The doomer case for the final death of crypto
to pick up the pieces and formulate one concrete picture of what the future might look like. Perhaps none of this will happen! Perhaps crypto will blossom into the foundations of a new financial system based on transparency and equal access! But even if you’re bullish, shouldn’t you try to think through the worst case scenarios?
Well, without further ado, everyone loves a bit of baseless prognostication, so…
Why are clinical trials so expensive? Tales from the beast’s belly
Today I read, with great interest, a recently published STAT News feature by Matt Herper, Here’s why we’re not prepared for the next wave of biotech innovation. The basic thesis of this article is as follows: In the last decade, we have seen dramatic advances in molecular biology, which have enabled the development of a vast array of novel drug modalities and the successful treatment of previously undruggable diseases. The article mentions CAR-T, CRISPR-Cas9, COVID-19 vaccines, and drugs for cystic fibrosis; I myself also think of PCSK9 inhibitors, semaglutide, bispecific antibodies, and many others. However, the infrastructural requirements of modern clinical trials are now so high, at times reaching hundreds of thousands of dollars per patient, that they are limiting our ability to fully capitalize upon these technological developments.
Herper makes a very strong case for this argument, which I will not reiterate here. Instead, I will share some anecdotes about clinical trial development from my time working in biotech. Typically, one reads about corporate inefficiency in a very abstract manner. Specters of “regulation” or “middle management” and so on are invoked, but seldom do the details of particular scenarios emerge. I suspect this is in part because almost anyone who has a complete, birds-eye view of the whole scenario has already devoted so much of their life to their industry of choice that they have become willfully blind to its flaws. Unusually, I was a machine learning engineer who had the opportunity to watch our Phase I and II trials unfold from a good vantage point, and I hope the stories I share will be informative. Overall, they paint a picture of an industry which is severely lacking in human capital and fully captured by bureaucratic tendencies.
A sociocultural comparison of Japanese and American high schools
Any anime appreciator has surely asked themselves: “Are Japanese high schools really like this?” After reading Thomas P. Rohlen’s Japan’s High Schools, I would be inclined to respond, “yes.”
In 1983, Rohlen published an anthropological study of the Japanese high school system based on a year’s worth of fieldwork across five different Japanese high schools in the city of Kobe. Upon reading this account of Japanese high school life, I could not help but draw comparisons to the American high school system ー comparisons which are deeply unflattering to America! Despite wide criticism of its inflexible, exam-focused educational system, the portrait of Japanese students in Rohlen’s study was striking in its description of their independence and extracurricular engagement.
High school is typically considered to be a formative gateway into the adult life of a university student. This is all the more true in Japan, where the admissions process sorts students into tiers of vastly differing abilities, in stark contrast to the robust mixing of socioeconomic classes in elementary and middle schools. I summarize some particular areas of interest below, which I hope to be of as much interest to my reader as they were to me.
Lessons from Citadel’s “Market Lens” reports
Citadel Securities, one of the world’s preeminent market-making firms, occasionally publishes short reports as part of an ongoing “Market Lens” series. Although relatively short, they are easy to read and contain interesting and unique analyses which are probably difficult for non-HFT entities to reproduce. For example, they discuss topics such as the effect of tick size on bid/ask spreads, HFT overall on market liquidity, continuous trading vs. frequent batch auctions, and so on. Below, I will briefly highlight several interesting points from each of their publications.
A response to Tyler Cowen’s “Classical liberalism vs. The New Right”
I am a loyal reader of the economist Tyler Cowen’s blog Marginal Revolution, and so I was pleased to see Tyler lay out his thoughts on classical liberalism vs. the New Right in a recent post. However, I feel that he underrates the descriptive accuracy of the New Right’s criticisms, even though I largely agree with him from a prescriptive perspective.
My recipe for homemade bagels
This is a recipe for homemade bagels that I have used many times with great success. The key is to age the poolish for a couple days, let the formed bagels proof in the fridge for an extended duration, and boil them in water with barley malt syrup added.
Limited evidence for neurotoxic effects of popper usage
“Poppers,” or inhaled alkyl nitrites, constitute a class of quasi-legal recreational drugs used to enhance sexual experience primarily through their vasodilatory effects. Thus far, the risks of alkyl nitrite inhalation remain poorly understood among the population of recreational users. Two concerns about potential neurotoxicity are often raised: first, comparison to other classes of inhaled organic solvents, and second, reference to a murine study by Cha et al. in 2016. These concerns do not appear to be well-founded. However, isopropyl nitrites specifically, rather than isobutyl or amyl nitrites, are known to cause adverse ophthalmic reactions and may pose a general neurotoxic risk. If isopropyl nitrites are avoided and recreational use is sufficiently limited, overall neurotoxic risk appears low.
A practical, low-cost supplementation regime of vitamins C, B2, and E before recreational use of alkyl nitrates as partial prophylaxis against adverse effects
“Poppers,” or inhaled alkyl nitrites, are commonly used recreationally to enhance sexual experience. Usage of inhaled nitrites is associated with both acute and chronic toxicity, but understanding of practical risk management strategies remains poor.1 Here, we examine one of the primary adverse effects of inhaled nitrites, methemoglobinemia. Drawing from an extensive assortment of published data, we propose that recreational users of poppers take oral antioxidant supplements (3 g vitamin C, 400 mg vitamin B2, and 800 mg vitamin E) two hours before anticipated usage. This supplementation regime has the potential to modestly ameliorate short-term methemoglobinemia associated with inhalation of alkyl nitrites.
On the supposed “nihilism” of the Mango Markets arbitrageur
For those unfamiliar with the context, Mango Markets recently lost ~$110m as a result of a series of trades performed by Avraham Eisenberg. A portion of the money was subsequently returned, so that depositors will be made whole, and the exchange itself will take on the remaining shortfall. These “open market operations” have been variously characterized as “market manipulation,” etc.
I would like to respond to various claims made by people such as Matt Levine or Evgeny Gaevoy that these “open market operations” represent a sort of “nihilistic” or perhaps “classless” behavior. In general, these comments seem misguided. I explain why below.
Legal justification of the backdoor & mega backdoor Roth
This document summarizes statutory provisions of the Internal Revenue Code in conjunction with IRS guidance pertaining to the popular “backdoor Roth” and “mega backdoor Roth” strategies. These strategies allow for fuller utilization of the tax-privileged retirement savings account known as the Roth IRA.