by Dan Nosowitz October 6, 2020

In 1989, David Bailey, a researcher in the field of clinical pharmacology (the study of how drugs affect humans), accidentally stumbled on perhaps the biggest discovery of his career, in his lab in London, Ontario. Follow-up testing confirmed his findings, and today there is not really any doubt that he was correct. “The hard part about it was that most people didn’t believe our data, because it was so unexpected,” he says. “A food had never been shown to produce a drug interaction like this, as large as this, ever.”
***
Eventually, with Bailey leading the effort, the mechanism became clear. The human body has mechanisms to break down stuff that ends up in the stomach. The one involved here is cytochrome P450, a group of enzymes that are tremendously important for converting various substances to inactive forms. Drugmakers factor this into their dosage formulation as they try to figure out what’s called the bioavailability of a drug, which is how much of a medication gets to your bloodstream after running the gauntlet of enzymes in your stomach. For most drugs, it is surprisingly little—sometimes as little as 10 percent.

Grapefruit has a high volume of compounds called furanocoumarins, which are designed to protect the fruit from fungal infections. When you ingest grapefruit, those furanocoumarins permanently take your cytochrome P450 enzymes offline. There’s no coming back. Grapefruit is powerful, and those cytochromes are donezo. So the body, when it encounters grapefruit, basically sighs, throws up its hands, and starts producing entirely new sets of cytochrome P450s. This can take over 12 hours.

This rather suddenly takes away one of the body’s main defense mechanisms. If you have a drug with 10 percent bioavailability, for example, the drugmakers, assuming you have intact cytochrome P450s, will prescribe you 10 times the amount of the drug you actually need, because so little will actually make it to your bloodstream. But in the presence of grapefruit, without those cytochrome P450s, you’re not getting 10 percent of that drug. You’re getting 100 percent. You’re overdosing.
***
Despite this, the Food and Drug Administration does not place warnings on many of the drugs known to have adverse interactions with grapefruit. Lipitor and Xanax have warnings about this in the official FDA recommendations, which you can find online and are generally provided with every prescription. But Zoloft, Viagra, Adderall, and others do not. “Currently, there is not enough clinical evidence to require Zoloft, Viagra, or Adderall to have a grapefruit juice interaction listed on the drug label,” wrote an FDA representative in an email.
***
more: https://www.atlasobscura.com/articles/grapefruit-history-and-drug-interactions

David S. Richeson
Contributing Columnist
September 14, 2020

***
People use the term “impossible” in a variety of ways. It can describe things that are merely improbable, like finding identical decks of shuffled cards. It can describe tasks that are practically impossible due to a lack of time, space or resources, such as copying all the books in the Library of Congress in longhand. Devices like perpetual-motion machines are physically impossible because their existence would contradict our understanding of physics.

Mathematical impossibility is different. We begin with unambiguous assumptions and use mathematical reasoning and logic to conclude that some outcome is impossible. No amount of luck, persistence, time or skill will make the task possible. The history of mathematics is rich in proofs of impossibility. Many are among the most celebrated results in mathematics. But it was not always so.
***
Many states require that districts be “compact,” a term with no fixed mathematical definition. In 1991, Daniel Polsby and Robert Popper proposed 4πA/P² as a way to measure the compactness of a district with area A and perimeter P. Values range from 1, for a circular district, to close to zero, for misshapen districts with long perimeters.

Meanwhile, Nicholas Stephanopoulos and Eric McGhee introduced the “efficiency gap” in 2014 as a measure of the political fairness of a redistricting plan. Two gerrymandering strategies are to ensure that the opposition party stays below the 50% threshold in districts (called cracking), or near the 100% level (stacking). Either tactic forces the other party to waste votes on losing candidates or on winning candidates who don’t need the votes. The efficiency gap captures the relative numbers of wasted votes.
***
more: https://www.quantamagazine.org/when-math-gets-impossibly-hard-20200914/


Not much more on Gerrymandering, but lots of interesting background.

Financial pressures explain why many campuses have brought students back. But there is a textbook solution, two economists say: government intervention.

By Sarah Cohodes and Susan Dynarski

Oct. 8, 2020

A perfectly functioning market is a beautiful thing. It’s also vanishingly rare. The main work of economists is figuring out how to make markets function well when the messy, real world intrudes on our textbooks’ elegant models.

