Influence of the timing of low-dose aspirin on tolerability of prolonged-release nicotinic acid in patients at elevated cardiovascular risk

OBJECTIVES: To investigate the effect of low-dose aspirin administered in the morning or evening on the rate of discontinuation of prolonged-release nicotinic acid (Niaspan) due to flushing in patients at elevated cardiovascular risk. RESEARCH DESIGN AND METHODS: This was an observational, non-interventional study in patients at elevated cardiovascular risk due to cardiovascular disease or type 2 diabetes. Patients received prolonged-release nicotinic acid and aspirin under the usual care of their physician for 15 weeks. MAIN OUTCOME MEASURES: The main outcome measure was the rate of treatment discontinuation for flushing. Other adverse drug reactions (ADRs) were also recorded. Lipid parameters were also measured. RESULTS: The patient population included 539 subjects (70% male); 36% had type 2 diabetes, 80% had prior cardiovascular disease, and 37% had a family history of cardiovascular disease. The rate of treatment discontinuation due to flushing did not differ (p = 0.3375) between the morning aspirin group (10.6%) and the evening aspirin group (13.8%). The overall incidence of flushing was 57%. Most flushes were of mild or moderate severity and decreases occurred over time in both frequency and intensity. ADRs unrelated to flushing occurred in 6.6% of the morning aspirin group and 7.4% of the evening aspirin group. HDL-cholesterol increased by +21.3% in the overall population, together with moderate improvements in other lipid parameters. CONCLUSIONS: Flushing was the most common ADR with prolonged-release nicotinic acid treatment, as expected. The timing of aspirin administration did not influence the rate of treatment discontinuations for flushing. Marked increases in HDL-cholesterol were observed.

Safe and effective variability-a criterion for dose individualization.

BACKGROUND: : A primary goal of clinical pharmacology is to understand the factors that determine the dose-effect relationship and to use this knowledge to individualize drug dose. METHODS: : A principle-based criterion is proposed for deciding among alternative individualization methods. RESULTS: : Safe and effective variability defines the maximum acceptable population variability in drug concentration around the population average. CONCLUSIONS: : A decision on whether patient covariates alone are sufficient, or whether therapeutic drug monitoring in combination with target concentration intervention is needed, can be made by comparing the remaining population variability after a particular dosing method with the safe and effective variability.

Individual prediction of automobile bodily injury claims liabilities

[spa] La mayoría de siniestros con daños corporales se liquidan mediante negociación, llegando a juicio menos del 5% de los casos. Una estrategia de negociación bien definida es, por tanto, fundamental para las compañías aseguradoras. En este artículo asumimos que la compensación monetaria concedida en juicio es la máxima cuantía que debería ser ofrecida por el asegurador en el proceso de negociación. Usando una base de datos real, implementamos un modelo log-lineal para estimar la máxima oferta de negociación. Perturbaciones no-esféricas son detectadas. Correlación ocurre cuando más de una siniestro se liquida en la misma sentencia judicial. Heterocedasticidad por grupos se debe a la influencia de la valoración del forense en la indemnización final.

Pharmacokinetic and pharmacodynamic analysis of efavirenz dose reduction using an in vitro-in vivo extrapolation model.

The pharmacokinetics (PK) of efavirenz (EFV) is characterized by marked interpatient variability that correlates with its pharmacodynamics (PD). In vitro-in vivo extrapolation (IVIVE) is a "bottom-up" approach that combines drug data with system information to predict PK and PD. The aim of this study was to simulate EFV PK and PD after dose reductions. At the standard dose, the simulated probability was 80% for viral suppression and 28% for central nervous system (CNS) toxicity. After a dose reduction to 400 mg, the probabilities of viral suppression were reduced to 69, 75, and 82%, and those of CNS toxicity were 21, 24, and 29% for the 516 GG, 516 GT, and 516 TT genotypes, respectively. With reduction of the dose to 200 mg, the probabilities of viral suppression decreased to 54, 62, and 72% and those of CNS toxicity decreased to 13, 18, and 20% for the 516 GG, 516 GT, and 516 TT genotypes, respectively. These findings indicate how dose reductions might be applied in patients with favorable genetic characteristics.

Produtividade e nutrição de mamona cultivada em área de reforma de canavial tratada com lodo de esgoto

