as automation advances. Even the most moderate estimates of automation's progress show that millions of people will have to adjust to leisurely, "nonfunctional" lives, a switch that will entail both an economic wrench and a severe test of the deeply ingrained ethic that work is the good and necessary calling of man...
... Many scientists hope that in time the computer will allow man to return to the Hellenic concept of leisure, in which the Greeks had time to cultivate their minds and improve their environment while slaves did all the labor. The slaves, in modern Hellenism, would be the computers...
... The computer has proved that many management decisions are routine and repetitive and can be handled nicely by a machine. Result: many of the middle management jobs of today will go to computers that can do just about everything but make a pass at a secretary...
... What it cannot do is to look upon two human faces and tell which is male and which is female, or remember what it did for Christmas five years ago." Bellman might get an argument about that from some computermen, but his point is valid...
... Most scientists now agree that too much was made in the early days of the apparent similarities between computers and the human brain. The vacuum tubes and transistors of computers were easy to compare to the brain's neurons—but the comparison has limited validity. "There is a crude similarity," says Honeywell's Bloch, "but the machine would be at about the level of an amoeba."... eventually the idea that a machine has humanlike intelligence will become part of folklore...
... In the years to come, computers will be able to converse with men, will themselves run supermarkets and laboratories, will help to find cures for man's diseases, and will automatically translate foreign languages on worldwide TV relayed by satellite. Optical scanning devices, already in operation in some companies, will eventually enable computers to gobble up all kinds of information visually. The machines will then be able to memorize and store whole libraries, in effect acquiring matchless classical and scientific educations by capturing all the knowledge to which man is heir....
... computers will eventually become as close to everyday life as the telephone—a sort of public utility of information...
... the computer is already upsetting old patterns of life, challenging accepted concepts, raising new specters to be conquered. Years from now man will look back on these days as the beginning of a dramatic extension of his power over his environment, an age in which technology began to recast human society. In the long run, the computer is not so much a challenge to man as a challenge for him: a triumph of technology to be developed, subdued and put to constantly increasing use.
Wednesday, October 27, 2021
Inline Skating San Francisco -- from 1997!
I wrote this in 1997 and found it in my old pre-blog Web 1.0 archives. I decided to republish it here because, you know, I could. Some of it may even be relevant today.
Before blogs we did this kind of thing in wysiwyg tools (FrontPage 97 for this piece) and then FTPd to a web server.
The original page is still on the web but it is not known to Google. Astonishingly it's in the Wayback Machine.
Sunday, October 03, 2021
2021, 3 causes
Copied from a tweet of mine, a cartoon explanation of our peculiar economic situation.
1. Wealth became extremely concentrated.
2. Returns on labor for 40% of Americans fell below modern standard for economic life.
3. Good investments became hard to find.
Something had to give. COVID broke the dam.
Wednesday, September 15, 2021
Trek's Mino Link of Doom - beware the lost spacer (Trek Fuel EX mountain bike)
Update Oct 18, 2021: I wrote Trek a paper letter (!) about my experience and they are working on removing any references to trailside Mino Link maintenance. They are also sending me some nice swag for my troubles. (Lastly, yesterday I found the lost Mino Link spacer in the dirt of my driveway. So now I have an extra!)
----
The Trek Mino Link is a feature of the Fuel EX. It lets you raise or lower the bottom bracket depending on whether you prefer fewer pedal strikes or a lower center of gravity. Trek says: "Mino Link lets you quickly and easily make small geometry adjustments to suit your riding style or terrain."
As of Sept 2021 Trek's Mino Link video claims you can even swap your geometry on the trail.
I am here to tell you that you we would be insane to touch the Mino Link over dirt. If you're going to mess with the Mino Link do it over light carpet so you can see what falls out and pick it up -- especially the critical spacer/washer. A sterile environment would be nice.
The 2021 Mino Link is a problematic design. (The YouTube videos I've seen describe an earlier version that the nut and the bolt, I can't speak to that design.) That doesn't mean you should avoid the Fuel EX -- I really like mine. It does mean you should treat the Mino Link cautiously. If you aren't mechanically inclined have your local shop swap it. If you are then do it over that light carpet. Check that it's secure each time you ride (I do before and after).
The problem is the washer:
SUSPENSION PART GENERIC WASHER 10 X 16 X 3.0 Item: 601479594559
Those two black washers fit are supposed to fit on the inside of the bearing race shown below. The race that's scarred up because the washer fell out when I was adjusting the Mino Lake and it took weeks for me to figure out what had happened:
Wednesday, August 18, 2021
Exercise for Olds: year 63 (CrossFit and so on)
Sunday: CrossFit and family bike ride/Nordic ski, in winter coach special hockeyMonday: CrossFitTuesday: Home CrossFit with Emily and #2 (a relative rest day for me)Wed: Mountain bike (summer) or Fat bike (winter) ride with a friend - can be intenseThur: Inline skating or Mountain bike with #2 (rest day)Fri: CrossFit (plus Hockey in winter)Sat: Road bike ride, Fat bike in winter, sometimes just a rest day
In addition I do my rehab exercises at least 4/week. I've come to love the Romanian Deadlift (RDL). I struggled a few years ago when gyms eliminated the therapeutic back extension machine I was taught to use but my PT signed off on my RDL program and it's worked well.
