Later On

A blog written for those whose interests more or less match mine.

Archive for March 9th, 2020

He Was Dying. Antibiotics Weren’t Working. Then Doctors Tried a Forgotten Treatment.

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Thanks to JvR for pointing it out: Maryn McKenna reported in Mother Jones in May/June 2018:

Steffanie Strathdee hunched over her laptop, fretting. She barely noticed the kittens asleep next to her or the serene Buddha figure across the living room, anchored next to the glass doors that looked toward the gleaming Pacific. Her mind was 20 miles away in the intensive care unit of the University of California-San Diego’s medical center, where her husband, Tom Patterson, lay in a coma.

Patterson was 68; Strathdee was 49. They had been married 11 years, after meeting in a grant review group convened by the National Institutes of Health. He was a psychologist and she was an infectious-disease epidemiologist; when they fell in love, they also formed a powerhouse research team, studying the effect of the AIDS virus on vulnerable people in Tijuana, Mexico.

But it was a bacterium, not a virus, that was bedeviling them now. Three months earlier, on the last night of a Thanksgiving vacation in Egypt, Patterson had suddenly fallen ill, so severely that he had to be medevaced to Germany and then to UCSD. There were several things wrong—a gallstone, an abscess in his pancreas—but the core of the problem was an infection with a superbug, a bacterium named Acinetobacter baumannii that was resistant to every antibiotic his medical team tried to treat it with. Patterson had been a burly man, 6-foot-5 and more than 300 pounds, but now he was wasted, his cheekbones jutting through his skin. Intravenous lines snaked into his arms and neck, and tubes to carry away seepage pierced his abdomen. He was delirious and his blood pressure was falling, and the medical staff had sedated him and intubated him to make sure he got the oxygen he needed. He was dying.

Strathdee’s friends knew she was desperately searching for solutions, and one told her about an acquaintance with an intractable infection who had traveled to Eastern Europe to seek out a century-old cure. Strathdee spent days reading whatever she could find about it, and now she was composing a last-ditch email to the hospital’s head of infectious diseases, the person who would rule on whether they could use it to help her spouse.

“We are running out of options to save Tom,” she wrote. “What do you think about phage therapy?”

Strathdee didn’t realize it at the time, but her attempt to save her husband’s life would test the bounds of the American medical system—and throw its limitations into stark relief.

The treatment Strathdee had fixed on as a last-ditch hope is almost never used in the United States. The Food and Drug Administration has not licensed phage therapy, keeping it out of pharmacies and hospitals. Few physicians have used it even experimentally, and most civilians have never heard of it. But phages are a natural phenomenon, frequently deployed in the former Soviet Union. When used properly, they can save lives.

To understand how phage therapy works, it helps to know a little biology, starting with the distinction between bacteria and viruses. Most of the drug-resistant superbugs that cause medical havoc are bacteria, microscopic single-celled organisms that do most of the things that other living things do: seek nutrition, metabolize it into energy, produce offspring. Viruses, which are much smaller than bacteria, exist only to reproduce: They attach to a cell, hijack its reproductive machinery to make fresh viruses, and then, in most cases, explode the cell to let viral copies float free.

Phages are viruses. In the wild, they are the cleanup crew that keeps bacteria from taking over the world. Bacteria reproduce relentlessly, a new generation every 20 minutes or so, and phages kill them just as rapidly, preventing the burgeoning bacterial biomass from swamping the planet like a B-movie slime monster. But phages do not kill indiscriminately: Though there are trillions in the world, each is tuned evolutionarily to destroy only particular bacteria. In 1917, a self-taught microbiologist named Félix d’Herelle recognized phages’ talent for targeted killing. He imagined that if he could find the correct phages, he could use them to cure deadly bacterial infections.

That was a gleaming hope, because at the time, nothing else could. (Sir Alexander Fleming wouldn’t find the mold that makes penicillin, the first antibiotic, until 1928.) Treatments were primitive: aspirin and ice baths to knock down fever, injections of crude immunotherapy extracted from the blood of horses and sheep, and amputation when a scratch or cut let infection burgeon in a limb and threaten the rest of the body with sepsis. Phages—whose full name, bacteriophages (or “bacteria eaters”), was given by d’Herelle in 1916—did something that medicine had never before been able to accomplish: They vanquished the infections for which they were administered without otherwise harming patients. A medical sensation and a cultural phenomenon, they provided the key plot device in the novel Arrowsmith, about an idealistic doctor, that won the Pulitzer Prize in 1926, and they saved the life of the Hollywood cowboy actor Tom Mix, a 1930s superstar. . .

Continue reading.

