Interpretation, jurisdiction and the authority of law

El presente ensayo plantea la dicotomía existente entre el principio de autoridad del Derecho y la idea de autonomía individual partiendo de un análisis crítico de un trabajo clásico del iusfilósofo Joseph Raz sobre la teoría de la autoridad.This essay presents the dichotomy between the principie of authority of law and the idea of individual autonomy based on a critical analysis of a classical work of the legal philosopher Joseph Raz on the theory of authority

La vaguedad y el Estado de Derecho: Una crisis en la adjudicación de derechos humanos

Todo sistema legal necesita normas vagas, y luego el sistema necesita tribunalesque resuelvan disputas sobre la aplicación de normas vagas. La vaguedad y elEstado de Derecho no son necesariamente incompatibles. Pero tampoco son necesariamente compatibles. Cuando las leyes vagas llevan a decisiones judiciales arbitrarias, un sistema legal pierde el Estado de Derecho hasta cierto punto. ¿Cómo podemos distinguir entre situaciones en las que la vaguedad desvirtúa o no el Estado de Derecho? Voy a abordar esta pregunta discutiendo la adjudicación de Derechos Humanos. Algunas de las normas más vagas de los sistemas legales se usan en las cartas de Derechos, y estas disposiciones pueden resultar en litigios que desafían la racionalidad, y por lo tanto, la legitimidad de la toma de decisión judicial

Parallel Optimisation of Potency and Pharmacokinetics Leading to the Discovery of a Pyrrole Carboxamide ERK5 Chemical Tool

[Image: see text] The nonclassical extracellular signal-related kinase 5 (ERK5) mitogen-activated protein kinase pathway has been implicated in increased cellular proliferation, migration, survival, and angiogenesis; hence, ERK5 inhibition may be an attractive approach for cancer treatment. However, the development of selective ERK5 inhibitors has been challenging. Previously, we described the development of a pyrrole carboxamide high-throughput screening hit into a selective, submicromolar inhibitor of ERK5 kinase activity. Improvement in the ERK5 potency was necessary for the identification of a tool ERK5 inhibitor for target validation studies. Herein, we describe the optimization of this series to identify nanomolar pyrrole carboxamide inhibitors of ERK5 incorporating a basic center, which suffered from poor oral bioavailability. Parallel optimization of potency and in vitro pharmacokinetic parameters led to the identification of a nonbasic pyrazole analogue with an optimal balance of ERK5 inhibition and oral exposure

Stimulant Reduction Intervention using Dosed Exercise (STRIDE) - CTN 0037: Study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>There is a need for novel approaches to the treatment of stimulant abuse and dependence. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse, with direct effects on decreased use and craving. In addition, exercise has the potential to improve other health domains that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight gain, quality of life, and anhedonia, since it has been shown to improve many of these domains in a number of other clinical disorders. Furthermore, neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes. The current manuscript presents the rationale, design considerations, and study design of the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) CTN-0037 Stimulant Reduction Intervention using Dosed Exercise (STRIDE) study.</p> <p>Methods/Design</p> <p>STRIDE is a multisite randomized clinical trial that compares exercise to health education as potential treatments for stimulant abuse or dependence. This study will evaluate individuals diagnosed with stimulant abuse or dependence who are receiving treatment in a residential setting. Three hundred and thirty eligible and interested participants who provide informed consent will be randomized to one of two treatment arms: Vigorous Intensity High Dose Exercise Augmentation (DEI) or Health Education Intervention Augmentation (HEI). Both groups will receive TAU (i.e., usual care). The treatment arms are structured such that the quantity of visits is similar to allow for equivalent contact between groups. In both arms, participants will begin with supervised sessions 3 times per week during the 12-week acute phase of the study. Supervised sessions will be conducted as one-on-one (i.e., individual) sessions, although other participants may be exercising at the same time. Following the 12-week acute phase, participants will begin a 6-month continuation phase during which time they will attend one weekly supervised DEI or HEI session.</p> <p>Clinical Trials Registry</p> <p>ClinicalTrials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT01141608">NCT01141608</a></p> <p><url>http://clinicaltrials.gov/ct2/show/NCT01141608?term=Stimulant+Reduction+Intervention+using+Dosed+Exercise&rank=1</url></p

Interpretation, jurisdiction, and the authority of law

People can be autonomous, if they are subject to authority. In particular, they can be autonomous if they are subject to the authority of law. I defend the first claim through a study of Joseph Raz's compelling account of authority; I claim that his work leads to the conclusion that autonomous judgment is needed to determine the jurisdiction of an authority, and to interpret its directives. I defend the second claim by arguing (contrary to remarks by Raz) that law does not claim unlimited jurisdiction, and need not claim unlimited scope for its directives. But the requirements of the rule of law create a standing risk that the law will not adequately recognize the autonomy of its subjects, because of its artificial techniques for controlling its own jurisdiction and for controlling the scope of its own directives