Biological markers of alcohol consumption in alcoholised drivers: Comparison of capillary electrophoresis (CZE CDT) and a direct immunoassay (N Latex CDT) with the traditional method of anion-exchange chromatography-immunoturbidimetry (%CDT TIA).

Objectives: The aim of this study was to compare specificity and sensitivity of different biological markers that can be used in a forensic field to identify potentially dangerous drivers because of their alcohol habits. Methods: We studied 280 Swiss drivers after driving while under the alcohol influence. 33 were excluded for not having CDT N results, 247 were included (218 men (88%) and 29 women (12%). Mean age was 42,4 (SD:12, min: 20 max: 76). The evaluation of the alcohol consumption concerned the month before the CDT test and was considered as such after the interview: Heavy drinkers (>3 drinks per day): 60 (32.7%), < 3 drinks per day and moderate: 127 (51.4%) 114 (46.5%), abstinent: 60 (24.3%) 51 (21%). Alcohol intake was monitored by structured interviews, self-reported drinking habits and the C-Audit questionnaire as well as information provided by their family and general practitioner. Consumption was quantified in terms of standard drinks, which contain approximately 10 grams of pure alcohol (Ref. WHO). Results: comparison between moderate (less or equal to 3 drinks per day) and excessive drinkers (more than 3 drinks) Marker ROC area 95% CI cut-off sensitivity specificity CDT TIA 0.852 0.786-0917 2.6* 0.93 LR+1.43 0.35 LR-0.192 CDT N latex 0.875 0.821-0.930 2.5* 0.66 LR+ 6.93 0.90 LR- 0.369 Asialo+disialo-tf 0.881 0.826-0.936 1.2* 0.78 LR+4.07 0.80 LR-0.268 1.7° 0.66 LR+8.9 0.93 LR-0.360 GGT 0.659 0.580-0.737 85* 0.37 LR+2.14 0.83 LR-0.764 * cut-off point suggested by the manufacturer ° cut-off point suggested by our laboratory Conclusion: With the cut-off point established by the manufacturer, CDT TIA performed poorly in term of specificity. N latex CDT and CZE CDT were better, especially if a 1.7 cut-off is used with CZE

Traitement des epilepsies réfractaires: rôle de la stimulation electrique [Treatment of pharmacoresistant epilepsy: stimulated refractoriness].

Antiepileptic drugs allow controlling seizures in 70% of patients. For the others, a presurgical work-up should be undertaken, especially if a focal seizure origin is suspected; however, only a fraction of pharmacoresistant patients will be offered resective (curative) surgery. In the last 15 years, several palliative therapies using extra- or intracranial electrical stimulations have been developed. This article presents the vagal nerve stimulation, the deep brain stimulation (targeting the mesiotemporal region or the thalamus), and the cortical stimulation "on demand". All show an overall long-term responder rate between 30-50%, but less than 5% of patients becoming seizure free. It is to hope that a better understanding of epileptogenic mechanisms and of the implicated neuronal networks will lead to an improvement of these proportions.

Aspectos físicos del monitoreo oceanográfico pesquero en áreas seleccionadas (MOPAS)

Presenta los resultados del segundo Monitoreo Oceanográfico Pesquero en Áreas Seleccionadas (MOPAS) en donde se detectó que la temperatura superficial del mar varió entre 20.9ºC a 14.6 °C, observándose las áreas más cálidas al norte de San Gallán (Pisco) y sur de Ilo, mientras que las principales áreas frías se observaron frente a Salaverry y sur de Pisco. Por tanto se concluye que el ambiente marino ha incrementado ligeramente sus valores térmicos y halinos en las superficies con respecto al mes de agosto, mientras que en la capa subsuperficial se ha enfriado ligeramente por el ascenso de las isotermas.

The economics of organized crime and optimal law enforcement

This paper extends the optimal law enforcement literature to organized crime.We model the criminal organization as a vertical structure where the principal extracts some rents from the agents through extortion. Depending on the principal's information set, threats may or may not be credible. As long as threats are credible, the principal is able to fully extract rents.In that case, the results obtained by applying standard theory of optimal law enforcement are robust: we argue for a tougher policy. However, when threats are not credible, the principal is not able to fully extract rents and there is violence. Moreover, we show that it is not necessarily true that a tougher law enforcement policy should be chosen when in presence of organized crime.

