Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety.

BACKGROUND AND PURPOSE: The major drug-metabolizing enzymes for the oxidation of oxycodone are CYP2D6 and CYP3A. A high interindividual variability in the activity of these enzymes because of genetic polymorphisms and/or drug-drug interactions is well established. The possible role of an active metabolite in the pharmacodynamics of oxycodone has been questioned and the importance of CYP3A-mediated effects on the pharmacokinetics and pharmacodynamics of oxycodone has been poorly explored. EXPERIMENTAL APPROACH: We conducted a randomized crossover (five arms) double-blind placebo-controlled study in 10 healthy volunteers genotyped for CYP2D6. Oral oxycodone (0.2 mg x kg(-1)) was given alone or after inhibition of CYP2D6 (with quinidine) and/or of CYP3A (with ketoconazole). Experimental pain (cold pressor test, electrical stimulation, thermode), pupil size, psychomotor effects and toxicity were assessed. KEY RESULTS: CYP2D6 activity was correlated with oxycodone experimental pain assessment. CYP2D6 ultra-rapid metabolizers experienced increased pharmacodynamic effects, whereas cold pressor test and pupil size were unchanged in CYP2D6 poor metabolizers, relative to extensive metabolizers. CYP2D6 blockade reduced subjective pain threshold (SPT) for oxycodone by 30% and the response was similar to placebo. CYP3A4 blockade had a major effect on all pharmacodynamic assessments and SPT increased by 15%. Oxymorphone C(max) was correlated with SPT assessment (rho(S)= 0.7) and the only independent positive predictor of SPT. Side-effects were observed after CYP3A4 blockade and/or in CYP2D6 ultra-rapid metabolizers. CONCLUSIONS AND IMPLICATIONS: The modulation of CYP2D6 and CYP3A activities had clear effects on oxycodone pharmacodynamics and these effects were dependent on CYP2D6 genetic polymorphism.

Rural Expressway Intersection Safety Toolbox Desktop Reference, June 17, 2011

This document is intended to be a guide for planning-level decisions concerning safety issues and subsequent potential improvements at rural expressway intersections. It is NOT a design guide. It simply presents the gamut of safety treatment options and available strategies that have been employed in an attempt to reduce the number and severity of collisions at unsignalized rural expressway intersections.

Aplicación de una técnica operativa con carácter discriminatorio en los procesos de selección de personal

Existen técnicas clásicas cuya función es seleccionar aquellas personas que son idóneas para un determinado puesto de trabajo. El punto fundamental consiste en adaptar una persona a un perfíl de tareas que esa persona debe desarrollar y al mismo tiempo esa persona debe sentirse parte integrante de la empresa, para conseguirlo, en el presente trabajo expondremos una nueva técnica para la selección de personal ejecutivo y basada en la teoría de los subconjuntos borrosos dentro de las nuevas técnicas operativas de gestión.

Getting to know about health and safety related to products used in painting, drawing and printmakin

Practicing art is not a high risk activity. This statement, along with the creative, expressive and intangible aims of this activity, as well as the lack of information, promotion of safety awareness and training of thepeople in charge of art studios, may have pushed the implications of practicing art as regards health, safety and environment into the background. Faced with this prospect, a comprehensive study of the facilities and the activities carried out in art studios becomes necessary. The study concerns experimental activities involving Health and Safety risks for both the artists and the teachers and students, especially those carried out in the studios located in educational institutions.

La història cultural i l'intel·lectual professional. Una visió personal

The author exposes the main research lines in the history of local culture. He briefly considers the main lines in cultural contemporary history investigation. The author studies the introduction and development of cultural history based on the concept of intellectual professional in Catalan historiography at a moment when economical and social research were preferred by a large part of local historians.

Road Safety Audit for IA 28 from the South Corporate Limits of Norwalk in Warren County through the IA 5 Interchange in Polk County, Iowa, November 2012

In response to local concerns, the Iowa Department of Transportation (DOT) requested a road safety audit (RSA) for the IA Highway 28 corridor through the City of Norwalk in Warren County, Iowa, from the south corporate limits of Norwalk through the IA 5 interchange in Polk County, Iowa. The audit included meeting with City staff to discuss concerns, review crash history and operational issues, observe the route under daylight and nighttime conditions, and analyze available data. This report outlines the findings and recommendations of the audit team for addressing the safety concerns and operational matters along this corridor.

Identidad personal y subjetividad social: educación y constitución subjetiva

La constitución subjetiva en nuestra sociedad contemporánea debe ser abordada dentro de la compleja trama de relaciones intersubjetivas y desde diferentes formulaciones teóricas. La construcción del sujeto involucra la existencia de un "otro", que le da sentido a su existencia y a la constitución/adquisición de identidades sociales/colectivas. Ese proceso se aborda en términos de representaciones sociales, como expresión del sentido común, que se desarrollan en complejos procesos que involucran estabilidad de largo alcance y antinomias -themata- que definen las situaciones de tensión, inherentes y propias, del devenir del sentido común. Se considerarán cuatro procesos psicosociales: 1) La Identidad como producto intersubjetivo. 2) La Representación social como expresión de la identidad. 3) Los themata como constitutivos de la Representación social. 4) La interdependencia simbólica Yo/Otros. Se ilustrará con ejemplos de dos investigaciones, en Ciers-ed y en Universidad de Buenos Aires sobre educación

La història cultural i l'intel·lectual professional. Una visió personal

The author exposes the main research lines in the history of local culture. He briefly considers the main lines in cultural contemporary history investigation. The author studies the introduction and development of cultural history based on the concept of intellectual professional in Catalan historiography at a moment when economical and social research were preferred by a large part of local historians.

