Sunday, November 13, 2022

Colorado legalizes magic mushroom/psilocybin therapies

 Denver is the mile high city, and the 2022 midterm elections have now legalized therapy with magic mushrooms/psilocybin, which has medical uses in treating post-traumatic stress disorder, among other things.

Colorado becomes second state with legalized ‘medicinal psychedelics’ by Olivia Goldhill in Statnews

"Colorado is the second state to legalize psychedelics, following Oregon’s 2020 passage of a similar ballot question. Like Oregon, Colorado plans to create licensed “healing centers” where people can take magic mushrooms under supervision.

“This is a truly historic moment. Colorado voters saw the benefit of regulated access to natural medicines, including psilocybin, so people with PTSD, terminal illness, depression, anxiety and other mental health issues can heal,” Kevin Matthews and Veronica Lightning Horse Perez, leaders of Natural Medicine Colorado, which campaigned for the measure, wrote in a statement emailed to STAT.

...

"The most advanced study for psilocybin, a Phase 2b trial on the drug for treatment-resistant depression published earlier this month, found the drug was effective at inducing remission in many patients, but the results were less striking than in earlier studies."

**************

And from Time Magazine:

Colorado Voted to Decriminalize Psilocybin and Other Psychedelics,  by Tara Law

"Colorado voters have approved the broadest psychedelic legalization in the U.S., which would decriminalize five psychedelic substances and enable adults to receive psychedelics at licensed centers.

...

"The ballot measure decriminalizes the possession of certain psychedelic drugs for personal use in the state and specifically legalize psilocybin, the psychedelic component of magic mushrooms, for use at licensed facilities starting in 2024. (In those ways, it’s similar to 2020 measures approved in Oregon, which decriminalized possession of small amounts of drugs in 2021 and is launching a psilocybin access program in 2023.)

"However, Colorado’s Proposition 122 goes further in several ways. In addition to decriminalizing possession, it decriminalizes the growing and sharing of five psychedelics for personal use: psilocybin, psilocyn (a psychedelic also found in magic mushrooms), dimethyltryptamine (commonly known as DMT, which is found in plants and animals, including certain tree frogs), ibogaine (derived from the bark of an African shrub), and mescaline (which is primarily found in cacti; however, Prop 122 excludes peyote). It also clears a pathway for the use of all these psychedelics at “healing centers”—facilities licensed by the state’s Department of Regulatory Agencies where the public can buy, consume, and take psychedelics under supervision. The regulated access program would initially be limited to psilocybin, which would launch in late 2024, but if recommended by a Natural Medicine Advisory Board appointed by the governor, it could be expanded to include DMT, ibogaine, and mescaline in 2026."

Saturday, November 12, 2022

Deceased donor organ discards on weekends, in the the Annals of Transplantation

 Hospital resources and physician incentives can be stressed on weekends, and there is historical evidence that organ discards are higher on weekends.  Here's a study suggesting that is still a thing.

Yamamoto, T., A. Shah, M. Fruscione, S. Kimura, N. Elias, H. Yeh, T. Kawai, and J. F. Markmann.  Revisiting the "Weekend Effect" on Adult and Pediatric Liver and Kidney Offer Acceptance. Annals of Transplantation. 2022 Nov;27:e937825. DOI: 10.12659/aot.937825. PMID: 36329622.

"BACKGROUND: Weekends can impose resource and manpower constraints on hospitals. Studies using data from prior allocation schemas showed increased adult organ discards on weekends. We examined the impact of day of the week on adult and pediatric organ acceptance using contemporary data.

"MATERIAL AND METHODS: Retrospective analysis of UNOS-PTR match-run data of all offers for potential kidney and liver transplant from 1/1/2016 to 7/1/2021 were examined to study the rate at which initial offers were declined depending on day of the week. Risk factors for decline were also evaluated.

"RESULTS: Of the total initial adult/pediatric liver and kidney offers, the fewest offers occurred on Mondays and Sundays. The decline rate for adult/pediatric kidneys was highest on Saturdays and lowest on Tuesdays. The decline rate for adult livers was highest on Saturday and lowest on Wednesday. In contrast, the decline rate for pediatric livers was highest on Tuesdays and lowest on Wednesdays. Independent risk factors from multivariate analysis of the adult/pediatric kidney and liver decline rate were analyzed. The weekend offer remains an independent risk factor for adult kidney and liver offer declines, but for pediatric offers, these were not significant independent risk factors.