Carte itinéraire d'Espagne et de Portugal : Indiquant les différentes espèces de Routes et les distances de villes à autres, en lieues de postes de ces Royaumes / par Desimencourt

Échelle(s) : [ca 1:1 600 000]

Composición, abundancia y distribución del fitoplancton frente a la costa peruana en el verano 2004. Crucero 0402-03

Los volúmenes de plancton variaron entre 0,09 y 3,15 mL.m-3, promedio 0,76 mL.m-3. El fitoplancton de red fue predominante sólo en 32% de las muestras dentro de 30 mn. A 10 m de profundidad las concentraciones fluctuaron entre 26 x 103 cel.L-1 en Pisco y 4 930 x 103 cel.L-1 en Callao; la diversidad varió entre 0,54 bits.cel-1 en Chicama y 3,03 bits.cel-1 frente a Pisco. El microplancton presentó las mayores densidades seguido del nanoplancton. Protoperidinium obtusum, indicador de ACF estuvo costero desde Punta Falsa hasta San Juan; en Chicama, Pisco y entre Punta Mendieta-Punta Caballas se distribuyó hasta 40 mn. Ceratium praelongum, indicador de ASS presentó una distribución variada entre Paita y Matarani, alcanzó máximo acercamiento a la costa en Chala.

Sedimentos superficiales y morfología de la plataforma y talud continental superior entre 3°30’S y 15°30’S, Perú

Basados en la compilación de resultados de análisis sedimentológicos (granulometría, contenido orgánico) de 1191 estaciones realizadas por IMARPE, de 1975 a 2001, la compilación de información sobre el tema entre los 3°30’S y los 15°30’S y con el conocimiento de la morfología del fondo marino de esta región, se definen tres grandes áreas: al norte de los 6°15’S, de 6°15’S a 9°30’S y entre 9°30’ y 15°30’S. Entre los 3°30’ y los 6°15’S los contenidos de materia orgánica son mayores a 5% y menores a 10%, el carbono orgánico predomina con valores <1% a 2%. Los sedimentos corresponden a facies de fango y arenas, de origen terrígeno. El ancho de la plataforma es variable aproximadamente de 3 a 30 mn (14 mn promedio), la pendiente del talud superior es bastante pronunciada, presenta caídas bruscas. El relieve es disparejo, con fuertes desmembramientos en el borde exterior de la plataforma y el talud superior debido a que se encuentra surcado por cañones submarinos. En el extremo noroccidental de esta zona, se halla el Banco de Máncora cuyo fondo es rocoso e irregular. Entre los 6°30’S y los 9°30’S los contenidos de materia orgánica se incrementan de 5% a 15%, los contenidos de carbono orgánico son >2% y llegan a 5%, en algunos casos localmente superan este valor casi en tres puntos más. En los sedimentos del sector norte de esta zona predominan facies texturales de arenas y fango de origen terrígeno y también biógenos (foraminíferos), hacia el sur de esta zona predominan sedimentos de origen biogénico y autigénico (principalmente fosforita). El ancho de la plataforma se incrementa hasta alcanzar su máxima magnitud, esta es variable, aproximadamente de 22 a 70 mn. El talud superior tiene un declive moderado. El relieve del fondo marino en el borde exterior de la plataforma y talud superior se hallan surcados por cañones submarinos (7° - 9°S). Frente a Punta Chao aproximadamente a 65 mn se encuentra el Banco de Chimbote cuyo fondo es rocoso e irregular. La granulometría de los sedimentos y sus estadígrafos muestran un cambio definido desde los 10°30’S. Desde los 9°30’ a los 15°45’S los valores de materia orgánica por lo general sobrepasan el 15% y pueden alcanzar hasta 32,12%, los contenidos de carbono orgánico varían de 5% a 11,14%. En esta zona se encuentra presente, principalmente fango limoso y fango arcilloso terrígeno y biógeno (diatoméico). El ancho de la plataforma varía de modo general entre 10 y 50 mn (24 mn promedio aproximadamente). La pendiente del talud superior es suave en casi toda su extensión, el relieve del fondo marino es bastante uniforme, surcado por algunos pequeños cañones submarinos que no afectan la regularidad del relieve. De la interpretación de la data, análisis de parámetros estadísticos generados y condiciones de los sedimentos, se encontró coincidencia en la zona de la plataforma y talud superior de más de uno de los factores medio ambiente deposicional que permiten la preservación del contenido de materia orgánica tales como: Tipo y condiciones geoquímicas del sedimento y fondo marino, morfología del fondo marino, hidrodinámica, fuente de suministro, tasa de sedimentación, bioturbación.

Differential effectiveness of microbially induced resistance against herbivorous insects in Arabidopsis.

Rhizobacteria-induced systemic resistance (ISR) and pathogen-induced systemic acquired resistance (SAR) have a broad, yet partly distinct, range of effectiveness against pathogenic microorganisms. Here, we investigated the effectiveness of ISR and SAR in Arabidopsis against the tissue-chewing insects Pieris rapae and Spodoptera exigua. Resistance against insects consists of direct defense, such as the production of toxins and feeding deterrents and indirect defense such as the production of plant volatiles that attract carnivorous enemies of the herbivores. Wind-tunnel experiments revealed that ISR and SAR did not affect herbivore-induced attraction of the parasitic wasp Cotesia rubecula (indirect defense). By contrast, ISR and SAR significantly reduced growth and development of the generalist herbivore S. exigua, although not that of the specialist P. rapae. This enhanced direct defense against S. exigua was associated with potentiated expression of the defense-related genes PDF1.2 and HEL. Expression profiling using a dedicated cDNA microarray revealed four additional, differentially primed genes in microbially induced S. exigua-challenged plants, three of which encode a lipid-transfer protein. Together, these results indicate that microbially induced plants are differentially primed for enhanced insect-responsive gene expression that is associated with increased direct defense against the generalist S. exigua but not against the specialist P. rapae.

