An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'

Material and methods. Methylone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (15 and 30 mg/kg). Plasma concentrations and metabolites were characterized by LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results. Oral administration of methylone induced a dose-dependent increase in locomotor activity in rats. The plasma concentrations after i.v. administration were described by a two-compartment model with distribution and terminal elimination phases of α = 1.95 h− 1 and β = 0.72 h− 1. For oral administration, peak methylone concentrations were achieved between 0.5 and 1 h and fitted to a flip-flop model. Absolute bioavailability was about 80% and the percentage of methylone protein binding was of 30%. A relationship between methylone brain levels and free plasma concentration yielded a ratio of 1.42 ± 0.06, indicating access to the central nervous system. We have identified four Phase I metabolites after oral administration. The major metabolic routes are N-demethylation, aliphatic hydroxylation and O-methylation of a demethylenate intermediate. Discussion. Pharmacokinetic and pharmacodynamic analysis of methylone showed a correlation between plasma concentrations and enhancement of the locomotor activity. A contribution of metabolites in the activity of methylone after oral administration is suggested. Present results will be helpful to understand the time course of the effects of this drug of abuse in humans.

An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'

Material and methods. Methylone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (15 and 30 mg/kg). Plasma concentrations and metabolites were characterized by LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results. Oral administration of methylone induced a dose-dependent increase in locomotor activity in rats. The plasma concentrations after i.v. administration were described by a two-compartment model with distribution and terminal elimination phases of α = 1.95 h− 1 and β = 0.72 h− 1. For oral administration, peak methylone concentrations were achieved between 0.5 and 1 h and fitted to a flip-flop model. Absolute bioavailability was about 80% and the percentage of methylone protein binding was of 30%. A relationship between methylone brain levels and free plasma concentration yielded a ratio of 1.42 ± 0.06, indicating access to the central nervous system. We have identified four Phase I metabolites after oral administration. The major metabolic routes are N-demethylation, aliphatic hydroxylation and O-methylation of a demethylenate intermediate. Discussion. Pharmacokinetic and pharmacodynamic analysis of methylone showed a correlation between plasma concentrations and enhancement of the locomotor activity. A contribution of metabolites in the activity of methylone after oral administration is suggested. Present results will be helpful to understand the time course of the effects of this drug of abuse in humans.

Hysteresis and avalanches in the T=0 random field ising model with 2-spin flip dynamics

We study the nonequilibrium behavior of the three-dimensional Gaussian random-field Ising model at T=0 in the presence of a uniform external field using a two-spin-flip dynamics. The deterministic, history-dependent evolution of the system is compared with the one obtained with the standard one-spin-flip dynamics used in previous studies of the model. The change in the dynamics yields a significant suppression of coercivity, but the distribution of avalanches (in number and size) stays remarkably similar, except for the largest ones that are responsible for the jump in the saturation magnetization curve at low disorder in the thermodynamic limit. By performing a finite-size scaling study, we find strong evidence that the change in the dynamics does not modify the universality class of the disorder-induced phase transition.

Corrigendum stable matchings and preferences of couples

We correct an omission in the definition of our domain of weakly responsive preferences introduced in Klaus and Klijn (2005) or KK05 for short. The proof of the existence of stable matchings (KK05, Theorem 3.3) and a maximal domain result (KK05, Theorem 3.5) are adjusted accordingly.

Median stable matching for college admission

We give a simple and concise proof that so-called generalized median stable matchings are well-defined stable matchings for college admissions problems. Furthermore, we discuss the fairness properties of median stable matchings and conclude with two illustrative examples of college admissions markets, the lattices of stable matchings, and the corresponding generalized median stable matchings.

Corrigendum to "On randomized matching mechanisms" [Economic Theory 8(1996)377-381]

Ma (1996) studied the random order mechanism, a matching mechanism suggested by Roth and Vande Vate (1990) for marriage markets. By means of an example he showed that the random order mechanism does not always reach all stable matchings. Although Ma's (1996) result is true, we show that the probability distribution he presented - and therefore the proof of his Claim 2 - is not correct. The mistake in the calculations by Ma (1996) is due to the fact that even though the example looks very symmetric, some of the calculations are not as ''symmetric.''

Employment by lotto revisited

We study employment by lotto (Aldershof et al., 1999), a matching algorithm for the so-called stable marriage problem. We complement Aldershof et al.'s analysis in two ways. First, we give an alternative and intuitive description of employment by lotto. Second, we disprove Aldershof et al.'s conjectures concerning employment by lotto for general matching markets.