"CONCLUSIONS: Although allocation systems have changed, and the availability of kidneys and livers have increased in the USA over the past 5 years, the weekend effect remains significant for adult liver and kidney offers for declines. Interestingly, the weekend effect was not seen for pediatric liver and kidney offers.

Friday, November 11, 2022

Marijuana legalization advances in the 2022 elections

Time Magazine published this map under the headline "Why Marijuana Had a Terrible Night in the 2022 Midterm Elections"

It doesn't look so terrible to me, so much as increasingly inevitable. The grey states on the map (where marijuana remains entirely illegal) are shrinking steadily: it doesn't appear that opponents will succeed in making America grey again.


 "Nineteen states and the District of Columbia allow recreational use of marijuana; 13 states outlaw it entirely. The rest of the states—including Arkansas, South Dakota and North Dakota—allow its use for medicinal purposes. It remains illegal under federal law."

*********

It's going to become increasingly hard for States to enforce draconian laws against something that is legal in neighboring states.  That doesn't mean that legalization is always going to go smoothly--the end of Prohibition didn't end alcoholism, and the end of marijuana prohibition won't make marijuana chemically safer (in fact competition will develop strains that are chemically more potent).  But removing legal risks from what would otherwise be uncontrolled black markets, and taking them out of the hands of criminals, still seems to have momentum.

Thursday, November 10, 2022

Challenge trials for future Covid vaccines are still needed, by Stanley Plotkin and Josh Morrison

 Covid is still with us, new vaccines are needed and will likely continue to be needed into the forseeable future, and the case for human challenge trials to speed selection among promising candidates is stronger than ever.  Two veteran advocates make the case:

Human Challenge Trials Hold Promise for Next-Generation COVID Vaccines— These investigations could accelerate effective development of a pan-coronavirus vaccine as well by Stanley Plotkin, MD, and Josh Morrison, JD November 7, 2022

"Two years ago, the prospect of deliberately infecting fully informed volunteers with COVID-19 to aid in vaccine research and development was controversial. We and many others argued that the risks were justifiable, and the reservations of some bioethicists did not deter nearly 40,000 people from over 160 countries from expressing interest in volunteering for these investigations, called human challenge trials. Yet in the end, while they have been extensively pursued in the U.K.*, there were no such studies in the U.S.

"We have made great strides against COVID-19 illness in the form of vaccination and treatments, but there are still thousands of deaths in the U.S. every week.

...

"The White House hosted a summit on the issue in July, showcasing the myriad ways researchers are going about developing new vaccines. There are hundreds of candidates in early stages around the world, but the resources devoted to COVID-19 vaccine research are a fraction of what they were 2 years ago. Human challenge trials can greatly speed the selection of the most promising in this field of candidates, providing scientific and economic benefits over uniform reliance on large field studies.

...

"The use of human challenge trials offers the greatest promise for testing intranasal vaccines for their ability to reduce infection and transmission. In the case of a live attenuated vaccine, something as simple as regular nasal swabbing can reveal just how much of the live virus is present in the nose over time -- and how much would spread when a patient sneezes, for example.

...

"There are obviously risks to COVID-19 challenge studies, and it was on these grounds that initial proposals for such research faced opposition. However, the risk of death is now lower than it was early on in the pandemic given better immune protection garnered from both vaccination and natural exposure, and various treatments options further reduce the risk.

Of course, long-COVID still looms large, but this risk can also be managed by selecting trial participants at lower risk of serious illness, as more severe COVID-19 illness is correlated with lingering post-COVID symptoms. Ultimately, if COVID-19 becomes endemic, long-COVID may well be a threat to everyone, whether or not they sign up for a challenge trial -- all the more reason we must act quickly to develop vaccines that stop transmission.

"We believe that volunteers are perfectly capable of considering these risks rationally. Those who decide to make a potential sacrifice for the good of humanity should be lauded, not dismissed as naive. (Notably, a study of the nearly 40,000-strong prospective volunteers organized by 1Day Sooner showed that their risk tolerance was the same as a control group, and they were driven primarily by altruistic motivations.)"