Subproduto da indústria de alumínio como amenizante de solos contaminados com cádmio e chumbo

A poluição do solo com elementos-traço tem sido motivo de preocupação nos últimos anos, o que justifica melhor conhecimento da disponibilidade desses elementos no ambiente, visando amenizar seus efeitos em áreas contaminadas. Este trabalho teve como objetivo avaliar o desempenho de um subproduto da indústria de alumínio como amenizante de solos contaminados com Cd e Pb. Foram utilizados um Neossolo Quartzarênico (930 g kg-1 de areia, 20 g kg-1 de silte e 50 g kg-1 de argila) e um Latossolo Vermelho (360 g kg-1 de areia, 100 g kg-1 de silte e 540 g kg-1 de argila) contendo 15 % de solo contaminado com Cd e Pb. Foram feitas cinco repetições testando-se o efeito da aplicação do subproduto in natura a 0; 0,25; 0,50; 1,00; e 2,00 %. Para comparação, utilizaram-se calcário, silicato e turfa a 0,25; 0,50; e 2,00 %, respectivamente, e cada um dos solos sem contaminação. Cultivou-se B. decumbens, fazendo coletas de lixiviado e determinando o pH e a CE. As concentrações de Cd e Pb foram avaliadas no lixiviado não-filtrado e filtrado (0,45 µm). Avaliaram-se a produção de matéria seca de raízes (MSR) e da parte aérea (MSPA) e as quantidades de Cd e Pb em ambas após digestão nitroperclórica. Os amenizantes contribuíram para aumentar o pH dos lixiviados do Neossolo Quartzarênico e do Latossolo Vermelho, tendo este último apresentado menores valores de condutividade eletrolítica quando comparado ao primeiro. Os teores de Cd nos lixiviados filtrados (fração solúvel) foram os mesmos dos lixiviados não-filtrados, enquanto os de Pb apresentaram diferenças. As produções de MSR e MSPA aumentaram com o aumento das taxas de aplicação do subproduto, e a quantidade de Cd na MSPA da B. decumbens foi maior que a de Pb.

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·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 Cmax was correlated with SPT assessment (ρS= 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.

Defining the level of evidence for technology adoption in the localized prostate cancer pathway.

New technologies in prostate cancer are attempting to change the current prostate cancer pathway by aiming to reduce harms while maintaining the benefits associated with screening, diagnosis, and treatment. In this article, we discuss the optimal evaluation that new technologies should undergo to provide level 1 evidence typically required to change the practice. With this in mind, we focus on feasible and pragmatic trials that could be delivered in a timely fashion by many centers while retaining primary outcomes that focus on clinically meaningful outcomes.

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.

Säännöstelty huvi : suomalainen ravintola 1900-luvulla

Väitöskirja,Tampereen yliopisto

Níveis de cromo-ácido nicotínico em dietas de suínos em crescimento e terminação

O objetivo deste estudo foi avaliar os efeitos de níveis crescentes de cromo dietético, na forma de ácido nicotínico, sobre o desempenho e nas características de carcaça de suínos. Noventa e seis suínos (Landrace x Large White x Duroc), machos castrados e fêmeas, com peso médio inicial de 25,93±0,57 kg foram distribuídos ao acaso em baias de dois animais do mesmo sexo, segundo um esquema fatorial 6 x 2 (6 níveis de Cr e 2 sexos). Uma dieta basal (0 ppb Cr) foi suplementada com 100, 200, 300, 400 e 500 ppb de Cr, na forma de Cr-ácido nicotínico, incluído através do premix vitamínico. Os animais, aos 70 dias de experimento, foram pesados, abatidos, e as carcaças avaliadas utilizando-se a pistola Hennessy e o Método Brasileiro de Classificação de Carcaças. Houve efeito significativo (P<0,006) de sexo em ganho de peso e consumo de ração diários, analisados isoladamente ou em conjunto, e em todas as características de carcaça, com exceção de profundidade de lombo e área de olho de lombo. Não houve efeito (P>0,05) do nível de Cr sobre qualquer dos parâmetros estudados, seja de desempenho ou de avaliação de carcaça por qualquer dos métodos utilizados. A adição de níveis de até 500 ppb de Cr, na forma de Cr-ácido nicotínico, não altera o desempenho e a qualidade de carcaça de suínos em crescimento e em terminação.