Pedal : identification of models for duodenal administration of levodopa

Backgound and aims: The main purpose of the PEDAL study is to identify and estimate sample individual pharmacokinetic- pharmacodynamic (PK/PD) models for duodenal infusion of levodopa/carbidopa (Duodopa®) that can be used for in numero simulation of treatment strategies. Other objectives are to study the absorption of Duodopa® and to form a basis for power calculation for a future larger study. PK/PD based on oral levodopa is problematic because of irregular gastric emptying. Preliminary work with data from [Gundert-Remy U et al. Eur J Clin Pharmacol 1983;25:69-72] suggested that levodopa infusion pharmacokinetics can be described by a two-compartment model. Background research led to a hypothesis for an effect model incorporating concentration-unrelated fluctuations, more complex than standard E-max models. Methods: PEDAL involved a few patients already on Duodopa®. A bolus dose (normal morning dose plus 50%) was given after a washout during night. Data collection continued until the clinical effect was back at baseline. The procedure was repeated on two non-consecutive days per patient. The following data were collected in 5 to 15 minutes intervals: i) Accelerometer data. ii) Three e-diary questions about ability to walk, feelings of “off” and “dyskinesia”. iii) Clinical assessment of motor function by a physician. iv) Plasma concentrations of levodopa, carbidopa and the metabolite 3-O-methyldopa. The main effect variable will be the clinical assessment. Results: At date of abstract submission, lab analyses were currently being performed. Modelling results, simulation experiments and conclusions will be presented in our poster.

Self-reported symptoms and motor tests via telemetry in a 36-month levodopa-carbidopa intestinal gel infusion trial

Objective To investigate if a home environment test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression. Background Seventy-seven patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study at 10 clinics in Sweden and Norway; 40 of them were treated with levodopa-carbidopa intestinal gel (LCIG) and 37 patients were candidates for switching from oral PD treatment to LCIG. They utilized a mobile device test battery, consisting of self-assessments of symptoms and objective measures of motor function through a set of fine motor tests (tapping and spiral drawings), in their homes. Both the LCIG-naïve and LCIG-non-naïve patients used the test battery four times per day during week-long test periods. Methods Assessments The LCIG-naïve patients used the test battery at baseline (before LCIG), month 0 (first visit; at least 3 months after intraduodenal LCIG), and thereafter quarterly for the first year and biannually for the second and third years. The LCIG-non-naïve patients used the test battery from the first visit, i.e. month 0. Out of the 77 patients, only 65 utilized the test battery; 35 were LCIG-non-naïve and 30 LCIG-naïve. In 20 of the LCIG-naïve patients, assessments with the test battery were available during oral treatment and at least one test period after having started infusion treatment. Three LCIG-naïve patients did not use the test battery at baseline but had at least one test period of assessments thereafter. Hence, n=23 in the LCIG-naïve group. In total, symptom assessments in the full sample (including both patient groups) were collected during 379 test periods and 10079 test occasions. For 369 of these test periods, clinical assessments including UPDRS and PDQ-39 were performed in afternoons at the start of the test periods. The repeated measurements of the test battery were processed and summarized into scores representing patients’ symptom severities over a test period, using statistical methods. Six conceptual dimensions were defined; four subjectively-reported: ‘walking’, ‘satisfied’, ‘dyskinesia’, and ‘off’ and two objectively-measured: ‘tapping’ and ‘spiral’. In addition, an ‘overall test score’ (OTS) was defined to represent the global health condition of the patient during a test period. Statistical methods Change in the test battery scores over time, that is at baseline and follow-up test periods, was assessed with linear mixed-effects models with patient ID as a random effect and test period as a fixed effect of interest. The within-patient variability of OTS was assessed using intra-class correlation coefficient (ICC), for the two patient groups. Correlations between clinical rating scores and test battery scores were assessed using Spearman’s rank correlations (rho). Results In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. However, there were no significant changes in mean OTS scores of LCIG-non-naïve patients, except for worse mean OTS at month 36 (p<0.01, n=16). The mean scores of all subjectively-reported dimensions improved significantly throughout the course of the study, except ‘walking’ at month 36 (p=0.41, n=4). However, there were no significant differences in mean scores of objectively-measured dimensions between baseline and other test periods, except improved ‘tapping’ at month 6 and month 36, and ‘spiral’ at month 3 (p<0.05). The LCIG-naïve patients had a higher within-subject variability in their OTS scores (ICC=0.67) compared to LCIG-non-naïve patients (ICC=0.71). The OTS correlated adequately with total UPDRS (rho=0.59) and total PDQ-39 (rho=0.59). Conclusions In this 3-year follow-up study of advanced PD patients treated with LCIG we found that it is possible to monitor PD progression over time using a home environment test battery. The significant improvements in the mean OTS scores indicate that the test battery is able to measure functional improvement with LCIG sustained over at least 24 months.