"Stanley Plotkin, MD, is professor emeritus in pediatrics at the University of Pennsylvania, a veteran vaccinologist, and a board member of 1Day Sooner, an organization that advocates on behalf of challenge trial volunteers. Josh Morrison, JD, is co-founder and president of 1Day Sooner, and a founder of Waitlist Zero and the Rikers Debate Project."

********

Earlier:

Monday, June 20, 2022

Report of a SARS-CoV-2 human challenge trial. In Britain.


* Josh Morrison writes:

there are four COVID challenge studies announced or underway in the UK, though only imperial [the study above] has published results. Besides the imperial one, there’s an Oxford reinfection study, 

https://www.ox.ac.uk/news/2021-04-19-human-challenge-trial-launches-study-immune-response-covid-19 (interestingly the talk one of our staff saw indicated they were having a difficult time getting any infections in previously infected people even when using doses 1,000 times higher than the infectious imperial dose).

 

There has also been an Imperial delta study that’s recruiting now — 

https://www.imperial.ac.uk/infectious-disease/research/human-challenge/covhic002/register-your-interest/

 

And HVIVO has announced an omicron challenge study, though I’m not sure that will happen. 

https://investors.vaxart.com/news-releases/news-release-details/vaxart-announces-agreement-hvivo-develop-worlds-first-human


Wednesday, November 9, 2022

Market design coffee m&ms

 Here's an inside joke, for market design coffee (and candy) fans, particularly for regulars at our market design coffees at Stanford.



Here's a clue:

D4Market Structure, Pricing, and Design
D40General
D41Perfect Competition
D42Monopoly
D43Oligopoly and Other Forms of Market Imperfection
D44Auctions
D45Rationing • Licensing
D46Value Theory
D47Market Design
D49Other

HT: Carmen Wang


Tuesday, November 8, 2022

Mathematics and Computer Science of Market and Mechanism Design, at Berkeley MSRI, August 21-December 20, 2023 (applications open)

 Apply now to join a semester of interdisciplinary workshops on market and mechanism design, from the point of view of mathematicians, computer scientists, and economists.

Mathematicsand Computer Science of Market and Mechanism Design at the Mathematical Sciences Research Institute in Berkeley, California, August 21, 2023 to December 20, 2023

 Seeking applications for Research Members and Postdoctoral Fellows:

  • Research Members are scholars in economics, computer science, operations research, mathematics, or related fields who have a PhD at the time of application and will be in residence for at least 30 consecutive days of the program.
  • Postdoctoral Fellows are scholars in those fields who received their PhD on or after August 31, 2018, and will be in residence for the entire program.

Apply here by December 1, 2022https://www.msri.org/web/msri/scientific/member-application

 Program Summary:

In recent years, economists and computer scientists have collaborated with mathematicians, operations research experts, and practitioners to improve the design and operations of real-world marketplaces. Such work relies on robust feedback between theory and practice, inspiring new mathematics closely linked – and directly applicable – to market and mechanism design questions. This cross-disciplinary program seeks to expand the domains in which existing market design solutions can be applied; address foundational questions regarding our ways of developing and evaluating mechanisms; and build useful analytic frameworks for applying theory to practical marketplace design.

 https://www.msri.org/programs/333

 Program Organizers:

Michal Feldman (Tel-Aviv University); Nicole Immorlica (Microsoft Research); Scott Kominers (Harvard Business School); Shengwu Li (Harvard University); Paul Milgrom (Stanford University); Alvin Roth (Stanford University); Tim Roughgarden (Columbia University); Eva Tardos (Cornell University)

 About MSRI:

Acknowledged as the premier center for collaborative mathematical research, MSRI  organizes and hosts semester-length programs that become the leading edge in that field of study. Mathematicians worldwide come to the Institute to engage in the research of classical fundamental mathematics, modern applied mathematics, statistics, computer science and other mathematical sciences.

 Questions? See attached flyer, or reach out to mcsorgs@msri.org

**********

This could be a nice way to spend a semester--apply now (MSRI loves company:)


Monday, November 7, 2022

Stanford Economics Ph.D. Job Market Candidates for the 2022-23 Economics Job Market.

