Constructing robust and efficient experimental designs in groundwater modeling using a Galerkin method, proper orthogonal decomposition, and metaheuristic algorithms.

Estimating parameters accurately in groundwater models for aquifers is challenging because the models are non-explicit solutions of complex partial differential equations. Modern research methods, such as Monte Carlo methods and metaheuristic algorithms, for searching an efficient design to estimate model parameters require hundreds, if not thousands of model calls, making the computational cost prohibitive. One method to circumvent the problem and gain valuable insight on the behavior of groundwater is to first apply a Galerkin method and convert the system of partial differential equations governing the flow to a discrete problem and then use a Proper Orthogonal Decomposition to project the high-dimensional model space of the original groundwater model to create a reduced groundwater model with much lower dimensions. The reduced model can be solved several orders of magnitude faster than the full model and able to provide an accurate estimate of the full model. The task is still challenging because the optimization problem is non-convex, non-differentiable and there are continuous variables and integer-valued variables to optimize. Following convention, heuristic algorithms and a combination is used search to find efficient designs for the reduced groundwater model using various optimality criteria. The main goals are to introduce new design criteria and the concept of design efficiency for experimental design research in hydrology. The two criteria have good utility but interestingly, do not seem to have been implemented in hydrology. In addition, design efficiency is introduced. Design efficiency is a method to assess how robust a design is under a change of criteria. The latter is an important issue because the design criterion may be subjectively selected and it is well known that an optimal design can perform poorly under another criterion. It is thus desirable that the implemented design has relatively high efficiencies under a few criteria. As applications, two heuristic algorithms are used to find optimal designs for a small synthetic aquifer design problem and a design problem for a large-scale groundwater model and assess their robustness properties to other optimality criteria. The results show the proof of concept is workable for finding a more informed and efficient model-based design for a water resource study.

Molecular characterization of patient-derived human pancreatic tumor xenograft models for preclinical and translational development of cancer therapeutics.

Preclinical evaluation of novel cancer agents requires models that accurately reflect the biology and molecular characteristics of human tumors. Molecular profiles of eight pancreatic ductal adenocarcinoma patient tumors were compared to corresponding passages of xenografts obtained by grafting tumor fragments into immunocompromised mice. Molecular characterization was performed by copy number analysis, gene expression and microRNA microarrays, mutation analysis, short tandem repeat (STR) profiling, and immunohistochemistry. Xenografts were found to be highly representative of their respective tumors, with a high degree of genetic stability observed by STR profiling and mutation analysis. Copy number variation (CNV) profiles of early and late xenograft passages were similar, with recurrent losses on chromosomes 1p, 3p, 4q, 6, 8p, 9, 10, 11q, 12p, 15q, 17, 18, 20p, and 21 and gains on 1q, 5p, 8q, 11q, 12q, 13q, 19q, and 20q. Pearson correlations of gene expression profiles of tumors and xenograft passages were above 0.88 for all models. Gene expression patterns between early and late passage xenografts were highly stable for each individual model. Changes observed in xenograft passages largely corresponded to human stromal compartment genes and inflammatory processes. While some differences exist between the primary tumors and corresponding xenografts, the molecular profiles remain stable after extensive passaging. Evidence for stability in molecular characteristics after several rounds of passaging lends confidence to clinical relevance and allows for expansion of models to generate the requisite number of animals required for cohorts used in drug screening and development studies.

Avaliação da acuidade visual em escolares no município de Herval d'Oeste, Santa Catarina, Brasil / Visual acuity assessment in schoolchildren in the municipality of Herval d'Oeste, Santa Catarina state, Brazil / Evaluación de la agudeza visual en estudiantes en el municipio de Herval d'Oeste, Santa Catarina, Brasil

Objetivos: Avaliar a acuidade visual por meio da aplicação de um teste de triagem, identificar a prevalência de baixa visão e providenciar o seu manejo adequado. Métodos: Estudo quantitativo e transversal, no qual foram avaliados escolares de 1ª a 5ª série do ensino fundamental de duas escolas municipais de Herval d'Oeste-SC, no segundo semestre de 2011, por meio da aplicação de um questionário com as variáveis: sexo, idade, uso prévio de óculos, percepção da própria visão e pela aplicação do Teste de Snellen para levantar medidas de acuidade visual (AV). Os alunos que apresentaram AV <0,7 e sinais e sintomas de alteração ocular foram encaminhados para exame oftalmológico. Resultados: A amostragem foi de 318 alunos: 158 (49,6%) do sexo masculino e 160 (50,3%) do sexo feminino, com idade entre 5 e 15 anos. Desses, 30 alunos apresentaram baixa acuidade visual e foram encaminhados ao atendimento oftalmológico, sendo que 24 crianças compareceram às consultas oftalmológicas e, destas, 19 (79,16%) necessitaram de correção óptica. Os diagnósticos mais prevalentes foram: astigmatismo, hipermetropia e miopia. Conclusão: A detecção da baixa visão na população escolar por meio de testes de triagem é importante tarefa de promoção da saúde e estratégia eficaz à prevenção de distúrbios visuais, os quais podem interferir no desenvolvimento intelectual, psicológico e social. Deve-se considerar a efetiva implantação dos programas e ações de promoção da saúde por meio da integração entre saúde, educação e comunidade.

