Innovative Methods for Some Statistical Issues in Clinical Trials

Clinical trials have many different aspects to them, and here three topics will be explored: Bayesian sensitivity analysis in survival models, ROC methods in the presence of verification bias, and non-parametric adjustment of covariates in randomized clinical trial with and without missing data. The aim of the first paper is to develop several Bayesian influence measures to assess the influence of the prior, the sampling distribution, and individual observations in survival analysis with the presence of missing covariate data and describe these changes in a modified likelihood model (the perturbation model). We construct a Bayesian perturbation manifold to the perturbation model and calculate its associated geometric quantities and influence measures based on several objective functions to quantify the degree of various perturbations to statistical models. We carry out several simulation studies and analyze a real data set to illustrate the finite sample performance of our Bayesian influence method. While clinical trials concerned with survival track how long people will live given that they have the disease, some trials are concerned with using screeners to predict disease in the first place. Chronic obstructive pulmonary disease (COPD) affects 5% of the adult population in the United States, but a general screener has not been evaluated for the disease at a large scale. In this paper a COPD screener is evaluated using an innovative application of sampling weights. With these sampling weights, which help us adjust for verification bias, we explore the different variables to use in the screener. The optimal variable on the pocket screener was forced expiratory volume in 1 second as compared to peak expiratory flow. While screeners can help predict disease, mainly clinical trials are designed to evaluate treatments that cure disease or improve health outcomes. Non-parametric adjustment of covariates is an attractive methodology in the regulatory setting as it requires few assumptions. We develop methodology to estimate the treatment effect in a longitudinal logistic randomized trial after non-parametrically adjusting for covariates. We also develop methodology to estimate treatment effect when the outcome is ordinal (with more than two groups) instead of binary, when there is missing data among the baseline covariates, and when there are multiple treatment groups to be evaluated. This methodology and it’s extensions are applied to a data set evaluating Cushing’s disease and another data set evaluating multiple doses of a neurological disorder medication.Doctor of Philosoph

Emotional Eating and Diet-related Self-Efficacy, Motivation, and Norms in Adolescents

The objective of the current study was to examine the association between emotional eating and self-efficacy, motivation, and social norms for consumption of fruits and vegetables (F/V) and energy-dense, nutrient-poor (EDNP) foods and beverages, as well as interactions with body mass index-z score (BMI-z). Adolescents completed self-report measures of demographics, emotional eating, and dietary health behavior theory constructs. Emotional eating was associated with lower self-efficacy for consumption of F/V and for limiting EDNP foods/beverages; greater motivation for limiting of EDNP foods/beverages; lower social norms for consumption of F/V; and greater social norms for consumption of EDNP foods/beverages. There were no interactions with BMI-z. Evidence-based nutrition programs that leverage health behavior theories should be tailored to adolescents’ emotional eating

OCT-Documented Incision Features and Natural History of Clear Corneal Incisions Used for Bimanual Microincision Cataract Surgery

Use of anterior segment OCT to identify features and natural history of bimanual incisions used only for phacoemulsification and a main incision used only for intraocular lens insertion

Aplicación de la gestión por procesos para mejorar la satisfacción del cliente en el área de Fiscalización Minera de la Gerencia de Energía, Minas e Hidrocarburos La Libertad, 2018