 22 candidates for the 2022-23 Economics Job Market, from B to Z.

Stanford, Department of Economics Job Market Candidates

Available November 2022 for positions in Summer/Fall 2023

Placement Officers: Pete Klenow 650-725-2620 klenow@stanford.edu and Liran Einav 650-723-3704  leinav@stanford.edu

Trevor Bakker

Aniket Baksy

Lukas Bolte

Yue Cao

Daniele Caratelli

Alex Chan

Fulya Ersoy

Tony Fan

Robin Han

Brian Higgins

Tingyan Jia

Matteo Leombroni

Gina Li

Negar Matoorian Pour

Agathe Pernoud

Beatriz Pousada

Maxwell Rong

Rachel Schuh

Martin Souchier

Reka Zempleni

Adam Zhang

Sally Zhang

Sunday, November 6, 2022

Limiting congestion by limiting applications, or making them costly

 Here's a paper that investigates two alternatives to limiting congestion in college admissions: one is to limit applications, and the other is to add a small cost for each additional application. (This is a current topic of discussion in a number of other applications, including matching of new doctors to residencies.)

Application Costs and Congestion in Matching Markets by YingHua He and Thierry Magnac, The Economic Journal,  https://doi.org/10.1093/ej/ueac038 (online early)

Abstract: "A matching market often requires recruiting agents, or ‘programmes’, to costly screen ‘applicants’, and congestion increases with the number of applicants to be screened. We investigate the role of application costs: higher costs reduce congestion by discouraging applicants from applying to certain programmes; however, they may harm match quality. In a multiple-elicitation experiment conducted in a real-life matching market, we implement variants of the Gale-Shapley deferred-acceptance mechanism with different application costs. Our experimental and structural estimates show that a (low) application cost effectively reduces congestion without harming match quality."

"Our empirical strategy is novel. It begins with a multiple-elicitation field experiment that enables us to directly evaluate the effects of application costs. The experiment involves the real-life matching of 129 applicants to the seven master’s programmes at the Toulouse School of Economics (TSE), and was conducted in May 2013 for admission in the 2013–4 academic year. The experimental market designs are three variants of the Gale-Shapley deferred-acceptance (DA) mechanism encountered in practice: the traditional DA mechanism, under which applicants can apply to all programmes without any cost; the DA mechanism with truncation (DA-T), under which applicants can apply to no more than four programmes (hence, DA-T-4); and the DA mechanism with cost (DA-C), under which applicants must write a motivation letter for each additional application beyond the first three applications. Under each mechanism, every applicant is required to submit a rank-ordered list of programmes (ROL). As applicants are informed that one of the mechanisms will be implemented, they have incentives to behave optimally under each mechanism.

"To evaluate the performance of a matching procedure, we focus on two dimensions of a matching outcome: the congestion and match quality. The former is measured by screening costs and approximated by the number of applicants to screen; the latter is measured by the welfare of both sides, the number of unmatched applicants, as well as the number of blocking pairs. A pair comprising applicant and programme blocks a matching if both would be better off by being matched together after leaving their current matches. The stability of a matching, defined as the absence of any blocking pair, is the key to the success of matching markets (Roth, 1991). Importantly, stability implies Pareto efficiency when both sides are endowed with strict preferences (Abdulkadiroğlu and Sönmez, 2013)."



Saturday, November 5, 2022

Liver exchange--a review by Agrawal, Gupta and Saigal

 

 Here's a review of liver exchange in the transplant literature, with some comparisons to kidney exchange.

Paired exchange Living donor Liver Transplantation: Indications, stumbling blocks, and future considerations by Dhiraj Agrawal, Subhash Gupta,  and Sanjiv Saigal, Journal of Hepatology, In Press,  Pre-proof https://doi.org/10.1016/j.jhep.2022.10.019 

Abstract: "The last decade has seen Liver Paired exchange (LPE) as an increasingly used modality across the transplant community by which pairs of incompatible living Liver donors and their intended recipients swap Livers resulting in compatible transplants. The feasibility and benefit of LPE in providing excellent recipient outcomes and robust donor safety have been proven in uncomplicated swaps. Began initially as single-centre two-way or three-way exchanges, LPE has tremendous potential to grow into more complicated chains over days and over multiple centres. Also, LPE is associated with unique technical, logistical, ethical and legislative challenges. This review discusses the indications, potential types of LPE, unique solutions to stumbling blocks in performing LPE, and future considerations on how LPE can expand the living donor liver pool and the armamentarium of living donor liver transplantation (LDLT)".