So far I'm still on the the 30 year plan. In 2014 I figured I'd have to downshift at 65; that sounds about right with another drop at mid-70s and dead at 85.
What's changing? With age I do a better job of relative rest days (2-3 a week of easy activity) but there are still more things I want to do than I have time for. I'm having trouble eating enough to build muscle (also limited by age related stem cell depletion). If/when I retire I will have more time to work on strength development, that's currently hard to fit in. Mountain biking is an odd problem -- it's great exercise, I love doing it -- and I'm getting too good at it. I'm good enough to do trails where a mechanical failure or a personal mistake could lead to serious injury. I should be wearing a full face helmet -- but at my age that's insane. So I have to back off a bit. It's hard to do ...
Saturday, August 07, 2021
Schwinn IC 4 / Bowflex / Nautilus cycle trainer - review with Zwift and Peloton apps
We've used our Schwinn IC 4 cycle trainer for about 10 months now. It was a pandemic purchase in December of 2020. The same trainer is sold as a Schwinn IC4, a Bowflex and a Nautilus.
We paid $900 from Dicks sporting goods. In September 2021 it's closer to $1000. It may be the only decent trainer left that doesn't require a Peloton-style subscription.
It's worked well for us. The only crappy part was the pedals, but the manufacturer expects those to be replaced. My son likes SPD clips so we use those with an adapter for shoes. The magnetic resistance is easy to adjust and quiet. Unlike trainers that attach to a bicycle it's easy to move and adjust for different heights (in our home 4'11" to 5'11"). There's a mount for iPad and a USB power out.
The trainer connects with Zwift on my son's iPad via Bluetooth and transfers the calculated power output. So if you adjust the magnetic resistance but keep a constant pedaling cadence then the power output goes up. The power output is reflected in Zwift cycling speeds. Unlike more expensive units the resistance doesn't vary based on the Zwift simulated course -- but if you go "uphill" in the simulation your power output converts to slower speeds. So it works.
It comes with a heart monitor that worked when we tested it but we never use it.
It weighs 106 lbs and comes with front wheels that make it easy for me to move. That turned out to be much more important than I expected, we move it around depending on what we're doing in the home gym.
Besides Zwift (my son has a subscription for $15/month) I tested connecting it to a bundled "ExploreTheWorld.app" and "Peloton.app". You can't connect to an Apple Watch. ExploreTheWorld came with 4 free videos ws not very interesting.
Peloton is all classes ... lots and lots of classes. It behaves like a real iOS app with a slick signup. You get 1 month free then it's $14/user. You have to adjust the resistance yourself, the Peloton app can't change it.
Zwift is simulated rides with an avatar and lots and lots of group rides and routes. The UI is pretty crude on an iPad, I think it's made for a giant low res display or maybe a remote monitor. You get 23KM free then it's $15/user/month. We got a Zwift account for my son, the rest of us just watch our iPad or use the trainer for intervals in our family CrossFit workouts.
Sunday, June 13, 2021
Alzheimer's and Amyloid: How even a perfect aducanumab could help some and hurt others.
Representational drift, if validated, tells us that a memory is a set of relationships, not the specific neurons that embody those relationships. This sentence might be rendered in electrons or ink, but it has the same meaning.
Reading an article about this reminded me about an old concern with drugs that aim to treat Alzheimer's by reducing amyloid accumulation in neurons. Drugs like the recently approved (and seemingly minimally effective) monoclonal medication aducanumab. The root problem is that we don't know why neurons accumulate amyloid. There's been a growing suspicion over the past few years that amyloidization might in some way be helpful.
I wrote about one way this might play out in a twitter post which I've revised here:
Representational drift reminds me of a theoretical problem with aducanumab and amyloid therapy for Alzheimer’s dementia. It begins with recognizing that we don’t know why neurons accumulate amyloid.
Many suspect amyloid has a physiological reason to appear in neurons. Suppose, for example, amyloid is the way old crappy neurons are "retired" from forming memory relationships. Amyloidization would then be the brain equivalent of marking a SSD region as unusable.
A system like this would have 2 kinds of bugs. It might be too aggressive or not aggressive enough.
If the retirement mechanism is too aggressive then neurons will be amyloidized prematurely. They could have still formed useful memories, but now they're dead. The brain can only produce so many neurons so it runs out prematurely. Early dementia develops. In this case a drug that cleared amyloid could help -- as long as it wasn't too aggressive. The balance may be fine and hard to get right.
If the retirement mechanism is too permissive then a lot of flaky neurons accumulate without much amyloid. Dementia follows from this too -- but it might look clinically quite different. In this case a drug that cleared amyloid would make the dementia worse! Even more flaky neurons would accumulate.
