A new method for the estimation of variance matrix with prescribed zeros in nonlinear mixed effects models

We propose a new method for the Maximum Likelihood Estimator (MLE) of nonlinear mixed effects models when the variance matrix of Gaussian random effects has a prescribed pattern of zeros (PPZ). The method consists in coupling the recently developed Iterative Conditional Fitting (ICF) algorithm with the Expectation Maximization (EM) algorithm. It provides positive definite estimates for any sample size, and does not rely on any structural assumption on the PPZ. It can be easily adapted to many versions of EM.Comment: Accepted for publication in Statistics and Computin

Automatic text classification of drug-induced liver injury using document-term matrix and XGBoost

Introduction: Regulatory agencies generate a vast amount of textual data in the review process. For example, drug labeling serves as a valuable resource for regulatory agencies, such as U.S. Food and Drug Administration (FDA) and Europe Medical Agency (EMA), to communicate drug safety and effectiveness information to healthcare professionals and patients. Drug labeling also serves as a resource for pharmacovigilance and drug safety research. Automated text classification would significantly improve the analysis of drug labeling documents and conserve reviewer resources. Methods: We utilized artificial intelligence in this study to classify drug-induced liver injury (DILI)-related content from drug labeling documents based on FDA’s DILIrank dataset. We employed text mining and XGBoost models and utilized the Preferred Terms of Medical queries for adverse event standards to simplify the elimination of common words and phrases while retaining medical standard terms for FDA and EMA drug label datasets. Then, we constructed a document term matrix using weights computed by Term Frequency-Inverse Document Frequency (TF-IDF) for each included word/term/token. Results: The automatic text classification model exhibited robust performance in predicting DILI, achieving cross-validation AUC scores exceeding 0.90 for both drug labels from FDA and EMA and literature abstracts from the Critical Assessment of Massive Data Analysis (CAMDA). Discussion: Moreover, the text mining and XGBoost functions demonstrated in this study can be applied to other text processing and classification tasks

Sward structure of marandu palisadegrass subjected to continuous stocking and nitrogen-induced rhythms of growth

Acceleration of the growth rhythm of plants using nitrogen fertiliser alters the rates of physiological processes like growth and senescence and may cause significant changes in sward structure, interfering with plant and animal responses. The objective of this experiment was to evaluate sward structure of marandu palisadegrass (Brachiaria brizantha) maintained at 30 cm under continuous stocking and subjected to contrasting rhythms of growth from January 2007 to April 2008. These were generated using or not nitrogen fertiliser, and comprised four experimental treatments as follows: control (non-fertilised), 150, 300 and 450 kg ha-1 of N. Acceleration of the growth rhythm of plants was associated with increases in leaf and stem bulk density, and resulted in larger LAI and total bulk density on swards subjected to faster (fertilised with 300 and 450 kg ha-1 of N) than those subjected to slower rhythms of growth (non-fertilised or fertilised with 150 kg ha-1 of N). Variations in dead material bulk density were associated with seasonal variations in climatic conditions, and were not influenced by growth rhythms. During autumn/winter and early spring (dry period of the year) swards subjected to faster, relative to those subjected to slower rhythms of growth, had larger proportion of leaves on the top horizons. On the other hand, sward structure did not vary among rhythms of growth at times of the year when there was no limitation in the availability of climatic growth factors (late spring and summer), indicating that when control of the grazing process is efficient, changes in sward structure are basically a function of seasonal variations in climatic growth conditions and phenological state of plants.A aceleração do ritmo de crescimento das plantas por meio da adubação nitrogenada altera a velocidade dos processos fisiológicos, atuando sobre o crescimento e a senescência, podendo refletir-se em alterações importantes sobre a estrutura do dossel. Avaliou-se a estrutura do dossel forrageiro de pastos de capim-marandu (Brachiaria brizantha) mantidos a 30 cm de altura por meio de lotação contínua e submetidos a ritmos de crescimento contrastantes de janeiro de 2007 a abril de 2008. Os distintos ritmos de crescimento foram criados por meio da utilização de adubação nitrogenada, segundo os tratamentos: sem adubação (controle), 150, 300 e 450 kg ha-1 de N. A aceleração do ritmo de crescimento dos pastos resultou em aumentos de densidade volumétrica de folhas e de colmos, refletindo em maior IAF e densidade volumétrica total em pastos submetidos aos ritmos de crescimento mais acelerados (adubados com 300 e 450 kg ha-1 de N) relativamente àqueles submetidos a ritmos de crescimento mais lentos (pastos não adubados e/ou adubados com 150 kg ha-1 de N). Variações em densidade volumétrica do material morto estiveram associadas a flutuações estacionais das condições climáticas, e não foram influenciadas pelos ritmos de crescimento avaliados. Na época da seca (outono/inverno e início de primavera), os pastos submetidos aos ritmos de crescimento mais acelerados apresentaram maior proporção de folhas no horizonte superior do dossel. Por outro lado, a estrutura do dossel não variou entre os ritmos de crescimento nas épocas de maior disponibilidade de fatores de crescimento (final de primavera e verão), indicando que quando o controle do processo de pastejo é feito de maneira eficiente, mudanças em estrutura são função basicamente de variações estacionais em condições climáticas e estádio fenológico das plantas

Estimation of (co)variance components and genetic parameters for weights of red-winged tinamou using random regression models

The objective of this work was to determine genetic parameters for body weight of tinamou in captivity. It was used random regression models in analyses of data by considering the direct additive genetic (DA) and permanent environmental effects of the animal (PE) as random effects. Residual variances were modeled by using a fifth-order variance function. The mean population growth curve was fitted by sixth-order Legendre orthogonal polynomials. Direct additive genetic effects and animal environmental permanent effect were modeled by using Legendre polynomials of order two to nine. The best results were obtained by models with orders of fit of 6 for direct additive genetic effect and of order 3 for permanent effect by Akaike information criterion and of order 3 for both additive genetic effect and permanent effect by Schwarz Bayesian information criterion and likelihood ratio test. Heritability estimates ranged from 0.02 to 0.57. The first eigenvalue explained 94% and 90% of the variation from additive direct and permant environmental effects, respectively. Selection of tinamou for body weight is more effective after 112 days of age.Com este trabalho objetivou-se determinar parâmetros genéticos para peso corporal de perdizes em cativeiro. Foram utilizados modelos de regressão aleatória na análise dos dados considerando os efeitos genéticos aditivos diretos (AD) e de ambiente permanente de animal (AP) como aleatórios. As variâncias residuais foram modeladas utilizando-se funções de variância de ordem 5. A curva média da população foi ajustada por polinômios ortogonais de Legendre de ordem 6. Os efeitos genéticos aditivos diretos e de ambiente permanente de animal foram modelados utilizando-se polinômios de Legendre de segunda a nona ordem. Os melhores resultados foram obtidos pelos modelos de ordem 6 de ajuste para os efeitos genéticos aditivos diretos e de ordem 3 para os de ambiente permanente pelo Critério de Informação de Akaike e ordem 3 para ambos os efeitos pelos Critério de Informação Bayesiano de Schwartz e Teste de Razão de Verossimilhança. As herdabilidades estimadas variaram de 0,02 a 0,57. O primeiro autovalor respondeu por 94 e 90% da variação decorrente de efeitos aditivos diretos e de ambiente permanente, respectivamente. A seleção de perdizes para peso corporal é mais efetiva a partir de 112 dias de idade