"
The published literature on LPE has nine reports (5 original articles and 4 case reports), including 74 LPEs from Asia and North America.1), 2), 3), 4), 5), 6), 7), 8), 9) LPE constitutes approximately 1.2 to 8.3 % of the total LDLTs performed at the individual centre1), 2), 3), 4), signifying a substantial potential of this form of LDLT to mitigate the liver allograft shortage."

...

1. D. Agrawal, S. Saigal, S.S. Jadaun, S.A. Singh, S. Agrawal, S. Gupta
Paired Exchange Living Donor Liver Transplantation: A Nine-year Experience From North India
Transplantation (2022 Jun 30), 10.1097/TP.0000000000004210
Epub ahead of print. PMID: 35777310
2)
S. Hwang, S.G. Lee, D.B. Moon, G.W. Song, C.S. Ahn, K.H. Kim, et al.
Exchange living donor liver transplantation to overcome ABO incompatibility in adult patients
Liver Transpl, 16 (4) (2010 Apr), pp. 482-490, 10.1002/lt.22017
PMID: 20222052
3)
D.H. Jung, S. Hwang, C.S. Ahn, K.H. Kim, D.B. Moon, S.G. Lee, et al.
Section 16. Update on experience in paired-exchange donors in living donor liver transplantation for adult patients at ASAN Medical Center
Transplantation, 97 (Suppl 8) (2014 Apr 27), pp. S66-S69, 10.1097/01.tp.0000446280.81922.bb
PMID: 24849838
4)
V. Gunabushanam, S. Ganesh, K. Soltys, G. Mazariegos, A. Ganoza, M. Molinari, et al.
Increasing Living Donor Liver Transplantation Using Liver Paired Exchange
J Am Coll Surg, 234 (2) (2022 Feb 1), pp. 115-120, 10.1097/XCS.0000000000000036
PMID: 35213430
5)
A. Kaplan, R. Rosenblatt, W. Jackson, B. Samstein, R.S. Brown Jr.
Practices and Perceptions of Living Donor Liver Transplantation, Non-directed Donation, and Liver Paired Exchange: A National Survey
Liver Transpl, 28 (5) (2022 May), pp. 774-781, 10.1002/lt.26384
Epub 2021 Dec 26. PMID: 34862704; PMCID: PMC9018478
6)
H.J. Braun, A.M. Torres, F. Louie, S.D. Weinberg, S.M. Kang, N.L. Ascher, et al.
Expanding living donor liver transplantation: Report of first US living donor liver transplant chain
Am J Transplant, 21 (4) (2021 Apr), pp. 1633-1636, 10.1111/ajt.16396
Epub 2020 Dec 8. PMID: 33171017; PMCID: PMC8016700
7)
M.S. Patel, Z. Mohamed, A. Ghanekar, G. Sapisochin, I. McGilvray, N. Selzner, et al.
Living donor liver paired exchange: A North American first
Am J Transplant, 21 (1) (2021 Jan), pp. 400-404, 10.1111/ajt.16137
Epub 2020 Jul 10. PMID: 32524750
8)
S.C. Chan, C.M. Lo, B.H. Yong, W.J. Tsui, K.K. Ng, S.T. Fan
Paired donor interchange to avoid ABO-incompatible living donor liver transplantation
Liver Transpl, 16 (4) (2010 Apr), pp. 478-481, 10.1002/lt.21970
PMID: 20373459
9)
S.C. Chan, Chok KSh, W.W. Sharr, A.C. Chan, S.H. Tsang, W.C. Dai, et al.
Samaritan donor interchange in living donor liver transplantation
Hepatobiliary Pancreat Dis Int, 13 (1) (2014 Feb), pp. 105-109, 10.1016/s1499-3872(14)60016-3
PMID: 24463089