Two middle-aged females presented with a mass located in the lateral quadrant of the breast. Both patients received modified radical surgery for breast cancer, radiotherapy, and chemotherapy and have ...been living without evidence of disease for more than one year. Under the microscope, we observed that the tumour cells were organised in a solid nest-like or leafy distribution and comprised sebaceous gland cells and oval or fusiform cells. The differences between the two cases are as follows: First, the mass in the first case had a mixed echo pattern on ultrasound, whereas that in the second case had a hypoechoic pattern. Pathology revealed the presence of irregular cysts in the first case, which was consistent with the ultrasound features, and microscopy revealed the presence of necrosis in the tumour. Second, the first case was strongly positive for HER-2 expression, but the second case was negative. In contrast, the second case was positive for ER expression, whereas the first case was negative. Third, the second patient had two axillary lymph node metastases, whereas the first patient had none. We analysed the obtained data to derive the following conclusions: breast sebaceous carcinoma typically occurs in middle-aged women. Under the microscope, two types of cells can be observed in a solid nest-like or leafy distribution. One cell population consists of sebaceous gland-like tumour cells, which are mostly located in the centre of the lobules or cell nests. These represent a more differentiated cell type and are rich in vacuolar cytoplasm. The other cell population consists of smaller oval or fusiform non-vacuolar cells, mostly located at the periphery of the lobules or cell nests. These cells are usually undifferentiated and are thus difficult to distinguish from typical ductal carcinoma cells. Breast sebaceous carcinoma has a high rate of positive expression of ER, PR, p53, and EMA and a low rate of positive expression of HER-2 and GCDFP-15. Primary breast sebaceous cancer has the following diagnostic characteristics: sebaceous differentiation in at least 50% of cells in the absence of any evidence of originating in the cutaneous adnexa; features, such as ductal carcinoma differentiation, lobular carcinoma differentiation, and others, which can be found in primary breast sebaceous cancer, distinct from those in skin sebaceous adenocarcinoma; and a typical transitional structure between the cancer tissue and ductal epithelium. Breast sebaceous carcinoma should be distinguished from skin sebaceous adenocarcinoma, lipid-rich carcinoma, apocrine carcinoma, and glycogen-rich clear cell carcinoma, among others. Furthermore, this is a hormone receptor-dependent type of breast cancer that requires comprehensive treatment. Thus, after extensive analysis, we conclude that breast sebaceous carcinoma has low invasiveness and good prognosis.
Traditional Chinese medicine (TCM) formulas can be adjusted on the basis of TCM basic theory to achieve the best curative effect, especially for diseases with complex pathogenesis, such as ...post-weaning diarrhea (PWD). Shugan Jianwei Sijunzi decoction (SJ-SJZD) can be recognized as modified Sijunzi Decoction (SJZD) supplemented with
Astragalus mongholicus Bunge, Bupleurum chinense DC, Citrus
×
aurantium L., and Crataegus pinnatifida Bunge (fruit)
in a fixed dosage ratio. The inactive ingredients were subsequently added to make granule, which was Shugan Jianwei Sijunzi granule (SJ-SJZG). Previous studies have confirmed the antagonism of SJ-SJZG to PWD. However, the mechanism of SJ-SJZG protective effects on small intestine in weaned Rex rabbits remained unclear. Animals were randomly divided into negative control (NC), low dose (LD), medium dose (MD), high dose (HD), and positive control (PC). SJ-SJZG significantly increased the intestinal length and the jejunum villi length. The SIgA level was statistically increased in duodenum and jejunum with the ELISA. Immunohistochemical detection showed that SIgA protein expression was also increased significantly in jejunum. Meanwhile, the relative expression of Zo1 in duodenum and jejunum of SJ-SJZG group increased significantly. SJ-SJZG significantly increased the relative expression of occludin in duodenum and jejunum as well. Moreover, real-time PCR results showed a significant increase in GLUT2 and SGLT1 relative expression in ileum. SJ-SJZG could also obviously enhance the expression of GLUT2 in jejunum and the expression of SGLT1 in duodenum. In conclusion, SJ-SJZG had been proven to be effective in promoting the development of small intestine and improving the immunity of small intestine. Moreover, SJ-SJZG could ensure the integrity of mucosal barrier and increase the ability of intestine to absorb glucose in small intestine.