Fitting conditional and simultaneous autoregressive spatial models in hglm

We present a new version (> 2.0) of the hglm package for fitting hierarchical generalized linear models (HGLMs) with spatially correlated random effects. CAR() and SAR() families for conditional and simultaneous autoregressive random effects were implemented. Eigen decomposition of the matrix describing the spatial structure (e.g., the neighborhood matrix) was used to transform the CAR/SAR random effects into an independent, but eteroscedastic, Gaussian random effect. A linear predictor is fitted for the random effect variance to estimate the parameters in the CAR and SAR models. This gives a computationally efficient algorithm for moderately sized problems.

Does Gibrat’s Law hold for Swedish energy firms?

Gibrat's law predicts that firm growth is purely random and should be independent of firm size. We use a random effects-random coefficient model to test whether Gibrat's law holds on average in the studied sample as well as at the individual firm level in the Swedish energy market. No study has yet investigated whether Gibrat's law holds for individual firms, previous studies having instead estimated whether the law holds on average in the samples studied. The present results support the claim that Gibrat's law is more likely to be rejected ex ante when an entire firm population is considered, but more likely to be confirmed ex post after market selection has "cleaned" the original population of firms or when the analysis treats more disaggregated data. From a theoretical perspective, the results are consistent with models based on passive and active learning, indicating a steady state in the firm expansion process and that Gibrat's law is violated in the short term but holds in the long term once firms have reached a steady state. These results indicate that approximately 70 % of firms in the Swedish energy sector are in steady state, with only random fluctuations in size around that level over the 15 studied years.

Some benefits of cyclical monetary policy

In this paper, we present a simple random-matching model of seasons, where di§erent seasons translate into di§erent propensities to consume and produce. We Önd that the cyclical creation and destruction of money is beneÖcial for welfare under a wide variety of circumstances. Our model of seasons can be interpreted as providing support for the creation of the Federal Reserve System, with its mandate of supplying an elastic currency for the nation.

Microcrédito, emprego e renda: uma pesquisa empírica na ICC-BLUSOL/SC

Esta pesquisa objetivou analisar o impacto do microcrédito junto aos microempreendedores beneficiados pela Instituição de Microcrédito ICC-Blusol de Blumenau, Santa Catarina. De um total de 5.451 clientes foram selecionados e analisados 94, os quais obtiveram microcrédito durante os 10 últimos anos. Para testar a veracidade da afirmação, utilizou-se modelo econométrico utilizando a técnica de dados em painel, através da estimação das variáveis no modelo de efeitos fixos e efeitos aleatórios. Como variável independente utilizou-se a premissa "Valor do Empréstimo" e como variáveis dependentes "Vendas", "Resultado Operacional", "Garantia Real", "Garantia Aval", "Recursos Humanos", "Custos Fixos" e "Custos Variáveis". Conclui -se que somente as variáveis "Vendas" e "Resultado Operacional" validam a afirmação de que o acesso ao microcrédito resulta em incremento de Faturamento e Renda. A criação e manutenção de empregos, embora não tenha sido comprovada na análise estatística, ficou evidente, pois a simples sobrevivência da empresa já pressupõe isto.

Using common features to understand the behavior of metal-commodity prices and forecast them at different horizons

The objective of this article is to study (understand and forecast) spot metal price levels and changes at monthly, quarterly, and annual frequencies. Data consists of metal-commodity prices at a monthly and quarterly frequencies from 1957 to 2012, extracted from the IFS, and annual data, provided from 1900-2010 by the U.S. Geological Survey (USGS). We also employ the (relatively large) list of co-variates used in Welch and Goyal (2008) and in Hong and Yogo (2009). We investigate short- and long-run comovement by applying the techniques and the tests proposed in the common-feature literature. One of the main contributions of this paper is to understand the short-run dynamics of metal prices. We show theoretically that there must be a positive correlation between metal-price variation and industrial-production variation if metal supply is held fixed in the short run when demand is optimally chosen taking into account optimal production for the industrial sector. This is simply a consequence of the derived-demand model for cost-minimizing firms. Our empirical evidence fully supports this theoretical result, with overwhelming evidence that cycles in metal prices are synchronized with those in industrial production. This evidence is stronger regarding the global economy but holds as well for the U.S. economy to a lesser degree. Regarding out-of-sample forecasts, our main contribution is to show the benefits of forecast-combination techniques, which outperform individual-model forecasts - including the random-walk model. We use a variety of models (linear and non-linear, single equation and multivariate) and a variety of co-variates and functional forms to forecast the returns and prices of metal commodities. Using a large number of models (N large) and a large number of time periods (T large), we apply the techniques put forth by the common-feature literature on forecast combinations. Empirically, we show that models incorporating (short-run) common-cycle restrictions perform better than unrestricted models, with an important role for industrial production as a predictor for metal-price variation.

Inflation when the planner wants less spending

I study optima in a random-matching model of outside money. The examples in this paper show a conflict between private and collective interests. While the planner worry about the extensive and intensive margin effects of trades in a steady state, people want the exhaust the gains from trades immediately, i.e., once in a meeting, consumers prefer spend more for a better output than take the risk of saving money and wait for good meetings in the future. Thus, the conflict can force the planner to choose allocations with a more disperse money distribution, mainly if people are im- patient. When the patient rate is low enough, the planner uses a expansionary policy to generate a better distribution of money for future trades.