A cooperative appproach to queue allocation of indivisible objects

We consider the allocation of a finite number of indivisible objects to the same number of agents according to an exogenously given queue. We assume that the agents collaborate in order to achieve an efficient outcome for society. We allow for side-payments and provide a method for obtaining stable outcomes.

Sequencing games without initial order

In this note we study uncertainty sequencing situations, i.e., 1-machine sequencing situations in which no initial order is specified. We associate cooperative games with these sequencing situations, study their core, and provide links with the classic sequencing games introduced by Curiel et al. (1989). Moreover, we propose and characterize two simple cost allocation rules for uncertainty sequencing situations with equal processing times.

Fair and efficient student placement with couples

We study situations of allocating positions or jobs to students or workers based on priorities. An example is the assignment of medical students to hospital residencies on the basis of one or several entrance exams. For markets without couples, e.g., for ``undergraduate student placement,'' acyclicity is a necessary and sufficient condition for the existence of a fair and efficient placement mechanism (Ergin, 2002). We show that in the presence of couples, which introduces complementarities into the students' preferences, acyclicity is still necessary, but not sufficient (Theorem 4.1). A second necessary condition (Theorem 4.2) is ``priority-togetherness'' of couples. A priority structure that satisfies both necessary conditions is called pt-acyclic. For student placement problems where all quotas are equal to one we characterize pt-acyclicity (Lemma 5.1) and show that it is a sufficient condition for the existence of a fair and efficient placement mechanism (Theorem 5.1). If in addition to pt-acyclicity we require ``reallocation-'' and ``vacancy-fairness'' for couples, the so-called dictator-bidictator placement mechanism is the unique fair and efficient placement mechanism (Theorem 5.2). Finally, for general student placement problems, we show that pt-acyclicity may not be sufficient for the existence of a fair and efficient placement mechanism (Examples 5.4, 5.5, and 5.6). We identify a sufficient condition such that the so-called sequential placement mechanism produces a fair and efficient allocation (Theorem 5.3).

Paths to stability for matching markets with couples

We study two-sided matching markets with couples and show that for a natural preference domain for couples, the domain of weakly responsive preferences, stable outcomes can always be reached by means of decentralized decision making. Starting from an arbitrary matching, we construct a path of matchings obtained from `satisfying' blocking coalitions that yields a stable matching. Hence, we establish a generalization of Roth and Vande Vate's (1990) result on path convergence to stability for decentralized singles markets. Furthermore, we show that when stable matchings exist, but preferences are not weakly responsive, for some initial matchings there may not exist any path obtained from `satisfying' blocking coalitions that yields a stable matching.

Distribution center consolidation games

We study the location-inventory model as introduced by Teo et al. (2001) to analyze the impact of consolidation of distribution centers on facility and inventory costs. We extend their result on profitability of consolidation. We associate a cooperative game with each location-inventory situation and prove that this game has a non-empty core for identical and independent demand processes. This illustrates that consolidation does not only lower joint costs (which was shown by Teo et al. (2001)), but it allows for a stable division of the minimal costs as well.

Procedurally fair and stable matching

We motivate procedural fairness for matching mechanisms and study two procedurally fair and stable mechanisms: employment by lotto (Aldershof et al., 1999) and the random order mechanism (Roth and Vande Vate, 1990, Ma, 1996). For both mechanisms we give various examples of probability distributions on the set of stable matchings and discuss properties that differentiate employment by lotto and the random order mechanism. Finally, we consider an adjustment of the random order mechanism, the equitable random order mechanism, that combines aspects of procedural and "endstate'' fairness. Aldershof et al. (1999) and Ma (1996) that exist on the probability distribution induced by both mechanisms. Finally, we consider an adjustment of the random order mechanism, the equitable random order mechanism.

Manipulation of optimal matchings via predonation of endowment

In this paper we answer a question posed by Sertel and Özkal-Sanver (2002) on the manipulability of optimal matching rules in matching problems with endowments. We characterize the classes of consumption rules under which optimal matching rules can be manipulated via predonation of endowment.

On games corresponding to sequencing situations with precedence relations

In this paper we study a class of cooperative sequencing games that arise from one-machine sequencing situations in which chain precedence relations are imposed on the jobs. It is shown that these sequencing games are convex.