At the link is an podcast of the article.

Written by LeisureGuy

9 March 2020 at 8:06 pm

Why the US Sucks at Building Public Transit

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As a new bus rider on what seems to be a fairly good transit system, I found Aaron Gordon’s article in Vice of interest:

American cities are facing a transportation crisis. There’s terrible traffic. Public transit doesn’t work or go where people need it to. The cities are growing, but newcomers are faced with the prospects of paying high rents for reasonable commutes or lower rents for dreary, frustrating daily treks. Nearly all Americans, including those in cities, face a dire choice: spend thousands of dollars a year owning a car and sitting in traffic, or sacrifice hours every day on ramshackle public transit getting where they need to go. Things are so broken that, increasingly, they do both. Nationwide, three out of every four commuters drive alone. The rate in metro areas is not much different.

“Without an integrated system of transit in our metropolitan areas the great anticipated growth will become a dream that will fail,” predicted Ralph Merritt, general manager of the Los Angeles Metropolitan Transportation Authority, “because people cannot move freely, safely, rapidly, and economically from where they live to where they work.”

Although Merritt’s words could just as well apply today, he said them 66 years ago in 1954. This is a crisis facing American cities right now in 2020, but it’s an old crisis. The only thing that has changed is the problem has gotten worse.

Like most crises, there is no single cause. Our cities, and our federal government, have made a lot of mistakes. Some were obvious at the time, others only in hindsight, but most have been a combination of the two. We keep doing things that stopped being good ideas a long time ago.

Many of those mistakes have to do with housing policy, which is inextricably linked to transportation policy. But the most obvious cause of our transportation crisis is a simple one: America sucks at building public transportation.

Why is this? Why does the U.S. suck at building good, useful public transit?

It’s a question that has vexed me for years. Just when I think I’ve figured it out, some other facet I had never previously considered comes to my attention. I have spoken to a dozen transit experts and historians. I have read several histories of American mass transportation policy written by independent scholars as well as government agencies. I’ve scoured federal archives and interviewed employees of transit agencies planning their own big projects. I’ve analyzed budgets and construction costs and compared them to our international peers. The tangle of American governmental dysfunction is so profound, digging into it can feel like undoing a rubber band ball with your teeth.

But the failure itself is simple and obvious. It’s apparent to anyone who has traveled abroad in the last several decades. Whether it’s traditional subway and commuter rail systems, modern streetcars and light rails, high-speed intercity rail, or even the humble bus with dedicated lanes and train-like stops, the U.S. lags perilously behind. It is a national embarrassment and a major reason our cities are less pleasant, more expensive places to live.

Just to name a few recent accomplishments abroad lacking an American parallel: Paris . . .

Continue reading. There’s much, much more.

Later in the article:

There is, of course, no simple answer why our transportation systems are broken, in much the same way there’s no simple answer to why our healthcare system is broken or why our criminal justice system is broken, beyond, as Freemark put it, that our “dysfunctional, irascible political system [is] woefully unprepared to commit to anything particularly significant.”

Ultimately, this is not about trains and buses. This is about a political system uninterested in reform, a system unconcerned with fixing what’s broken. If we can understand how politics failed American transportation systems, perhaps we can make the solution part of broader reform that must occur if American government is to start addressing the needs of the people in all aspects of life, from health care to criminal justice to housing to employment law to digital privacy to climate change.

Written by LeisureGuy

9 March 2020 at 7:12 pm

Machine Learning Takes On Antibiotic Resistance

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Antibiotic resistance is a problem only because evolution is a fact (not a hoax, as some conservatives — particularly evangelicals — maintain). Katharine Harmon Courage writes in Quanta:

Once-powerful antibiotics are losing their efficacy at a disconcerting pace as bacteria evolve immunity to our drugs. At least 700,000 people around the world now die each year from infections that could formerly be treated with antibiotics. A report last year from the United Nations Interagency Coordination Group on Antimicrobial Resistance warned that if no new major advances are made by 2050, mortality could leap to 10 million deaths a year.

What makes this prognosis all the more dire is that the antibiotic pipeline has slowed to a trickle. In the past two decades, only a few new antibiotics have been found that kill bacteria in novel ways, and rising resistance is a problem for all of them. Meanwhile, traditional methods of identifying antibiotics by screening natural compounds continue to come up short. Because of this, some researchers are now turning from the wet lab to silicon power in hopes of finding an answer.

In the February 20 issue of Cell, one team of scientists announced that they — and a powerful deep learning algorithm — had found a totally new antibiotic, one with an unconventional mechanism of action that allows it to fight infections that are resistant to multiple drugs. The compound was hiding in plain sight (as a possible diabetes treatment) because humans didn’t know what to look for. But the computer did.