La presente investigación titulada Aplicacion de la Gestión por procesos en la satisfacción del cliente en el área de fiscalización minera de la Gerencia de Energía, minas e Hidrocarburos, en el año 2018, enmarcado en las teorías de la gestión por procesos ayuda a mejorar los ámbitos de la gestión de la empresa y la satisfacción del cliente es un requisito indispensable para ganarse un lugar en la mente de los clientes; para lo cual empleó el método deductivo, con una investigación de tipo experimental, aplicándolo a una muestra de 384 clientes que ingresan al área de fiscalización minera, 1 jefe del área de fiscalización, 15 trabajadores del área de fiscalización y 5 procesos que se realizan en dicha area. Para lo cual empleó una entrevista, mapeo de procesos, diagrama de ishikawa y Pareto para el diagnostico, para el nivel de satisfacción se usó una encuesta, diagrama de flujo para el plan, y la misma encuesta para la satisfacción y evaluar el después. Obteniendo como principales resultados el nivel de satisfacción del cliente actual donde, se observó que el 24% están totalmente insatisfecho, el 74% insatisfecho y el nivel de la satisfacción de los clientes, después de la aplicación de la gestión por procesos, se observó que el 96% están satisfecho y el 4% medianamente satisfecho. La hipótesis planteada con la prueba estadística de T-student al dar un valor t = 133.925 y p = 0.000, el cual es menor que el 5%, por ello, se acepta la hipótesis alternativa, donde la Aplicación de la Gestión por Procesos si mejora la satisfacción del cliente en la Gerencia de Energía, minas e Hidrocarburos La Libertad, 2018

Evaluation of the ability of C. albicans to form biofilm in the presence of phage-resistant phenotypes of P. aeruginosa

Pseudomonas aeruginosa and Candida albicans are disparate microbial species, but both are known to be opportunistic pathogens frequently associated with nosocomial infections. The aim of this study was to provide a better understanding of the interactions between these microorganisms in dual-species biofilms. Several bacteriophage-resistant P. aeruginosa phenotypes have been isolated and were used in dual-species mixed-biofilm studies. Twenty-four and 48 h mixed-biofilms were formed using the isolated phenotypes of phage-resistant P. aeruginosa and these were compared with similar experiments using other P. aeruginosa strains with a defined lipopolysaccharide (LPS) deficiency based on chromosomal knockout of specific LPS biosynthetic genes. Overall, the results showed that the variants of phage-resistant P. aeruginosa and LPS mutants were both less effective in inhibiting the growth of C. albicans in mixed-biofilms compared to the wild-type strains of P. aeruginosa. Conversely, the proliferation of P. aeruginosa was not influenced by the presence of C. albicans. In conclusion, the ability of strains of P. aeruginosa to inhibit the formation of a biofilm of C. albicans appears to be correlated with the LPS chain lengths of phenotypes of P. aeruginosa, suggesting that LPS has a suppressive effect on the growth of C. albicans.D. P. P. acknowledges the grant from the project [PTDC/EBB-BIO/114760/2009] from the Portuguese Foundation for Science and Technology (FCT). J.S.L. holds a Canada Research Chair in Cystic Fibrosis and Microbial Glycobiology and research in his laboratory is supported by operating grants from Cystic Fibrosis Canada and the Canadian Institutes of Health Research (CIHR) [Grant MOP-14687]

Cumulative Risk Distribution for Interval Invasive Second Breast Cancers After Negative Surveillance Mammography.

The aim of the current study was to characterize the risk of interval invasive second breast cancers within 5 years of primary breast cancer treatment. We examined 65,084 surveillance mammograms from 18,366 women with a primary breast cancer diagnosis of unilateral ductal carcinoma in situ or stage I to III invasive breast carcinoma performed from 1996 to 2012 in the Breast Cancer Surveillance Consortium. Interval invasive breast cancer was defined as ipsilateral or contralateral cancer diagnosed within 1 year after a negative surveillance mammogram. Discrete-time survival models—adjusted for all covariates—were used to estimate the probability of interval invasive cancer, given the risk factors for each surveillance round, and aggregated across rounds to estimate the 5-year cumulative probability of interval invasive cancer