Objectives: To evaluate visual acuity through the application of a screening test; identify the prevalence of low vision; and provide proper management to it. Methods: A cross-sectional and quantitative study in which first-to-fifth grade students of two elementary schools in the municipality of Herval d'Oeste were evaluated in the second half of 2011, by means of a questionnaire with the following variables: gender, age, previous use of glasses, perception of their own vision, and application of the Snellen Test to assess visual acuity (VA). Students presenting VA<0.7 and signs and symptoms of ocular disorders were referred to an ophthalmologist. Results: The sample comprised 318 students: 158 (49.6%) males and 160 (50.3%) females, between 5 and 15 years old. Thirty of these students showed low visual acuity and were referred to eye care, and 24 children attended ophthalmic examinations - 19 (79.16%) needed optical correction. The most prevalent diagnoses were astigmatism, hyperopia, and myopia. Conclusion: The detection of low vision among schoolchildren through screening tests is an important task of health promotion and an effective strategy to prevent visual disorders, which can interfere with intellectual, psychological and social development. The effective implementation of programs and actions to promote health through the integration of health, education and community should be considered.

Objetivos: Evaluar la agudeza visual mediante la aplicación de una prueba de selección, identificar la prevalencia de la baja visión y proporcionar bases para su adecuado tratamiento. Métodos: Estudio cuantitativo y transversal en el que fueron evaluados estudiantes de primero a quinto año de educación primaria en dos escuelas de Herval d'Oeste-SC, en el segundo semestre de 2011, mediante la aplicación de un cuestionario con las siguientes variables: sexo, edad, uso previo de anteojos, percepción de su propia visión y aplicación de la prueba de Snellen de agudeza visual (AV). Los estudiantes que presentaron AV <0,7 y signos y síntomas de problemas visuales fueron remitidos a un oftalmólogo. Resultados: La muestra fue de 318 alumnos: 158 (49,6%) varones y 160 (50,3%) mujeres, con edades comprendidas entre 5 y 15 años. De éstos, 30 estudiantes presentaron agudeza visual baja y fueron remitidos a la atención oftalmológica, siendo que 24 niños asistieron a los exámenes oftalmológicos y, de éstos, 19 (79,16%) requirieron corrección óptica. Los diagnósticos más frecuentes fueron astigmatismo, hipermetropía y miopía. Conclusión: La detección de baja visión a través de pruebas de selección es una tarea importante de promoción de la salud y una estrategia efectiva para prevenir alteraciones visuales que pueden interferir con el desarrollo intelectual, psicológico y social de los estudiantes. Se debe tener en cuenta la aplicación efectiva de los programas y acciones de promoción de la salud a través de la integración entre salud, educación y comunidad.

Comparative profiling of primary colorectal carcinomas and liver metastases identifies LEF1 as a prognostic biomarker.

PURPOSE: We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC). PATIENTS AND METHODS: We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) to identify genes differentially expressed between these two groups. To characterize the clinical relevance of two highly-ranked differentially-expressed genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC. RESULTS: Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to primary CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP1 and LEF1 protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF1 (chi-square p = 0.042), but not SPP1 (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF1 (p<0.01), but not SPP1 (p = 0.11). Both univariate and multivariate analyses identified stage (p<0.0001) and LEF1 overexpression (p<0.05) as important prognostic markers, but not tumor grade or SPP1. CONCLUSION: Among genes differentially expressed between CLM and primary CRC, we demonstrate overexpression of LEF1 in primary CRC to be a prognostic factor for poor survival and increased risk for liver metastasis.

A combinatorial optimization scheme for parameter structure identification in ground water modeling.

This research develops a methodology for parameter structure identification in ground water modeling. For a given set of observations, parameter structure identification seeks to identify the parameter dimension, its corresponding parameter pattern and values. Voronoi tessellation is used to parameterize the unknown distributed parameter into a number of zones. Accordingly, the parameter structure identification problem is equivalent to finding the number and locations as well as the values of the basis points associated with the Voronoi tessellation. A genetic algorithm (GA) is allied with a grid search method and a quasi-Newton algorithm to solve the inverse problem. GA is first used to search for the near-optimal parameter pattern and values. Next, a grid search method and a quasi-Newton algorithm iteratively improve the GA's estimates. Sensitivities of state variables to parameters are calculated by the sensitivity-equation method. MODFLOW and MT3DMS are employed to solve the coupled flow and transport model as well as the derived sensitivity equations. The optimal parameter dimension is determined using criteria based on parameter uncertainty and parameter structure discrimination. Numerical experiments are conducted to demonstrate the proposed methodology, in which the true transmissivity field is characterized by either a continuous distribution or a distribution that can be characterized by zones. We conclude that the optimized transmissivity zones capture the trend and distribution of the true transmissivity field.