A pharmacokinetic-pharmacodynamic model for duodenal levodopa infusion

Objective Levodopa in presence of decarboxylase inhibitors is following two-compartment kinetics and its effect is typically modelled using sigmoid Emax models. Pharmacokinetic modelling of the absorption phase of oral distributions is problematic because of irregular gastric emptying. The purpose of this work was to identify and estimate a population pharmacokinetic- pharmacodynamic model for duodenal infusion of levodopa/carbidopa (Duodopa®) that can be used for in numero simulation of treatment strategies. Methods The modelling involved pooling data from two studies and fixing some parameters to values found in literature (Chan et al. J Pharmacokinet Pharmacodyn. 2005 Aug;32(3-4):307-31). The first study involved 12 patients on 3 occasions and is described in Nyholm et al. Clinical Neuropharmacology 2003:26:156-63. The second study, PEDAL, involved 3 patients on 2 occasions. A bolus dose (normal morning dose plus 50%) was given after a washout during night. Plasma samples and motor ratings (clinical assessment of motor function from video recordings on a treatment response scale between -3 and 3, where -3 represents severe parkinsonism and 3 represents severe dyskinesia.) were repeatedly collected until the clinical effect was back at baseline. At this point, the usual infusion rate was started and sampling continued for another two hours. Different structural absorption models and effect models were evaluated using the value of the objective function in the NONMEM package. Population mean parameter values, standard error of estimates (SE) and if possible, interindividual/interoccasion variability (IIV/IOV) were estimated. Results Our results indicate that Duodopa absorption can be modelled with an absorption compartment with an added bioavailability fraction and a lag time. The most successful effect model was of sigmoid Emax type with a steep Hill coefficient and an effect compartment delay. Estimated parameter values are presented in the table. Conclusions The absorption and effect models were reasonably successful in fitting observed data and can be used in simulation experiments.

Arbetslöshet som en icke önskvärd konsekvens av socialbidrag : Resultat från en tidsserieanalys på befolkningsnivå i Sverige 1946–1990

Unemployment as an unintended consequence of social assistance recipiency: results from a time-series analysis of aggregated population data Does the frequency of unemployment have a tendency to increase the number of social assistance recipients, or does the relationship work the other way around? This article utilizes Swedish annual data on aggregated unemployment and means-tested social assistance recipiency in the period 1946–1990 and proposes a multiple time-series approach based on vector error-correction modelling to establish the direction of influence. First, we show that rates of unemployment and receipt of social assistance is co-integrated. Second, we demonstrate that adjustments to the long-run equilibrium are made through adjustments of the unemployment. This indicates that the level of unemployment reacts to changes in rates of social assistance recipiency rather than vice versa. It is also shown that lagged changes in the level of unemployment do not predict changes in rates of social assistance recipients in short-term. Together these findings demonstrate that the number of social assistance recipients does increase the number of unemployed in a period characterized by low unemployment and high employment.

Condição ocular dos indivíduos facectomizados na região centro-oeste do estado de São Paulo: estudo populacional

OBJETIVO: Avaliar as causas de baixa visão e cegueira em indivíduos facectomizados, de amostra da população de cidades da região centrooeste do estado de São Paulo. Métodos: Estudo transversal, observacional, feito em cinco cidades da região centro-oeste do estado de São Paulo, em amostra domiciliar e baseada nos dados do último Censo Demográfico (IBGE, 1995), com escolha sistemática dos domicílios. Foi considerada para o presente estudo uma subamostra de indivíduos facectomizados, dos quais foram obtidos dados de identificação e exame oftalmológico completo. Os dados foram avaliados por estatísticas descritivas, análise de freqüência de ocorrência e proporção de concordância, com intervalo de confiança de 95%. RESULTADOS: Dos indivíduos amostrados, 2,37% haviam sido submetidos à facectomia. Dos 201 olhos operados, 26,9% apresentavam acuidade visual compatível com cegueira ou deficiência visual. Com a melhor correção óptica, a acuidade visual permaneceu <0,3 em 19,0%. O exame refracional proporcionou melhora da acuidade visual para 27,9% dos indivíduos facectomizados. As causas de baixa visão foram os erros refrativos não corrigidos, opacidade de cápsula posterior (19,4%), ceratopatia bolhosa (8,3%) coriorretinite cicatricial (8,3%), afacia (8,3%), degeneração macular relacionada a idade (5,5%), leucoma (5,5%), glaucoma (5,5%), atrofia de papila (5,5,%), descolamento de retina (2,8%), atrofia de epitelio pigmentado da retina (2,8%) e alta miopia (2,8%). CONCLUSÃO: Apesar da catarata ser causa de cegueira que pode ser evitável, mesmo após a correção cirúrgica porcentagem expressiva de indivíduos permanece com baixa visão, em geral, em decorrência de fatores relacionados ao seguimento pós-operatório negligenciado.

Prevalence and causes of visual impairment in a Brazilian population: The Botucatu Eye Study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Safety illusion and error trap in a collectively-operated machine accident

Workplace accidents involving machines are relevant for their magnitude and their impacts on worker health. Despite consolidated critical statements, explanation centered on errors of operators remains predominant with industry professionals, hampering preventive measures and the improvement of production-system reliability. Several initiatives were adopted by enforcement agencies in partnership with universities to stimulate production and diffusion of analysis methodologies with a systemic approach. Starting from one accident case that occurred with a worker who operated a brake-clutch type mechanical press, the article explores cognitive aspects and the existence of traps in the operation of this machine. It deals with a large-sized press that, despite being endowed with a light curtain in areas of access to the pressing zone, did not meet legal requirements. The safety devices gave rise to an illusion of safety, permitting activation of the machine when a worker was still found within the operational zone. Preventive interventions must stimulate the tailoring of systems to the characteristics of workers, minimizing the creation of traps and encouraging safety policies and practices that replace judgments of behaviors that participate in accidents by analyses of reasons that lead workers to act in that manner.