Improving Traffic Safety Culture in Iowa – Phase II, July 2013

Phase II of Improving Traffic Safety Culture in Iowa focuses on producing actions that will improve the traffic safety culture across the state, and involves collaboration among the three large public universities in Iowa: Iowa State University, University of Northern Iowa, and University of Iowa. More specifically, this second phase synthesizes the expert opinions solicited in Phase I with prevailing public views and/or opinions gathered from a follow-up survey on Iowa’s 2000 public opinion survey, which the University of Northern Iowa, Center for Social and Behavioral Research, administered. More recent data on the opinions of Iowans and of people nationally contrasted with past data will help better define the public’s position on top safety culture issues. This, in turn, will provide a better basis for developing actionable, fundable, and ultimately successful strategies that will make a tangible difference in improving traffic safety in Iowa.

Evaluation of Mitigation for Safety Concerns on Low-Volume, Unpaved Rural Roads, 2013.

The Institute for Transportation (InTrans) at Iowa State University completed work on an in-depth study of crash history on lowvolume, rural roads in Iowa in December 2010. Results indicated that unpaved roads with traffic volumes greater than 100 vehicles per day (vpd) exhibit significantly higher crash frequencies, rates, and densities than any other class of low-volume road examined, paved or unpaved. The total mileage for this class of roadway in Iowa is only about 4,400 miles, spread over 99 counties in the state, which is certainly a manageable number of miles for individual rural agencies. The purpose of this study was to identify and examine several unpaved, local road segments with higher than average crash frequencies, select and undertake potentially-beneficial mitigation, and evaluate the results as time allowed. A variety of low-cost options were considered, including engineering improvements, enhanced efforts by law enforcement, and educational initiatives. Using input, active support, and participation from local agencies and state and Federal safety advocates, the study afforded a unique opportunity to examine useful tools for local rural agencies to utilize in addressing safety on this particular type of roadway.

Evaluation of Mitigation for Safety Concerns on Low-Volume, Unpaved Rural Roads: Tech Transfer Summary, 2013.

The Institute for Transportation (InTrans) at Iowa State University completed work on an in-depth study of crash history on lowvolume, rural roads in Iowa in December 2010. Results indicated that unpaved roads with traffic volumes greater than 100 vehicles per day (vpd) exhibit significantly higher crash frequencies, rates, and densities than any other class of low-volume road examined, paved or unpaved. The total mileage for this class of roadway in Iowa is only about 4,400 miles, spread over 99 counties in the state, which is certainly a manageable number of miles for individual rural agencies. The purpose of this study was to identify and examine several unpaved, local road segments with higher than average crash frequencies, select and undertake potentially-beneficial mitigation, and evaluate the results as time allowed. A variety of low-cost options were considered, including engineering improvements, enhanced efforts by law enforcement, and educational initiatives. Using input, active support, and participation from local agencies and state and Federal safety advocates, the study afforded a unique opportunity to examine useful tools for local rural agencies to utilize in addressing safety on this particular type of roadway.

Analysis of Existing Work-Zone Devices with MASH Safety Performance Criteria, TPF-5(018), 2009

Crashworthy, work-zone, portable sign support systems accepted under NCHRP Report No. 350 were analyzed to predict their safety peformance according to the TL-3 MASH evaluation criteria. An analysis was conducted to determine which hardware parameters of sign support systems would likely contribute to the safety performance with MASH. The acuracy of the method was evaluated through full-scale crash testing. Four full-scale crash tests were conducted with a pickup truck. Two tall-mounted, sign support systems with aluminum sign panels failed the MASH criteria due to windshield penetration. One low-mounted system with a vinyl, roll-up sign panel failed the MASH criteria due to windshield and floorboard penetration. Another low-mounted system with an aluminum sign panel successfully met the MASH criteria. Four full-scale crash tests were conducted with a small passenger car. The low-mounted tripod system with an aluminum sign panel failed the MASH criteria due to windshield penetration. One low-mounted system with aluminum sign panel failed the MASH criteria due to excessive windshield deformation, and another similar system passed the MASH criteria. The low-mounted system with a vinyl, roll-up sign panel successfully met the MASH criteria. Hardware parameters of work-zone sign support systems that were determined to be important for failure with MASH include sign panel material, the height to the top of the mast, the presence of flags, sign-locking mechanism, base layout and system orientation. Flowcharts were provided to assist manufacturers when designing new sign support systems.

ICD-11 for quality and safety: overview of the who quality and safety topic advisory group.

This paper outlines the approach that the WHO's Family of International Classifications (WHO-FIC) network is undertaking to create ICD-11. We also outline the more focused work of the Quality and Safety Topic Advisory Group, whose activities include the following: (i) cataloguing existing ICD-9 and ICD-10 quality and safety indicators; (ii) reviewing ICD morbidity coding rules for main condition, diagnosis timing, numbers of diagnosis fields and diagnosis clustering; (iii) substantial restructuring of the health-care related injury concepts coded in the ICD-10 chapters 19/20, (iv) mapping of ICD-11 quality and safety concepts to the information model of the WHO's International Classification for Patient Safety and the AHRQ Common Formats; (v) the review of vertical chapter content in all chapters of the ICD-11 beta version and (vi) downstream field testing of ICD-11 prior to its official 2015 release. The transition from ICD-10 to ICD-11 promises to produce an enhanced classification that will have better potential to capture important concepts relevant to measuring health system safety and quality-an important use case for the classification.

Consumer Advisory: Social Media Safety & Security, October 2013

The Attorney General’s Consumer Protection Division receives hundreds of calls and consumer complaints every year. Follow these tips to avoid unexpected expense and disappointments. This record is about: Social Media Safety & Security