Summary
We consider the problem of estimating and inferring treatment effects in randomized experiments. In practice, stratified randomization, or more generally, covariate-adaptive randomization, is ...routinely used in the design stage to balance treatment allocations with respect to a few variables that are most relevant to the outcomes. Then, regression is performed in the analysis stage to adjust the remaining imbalances to yield more efficient treatment effect estimators. Building upon and unifying recent results obtained for ordinary-least-squares adjusted estimators under covariate-adaptive randomization, this paper presents a general theory of regression adjustment that allows for model mis-specification and the presence of a large number of baseline covariates. We exemplify the theory on two lasso-adjusted treatment effect estimators, both of which are optimal in their respective classes. In addition, nonparametric consistent variance estimators are proposed to facilitate valid inferences, which work irrespective of the specific randomization methods used. The robustness and improved efficiency of the proposed estimators are demonstrated through numerical studies.
Randomized block factorial experiments are widely used in industrial engineering, clinical trials, and social science. Researchers often use a linear model and analysis of covariance to analyze ...experimental results; however, limited studies have addressed the validity and robustness of the resulting inferences because assumptions for a linear model might not be justified by randomization in randomized block factorial experiments. In this article, we establish a new finite population joint central limit theorem for usual (unadjusted) factorial effect estimators in randomized block 2K factorial experiments. Our theorem is obtained under a randomization-based inference framework, making use of an extension of the vector form of the Wald–Wolfowitz–Hoeffding theorem for a linear rank statistic. It is robust to model misspecification, numbers of blocks, block sizes, and propensity scores across blocks. To improve the estimation and inference efficiency, we propose four covariate adjustment methods. We show that under mild conditions, the resulting covariate-adjusted factorial effect estimators are consistent, jointly asymptotically normal, and generally more efficient than the unadjusted estimator. In addition, we propose Neyman-type conservative estimators for the asymptotic covariances to facilitate valid inferences. Simulation studies and a clinical trial data analysis demonstrate the benefits of the covariate adjustment methods. Supplementary materials for this article are available online.
Linear regression is arguably the most fundamental statistical model; however, the validity of its use in randomized clinical trials, despite being common practice, has never been crystal clear, ...particularly when stratified or covariate‐adaptive randomization is used. In this article, we investigate several of the most intuitive and commonly used regression models for estimating and inferring the treatment effect in randomized clinical trials. By allowing the regression model to be arbitrarily misspecified, we demonstrate that all these regression‐based estimators robustly estimate the treatment effect, albeit with possibly different efficiency. We also propose consistent non‐parametric variance estimators and compare their performances to those of the model‐based variance estimators that are readily available in standard statistical software. Based on the results and taking into account both theoretical efficiency and practical feasibility, we make recommendations for the effective use of regression under various scenarios. For equal allocation, it suffices to use the regression adjustment for the stratum covariates and additional baseline covariates, if available, with the usual ordinary‐least‐squares variance estimator. For unequal allocation, regression with treatment‐by‐covariate interactions should be used, together with our proposed variance estimators. These recommendations apply to simple and stratified randomization, and minimization, among others. We hope this work helps to clarify and promote the usage of regression in randomized clinical trials.
Lung allografts are prone to reperfusion injury and acute rejection, which, in addition to infiltrating lymphocytes, are accompanied by neutrophil infiltration and neutrophil-associated oxidative ...stress. Indoleamine 2,3-dioxygenase (IDO) is a unique cytosolic enzyme that possesses T-cell-suppressive and antioxidant properties.
The purpose of this study was to determine if genetic up-regulation of IDO could ameliorate acute lung allograft injury.
Lung orthotopic transplants were performed using Lewis donors and Sprague-Dawley rat recipients (allografts) or the same strain (isografts). Plasmid-encoding human IDO was delivered to donor lungs in vivo using a nonviral gene-transfer vector, polyethylenimine. Transplanted lungs were evaluated at 6 d post-transplantation based on pulmonary function, histology, inflammatory responses, and their associated oxidative stress. Basic biology of the IDO-overexpressing lung cells was evaluated in vitro in response to external oxidant.
This gene delivery method led to uniform transgene expression in lung tissue distributed in airway, alveolar epithelial, and endothelial cells. IDO overexpression in lung allografts resulted in a significant protective effect with improvement in functional properties (peak airway pressure and oxygenation) and histologic appearance. Although IDO was able to block local T-cell responses, it failed to abrogate neutrophilic infiltration and the inflammation-associated oxidative stress. IDO-enhanced lung cells were resistance to oxidant-induced necrosis and apoptosis by limiting intracellular reactive oxygen species formation.
These results demonstrate that IDO prevents acute lung allograft injury through augmenting the local antioxidant defense system and inhibiting alloreactive T-cell responses.