Using computers and machine learning to make sense of mountains of biomedical data is nothing new. But the team at the Massachusetts Institute of Technology, led by James Collins, who studies applications of systems biology to antibiotic resistance, and Regina Barzilay, an artificial intelligence researcher, achieved success by developing a neural network that avoids scientists’ potentially limiting preconceptions about what to look for. Instead, the computer develops its own expertise.

With this discovery platform, which has been made freely available, “you’re going to identify molecules that don’t look like antibiotics you’re used to seeing,” Collins said. “It really shows how you can use the emerging technology of deep learning in an innovative manner to discover new chemistries.”

Nature’s Dry Well

Ever since Alexander Fleming derived the first antibiotic from fungus, nature has been the font for our antibacterial drugs. But isolating, screening and synthesizing thousands of natural compounds for laboratory tests is extremely expensive and time-consuming.

To narrow the search, researchers have sought to understand how bacteria live and multiply, and then pursued compounds that attack those processes (such as by damaging bacteria’s cell walls, blocking their reproduction, or inhibiting their protein production). “You start with the mechanisms, and then you reverse-engineer the molecule,” Barzilay said.

Even with the introduction of computer-assisted, high-throughput screening methods in the 1980s, however, progress in antibiotic development was virtually nonexistent in the decades that followed. Screening occasionally turned up drug candidates that were toxic to bacteria, but they were too similar to existing antibiotics to be effective against resistant bacteria. Pharmaceutical companies have since largely abandoned antibiotic development, despite the need, in favor of more lucrative drugs for chronic conditions. [Emphasis added. A surprising number of chronic conditions can (in many but not all) cases be effectively treated by lifestyle changes (such as changes in diet and level of exercise). I’ll point out How Not to Die as a useful guide. However, pharmaceutical companies derive no income from patient changes in diet and exercise, only from selling drugs, and thus pharmaceutical companies spend an enormous amount pushing drugs and encouraging a de-emphasis of lifestyle changes. – LG]

The new work by Barzilay, Collins and their colleagues, however, takes a radically fresh, almost paradoxical approach to drug discovery: It ignores how the medicine works. It’s an approach that can succeed only with the support of extremely powerful computing.

Agnostic Learning

Behind the new antibiotic finding is a deep neural network, in which the nodes and connections of its learning architecture are inspired by the interconnected neurons in the brain. Neural networks, which are adept at recognizing patterns, are deployed across various industries and consumer technologies for uses such as image and speech recognition. Conventional computer programs might screen a library of molecules to find certain defined chemical structures, but neural networks can be trained to learn for themselves which structural signatures might be useful — and then find them.

Collins, Barzilay and their team trained their network to look for any compound that would inhibit the growth of the bacterium Escherichia coli. They did so by  . . .

Continue reading.

Written by LeisureGuy

9 March 2020 at 6:46 pm

More coronavirus safeguard suggestions

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Read this. And wash your hands.

Written by LeisureGuy

9 March 2020 at 6:14 pm

I would call this “surreal,” but perhaps “dada” is better

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Written by LeisureGuy

9 March 2020 at 5:50 pm

Posted in Art, Video

“I Quit Smoking After Many Failed Attempts”

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I would say “practice attempts” rather than “failed attempts,” but in any even the Medium story Felix Wankel writes about what he discovered is worth reading — and applying. He begins:

In 2018, I was working at an office on the 4th floor. I took the stairs for the first time on the day the elevator broke down. Until that moment, I didn’t know my lungs were not capable of climbing stairs, even to the 4th floor. I was out of breath and almost started to sweat when I finally sit at my table. I thought about how my life will be like in 10 years while waiting for my breath to get back to normal. I imagined myself covered in tubes and wires lying in a hospital bed, maybe I’ll not be able to speak properly, even thinking about it was terrifying. On that day, thanks to the elevator, I decided to quit smoking.

After quick research on the internet, I found Allen Carr’s famous method. There were hundreds of people saying that they finally quit smoking by following his advice despite their previous unsuccessful attempts. Comments on the internet were convincing, I decided to give it a try. The method helped me to understand the addiction, also clearly showed me that biases and fears play an important role as well as the physical effects of nicotine. It worked for me but didn’t last long, I found myself smoking a cigarette after 4 days. But I didn’t see it as a failure, not smoking for 4 days was a record for me. I tried to quit several more times by the same method but the results didn’t change, I kept smoking after short periods.