A utilização de lodo de esgoto (LE) em solos agrícolas é uma das maneiras mais viáveis de destinação desse resíduo. O objetivo deste trabalho foi avaliar o efeito da aplicação de LE na nutrição e na produtividade da mamona cultivada em área de reforma de canavial, num Argissolo Vermelho-Amarelo distrófico textura argilosa. Os tratamentos testados constaram de quatro doses de lodo de esgoto: 0, 5, 10 e 20 t ha-1 (base seca), calculadas para fornecer N equivalente a 0, 37,5, 75 e 150 kg ha-1; um tratamento com fertilização mineral N-P2O5-K2O (75-40-80 kg ha-1respectivamente) e um controle sem qualquer fertilização. Os tratamentos com LE também receberam 40 kg ha-1 de P2O5 e 80 kg ha-1 de K2O. A mamoneira, cultivar IAC-Guarani, foi cultivada por cerca de 180 dias entre novembro de 2004 e maio de 2005. A aplicação de LE resultou em incremento estatisticamente significativo (p < 0,05) na produtividade e em outras características biométricas da mamona. A aplicação da dose equivalente a 10 t ha-1 de lodo resultou em um índice de eficiência agronômica de 85 %, em relação à adubação mineral. A disponibilidade de N foi o fator mais limitante no crescimento e na produtividade da mamona, e a taxa de mineralização do N utilizada subestimou o fornecimento de N pelo lodo em campo. Houve aumento significativo de Cu e Zn no solo com a aplicação das doses de lodo, mas tanto os teores no solo quanto na planta estiveram dentro dos limites aceitos pela legislação ambiental.

The effects of electron-hole separation on the photoconductivity of individual metal oxide nanowires

The responses of individual ZnO nanowires to UV light demonstrate that the persistent photoconductivity (PPC) state is directly related to the electron¿hole separation near the surface. Our results demonstrate that the electrical transport in these nanomaterials is influenced by the surface in two different ways. On the one hand, the effective mobility and the density of free carriers are determined by recombination mechanisms assisted by the oxidizing molecules in air. This phenomenon can also be blocked by surface passivation. On the other hand, the surface built-in potential separates the photogenerated electron¿hole pairs and accumulates holes at the surface. After illumination, the charge separation makes the electron¿hole recombination difficult and originates PPC. This effect is quickly reverted after increasing either the probing current (self-heating by Joule dissipation) or the oxygen content in air (favouring the surface recombination mechanisms). The model for PPC in individual nanowires presented here illustrates the intrinsic potential of metal oxide nanowires to develop optoelectronic devices or optochemical sensors with better and new performances.

Efeito de substâncias húmicas na cinética de absorção de potássio, crescimento de plantas e concentração de nutrientes em Phaseolus vulgaris L.

As substâncias húmicas podem influenciar direta ou indiretamente o metabolismo das plantas, alterando assim o seu crescimento. O objetivo deste trabalho foi avaliar o efeito de substâncias húmicas (SH) no crescimento e na concentração de nutrientes em plantas de feijão (Phaseolus vulgaris, L.) e nos parâmetros cinéticos de absorção de K. O experimento foi realizado em bancada de laboratório, com luz artificial. As plantas cresceram em vasos contendo solução nutritiva completa acrescida de cinco doses (0; 2,5; 5; 10; e 20 mg L-1 de C) de SH solúveis em meio alcalino (ácido húmico + ácido fúlvico), extraídos de amostra de carvão mineral da mina de Candiota, RS, da Companhia Riograndense de Mineração, num delineamento completamente ao acaso, com três repetições. Aos 28 dias de cultivo, foram avaliados parâmetros cinéticos de absorção de K, massa da parte aérea e da raiz seca, teores de N, P, K, Ca e Mg no tecido da parte área e as características morfológicas de raízes (comprimento, área e raio). Os resultados evidenciaram que a adição de SH extraída de carvão mineral estimulou o crescimento do feijão e afetou a cinética de absorção de K. A produção de massa da parte aérea seca das plantas mostrou resposta quadrática à adição de substâncias húmicas, atingindo valor máximo na dose equivalente a 11 mg L-1 de C, enquanto a massa das raízes secas aumentou linearmente em até 41 %, com as doses testadas. As características morfológicas de raiz e o estado nutricional das plantas não foram significativamente afetados pelas SH. Os parâmetros cinéticos de absorção de K, Imáx, Cmín e Km, decresceram linearmente com o aumento das doses de SH, causando redução na taxa de absorção de K nas concentrações deste nutriente na solução superiores a 10 μmol L-1.

Raman microstructural analysis of silicon-on-insulator formed by high dose oxygen ion implantation: As-implanted structures

A microstructural analysis of silicon-on-insulator samples obtained by high dose oxygen ion implantation was performed by Raman scattering. The samples analyzed were obtained under different conditions thus leading to different concentrations of defects in the top Si layer. The samples were implanted with the surface covered with SiO2 capping layers of different thicknesses. The spectra measured from the as-implanted samples were fitted to a correlation length model taking into account the possible presence of stress effects in the spectra. This allowed quantification of both disorder effects, which are determined by structural defects, and residual stress in the top Si layer before annealing. These data were correlated to the density of dislocations remaining in the layer after annealing. The analysis performed corroborates the existence of two mechanisms that generate defects in the top Si layer that are related to surface conditions during implantation and the proximity of the top Si/buried oxide layer interface to the surface before annealing.