Stratification and rerandomization are two well-known methods used in randomized experiments for balancing the baseline covariates. Renowned scholars in experimental design have recommended combining ...these two methods; however, limited studies have addressed the statistical properties of this combination. This article proposes two rerandomization methods to be used in stratified randomized experiments, based on the overall and stratum-specific Mahalanobis distances. The first method is applicable for nearly arbitrary numbers of strata, strata sizes, and stratum-specific proportions of the treated units. The second method, which is generally more efficient than the first method, is suitable for situations in which the number of strata is fixed with their sizes tending to infinity. Under the randomization inference framework, we obtain the asymptotic distributions of estimators used in these methods and the formulas of variance reduction when compared to stratified randomization. Our analysis does not require any modeling assumption regarding the potential outcomes. Moreover, we provide asymptotically conservative variance estimators and confidence intervals for the average treatment effect. The advantages of the proposed methods are exhibited through an extensive simulation study and a real-data example.
Diamond ball-end milling is an enabling technology to fabricate complex curved surfaces with a nanometer level roughness. However, limited by the errors of tool manufacturing and installation, the ...cutting edge profile of a single-bladed diamond milling tool cannot form an ideal sphere crown in rotation, which will significantly worsen the machining accuracy. Although a titled milling method and a tool error reduction method based on milling-test have been proposed to improve the machining accuracy, a complete analysis of the effects of multiple tool errors on the machining accuracy have not been performed. Therefore, the present work contributes an analytical model to accurately calculate the tool rotation profile under various position and orientation errors. The results reveal that the horizontal off-center error of tool cutting edge is the dominant error among all the tool errors. According to the results, a novel high precision identification process is developed to evaluate the horizontal off-center error in view of the cutting-mark, and subsequently a tool center shift method is proposed to compensate for such error. Finally, experiments on millimeter scale spherical surface, micro sphere array and micro sinusoidal surface confirm that the proposed tool error compensation method can significantly improve the form accuracy. The average form errors (PV) of three test surfaces are reduced from 2.29 μm, 0.90 μm and 0.88 μm, down to 0.61 μm, 0.28 μm and 0.18 μm, respectively.
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•An analytical model is established to determine the dominant tool error.•An identification method is developed to calibrate tool off-center error.•A tool center shift method is proposed to compensate tool off-center error.•Surface profile accuracy is significantly improved after tool error compensation.
Randomized block factorial experiments are widely used in industrial engineering, clinical trials, and social science. Researchers often use a linear model and analysis of covariance to analyze ...experimental results; however, limited studies have addressed the validity and robustness of the resulting inferences because assumptions for a linear model might not be justified by randomization in randomized block factorial experiments. In this article, we establish a new finite population joint central limit theorem for usual (unadjusted) factorial effect estimators in randomized block
2
K
factorial experiments. Our theorem is obtained under a randomization-based inference framework, making use of an extension of the vector form of the Wald-Wolfowitz-Hoeffding theorem for a linear rank statistic. It is robust to model misspecification, numbers of blocks, block sizes, and propensity scores across blocks. To improve the estimation and inference efficiency, we propose four covariate adjustment methods. We show that under mild conditions, the resulting covariate-adjusted factorial effect estimators are consistent, jointly asymptotically normal, and generally more efficient than the unadjusted estimator. In addition, we propose Neyman-type conservative estimators for the asymptotic covariances to facilitate valid inferences. Simulation studies and a clinical trial data analysis demonstrate the benefits of the covariate adjustment methods.
Supplementary materials
for this article are available online.
Micro diamond tools are indispensable for machining microstructured arrays. The cutting edge durability and consistency of micro diamond tools are the determinants of the microstructure quality and ...accuracy, in addition to the motion accuracy of the machine tool. A strength distribution model of the working area including the cutting edge and rake and flank faces was established considering diamond anisotropy and chip flow direction. Comprehensive wear resistances of micro diamond tools with different crystal orientation combinations were analyzed based on the model, and the wear prone areas of different tools were successfully predicted. The evolution processes of the sharpness and wear topography were monitored for every micro diamond tool in the micromachining experiments. The morphologies, profile errors and topological characteristic of the microstructures machined with different micro diamond tools with increasing cutting distance were analyzed. Finally, a conclusion was drawn that the wear resistances of the micro diamond tools in ascending order are Aγ{100}Aα{100}, Aγ{100}Aα{110}, Aγ{110}Aα{100}, and Aγ{110}Aα{110}. The three working areas of the Aγ{100}Aα{100} tool are prone to wear; in contrast, those of the Aγ{110}Aα{110}tool are resistant to wear. The tool wear of Aγ{100}Aα{110}is caused by flank face wear, and that of Aγ{110}Aα{100} is caused by rake face wear.
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•A 3D spatial strength model of micro diamond tool nose is developed for the micromachining.•Relative wear resistance and wear location of micro diamond tools are successfully predicted.•A wear resistant design scheme for the micro diamond tools is indicated to prolong tool life.•Dependence of the machined quality on the crystal orientation of micro diamond tool was revealed.
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