Characterization and functionality of proliferative human sertoli cells

It has long been thought that mammalian Sertoli cells are terminally differentiated and nondividing postpuberty. For most previous in vitro studies immature rodent testes have been the source of Sertoli cells and these have shown little proliferative ability when cultured. We have isolated and characterized Sertoli cells from human cadaveric testes from seven donors ranging from 12 to 36 years of age. The cells proliferated readily in vitro under the optimized conditions used with a doubling time of approximately 4 days. Nuclear 5-ethynyl-2´-deoxyuridine (EdU) incorporation confirmed that dividing cells represented the majority of the population. Classical Sertoli cell ultrastructural features, lipid droplet accumulation, and immunoexpression of GATA-4, Sox9, and the FSH receptor (FSHr) were observed by electron and fluorescence microscopy, respectively. Flow cytometry revealed the expression of GATA-4 and Sox9 by more than 99% of the cells, and abundant expression of a number of markers indicative of multipotent mesenchymal cells. Low detection of endogenous alkaline phosphatase activity after passaging showed that few peritubular myoid cells were present. GATA-4 and SOX9 expression were confirmed by reverse transcription polymerase chain reaction (RT-PCR), along with expression of stem cell factor (SCF), glial cell line-derived neurotrophic factor (GDNF), and bone morphogenic protein 4 (BMP4). Tight junctions were formed by Sertoli cells plated on transwell inserts coated with fibronectin as revealed by increased transepithelial electrical resistance (TER) and polarized secretion of the immunoregulatory protein, galectin-1. These primary Sertoli cell populations could be expanded dramatically in vitro and could be cryopreserved. The results show that functional human Sertoli cells can be propagated in vitro from testicular cells isolated from adult testis. The proliferative human Sertoli cells should have important applications in studying infertility, reproductive toxicology, testicular cancer, and spermatogenesis, and due to their unique biological properties potentially could be useful in cell therapy.Fil: Chui, Kitty. MandalMed Inc. ; Estados UnidosFil: Trivedi, Alpa. MandalMed Inc.; Estados Unidos. University of California; Estados UnidosFil: Cheng, C. Yan. Lonza Walkersville; Estados UnidosFil: Cherbavaz, Diana B.. MandalMed Inc.; Estados UnidosFil: Dazin, Paul F.. MandalMed; Estados UnidosFil: Huynh, Ai Lam Thu. MandalMed Inc.; Estados UnidosFil: Mitchel, James B.. Lonza Walkersville; Estados UnidosFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Noble Haeusslein, Linda J.. University of California; Estados UnidosFil: John, Constance M.. MandalMed Inc.; Estados Unido

Toxoplasma gondii en mujeres embarazadas en la provincia de El Oro, 2014 / Toxoplasma gondii in pregnant women in the province of El Oro, 2014

El objetivo de la presente investigación fue determinar los anticuerpos IgG- IgM de anti toxoplasma gondii en mujeres embarazadas, atendidas en una casa de salud privada, siendo el principal reservorio de esta infección el gato doméstico (Feliscatus), puede ocurrir en cualquier etapa  del embarazo, es muy  importante detectar en el primer trimestre  para evitar  trastornos del sistema nervioso central y retinocoroiditis.  El método clínico que se utilizó para el diagnóstico de los anticuerpos IgG-IgM fue electroquimiolumisencia de alta sensibilidad, los resultados obtenidos de anticuerpos IgG contra T. gondii en embarazadas, fue 16% IgG-IgM seropositivo para anti T. gondii, en relación con las mujeres embarazadas con serología positiva para T. gondii decreció linealmente con la edad de la paciente, siendo el grupo de 20-25años el más afectado 40(12%) para IgG positivo y IgM 25(10%), lo que referencia acerca de la prevalencia del Toxoplasma gondii. ABSTRACTThe aim of this study was the determination of IgM antibodies IgG anti toxoplasma gondii in pregnant women, attended in a private health place, being the main reservoir of this infection the domestic cat (Felis catus), can occur at any stage of pregnancy, it is important to detect the first trimester of pregnancy to prevent disorders of the central nervous system and retinochoroiditis. The clinical method used was electroquimiolumisencia high sensitivity for the diagnosis of IgG - IgM antibodies, the results of IgG antibodies against T. gondii in pregnant women was 16% IgG anti-IgM seropositive for T. gondii, in relation of pregnant women with positive serology for T. gondii decreased linearly with the age of the patient, being the group most affected 20-25años 40 (12%) for IgG and IgM positive 25 (10%) giving reference on prevalence of Toxoplasma gondii