Even if the balance is just write we do run out of viable neurons. Even a very healthy centenarian has only a fraction of the cognition they once had. Again, in this case, an amyloid clearing drug would make the brain worse.
If this was the way the brain worked then an amyloid reduction drug would make some dementia worse and some better. The net effect would be quite small -- even if the medication worked perfectly and was dosed correctly.
All speculative. Come back in 5 years and see how it turned out.
Wednesday, June 09, 2021
Why did the patient's leg swell up?
I'm a physician. Ok, so it's a very part-time practice; I'm mostly a bureaucrat trying to keep civilization together. Still I have the degree and the board status and I listen to The Curbsiders religiously. So I was really annoyed when my left leg swelled up after a modest knee injury and I didn't know why.
It wasn't just me; neither did my physician wife nor my colleagues nor the veteran ER doc I saw nor my CrossFit Physician colleagues. Nobody had an explanation. My rheumatologist had a story though, and I'll get to that one.
Legs swell for several reasons, but the textbook ones I know of are infection, bad veins, bad lymphatics and a backed up/overloaded drainage system (heart failure, kidney failure - usually both sides same). Less common causes are muscle damage (compression syndrome, rhabdomyolysis) and (rarely) tumors. Inactivity, esp sitting, makes most things worse.
My leg wasn't infected. I didn't think my veins had obstructed but I have a family history of clot [1] so I did get an ultrasound -- all good. My muscle, heart and kidneys are all reasonable for age. I didn't think my familial [1] "osteoarthritis" (better called mysterious arthritis) had messed up my lymphatics.
So I was mystified. Why had a knee tweak turned my left (below) leg* into a painless swollen ("edematous") bag with a good half-inch of tough pitting edema over my shin? True, I have an old somewhat arthritic cartilage-depleted knee ill-suited to 150 double-under badly executed rope jumps. True, after the jumps my knee had some kind of meniscal tear and a medial ligament strain. Still, it seemed disproportionate.
I bought a cheap Amazon compression sock that worked better than I expected and I did my usual careful injury care. Meaning I did a lot of mountain and road biking and whatever CrossFit my injured knee could handle. Sitting made the leg swell, sleep and exercise with the compression sock (esp. biking) made it better.
Over the course of about 3-4 weeks the knee improved and the leg swelling mostly resolved. I still didn't know what was going on though. For a while I wondered if I'd ruptured a Baker's cyst (an arthritis thing) doing a heavy squat, but my knee effusion didn't flatten out and the volume seemed too high and persistent.
So I asked my rheumatologist. He claimed I had "reflex sympathetic dystrophy"- see also fpnotebook's great summary. Textbook RSD (now more often called "complex regional pain syndrome") is a badly understood and ill-defined disorder with a dismal prognosis. Patients I've seen with it usually have debilitating chronic pain and often have mental health issues that predate the injury.
I had no pain that I noticed but he claimed this was not unusual in his experience. Reading the online references as a grumpy old seasoned physician I can confidently say we have no idea why things swell in RSD and that the handwaving talk about autonomic dysfunction and inflammation is mostly bullshit. I do believe there's a genetic component [1] and that the articles are correct to recommend exercise and compression. Once again my exercise addition led to a good outcome [2].
So, yeah, I'll go with RSD, which in this case translates as "it swells because you have a (somewhat rare) genetic malfunction in your injury response and the correct treatment is compression and exercise". It didn't show up in the differential of the textbooks I read, but I'll see if my friend Dr. Scott Moses will add it to his fpnotebook article on unilateral edema.
* technically and pedantically the leg is part of the lower limb below the knee but of course we use it to mean lower limb.
[1] All courtesy of my beloved mother who died age 87 of every possible medical condition (she lived on pure wilfullness). I inherited all her bad genes and, yes, she had bad leg edema. My father by contrast had only a bad back and post-90yo dementia but I inherited his back and probably the dementia disposition too. Happily my children are adopted.
[2] My back praises the Romanian deadlift.
Update 11/7/2021, wow, that's one ugly looking photo. I don't know what it was, or why it happened, but I guess I'll go with RSD plus some dubious lymphatics. My knee got better over 8-10 weeks and the edema resolved over 4 to 16 weeks. Sometimes I have trace pre-tibial edema but mostly nothing.
Update 4/12/2023: Never came back. So weird.
Sunday, April 18, 2021
Mountain bikes have come a long way very quickly
My trail bike is a 2010 Cannondale Scalpel I bought used. It was a state-of-the-art racing machine in the 26" era and it's light and fun to ride.
Today I rode a friend's 2018 Trek Fuel EX alloy bike with 27.5" wheels. The Scalpel is lighter and has nicer brake levers -- but in every other way the $2,500 Fuel EX is a much better bike. Faster to climb, faster to descend, faster to cross country, better on the bumps, better shifting over a 1x range.
Huge price drop for better quality in 8 years. That's faster progress than my MacBook.