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61.
In the study of depression, most randomized clinical trials have design features that attempt to sample from a stable patient population. One commonly used design feature is to require patients to maintain some minimum baseline symptom severity score during a placebo lead-in period. One intent of this design feature is to evaluate the behavior of patients prior to administration of active medication. If, during the lead-in period, patients do not maintain minimum symptom severity, the patients are excluded from the remainder of the study, the theory being that the excluded patients are not part of a stable patient population and hence are not likely to demonstrate efficacy of a truly effective treatment. This presentation investigates the effectiveness of a restrictive entry criterion and proposes an alternative explanation for what is usually defined as placebo response. 相似文献
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Rolando De la Cruz Márcia D. Branco 《Biometrical journal. Biometrische Zeitschrift》2009,51(4):588-609
We have considered a Bayesian approach for the nonlinear regression model by replacing the normal distribution on the error term by some skewed distributions, which account for both skewness and heavy tails or skewness alone. The type of data considered in this paper concerns repeated measurements taken in time on a set of individuals. Such multiple observations on the same individual generally produce serially correlated outcomes. Thus, additionally, our model does allow for a correlation between observations made from the same individual. We have illustrated the procedure using a data set to study the growth curves of a clinic measurement of a group of pregnant women from an obstetrics clinic in Santiago, Chile. Parameter estimation and prediction were carried out using appropriate posterior simulation schemes based in Markov Chain Monte Carlo methods. Besides the deviance information criterion (DIC) and the conditional predictive ordinate (CPO), we suggest the use of proper scoring rules based on the posterior predictive distribution for comparing models. For our data set, all these criteria chose the skew‐t model as the best model for the errors. These DIC and CPO criteria are also validated, for the model proposed here, through a simulation study. As a conclusion of this study, the DIC criterion is not trustful for this kind of complex model. 相似文献
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目的:探讨脑弥漫性轴索损伤(DAI)的磁共振成像(MRI)征象及其与格拉斯哥昏迷量表评分(GCS)计分和预后的关系。方
法:回顾性分析2012 年1 月-2014 年7 月我院收集的30 例DAI 患者的临床病历资料,根据病灶累及部位分析其与GCS 计分和
临床预后的关系。结果:30 例患者共53 个病灶,17例多发病灶,13 例单发病灶;42 个病灶T1WI显示出低信号或者是等信号,11
个病灶T1WI显示为高信号;T2WI显示为高信号,FLAIR 序列以及弥散加权像(DWI)上表现出的信号更高,范围更清晰;病灶形
态呈条索状27 例,斑片状11 例,卵圆形8 例,不规则斑点状7 例;病灶未累及脑中线部位的患者临床预后优于病灶累及脑中线
部位的患者,差异有统计学意义(Z=-2.636,P=0.008),病灶累及脑中线部位的患者GCS 计分情况比未累及组严重,计分更低,差
异有统计学意义(Z=-2.519,P=0.012)。结论:DAI病灶累及脑中线部位的患者GCS计分较低、预后差,MRI检查是诊断DAI 首选
的影像学方法,临床有重要的参考价值。 相似文献
65.
Chronic L‐DOPA induces hyperactivity,normalization of gait and dyskinetic behavior in MitoPark mice
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Dopamine (DA) replacement therapy continues to be the gold standard treatment for Parkinson's disease (PD), as it improves key motor symptoms including bradykinesia and gait disturbances. With time, treatment induces side effects in the majority of patients, known as L‐DOPA‐induced dyskinesia (LID), which are often studied in animals by the use of unilateral, toxin‐induced rodent models. In this study, we used the progressive, genetic PD model MitoPark to specifically evaluate bilateral changes in motor behavior following long‐term L‐DOPA treatment at three different stages of striatal DA depletion. Besides locomotor activity, we assessed changes in gait with two automated gait analysis systems and the development of dyskinetic behavior. Long‐term treatment with a moderate, clinically relevant dose of L‐DOPA (8 mg/kg) gradually produced age‐dependent hyperactivity in MitoPark mice. In voluntary and forced gait analyses, we show that MitoPark mice with severe DA depletion have distinct gait characteristics, which are normalized to control levels following long‐term L‐DOPA treatment. The cylinder test showed an age‐dependent and gradual development of bilateral LID. Significant increase in striatal FosB and prodynorphin expression was found to accompany the behavior changes. Taken together, we report that MitoPark mice model both behavioral and biochemical characteristics of long‐term L‐DOPA treatment in PD patients and provide a novel, consistent and progressive animal model of dyskinesia to aid in the discovery and evaluation of better treatment options to counteract LID. 相似文献
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Summary We propose a Bayesian dose‐finding design that accounts for two important factors, the severity of toxicity and heterogeneity in patients' susceptibility to toxicity. We consider toxicity outcomes with various levels of severity and define appropriate scores for these severity levels. We then use a multinomial‐likelihood function and a Dirichlet prior to model the probabilities of these toxicity scores at each dose, and characterize the overall toxicity using an average toxicity score (ATS) parameter. To address the issue of heterogeneity in patients' susceptibility to toxicity, we categorize patients into different risk groups based on their susceptibility. A Bayesian isotonic transformation is applied to induce an order‐restricted posterior inference on the ATS. We demonstrate the performance of the proposed dose‐finding design using simulations based on a clinical trial in multiple myeloma. 相似文献
69.
Zhang CX Danberry T Jacobs MA Augustine-Rauch K 《Birth defects research. Part B, Developmental and reproductive toxicology》2010,89(6):485-492
BACKGROUND: The rodent whole embryo culture (WEC) system is a well‐established model for characterizing developmental toxicity of test compounds and conducting mechanistic studies. Laboratories have taken various approaches in describing type and severity of developmental findings of organogenesis‐stage rodent embryos, but the Brown and Fabro morphological score system is commonly used as a quantitative approach. The associated score criteria is based upon developmental stage and growth parameters, where a series of embryonic structures are assessed and assigned respective scores relative to their gestational stage, with a Total Morphological Score (TMS) assigned to the embryo. This score system is beneficial because it assesses a series of stage‐specific anatomical landmarks, facilitating harmonized evaluation across laboratories. Although the TMS provides a quantitative approach to assess growth and determine developmental delay, it is limited to its ability to identify and/or delineate subtle or structure‐specific abnormalities. Because of this, the TMS may not be sufficiently sensitive for identifying compounds that induce structure or organ‐selective effects. METHOD: This study describes a distinct morphological score system called the “Dysmorphology Score System (DMS system)” that has been developed for assessing gestation day 11 (approximately 20–26 somite stage) rat embryos using numerical scores to differentiate normal from abnormal morphology and define the respective severity of dysmorphology of specific embryonic structures and organ systems. This method can also be used in scoring mouse embryos of the equivalent developmental stage. RESULT AND CONCLUSION: The DMS system enhances capabilities to rank‐order compounds based upon teratogenic potency, conduct structure‐ relationships of chemicals, and develop statistical prediction models to support abbreviated developmental toxicity screens. Birth Defects Res (Part B) 89:485–492, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
70.
Scott RJ 《The New phytologist》2007,173(2):227-230