I was determined to quit so I continued my research for alternative techniques and read a couple of books that focus on addiction in general. Among various other suggestions, . . .

Continue reading.

Written by LeisureGuy

9 March 2020 at 5:37 pm

Tips for the Depressed

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Though in fact, the tips offered seem to me to be good for anyone. n+1 has an excerpt from George Scialabba’s How to Be Depressed, out this month from the University of Pennsylvania Press. It begins:

THE PHENOMENOLOGY of depression is endlessly varied. Some of these tips may be useful to many readers; some to a few; some to none at all. If any of them helps lighten anyone’s suffering by a grain, it will be worth the effort. There is no authority behind any of these suggestions beyond my own long experience of depression and what I’ve gathered from reading about others’. I don’t think any of them are risky, but if you have any doubts, talk them over with partners, friends, caregivers, or fellow sufferers.


Waking Up

FOR MANY DEPRESSED PEOPLE—for me when depressed—waking up is the worst moment of the day. Emerging from unconsciousness, you are completely undefended. Sometimes there’s an instant of blankness and you wonder: is it gone, am I free? Then the horror seeps or surges back. Whatever strength you’ve gathered during sleep just seems to have amplified it. You’ve recharged the battery, but the static is louder than ever.

I don’t know what you can do about this, except be prepared for it. And see “Sleep” below.


Getting Out of Bed

A HIDEOUS ORDEAL. Probably the best way is to have an obnoxiously loud alarm clock on the other side of the room. It should have a “snooze” button, in case you crawl back into bed, as you probably will. At some point, perhaps after the third or fourth snooze, try to slip into the bathroom and splash cold water on your face.

You’ll know you’ve decided to stay up when you start shaking all over. Maybe you won’t, but I do. Just one semi-voluntary spasm after another for anything from five minutes to an hour. Take deep breaths, stretch, splash more cold water.

Years ago, somewhere or other, I read this advice: “The most important thing a depressed person can do is: Get dressed!” Curiously, it helps. Lying in bed seems like a natural response to agonizing pain, but usually the pain just gets worse. Maybe the few minutes it takes to make the bed, wash up, and put on clothes are enough to break some deadly mental circuit. Try.


Getting from One Room to Another

USUALLY CANNOT BE DONE with dignity. You will lurch, shuffle, careen. Your head will hang down, your shoulders hunch, you will be a slumping shambles. And when you get to the next room, you will discover that you forgot something you need in the room you just left.


How to Keep Your House from Becoming a Disaster Area

THIS IS STRAIGHTFORWARD: you pay someone to do it. Otherwise, forget it. After a while, depression is exhausting beyond words. Vacuuming, dusting, laundry, changing the sheets, washing the dishes, cooking, shopping—together these are as hard as running the Boston Marathon would be for the average out-of-shape non-depressed person. You will forget things, lose things, drop things, spill things, break things, run into things. Don’t be mad at yourself—remember, you’re being invisibly, silently, savagely tortured. You have a perfect right to let things go a bit.


Water

DON’T DEHYDRATE. Drink plenty of water, on a regular schedule. Don’t wait till you’re thirsty. Your urine should be pale, not vividly colored.

For some reason, being depressed burns up a lot of energy. Of course there’s no output—you don’t achieve anything—but your metabolism is racing. And you cry. Not enough water and you become slightly feverish and groggy. It’s very unpleasant, and it’s unnecessary. Fill three or four water bottles at the beginning of the day and put them around your house or workplace, where you can’t miss them. In cold weather, make yourself a lot of tea.


Food

EVERYTHING IS HARD when you’re depressed, even eating. And besides, you’re probably not moving around much, so you don’t build up an appetite easily. I always lose a lot of weight when depressed.

To minimize the damage, . . .

Continue reading.

Written by LeisureGuy

9 March 2020 at 4:57 pm

Walkies

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Nice day — 46ºF, clear sky, no wind — and I did 3.685 miles at 3.42mph, so 1:04:42 is the time. The route was two large loops and two smaller loops. When I include the two tiny loops for the “complete” route, the distance (as I’ve computed, not according to GPS Odometer) is 3.8 miles, which I do in 01:06:00, more or less: 3.45mph.

The effort has become pleasantly strenuous rather than desperately gasping for air.

Written by LeisureGuy

9 March 2020 at 4:22 pm

Why Can’t America Handle the Coronavirus Crisis?

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Photo shows Rep. Matt Gaetz (R-FL) making fun of the coronavirus warnings. Photo was take a day or two before one of his constituents died from COVID-19. Very funny.