A Corrupção burocrática inibe o empreendedorismo? uma análise empírica dos estados brasileiros

This work aims to investigate the relationship between the entrepreneurship and the incidence of bureaucratic corruption in the states of Brazil and Federal District. The main hypothesis of this study is that the opening of a business in Brazilian states is negatively affected by the incidence of corruption. The theoretical reference is divided into Entrepreneurship and bureaucratic corruption, with an emphasis on materialistic perspective (objectivist) of entrepreneurship and the effects of bureaucratic corruption on entrepreneurial activity. By the regression method with panel data, we estimated the models with pooled data and fixed and random effects. To measure corruption, I used the General Index of Corruption for the Brazilian states (BOLL, 2010), and to represent entrepreneurship, firm entry per capita by state. Tests (Chow, Hausman and Breusch-Pagan) indicate that the random effects model is more appropriate, and the preliminary results indicate a positive impact of bureaucratic corruption on entrepreneurial activity, contradicting the hypothesis expected and found in previous articles to Brazil, and corroborating the proposition of Dreher and Gassebner (2011) that, in countries with high regulation, bureaucratic corruption can be grease in the wheels of entrepreneurship

Persistência na lactação para vacas da raça Holandesa criadas no Estado do Rio Grande do Sul via modelos de regressão aleatória

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Predição de valores genéticos para a produção de leite no dia do controle e para a produção acumulada até 305 dias

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito da endogamia sobre características de crescimento de bovinos da raça Gir no Brasil

Esta pesquisa foi conduzida com o objetivo de avaliar o efeito da endogamia e suas possíveis influências sobre o crescimento de bovinos de corte. Foram utilizadas 27.406 observações de peso à desmama, padronizado aos 205 dias (PD), e 14.317 informações de peso ao ano, padronizado aos 365 dias (PA), de animais da raça Gir, no período de 1970 a 1995. As análises foram feitas pelo método dos quadrados mínimos, incluindo-se o efeito aleatório de grupo contemporâneo e os efeitos fixos de geração (discreto), idade da vaca ao parto e taxa de endogamia do bezerro e da vaca como variáveis contínuas, considerando-se os efeitos linear e quadrático. Apenas 11,65% das vacas, 19,84% dos touros e 9,23% dos bezerros da raça Gir estudados apresentaram algum grau de endogamia e as estimativas das médias de endogamia foram de pequena magnitude, constatando-se valores de 1,04; 0,96; e 1,66% para vacas, touros e bezerros, respectivamente. O efeito da endogamia do animal foi significativo e quadrático para as duas características estudadas. Os resultados mostraram depressão endogâmica para ambas as características (PD e PA). Recomenda-se evitar os acasalamentos, intencionalmente, endogâmicos e monitorar os acasalamentos com base no parentesco entre os indivíduos, visando manter baixas as taxas de endogamia.

Estimativas de herdabilidade para perímetro escrotal de animais da raça Nelore

Estimaram-se parâmetros genéticos e de ambiente para perímetro escrotal ao sobreano (PE) de 9.355 animais da raça Nelore. Foram considerados no modelo o efeito aleatório de animal e os efeitos fixos de grupo contemporâneo (GC) e os efeitos linear e quadrático das covariáveis idade ao sobreano (IDS) e peso ao sobreano ajustado aos 550 dias de idade (PSAJ). O grupo contemporâneo foi definido pelas variáveis: ano, estação e fazenda de nascimento, grupo de manejo ao nascimento, desmama e sobreano. As estimativas de herdabilidade foram 0,42 ± 0,04, quando considerados PSAJ e IDS como covariáveis; 0,41± 0,04, considerando-se PSAJ como covariável; e 0,35 ± 0,03, com apenas IDS como covariável.

Modelagem e medições de ondas de rádio para predição de perda de propagação em ambientes urbanos

In this dissertation new models of propagation path loss predictions are proposed by from techniques of optimization recent and measures of power levels for the urban and suburban areas of Natal, city of Brazilian northeast. These new proposed models are: (i) a statistical model that was implemented based in the addition of second-order statistics for the power and the altimetry of the relief in model of linear losses; (ii) a artificial neural networks model used the training of the algorithm backpropagation, in order to get the equation of propagation losses; (iii) a model based on the technique of the random walker, that considers the random of the absorption and the chaos of the environment and than its unknown parameters for the equation of propagation losses are determined through of a neural network. The digitalization of the relief for the urban and suburban areas of Natal were carried through of the development of specific computational programs and had been used available maps in the Statistics and Geography Brazilian Institute. The validations of the proposed propagation models had been carried through comparisons with measures and propagation classic models, and numerical good agreements were observed. These new considered models could be applied to any urban and suburban scenes with characteristic similar architectural to the city of Natal

Photoinduced orientation in natural rubber

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)