The center of the incisive papilla for the selection of complete denture maxillary anterior teeth in 4 racial groups

Objectives: To evaluate the use of the center of the incisive papilla as a guide for the selection of the proper width of maxillary dentures in 4 racial groups. Method and Materials: One hundred sixty stone casts were obtained from impressions of the maxillary arch of white, black, mixed, and Asian subjects. The occlusal surfaces of the casts were photocopied and the images placed on a digitizer. The most anterior and posterior points of the papilla and cusp tips of the canines were digitized. Dentofacial Planner Plus software was used to calculate the distance from a line passing through the cusp tips of the canines to the center of the papilla, defined as the midpoint of the anterior and posterior points of the papilla. The selection error (in millimeters) due to the clinical application of the method of the incisive papilla was calculated and analyzed. Results: In all studied racial groups, there was no coincidence between the center of the incisive papilla and the canine line. The utilization of the center of the papilla would lead to the selection of wider artificial teeth. In 24.9% of the white, 19.3% of the mixed, 32.9% of the black, and 15.5% of the Asian populations, errors greater than 4 mm would be present with the utilization of the papilla. Conclusion: The method of the center of the incisive papilla is not accurate, but may aid in initial artificial teeth selection for the racial groups studied. (Quintessence Int 2008;39:841-845)

Adaptação da máscara do analisador de gases VO2000 para mensuração de parâmetros cardiorrespiratórios em natação

O objetivo do presente estudo foi desenvolver um snorquel (SNQ) de baixo custo para mensuração de parâmetros cardiorrespiratórios em natação. Para isso, a máscara do analisador de gases VO2000 (MASC) foi adaptada a um SNQ desenvolvido artesanalmente com espaço morto de 250ml. Oito participantes foram submetidos a dois testes incrementais (TI) em cicloergômetro utilizando a MASC e o SNQ. Os TI foram realizados até a exaustão voluntária e foram compostos por estágios de 3min com carga inicial e incrementos de 35W. em ambas as situações, amostras gasosas foram coletadas em intervalos de 10s para determinação dos volumes de oxigênio (VO2), gás carbônico (VCO2), ventilatório (VE) e mensuração da freqüência cardíaca (FC). A comparação dos parâmetros cardiorrespiratórios (VO2, VE, VCO2 e FC) mensurados com o SNQ e a MASC foi realizada com o teste t de Student para amostras dependentes, enquanto que o teste de correlação de Pearson e a análise gráfica de Bland e Altman foram utilizados para verificar as associações e concordância entre parâmetros. em todos os casos, o nível de significância foi de P < 0,05. A adequação das equações de correção para os valores provenientes do SNQ foi verificada pelos erros sistemáticos (bias), aleatórios (precisão) e acurácia (ac). Não foram observadas diferenças significativas entre os valores de VO2, VCO2 e FC obtidos com a MASC e SNQ. Os valores de VE mensurados com o SNQ foram significativamente superiores aos obtidos com a MASC. No entanto, todos os parâmetros apresentaram elevada concordância e coeficiente de correlação (0,88 a 0,97). Além disso, foram verificados reduzidos valores de bias (VO2 = 0,11L/min; VE = 4,11L/min; VCO2 = 0,54L/min; 8,87bpm), precisão (VO2 = 0,24L/min; VE = 11,02L/ min; VCO2 = 0,18L/min; 7,42bpm) e ac (VO2 = 0,27L/min; VE = 11,76L/min; VCO2 = 0,56L/min; 11,56bpm). Desse modo, pode-se concluir que o SNQ desenvolvido neste estudo possibilita a mensuração válida de parâmetros cardiorrespiratórios em natação.

Errors due to the tropospheric and ionospheric effects on the geographic location of data collection platforms

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The symmetry group of Z(q)(n) in the Lee space and the Z(qn)-linear codes

The Z(4)-linearity is a construction technique of good binary codes. Motivated by this property, we address the problem of extending the Z(4)-linearity to Z(q)n-linearity. In this direction, we consider the n-dimensional Lee space of order q, that is, (Z(q)(n), d(L)), as one of the most interesting spaces for coding applications. We establish the symmetry group of Z(q)(n) for any n and q by determining its isometries. We also show that there is no cyclic subgroup of order q(n) in Gamma(Z(q)(n)) acting transitively in Z(q)(n). Therefore, there exists no Z(q)n-linear code with respect to the cyclic subgroup.

Using error bounds to compare aggregated generalized transportation models

A comparative study of aggregation error bounds for the generalized transportation problem is presented. A priori and a posteriori error bounds were derived and a computational study was performed to (a) test the correlation between the a priori, the a posteriori, and the actual error and (b) quantify the difference of the error bounds from the actual error. Based on the results we conclude that calculating the a priori error bound can be considered as a useful strategy to select the appropriate aggregation level. The a posteriori error bound provides a good quantitative measure of the actual error.