Generational effects on adult height in individual heterogeneity

As adult height is a well-established retrospective measure of health and standard of living, it is important to understand the factors that determine it. Among them, the influence of socio-environmental factors has been subjected to empirical scrutiny. This paper explores the influence of generational (or environmental) effects and individual and gender-specific heterogeneity on adult height. Our data set is from contemporary Spain, a country governed by an authoritarian regime between 1939 and 1977. First, we use normal position and quantile regression analysis to identify the determinants of self-reported adult height and to measure the influence of individual heterogeneity. Second, we use a Blinder-Oaxaca decomposition approach to explain the `gender height gap¿ and its distribution, so as to measure the influence on this gap of individual heterogeneity. Our findings suggest a significant increase in adult height in the generations that benefited from the country¿s economic liberalization in the 1950s, and especially those brought up after the transition to democracy in the 1970s. In contrast, distributional effects on height suggest that only in recent generations has ¿height increased more among the tallest¿. Although the mean gender height gap is 11 cm, generational effects and other controls such as individual capabilities explain on average roughly 5% of this difference, a figure that rises to 10% in the lowest 10% quantile.

Fitodisponibilidade de cobre e produção de matéria seca por plantas de milho em resposta à aplicação de dejetos de suínos

Os resíduos da produção de suínos têm grande potencial como condicionadores químicos de solos para a produção vegetal. O objetivo deste trabalho foi avaliar: (a) a produção de matéria seca pela cultura do milho após a adição de dejeto de suínos e de doses crescentes de Cu; (b) como os teores de Cu e de matéria orgânica no solo podem interferir na absorção e translocação deste elemento para a parte aérea do milho. Este estudo foi realizado em casa de vegetação da Universidade Estadual de Maringá (UEM). O milho foi cultivado em amostra de um Latossolo Vermelho eutroférrico textura argilosa, com dois teores de matéria orgânica (34,09 e 8,60 g dm-3 provenientes de duas profundidades de coleta). O experimento foi constituído de 14 tratamentos: solo com dois teores de matéria orgânica submetidos a sete tratamentos: testemunha, dejeto de suíno; NPK + dejeto de suíno; NPK + dejeto de suíno + 100 mg dm-3 de Cu; NPK + dejeto de suíno + 200 mg dm-3 de Cu; NPK + dejeto de suíno + 300 mg dm-3 de Cu; NPK + dejeto de suíno + 400 mg dm-3 de Cu. A dose de dejeto de suíno aplicada foi igual para todos os tratamentos e equivalente a 120.000 L ha-1. Constatou-se que o teor de matéria orgânica do solo influenciou na produção de matéria seca da parte aérea do milho. As raízes absorveram parte do excesso de Cu adicionado, mas não houve translocação do elemento, na mesma proporção, para a parte aérea.

Low-dose, simple, and fast grating-based X-ray phase-contrast imaging.

Phase sensitive X-ray imaging methods can provide substantially increased contrast over conventional absorption-based imaging and therefore new and otherwise inaccessible information. The use of gratings as optical elements in hard X-ray phase imaging overcomes some of the problems that have impaired the wider use of phase contrast in X-ray radiography and tomography. So far, to separate the phase information from other contributions detected with a grating interferometer, a phase-stepping approach has been considered, which implies the acquisition of multiple radiographic projections. Here we present an innovative, highly sensitive X-ray tomographic phase-contrast imaging approach based on grating interferometry, which extracts the phase-contrast signal without the need of phase stepping. Compared to the existing phase-stepping approach, the main advantages of this new method dubbed "reverse projection" are not only the significantly reduced delivered dose, without the degradation of the image quality, but also the much higher efficiency. The new technique sets the prerequisites for future fast and low-dose phase-contrast imaging methods, fundamental for imaging biological specimens and in vivo studies.

Deciding the sale of a life policy in the viatical market: Implications on individual welfare

[cat] En aquest article, es presenta un model econòmic que permet determinar la venda o no d'una pòlissa de vida (total o en part) per part d'un assegurat malalt terminal en el mercat dels viatical settlements. Aquest mercat va aparèixer a finals de la dècada dels 80 a conseqüència de l'epidèmia de la SIDA. Actualment, representa una part del mercat dels life settlements. Les pòlisses que es comercialitzen en el mercat dels viaticals són aquelles on l'assegurat és malalt terminal amb una esperança de vida de dos anys o menys. El model és discret i considera només dos períodes (anys), ja que aquesta és la vida residual màxima que contempla el mercat. L'agent posseix una riquesa inicial que ha de repartir entre consum i herència. S'introdueix en primer lloc la funció d'utilitat esperada del decisor i, utilitzant programació dinàmica, es dedueix l'estratègia que reporta una utilitat més gran (no vendre/vendre (en part) la pòlissa en el moment zero/vendre (en part) la pòlissa en el moment ú). L'òptim depèn del preu de la pòlissa venuda i de paràmetres personals de l'individu. Es troba una expressió analítica per l'estratègia òptima i es realitza un anàlisi de sensibilitat.