The pandemic, unfortunately, provides instructive examples of markets that are failing in predictable and harmful ways. The failures are particularly glaring in dozens of college towns across the United States that are coronavirus hot spots.

Introductory economics focuses on the “invisible hand of the market”: Independent actors, by pursuing their own interests, maximize the common good. In this idealized world, the best thing a government can do is get out of the way so the free market can work its magic.

But 95 percent of economics is about the imperfections of markets, and how the government can correct them. In fact, some market failures require government intervention for the invisible hand to do its work. Economic theory predicts when markets are likely to work with minimal intervention, and when they will fail without government involvement.

Pollution is the textbook example of a market failure. A manufacturer sending fumes into the air creates what economists call a “negative externality.” Simply by doing what it does — making its product — the firm harms others. Pollution reduces air quality for those living and breathing nearby, but since neighbors’ health doesn’t affect the bottom line that drives daily decisions at the factory, the pollution keeps flowing.

A pandemic is powered by the ultimate negative externality: The very act of breathing can spread a deadly disease.
***
more: https://www.nytimes.com/2020/10/08/business/colleges-pandemic-market-failure.html?action=click&algo=bandit-all-surfaces&block=trending_recirc&fellback=false&imp_id=694843697&impression_id=1f316835-0c0a-11eb-9dfa-1bd73345ce2e&index=8&pgtype=Article



The first few paras nicely sum up everything that's wrong with blind obeisance to the Invisible Bloody Hand of the Free Market.

By Jason Daley
smithsonianmag.com
August 10, 2018



In the 1980s, Howard-Yana Shapiro, now chief agricultural officer at Mars, Incorporated, was looking for new kinds of corn. He was in the Mixes District of Oaxaca in southern Mexico, the area where the precursors to maize (aka corn) first evolved, when he located some of the strangest corn ever seen. Not only was it 16 to 20 feet tall, dwarfing the 12-foot stuff in American fields, it took six to eight months to mature, far longer than the 3 months needed for conventional corn. Yet it grew to those impressive heights in what can charitably be called poor soil, without the use of fertilizer.. But the strangest part of the corn was its aerial roots--green and rose-colored, finger-like protrusions sticking out of the corn’s stalk, dripping with a clear, syrupy gel.

Shapiro suspected that those mucousy fingers might be the Holy Grail of agriculture. He believed that the roots allowed this unique variety of corn, dubbed Sierra Mixe and locally bred over hundreds or even thousands of years, to produce its own nitrogen, an essential nutrient for crops that is usually applied as fertilizer in epic amounts.

The idea seemed promising, but without DNA tools to look into the specifics of how the corn was making nitrogen, the discovery was shelved. Nearly two decades later, in 2005, Alan B. Bennett of the University of California, Davis—along with Shapiro and other researchers—began using cutting-edge technology to look into the nitrogen-fixing properties of the phlegmy corn, finding that indeed, bacteria living in the mucus were pulling nitrogen from the air, transmuting it into a form the corn could absorb.

Now, after over a decade of field research and genetic analysis, the team has published their work in the journal PLOS Biology. If the nitrogen-fixing trait could be bred into conventional corn, allowing it to produce even a portion of its own nitrogen, it could reduce the cost of farming, reduce greenhouse gas emissions and halt one of the major pollutants in lakes, rivers and the ocean. In other words, it could lead to a second nitrogen revolution.
***
Co-author Jean Michel-Ane from the University of Wisconsin, Madison, agrees that this discovery opens up all types of new possibilities. “Engineering corn to fix nitrogen and form root nodules like legumes has been a dream and struggle of scientists for decades. It turns out that this corn developed a totally different way to solve this nitrogen fixation problem. The scientific community probably underestimated nitrogen fixation in other crops because of its obsession with root nodules,” he says in a statement. “This corn showed us that nature can find solutions to some problems far beyond what scientists could ever imagine.”
***
more: https://www.smithsonianmag.com/science-nature/corn-future-hundreds-years-old-and-makes-its-own-mucus-180969972/




Not exactly LBN, but I had never heard of this before. There's lots more in the article, and some of the developments should be in the field soon.