Organ Entrepreneurs

The supply of human organs for transplantation might seem an unlikely place to begin thinking about entrepreneurship. After all, there is no production market for human organs and, with the surprising exception of Iran, legal rules around the world make the sale of human organs for transplantation a criminal offense. Yet entrepreneurs have been present throughout the history of organ transplantation — a history of the active exploration, innovation, and management of a potentially very controversial exchange at the seemingly clear boundaries that separate giving from selling, life from death, and right from wrong. This article explores the role of entrepreneurial activity in the organ transplantation industry, with the goal of showing how the specific case helps us understand the more general phenomenon of innovation in the shadow of the law, and the role of reciprocity and gift exchange in that process. We begin with a more general point about the connection between structures of exchange and their social legitimacy, illustrating it with a familiar current case from the (conventionally entrepreneurial) world of the “sharing economy”. We then describe three innovations in the world of organ transplantation, discussing the legitimation problems faced by innovators in each case, and the strategies they have drawn on. First, Kidney Paired Donation (KPD), one of the first entrepreneurial attempts to bridge the gap between kidney supply and demand, allows patients with willing, but biologically incompatible donors, to “swap” with a similarly situated pair. Second, Non-simultaneous, Extended Altruistic Donor chains (or “NEAD” chains), removed the simultaneity constraint imposed by KPD, allowing more flexibility and a greater number of transplants, but also inserting the possibility of strategic behavior by donor-recipient pairs. Finally, we consider the most recent innovation, Advanced Donation, in which a donor donates a kidney before her paired recipient has been matched to a specific donor or scheduled for surgery, creating new challenges and risks

Custom, Contract, and Kidney Exchange

In this Essay, we examine a case in which the organizational and logistical demands of a novel form of organ exchange (the nonsimultaneous, extended, altruistic donor (NEAD) chain) do not map cleanly onto standard cultural schemas for either market or gift exchange, resulting in sociological ambiguity and legal uncertainty. In some ways, a NEAD chain resembles a form of generalized exchange, an ancient and widespread instance of the norm of reciprocity that can be thought of simply as the obligation to pay it forward rather than the obligation to reciprocate directly with the original giver. At the same time, a NEAD chain resembles a string of promises and commitments to deliver something in exchange for some valuable consideration—that is, a series of contracts. Neither of these salient social imaginaries of exchange—gift giving or formal contract—perfectly meets the practical demands of the NEAD system. As a result, neither contract nor generalized exchange drives the practice of NEAD chains. Rather, the majority of actual exchanges still resemble a simpler form of exchange: direct, simultaneous exchange between parties with no time delay or opportunity to back out. If NEAD chains are to reach their full promise for large-scale, nonsimultaneous organ transfer, legal uncertainties and sociological ambiguities must be finessed, both in the practices of the coordinating agencies and in the minds of NEAD-chain participants. This might happen either through the further elaboration of gift-like language and practices, or through a creative use of the cultural form and motivational vocabulary, but not necessarily the legal and institutional machinery, of contract

Repugnance Management and Transactions in the Body

Researchers have made progress in understanding the role of repugnance in transactions involving the human body. Yet, often, the focus remains on exchange between individuals and how they mentally cope (or not) with repugnance. But these exchanges also entail a “vertical” dimension in which organizational and state actors both directly manage repugnance and also limit the repugnance management tools available to the marketplace. Analyzing repugnance and its management as an organizational and regulatory problem, in addition to an individual one, suggests that a single, harmonized system of exchange in bodily goods is unlikely to emerge with the passage of time

Experimental versus theoretical log D_7.4, pK_a and plasma protein binding values for benzodiazepines appearing as new psychoactive substances

The misuse of benzodiazepines as new psychoactive substances is an increasing problem around the world. Basic physicochemical and pharmacokinetic data is required on these substances in order to interpret and predict their effects upon humans. Experimental log D7.4, pKa and plasma protein binding values were determined for 11 benzodiazepines that have recently appeared as new psychoactive substances (3‐hydroxyphenazepam, 4’‐chlorodiazepam, desalkylflurazepam, deschloroetizolam, diclazepam, etizolam, flubromazepam, flubromazolam, meclonazepam, phenazepam and pyrazolam) and compared with values generated by various software packages (ACD/I‐lab, MarvinSketch, ADMET Predictor and PreADMET). ACD/I‐LAB returned the most accurate values for log D7.4 and plasma protein binding while ADMET Predictor returned the most accurate values for pKa. Large variations in predictive errors were observed between compounds. Experimental values are currently preferable and desirable as they may aid with the future ‘training’ of predictive models for these new psychoactive substances

Quantum thermometry using the ac Stark shift within the Rabi model

This work was supported by the EPSRC, the National Research Foundation and Ministry of Education, Singapore, and the Royal Society.A quantum two-level system coupled to a harmonic oscillator represents a ubiquitous physical system. New experiments in circuit QED and nanoelectromechanical systems (NEMS) achieve unprecedented coupling strength at large detuning between qubit and oscillator, thus requiring a theoretical treatment beyond the Jaynes-Cummings model. Here we present a new method for describing the qubit dynamics in this regime, based on an oscillator correlation function expansion of a non-Markovian master equation in the polaron frame. Our technique yields a new numerical method as well as a succinct approximate expression for the qubit dynamics. These expressions are valid in the experimentally interesting regime of strong coupling at low temperature. We obtain a new expression for the ac Stark shift and show that this enables practical and precise qubit thermometry of an oscillator.Peer reviewe

The use of a quantitative structure-activity relationship (QSAR) model to predict GABA-A receptor binding of newly emerging benzodiazepines

The illicit market for new psychoactive substances is forever expanding. Benzodiazepines and their derivatives are one of a number of groups of these substances and thus far their number has grown year upon year. For both forensic and clinical purposes it is important to be able to rapidly understand these emerging substances. However as a consequence of the illicit nature of these compounds, there is a deficiency in the pharmacological data available for these ‘new’ benzodiazepines. In order to further understand the pharmacology of ‘new’ benzodiazepines we utilised a quantitative structure-activity relationship (QSAR) approach. A set of 69 benzodiazepine-based compounds was analysed to develop a QSAR training set with respect to published binding values to GABAA receptors. The QSAR model returned an R2 value of 0.90. The most influential factors were found to be the positioning of two H-bond acceptors, two aromatic rings and a hydrophobic group. A test set of nine random compounds was then selected for internal validation to determine the predictive ability of the model and gave an R2 value of 0.86 when comparing the binding values with their experimental data. The QSAR model was then used to predict the binding for 22 benzodiazepines that are classed as new psychoactive substances. This model will allow rapid prediction of the binding activity of emerging benzodiazepines in a rapid and economic way, compared with lengthy and expensive in vitro/in vivo analysis. This will enable forensic chemists and toxicologists to better understand both recently developed compounds and prediction of substances likely to emerge in the future

The Hope Valley Shear Zone - A Major Late Paleozoic Ductile Shear Zone in Southeastern New England

Guidebook for field trips in Connecticut and adjacent areas of New York and Rhode Island: New England Intercollegiate Geological Conference 77th annual meeting, Yale University, New Haven, Connecticut, October 4-6, 1985: Trip B