The concomitant use of alcohol (EtOH) and the psychotherapeutic agent dl-methylphenidate (MPH) has risen as a consequence of an increase in ADHD diagnoses within the drinking age population. It was recently found that the combination of MPH and EtOH increases the self-report of pleasurable feelings relative to MPH alone. This finding raises concerns regarding the combined abuse liability for these two widely used drugs. The present behavioral study reports on the development of an adult male C57BL/6J (B6) mouse model to further characterize this MPH-EtOH interaction. We examined the effects of MPH on EtOH consumption in a limited access paradigm and EtOH stimulation of locomotor activity. B6 mice consumed about 2 g/kg EtOH daily and MPH dose-dependently reduced drinking. The most effective dose of MPH was 1.25 mg/kg, which produced a 41% decrease in drinking and had no effect on locomotor activity. However, when the 1.25 mg/kg dose of MPH was combined with a stimulatory dose of ethanol (1.75 g/kg) by intraperitoneal injection, there was a significantly enhanced stimulation of locomotor activity. The drug combination increased activity compared to the vehicle or MPH injections by 45% and increased the activity relative to EtOH alone by an additional 25%. The results of the EtOH and MPH interactions observed with the mouse model appear to be behaviorally relevant and suggest several converging mechanisms that may underlie MPH-EtOH interactions.

We tested the hypothesis that C57BL/6J mice will model human metabolic interactions between dl-methylphenidate (MPH) and ethanol, placing an emphasis on the MPH transdermal system (MTS). Specifically, we asked: (1) will ethanol increase d-MPH biological concentrations, (2) will MTS facilitate the systemic bioavailability of l-MPH, and (3) will l-MPH enantioselectively interact with ethanol to yield l-ethylphenidate (l-EPH)? Mice were dosed with MTS (¼ of a 12.5 cm2 patch on shaved skin) or a comparable oral dl-MPH dose (7.5 mg/kg), with or without ethanol (3.0 g/kg), and then placed in metabolic cages for 3 h. MPH and EPH isomer concentrations in blood, brain, and urine were analyzed by gas chromatographic–mass spectrometry monitoring of N-(S)-prolylpiperidyl fragments. As in humans, MTS greatly facilitated the absorption of l-MPH in this mouse strain. Similarly, ethanol led to the enantioselective formation of l-EPH and to an elevation in d-MPH concentrations with both MTS and oral MPH. Although only guarded comparisons between MTS and oral MPH can be made due to route-dependent drug absorption rate differences, MTS was associated with significant MPH–ethanol interactions. Ethanol-mediated increases in circulating concentrations of d-MPH carry toxicological and abuse liability implications should this animal model hold for ethanol-consuming attention-deficit hyperactivity disorder patients or coabusers.

The Americans with Disabilities Act (ADA) has greatly improved the lives of people with disabilities in the United States. Initially thought to primarily require removal of physical barriers, the ADA has consistently been applied broadly to encompass all aspect of entities' programs, services, and operations. As entities endeavored to comply with the ADA, several useful management strategies have emerged, one of which is this concept of Universal Design (UD). Universal Design guides managers in meeting their legal obligations under the ADA and also creating a more fully inclusive environment for employees and customers. "Universal Design is a framework for the design of places, things, information, communication and policy to be usable by the widest range of people operating in the widest range of situations without special or separate design" (IHCD, 2015b).

The discovery of a novel series of therapeutic agents that has been designed and optimized for treating chronic obstructive pulmonary disease is reported. The pharmacological strategy was based on the identification of compounds that inhibit a defined subset of kinase enzymes modulating inflammatory processes that would be effective against steroid refractory disease and exhibit a sustained duration of action after inhaled delivery.

Where two opposing sides are engaged in violent conflict and a process of political disintegration, the ability to protect an already-contested legitimacy becomes crucial to a negotiated agreement. Lord Carrington, the mediator between the government of Zimbabwe-Rhodesia and the guerrilla forces of the Patriotic Front, helped the parties save face at the Lancaster House Conference in 1979. Using a tactic of strong third-party mediation, Carrington accepted responsibility for the concessions the opposing delegations made, allowing them to protect their reputation among supporters. This paper examines the three primary ways the parties at Lancaster House attempted to save face: using the mediator as scapegoat, engaging in sharp confrontation in public and flexible conciliation in private, and conducting “shadow” negotiations through Commonwealth Secretary-General Sir Shridath Ramphal.