Matt Stoller writes in Big:

The stock market was down by roughly 8% today, and the Trump administration seems to have no coherent view of what to do in the face of an epidemic. The response has been pretty ugly, everything from the Centers for Disease Control refusing to allow states to test people for coronavirus to White House official Larry Kudlow going on TV saying that the stock market declines are an opportunity to buy stocks. Most of the people I know in politics are in a state of shock, unable to know what to do with an institutional breakdown of this magnitude.

Without downplaying the immediate catastrophic response, I’ll note that the roots of this dysfunction are deeper than just Donald Trump’s sense of denial of an event he can’t control. America has not handled crises well for twenty years now. For example, here’s a piece I wrote on the status of New York City utility Con Ed before Hurricane Sandy hit the city, summarizing a report put together by their unionized workforce.

The union noted a lack of redundancy in voltage equipment, smart meters paid for by the stimulus that were never turned on, and a lack of basic supplies. “Our members have worked on cable so old,” said the report, “that it has paper insulation, and on utility poles that were installed in the 1930s and remain in service today.”

The company used to have a policy of keeping a “safety stockpile” of basic supplies on hand in the event of an emergency. No longer. So when Sandy hit, Con Ed ran out of utility ladders and utility cable. It had to rush order parts that did not work on Con Ed systems, including “entire truckloads of utility transformers” which the utility could not return “because of their specialized nature.”

Imagine that. Before Hurricane Sandy hit the city, Con Ed didn’t bother stocking up on ladders. Ouch.

The reason America can’t handle the Coronavirus is the same reason we can’t do anything else right. We don’t let the people who do the work have any say over how or whether the work is done. That’s why America has mishandled various wars, the response to Katrina, the financial crisis, big tech monopolies, Boeing, the Iowa caucuses, and the crisis with Hurricane Maria in Puerto Rico. American institutions are organized entirely around the short-term horizon of financiers, and these financiers seek to create monopolies and to grab cash by thinning out supply lines and generating hidden risk. [Emphasis added. – LG]

Here’s how one reader put it when wondering where all our tax money goes.

Having served in the military and received an Ivy-league business education, I think the answer is simple: Our taxes pay for management consultants who make slides and defense contractors who can’t build anything. We also bail out the financiers (who deplore socialism) when they make bad decisions.

To put it a different way, this is who has been in charge of most of our political, cultural, and economic institutions for decades now.

How Should America Handle the Coronavirus Crisis?

Ok, so what should we do?

The basic answer can be . . .

Continue reading. There’s much more, and Stoller is always worth reading.

Written by LeisureGuy

9 March 2020 at 2:53 pm

The many-worlds hypothesis is probably true

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Derek Muller explains why in this episode of Veritasium. My thought: Given that the sum total energy of all the many worlds (that is, the total energy of the multiverse) is conserved, and so the energy contained in any one of the worlds is somewhat less, I wondered whether the loss of energy in any world line corresponds to the energy lost through entropy.

Here’s the episode:

 

Written by LeisureGuy

9 March 2020 at 2:29 pm

Posted in Science, Video

The parrots that understand probabilities

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Written by LeisureGuy

9 March 2020 at 12:15 pm

Boxed breakfast candy (pre-sugared cereal): A ghastly idea — but profitable

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Watch this and observe that corporations do not care about your health (and that’s worth keeping in mind). Restricting one’s diet to whole foods (that is, not eating any refined and preprocessed foods) nicely removes boxed cereals from consideration — and eliminates an entire aisle in your supermarket shopping.

Written by LeisureGuy

9 March 2020 at 9:27 am

Reacquaintance renews pleasure

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I’ve mentioned how interesting and pleasant badger brushes felt after using only synthetic knots for a while. This badger brush, Mr Pomp, felt quite nice, but I can tell I am becoming accustomed again to the feel of badger and thus do not find it so striking as when first returning.

After a few shaves with other soaps, I was struck this morning by the feel and overall goodness of this CK-6 soap from Phoenix Artisan. I believe his Doppelgänger series introduced CK-6, and this morning I was struck again by how much I like it — and I’m sure part of that is due to Mr Pomp and his excellent contribution. The lather was thick and creamy (and fragrant) and prepared the two-day stubble perfectly for the Stealth slant, which easily and efficiently made my face feel exceptionally smooth.

A splash of the aftershave/cologne, and the week starts very well indeed. It still strikes me how much the pleasure of the morning shave ritual enhances the start of the day, and well begun is half done, as the proverb has it.

My Temperfect mug full of oolong tea helps, of course. Oolong has a distinctive flavor that’s very appealing to me.

Written by LeisureGuy

9 March 2020 at 9:03 am

Posted in Shaving

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